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1
Riegel, JA. "Analysis of fluid dynamics in perfused glomeruli of the hagfish eptatretus stouti (Lockington)." Journal of Experimental Biology 201, no. 22 (November 1, 1998): 3097–104. http://dx.doi.org/10.1242/jeb.201.22.3097.
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The capillary tuft of glomeruli of the hagfish mesonephros contains both 'low'-pressure and 'high'-pressure glomerular vessels (LPGVs and HPGVs). The existence of the HPGV raised the possibility that pressure filtration could occur in the hagfish kidney when the blood pressure was sufficiently high. Therefore, measurements of glomerular capillary pressure were made in HPGVs and LPGVs whilst single glomeruli were perfused with hagfish Ringer's solution that contained the colloid Ficoll 70. Calculations of the effective colloid osmotic pressure in perfused capillaries were made; these showed that hydrostatic pressures within the HPGV were inadequate to effect pressure filtration except at high rates of perfusion. However, high rates of perfusion provoked perfusion pressures that exceeded the highest values measured in the renal blood supply of lightly anaesthetised hagfish. It was concluded that some process other than pressure filtration must account for formation of the primary urine by hagfish glomeruli. The proportion of the perfusate that became urine, the single glomerulus filtration fraction (SGFF), bore a strong positive relationship to the vascular resistance of perfused glomeruli. Both the SGFF and the vascular resistance were inversely related to the rate of perfusion except when that rate was very high. From these two observations it was concluded that at least two flow pathways exist in hagfish glomeruli: one that has a high vascular resistance and that contributes to the elaboration of the urine, and one that has a low vascular resistance and does not contribute to urine formation. The possible anatomical location of the various flow pathways through hagfish glomeruli and how they may function are discussed.
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Arendshorst, W. J., and C. W. Gottschalk. "Glomerular ultrafiltration dynamics: historical perspective." American Journal of Physiology-Renal Physiology 248, no. 2 (February 1, 1985): F163—F174. http://dx.doi.org/10.1152/ajprenal.1985.248.2.f163.
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Our knowledge of the structure and function of the renal glomerulus is reviewed in a historical context. The glomerular corpuscles were first described by Malpighi in 1666. Subsequent injection studies led to conflicting claims concerning a glomerular-tubular connection. This connection was accepted only after the convincing demonstration of the anatomical relationship essentially as we now know it by Bowman in 1842. Ludwig was the first to propose that the mechanism of separation of fluid in the glomeruli was by ultrafiltration. Estimates of the ultrafiltration forces in mammals led to conflicting speculation as to whether or not filtration-pressure equilibrium was reached in glomerular capillaries. Results of direct determinations in some Munich-Wistar rats indicate filtration pressure equilibrium, an ultrafiltration coefficient (Kf) of 0.08 nl X s-1 X mmHg-1, and a strong influence of plasma flow on filtration rate (GFR). In contrast, evidence has been presented that filtration dynamics in other Munich-Wistar rats and several other strains of rats are characterized by filtration disequilibrium, a Kf of 0.04 nl X s-1 X mmHg-1, and a weak dependence of GFR on plasma flow. In conscious and anesthetized rats, kidney GFR is usually relatively stable in the presence of renal vasodilation. Filtration disequilibrium is reported in the dog and equilibrium in the squirrel monkey. Although predictions for humans suggest filtration disequilibrium, final conclusions await an in-depth analysis of direct measurements.
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Dong, Jianghu J., Liangliang Wang, Jagbir Gill, and Jiguo Cao. "Functional principal component analysis of glomerular filtration rate curves after kidney transplant." Statistical Methods in Medical Research 27, no. 12 (June 20, 2017): 3785–96. http://dx.doi.org/10.1177/0962280217712088.
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This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.
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Squarer, A., K. V. Lemley, S. Ambalavanan, B. Kristal, W. M. Deen, R. Sibley, L. Anderson, and B. D. Myers. "Mechanisms of progressive glomerular injury in membranous nephropathy." Journal of the American Society of Nephrology 9, no. 8 (August 1998): 1389–98. http://dx.doi.org/10.1681/asn.v981389.
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Glomerular function and structure were serially evaluated in 15 patients with membranous nephropathy who exhibited relapsing nephrosis and chronic depression of GFR. GFR declined from 56+/-8 (mean+/-SEM) at onset to 31+/-4 ml/min per 1.73 m2 after a 2- to 5-yr period of observation (P < 0.05). An analysis of filtration dynamics suggested persistent elevation of net ultrafiltration pressure. To examine a possible role for declining intrinsic glomerular filtration capacity as the basis for the observed hypofiltration, glomeruli in the baseline and a repeat biopsy (performed after a median of 28 mo) were subjected to morphometric analysis and mathematical modeling. Analysis of the baseline biopsy revealed a reduction in filtration slit frequency and thickening of the glomerular basement membrane, lowering computed hydraulic permeability by 66% compared with normal kidney donors. In contrast, filtration surface area was increased by 37% as a result of glomerular hypertrophy. The repeat biopsy revealed persistent depression of hydraulic permeability, primarily owing to foot process broadening. An additional finding was a decrease in filtration surface area from baseline in patent glomeruli, possibly due to encroachment on the capillary lumen of an increasingly widened basement membrane. Also, a striking increase in the prevalence of global glomerulosclerosis from 7+/-2% to 23+/-4% was found between the two biopsies, suggesting a significant loss of functioning nephrons. It is concluded that hypofiltration in membranous nephropathy is the consequence of a biphasic loss of glomerular ultrafiltration capacity, initially owing to impaired hydraulic permeability that is later exacerbated by a superimposed loss of functioning glomeruli and of filtration surface area.
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Drummond, I. A., A. Majumdar, H. Hentschel, M. Elger, L. Solnica-Krezel, A. F. Schier, S. C. Neuhauss, et al. "Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function." Development 125, no. 23 (December 1, 1998): 4655–67. http://dx.doi.org/10.1242/dev.125.23.4655.
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The zebrafish pronephric kidney provides a simplified model of nephron development and epithelial cell differentiation which is amenable to genetic analysis. The pronephros consists of two nephrons with fused glomeruli and paired pronephric tubules and ducts. Nephron formation occurs after the differentiation of the pronephric duct with both the glomeruli and tubules being derived from a nephron primordium. Fluorescent dextran injection experiments demonstrate that vascularization of the zebrafish pronephros and the onset of glomerular filtration occurs between 40 and 48 hpf. We isolated fifteen recessive mutations that affect development of the pronephros. All have visible cysts in place of the pronephric tubule at 2–2.5 days of development. Mutants were grouped in three classes: (1) a group of twelve mutants with defects in body axis curvature and manifesting the most rapid and severe cyst formation involving the glomerulus, tubule and duct, (2) the fleer mutation with distended glomerular capillary loops and cystic tubules, and (3) the mutation pao pao tang with a normal glomerulus and cysts limited to the pronephric tubules. double bubble was analyzed as a representative of mutations that perturb the entire length of the pronephros and body axis curvature. Cyst formation begins in the glomerulus at 40 hpf at the time when glomerular filtration is established suggesting a defect associated with the onset of pronephric function. Basolateral membrane protein targeting in the pronephric duct epithelial cells is also severely affected, suggesting a failure in terminal epithelial cell differentiation and alterations in electrolyte transport. These studies reveal the similarity of normal pronephric development to kidney organogenesis in all vertebrates and allow for a genetic dissection of genes needed to establish the earliest renal function.
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Anderson, W. P., D. Alcorn, A. I. Gilchrist, J. M. Whiting, and G. B. Ryan. "Glomerular actions of ANG II during reduction of renal artery pressure: a morphometric analysis." American Journal of Physiology-Renal Physiology 256, no. 6 (June 1, 1989): F1021—F1026. http://dx.doi.org/10.1152/ajprenal.1989.256.6.f1021.
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The glomeruli of kidneys subjected to reduced perfusion pressure were examined morphometrically. The left renal artery was narrowed for 30 min in anesthetized dogs with (n = 6) or without (n = 7) converting-enzyme inhibition (captopril). The kidneys were then rapidly fixed by glutaraldehyde perfusion at high flow rate. In a comparison of glomeruli of kidneys subjected to pressure reduction in captopril-treated and untreated dogs, there was significantly greater mesangial contraction in the latter, but morphometric analysis revealed no significant differences in the glomerular surface area available for filtration as evidenced by glomerular capillary volume fractions, surface areas of the filtering basement membrane between epithelial and endothelial cells, or the length densities of the glomerular epithelial slits. In a comparison of the left (pressure reduction) and right (no pressure reduction) kidneys in the captopril-treated dogs, there was no significant effect of reduction of renal perfusion pressure per se on mesangial contraction or glomerular filtration surface area when angiotensin (ANG) II formation was blocked. Thus ANG II caused mesangial cell contraction after renal artery stenosis, but this did not significantly change glomerular ultrafiltration surface area.
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Scharschmidt, L. A., J. G. Douglas, and M. J. Dunn. "Angiotensin II and eicosanoids in the control of glomerular size in the rat and human." American Journal of Physiology-Renal Physiology 250, no. 2 (February 1, 1986): F348—F356. http://dx.doi.org/10.1152/ajprenal.1986.250.2.f348.
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We examined the possibility that glomerular prostaglandin E2 (PGE2) regulates the action of angiotensin II (ANG II) on mesangial contraction and filtration surface area. Using isolated rat glomeruli we indirectly assessed mesangial contraction and filtration surface area through measurements of glomerular planar surface area (GPSA) by image-analysis microscopy. ANG II reduced GPSA by approximately 20% in human and rat glomeruli, with threshold concentrations of 1 X 10(-13) M and maximum effect at 5 X 10(-11) M ANG II. Inhibition of glomerular PG synthesis with indomethacin or meclofenamate potentiated the threshold response of ANG II to reduce GPSA. Arachidonic acid (5 micrograms/ml) blunted both the threshold and the maximum responses of GPSA to ANG II. PGE2, 10(-8) and 10(-9) M, also decreased glomerular contraction to ANG II. Endoperoxide (EP) analogues decreased GPSA and EP 045, a thromboxane A2 (TXA2) receptor blocker, eliminated the contractile responses of glomeruli to the EP analogues. Authentic TXA2, synthesized from sheep platelet microsomes, also reduced GPSA. We conclude that glomerular products of arachidonate cyclooxygenation may either relax or contract the mesangium, thereby preserving or reducing filtration surface area. PGE2 exerts protective actions to reduce the mesangial contraction of ANG II, primarily through postreceptor effects. TXA2 may decrease glomerular filtration rate in certain diseases through direct actions on the mesangium.
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Uchio-Yamada, Kozue, Keiko Yasuda, Yoko Monobe, Ken-ichi Akagi, Osamu Suzuki, and Noboru Manabe. "Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier." American Journal of Physiology-Renal Physiology 318, no. 6 (June 1, 2020): F1520—F1530. http://dx.doi.org/10.1152/ajprenal.00055.2020.
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Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that Tns2-deficient mice exhibit defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-α2 accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that Tns2 deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-α2 in podocytes. Our study suggests that weakened podocyte-GBM interaction due to Tns2 deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-α2, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier.
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Myers, B. D., and L. Newton. "Cyclosporine-induced chronic nephropathy: an obliterative microvascular renal injury." Journal of the American Society of Nephrology 2, no. 2 (August 1991): S45. http://dx.doi.org/10.1681/asn.v22s45.
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Physiologic and morphologic techniques have been used to study kidneys of 200 cardiac transplant recipients treated with either low- or high-dose cyclosporine. After 12 months, both low- (4.6 +/- 0.4) and high-dose cyclosporine (6.3 +/- 0.3 mg/kg/24 h; P less than 0.01) were associated with depression of glomerular filtration rate below values in a third group of 100 recipients never exposed to cyclosporine by 40 to 47%. Determination of renovascular pressures and flows as well as analysis of transglomerular sieving of dextrans revealed renal vascular resistance in cyclosporine-treated recipients to be elevated greater than twofold, due largely to an increase in preglomerular resistance. Morphologic changes in renal tissue of both cyclosporine groups included an occlusive afferent arteriolopathy with downstream collapse or sclerosis of glomeruli. Ischemic nephrons were associated with patchy fibrosis of the surrounding interstitium. Follow-up for up to 9 yr reveals persistent but stable azotemia, on average. Longitudinal physiologic studies over a 48-month period (N = 15) during which cyclosporine was reduced in dosage (to 3.1 +/- 0.3 mg/kg) or withdrawn revealed a persistently reduced but constant level of glomerular filtration rate. Increasing ischemic glomerular collapse and sclerosis were observed at repeat renal biopsy. Remnant (spared) glomeruli exhibited hypertrophy; presumably elevated single nephron glomerular filtration rate maintained two-kidney glomerular filtration rate constant despite the declining fraction of functional glomeruli. By actuarial analysis, the cumulative incidence of end-stage renal failure in cardiac transplant recipients treated at this institution from 1980 onwards with continuous cyclosporine therapy has reached 10%.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hladunewich, M. A., R. A. Lafayette, G. C. Derby, K. L. Blouch, J. W. Bialek, M. L. Druzin, W. M. Deen, and B. D. Myers. "The dynamics of glomerular filtration in the puerperium." American Journal of Physiology-Renal Physiology 286, no. 3 (March 2004): F496—F503. http://dx.doi.org/10.1152/ajprenal.00194.2003.
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We evaluated the glomerular filtration rate (GFR) during the second postpartum week in 22 healthy women who had completed an uncomplicated pregnancy. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient ( Kf). We compared these findings with those in pregnant women previously studied on the first postpartum day as well as nongravid women of reproductive age. Healthy female transplant donors of reproductive age permitted the morphometric analysis of glomeruli and computation of the single-nephron Kf. The aforementioned physiological and morphometric measurements were utilized to estimate transcapillary hydraulic pressure (ΔP) from a mathematical model of glomerular ultrafiltration. We conclude that postpartum day 1 is associated with marked glomerular hyperfiltration (+41%). A theoretical analysis of GFR determinants suggests that depression of glomerular capillary oncotic pressure, the force opposing the formation of filtrate, is the predominant determinant of early elevation of postpartum GFR. A reversal of the gestational hypervolemia and hemodilution, still evident on postpartum day 1, eventuates by postpartum week 2. An elevation of oncotic pressure in the plasma that flows axially along the glomerular capillaries to supernormal levels ensues; however, GFR remains modestly elevated (+20%) above nongravid levels. An analysis of filtration dynamics at this time suggests that a significant increase in ΔP by up to 16%, an ∼50% increase in Kf, or a combination of smaller increments in both must be invoked to account for the persistent hyperfiltration.
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Murphy, M. J., S. C. Brown, N. B. Clark, and J. Q. Feng. "Compartmental analysis and glomerular filtration in chick embryos." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 6 (December 1, 1991): R1478—R1483. http://dx.doi.org/10.1152/ajpregu.1991.261.6.r1478.
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We have developed microtechniques that allow the determination of compartmental fluid distribution and glomerular filtration rate in chick embryos during three significant developmental periods: phase 1, the developmental period when the mesonephros alone is functioning; phase 2, periods of simultaneous meso/metanephric kidney function; and phase 3, the period during late development when the metanephros completely replaces the degenerated mesonephros. Water content of tissues is greater in younger embryos (89.4 +/- 0.2%, day 10) compared with older animals (78.3 +/- 0.5%, day 18). Although all major tissue components show an absolute increase in mass during this period, the embryo proper increases at five times the rate of the extraembryonic tissues. Glomerular filtration rate increases during development from 0.61 +/- 0.08 ml/h at day 10 to 2.31 +/- 0.11 ml/h at day 18. Glomerular filtration rate scales to body mass with an allometric exponent identical to adult birds only if total tissue mass (embryo + membranes) is considered. Our data suggest that significant errors in allometry will be encountered when scaling measurements are made on embryonic or fetal amniotes without taking into consideration the extraembryonic tissues.
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Drumond, M. C., and W. M. Deen. "Analysis of pulsatile pressures and flows in glomerular filtration." American Journal of Physiology-Renal Physiology 261, no. 3 (September 1, 1991): F409—F419. http://dx.doi.org/10.1152/ajprenal.1991.261.3.f409.
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Previous mathematical models of glomerular filtration have ignored the pulsatility of the glomerular capillary pressure, using only steady-state equations and time-averaged pressures and flows. Because the actual pressure pulses are rapid and of large amplitude and because the governing equations are nonlinear, it is questionable whether the effects of the pressure pulses average out in the manner that has been assumed. We have developed a model that includes sinusoidal variations in the glomerular transcapillary hydraulic pressure (delta P) and the afferent arteriolar plasma flow rate over each cardiac cycle. The analysis suggests that the previously ignored time derivatives in the luminal mass balance equations are not negligible. The amplitude of the oscillations in delta P was found to be sufficient to reverse the direction of the transmural fluxes over part of each cardiac cycle, at the more efferent locations in a capillary. However, the time-averaged values of single-nephron glomerular filtration rate and sieving coefficients for macro-molecules from the pulsatile model differed from that for a steady-state formulation by less than 0.1 and less than or equal to 10%, respectively. We conclude that use of the usual steady-state assumption introduces negligible errors in calculating glomerular membrane parameters from experimental data.
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Pagtalunan, M. E., R. Rasch, H. G. Rennke, and T. W. Meyer. "Morphometric analysis of effects of angiotensin II on glomerular structure in rats." American Journal of Physiology-Renal Physiology 268, no. 1 (January 1, 1995): F82—F88. http://dx.doi.org/10.1152/ajprenal.1995.268.1.f82.
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Micropuncture and morphometric studies related the effects of angiotensin II (ANG II) on glomerular function and structure. Compared with control animals, rats receiving an intrarenal infusion of ANG II at 40 ng.kg-1.min-1 exhibited a marked reduction in the glomerular ultrafiltration coefficient (Kf) (0.84 +/- 0.13 vs. 1.43 +/- 0.05 microliters.s-1.mmHg-1, ANG II vs. control), which caused a decrease in glomerular filtration rate (GFR) (1.04 +/- 0.11 vs. 1.27 +/- 0.11 ml/min) despite an increase in glomerular transcapillary hydraulic pressure difference (46 +/- 1 vs. 40 +/- 1 mmHg). Morphometric studies showed that these hemodynamic changes were not associated with any reduction in glomerular volume (1.27 +/- 0.05 vs. 1.31 +/- 0.07 x 10(6) microns3, ANG II vs. control), glomerular capillary volume (4.25 +/- 0.36 vs. 4.41 +/- 0.33 x 10(5) microns3), or glomerular peripheral capillary surface area (2.24 +/- 0.11 vs. 2.29 +/- 0.30 x 10(5) microns2). Higher-power electron micrographs showed that ANG II also did not alter mean foot process width (478 +/- 14 vs. 491 +/- 18 nm, ANG II vs. control), reduce the total filtration slit length overlying the peripheral capillary wall (7.0 +/- 0.6 vs. 6.6 +/- 0.5 x 10(5) microns), or reduce the average width of individual filtration slits (45 +/- 2 vs. 43 +/- 2 nm). ANG II infusion thus caused a 40% reduction in the value of Kf without causing detectable changes in epithelial cell or filtration slit structure.
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Mottl, Amy K., Suma Vupputuri, Shelley A. Cole, Laura Almasy, Harald H. H. Göring, Vincent P. Diego, Sandra Laston, et al. "Linkage analysis of glomerular filtration rate in American Indians." Kidney International 74, no. 9 (November 2008): 1185–91. http://dx.doi.org/10.1038/ki.2008.410.
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Guasch, A., R. K. Sibley, P. Huie, and B. D. Myers. "Extent and course of glomerular injury in human membranous glomerulopathy." American Journal of Physiology-Renal Physiology 263, no. 6 (December 1, 1992): F1034—F1043. http://dx.doi.org/10.1152/ajprenal.1992.263.6.f1034.
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Glomerular permselectivity and dynamics were evaluated serially in 14 nephrotic patients with membranous glomerulopathy (MG). Analysis of transglomerular dextran sieving, before and again after proteinuria remitted, revealed persistent depression by 60-80% of glomerular pore density and the two-kidney ultrafiltration coefficient, Kf. The glomerular filtration rate was lowered by half on each occasion. Morphometric examination of glomeruli in a second group of 16 nephrotic patients with MG revealed a low prevalence of glomerulosclerosis (5 +/- 3%) and a twofold increase in filtration surface due to marked glomerular hypertrophy. Presumably, widening by threefold of the basement membrane and/or epithelial podocytes accounted for the computed reduction in ultrafiltration capacity. There was no correlation between glomerular structure and the subsequent course of MG over the ensuing 24-96 mo. Rather, a twofold expansion of the interstitial compartment predicted those who went on to exhibit progressive renal insufficiency. We conclude that increasing resistance to water flow by walls of patent and perfused glomerular capillaries is the proximate cause of progressive renal insufficiency in MG.
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Rahmawati, Febtarini. "Aspek Laboratorium Gagal Ginjal Kronik." Jurnal Ilmiah Kedokteran Wijaya Kusuma 6, no. 1 (March 2, 2018): 14. http://dx.doi.org/10.30742/jikw.v6i1.323.
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Chronic renal disease is a disorder of renal function or structure that lasts for more than three months, accompanied by a decrease in glomerular filtration rate. Decreasing of renal function monitoring is performed by measuring glomerular filtration rate, determining blood urea, creatinine, creatinine clearance, electrolytes, uric acid, blood gas analysis and tubular function. The Recent method for measuring glomerular filtration rate using inulin clearance, however, is not efficient. Further measurements of creatinine glomerular filtration rate were developed. Measurements of urea, creatinine and uric acid are currently using enzymatic methods of spectrophotometry, while electrolyte examination by selective ion electrode method. Blood gas analysis determined pH, PCO2, PO2, HCO3-, CO2 total, base excess and SO2. Examination of urine protein and urine sediments helps establish a diagnosis of chronic kidney disease
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Detsika, Maria G., Vasiliki Lygirou, Vassileios Frantzis, Jerome Zoidakis, Vassilios Atsaves, Elpida Poulaki, Hariklia Gakiopoulou, Antonia Vlahou, and Elias A. Lianos. "Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics." American Journal of Nephrology 43, no. 6 (2016): 441–50. http://dx.doi.org/10.1159/000446859.
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Background: The cytoprotective effect of heme oxygenase (HO)-1 in various forms of renal glomerular injury is established. However, little is known on the role of HO-1 in preserving glomerular structural/functional integrity in the absence of injury. The present study addressed this question in HO-1-deficient rats. Methods: HO-1-deficient rats were generated using zinc finger nuclease-mediated HO-1 gene (Hmox1) disruption and studied. Glomeruli were isolated from HO-1-deficient (Hmox1-/-) rats and their wild type (WT) littermates for proteomic analysis. Results: Glomerular lesions were characterized and differentially expressed proteins important for preserving integrity of the glomerular filtration barrier were identified. HO-1-deficient (Hmox1-/-) rats developed albuminuria with decreased glomerular filtration rate. In albuminuric rats, there were lesions resembling focal and segmental glomerulosclerosis (FSGS). Western blot analysis of the integral slit diaphragm proteins, nephrin and podocin revealed a significant decrease in nephrin, with no change in podocin. Proteomic analysis of glomerular protein lysates from Hmox1-/- and WT rats revealed differential expression of proteins previously linked with FSGS pathogenesis. Specifically, α-actinin-4, actin related protein 3, cytokeratins and novel candidates including transgelin-2 and lamins. Bioinformatic analysis predicted the upregulation of pathways implicated in platelet aggregation and fibrin clot formation. Conclusion: HO-1 is a putative regulator of proteins important in preserving glomerular structural stability and integrity, and in minimizing the activity of proinflammatory pathways.
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Guasch, A., H. Hashimoto, R. K. Sibley, W. M. Deen, and B. D. Myers. "Glomerular dysfunction in nephrotic humans with minimal changes or focal glomerulosclerosis." American Journal of Physiology-Renal Physiology 260, no. 5 (May 1, 1991): F728—F737. http://dx.doi.org/10.1152/ajprenal.1991.260.5.f728.
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Fractional clearances (theta) of uncharged dextrans (radii 28-60 A) were used to characterize glomerular dysfunction in 34 nephrotic humans with either minimal-change nephropathy (MCN) or focal, segmental glomerulosclerosis (FSGS). A theoretical analysis of theta of dextran with a heteroporous membrane model revealed a similar alteration, more marked in FSGS than MCN. The number of restrictive pores perforating the major membrane component was reduced in parallel with the prevailing glomerular filtration rate (GFR). Parallel shuntlike pores in the remaining membrane component were more prominent, pointing to impaired size selectivity. However, the theta of large (60 A) dextrans attributable to these shunts exceeded control in FSGS only, suggesting that coexistent impairment of charge selectivity contributed importantly to the proteinuria in MCN. Membrane properties returned toward normal when MCN remitted. Glomerular morphometry revealed the frequency of epithelial filtration slits to vary with the extent of membrane dysfunction. Despite offsetting hypertrophy of remnant glomeruli in FSGS, a loss of filtration surface due to sclerosis likely contributed to the more marked reductions in pore number and GFR observed in this disorder than in MCN.
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A. Molitoris, Bruce, Daniel J. Meier, Exing Wang, Ruben M. Sandoval, Erinn Sheridan, and James S. Strickland. "Quantifying Glomerular Filtration Rates: Kidney Function Analysis Method and Apparatus." Recent Patents on Biomarkerse 2, no. 3 (August 1, 2012): 209–18. http://dx.doi.org/10.2174/2210309011202030209.
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Lee, M., J. L. Saver, K. H. Chang, H. W. Liao, S. C. Chang, and B. Ovbiagele. "Low glomerular filtration rate and risk of stroke: meta-analysis." BMJ 341, sep30 1 (September 30, 2010): c4249. http://dx.doi.org/10.1136/bmj.c4249.
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Mineev, V. N., A. A. Kuzmina, and T. M. Lalaeva. "Apelin/APJ signal system and glomerular filtration rate in various variants of bronchial asthma." Nephrology (Saint-Petersburg) 24, no. 4 (June 26, 2020): 55–60. http://dx.doi.org/10.36485/1561-6274-2020-24-4-55-60.
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INTRODUCTION. We have previously postulated the similarity of molecular pathogenetic mechanisms in bronchial asthma (BA) and chronic kidney disease (CKD). Understanding these mechanisms in such a comorbidity pathology is of interest to the clinicians. In recent years, the attention of BA pathogenesis researchers has attracted low-investigated adipokine – apelin. On the other hand, apelin is considered as a renoprotective adipokine that can prevent the progression of CKD. THE AIM of the study is to identify the relationship between apelin/APJ signaling system and glomerular filtration rate in different BA variants. PATIENTS AND METHODS. The 12 of practically healthy persons and 36 bronchial asthma patients were examined. Levels of apelin-12, apelin-36, and APJ receptor of apelines on peripheral blood lymphocytes were determined, as well as levels of TNF-α, IL-6 IL-4 by immunoenzyme method according to standard protocol. Glomerular filtration rate (eGFR) by CKD-EPI was calculated. RESULTS. With the help of factor analysis, it was revealed that the glomerular filtration rate in bronchial asthma is associated with the level of apelin-36. A high level of glomerular filtration rate corresponds to a high level of apelin-36. In bronchial asthma, the negative association of pro-inflammatory adipokines TNF-α and IL-6 with the glomerular filtration rate was revealed. On the other hand, the IL-4 was found to be directly related to the glomerular filtration rate according to the factorial analysis. CONCLUSION. The obtained data suggest a possible renoprotective effect of apelin-36 in bronchial asthma.
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Chang, Chia-Jung, Pi-Chao Wang, Tzou-Chi Huang, and Akiyoshi Taniguchi. "Change in Renal Glomerular Collagens and Glomerular Filtration Barrier-Related Proteins in a Dextran Sulfate Sodium-Induced Colitis Mouse Model." International Journal of Molecular Sciences 20, no. 6 (March 22, 2019): 1458. http://dx.doi.org/10.3390/ijms20061458.
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Renal disease is not rare among patients with inflammatory bowel disease (IBD) and is gaining interest as a target of research. However, related changes in glomerular structural have rarely been investigated. This study was aimed at clarifying the changes in collagens and glomerular filtration barrier (GFB)-related proteins of glomeruli in a dextran sulfate sodium (DSS)-induced colitis mouse model. Acute colitis was induced by administering 3.5% DSS in Slc:ICR strain mice for eight days. Histological changes to glomeruli were examined by periodic acid-Schiff (PAS) and Masson’s trichrome staining. Expressions of glomerular collagens and GFB-related proteins were analyzed by immunofluorescent staining and Western blot analysis. DSS-colitis mice showed an elevated disease activity index (DAI), colon shortening, massive cellular infiltration and colon damage, confirming that DSS-colitis mice can be used as an IBD animal model. DSS-colitis mice showed increased glycoprotein and collagen deposition in glomeruli. Interestingly, we observed significant changes in glomerular collagens, including a decrease in type IV collagen, and an increment in type I and type V collagens. Moreover, declined GFB-related proteins expressions were detected, including synaptopodin, podocalyxin, nephrin and VE-cadherin. These results suggest that renal disease in DSS-colitis mice might be associated with changes in glomerular collagens and GFB-related proteins. These findings are important for further elucidation of the clinical pathological mechanisms underlying IBD-associated renal disease.
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Asmar, Ali, Lene Simonsen, Meena Asmar, Sten Madsbad, Jens J. Holst, Erik Frandsen, Cedric Moro, Charlotte M. Sorensen, Thomas Jonassen, and Jens Bülow. "Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy." American Journal of Physiology-Endocrinology and Metabolism 310, no. 9 (May 1, 2016): E744—E753. http://dx.doi.org/10.1152/ajpendo.00518.2015.
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During acute administration of native glucagon-like peptide-1 (GLP-1), we previously demonstrated central hemodynamic effects in healthy males, whereas renal hemodynamics, despite renal uptake of GLP-1 in excess of glomerular filtration, was unaffected. In the present study, we studied hemodynamic effects of GLP-1 in patients with type 2 diabetes under fixed sodium intake. During a 3-h infusion of GLP-1 (1.5 pmol·kg−1·min−1) or saline, intra-arterial blood pressure and heart rate were measured continuously, concomitantly with cardiac output estimated by pulse contour analysis. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured using Fick's Principle after catheterization of a renal vein. Urine collection was conducted throughout the experiments at voluntary voiding, and patients remained supine during the experiments. During the GLP-1 infusion, systolic and diastolic blood pressure and cardiac output remained unchanged, whereas heart rate increased significantly. Arterio-venous gradients for GLP-1 exceeded glomerular filtrations significantly, but renal plasma flow and glomerular filtration rate as well as renal sodium and lithium excretion were not affected. In conclusion, acute administration of GLP-1 in patients with type 2 diabetes leads to a positive chronotropic effect, but in contrast to healthy individuals, cardiac output does not increase in patients with type 2 diabetes. Renal hemodynamics and sodium excretion are not affected.
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Serudji, Joserizal, and Rizanda Machmud. "PERBANDINGAN KEJADIAN PENINGKATAN TEKANAN DARAH PADA TRIMESTER II BERDASARKAN LAJU FILTRASI GLOMERULUS (LFG)." JOURNAL OBGIN EMAS 3, no. 1 (January 10, 2019): 15–26. http://dx.doi.org/10.25077/aoj.3.1.15-26.2019.
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During normal pregnancy, glomerolus filtration rate (GFR) is increased so that the concentration of urea and creatinine decreased. With the onset of hypertension in pregnancy, renal perfusion and glomerular filtration decreases, the greater of decline showed more severe illness. This was an observational analytic study with Cohort design and performed in Obgyn Department of M. Djamil Hospital Padang, general district hospital in Batusangkar and Achmad Mukhtar, Private Practice Midwife in Batusangkar from June-December 2014. 100 samples of first trimester of pregnancy, each subject were examined ureum, creatinine, cystatin-c and glomerular filtration rate (GFR) based on CKD-EPI Cystatin and Creatinine 2012 Equation formula. Then divided into two groups, high glomerular filtration rate (GFR) high and low glomerular filtration rate (GFR) group. Each subject was evaluated blood pressure every 3 weeks and statistical analysis was done using the Independent samples test and chi square. There was significant association difference in the levels of urea, creatinine and cystatin-c between high GFR group and low GFR group (p <0.05). There was a statistically significant relationship between low GFR group of pregnant women with changes in systolic and diastolic blood pressure that persists or increases of 5-10 mmHg (p <0.05).Keywords: Preeclampsia, glomerular filtration rate (GFR), ureum, creatinine, cystatin-c, blood pressure
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Syutkin, V. E., A. A. Salienko, O. D. Olisov, S. V. Zhuravel, and M. S. Novruzbekov. "The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up." Transplantologiya. The Russian Journal of Transplantation 13, no. 2 (June 21, 2021): 121–29. http://dx.doi.org/10.23873/2074-0506-2021-13-2-121-129.
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Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.
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Deng, Aihua, and Scott C. Thomson. "Renal NMDA receptors independently stimulate proximal reabsorption and glomerular filtration." American Journal of Physiology-Renal Physiology 296, no. 5 (May 2009): F976—F982. http://dx.doi.org/10.1152/ajprenal.90391.2008.
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N-methyl-d-aspartate receptors (NMDA) are expressed in the kidney, where little is known of their functional role. Several series of micropuncture experiments were performed in hydropenic rats using the NMDA channel blocker, MK801, and the NMDA coagonist, l-glycine, to probe NMDA for effects on single-nephron glomerular filtration rate (SNGFR) and proximal reabsorption ( Jprox). During intravenous infusion of MK801 or l-glycine, Henle's loop was perfused to manipulate SNGFR via tubuloglomerular feedback (TGF), thereby facilitating analysis of glomerulotubular balance. To confirm local actions on the kidney, MK801 was delivered to the glomerulus by microperfusion past the macula densa and to the proximal tubule by microperfusion into the early S1 segment. By all measures, MK801 acted on the glomerulus to reduce SNGFR, and acted on the proximal tubule to suppress Jprox, while having no effect on the responsiveness of TGF. l-Glycine raised SNGFR, dampened the TGF response, and could not be proved to independently stimulate proximal reabsorption. NMDA exerts a tonic vasodilatory influence on the glomerulus and a proreabsorptive effect on the proximal tubule. These combined effects allow NMDA to modulate SNGFR with minimal impact on late proximal flow. The full effects of l-glycine infusion on proximal tubule and TGF response do not extrapolate from the response to NMDA blockade.
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Satchell, Simon C., Steve J. Harper, John E. Tooke, Dontscho Kerjaschki, Moin A. Saleem, and Peter W. Mathieson. "Human Podocytes Express Angiopoietin 1, a Potential Regulator of Glomerular Vascular Endothelial Growth Factor." Journal of the American Society of Nephrology 13, no. 2 (February 2002): 544–50. http://dx.doi.org/10.1681/asn.v132544.
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ABSTRACT. Vascular endothelial growth factor (VEGF) is abundantly expressed by podocytes, but its role in glomeruli is unknown. Angiopoietins are endothelial cell growth factors that function in concert with VEGF but have not previously been observed in human glomeruli. Angiopoietin 1 (Ang1) acts via the endothelial receptor Tie2 to promote maturation and stabilization of blood vessels, resisting angiogenesis and opposing some actions of VEGF. Ang1, Ang2, Tie2, and VEGF expression in normal human renal cortex was examined with immunofluorescence and immunohistochemical analyses. High-power, multiple-color, immunofluorescence analyses and additional antibodies (specific for particular components of the glomerular filtration barrier) were used to determine the exact locations of Ang1 and Tie2 in the glomerular capillary wall. Immuno-electron-microscopic analysis of rat glomeruli was used to further localize endothelial Tie2 expression. RNA and protein extracted from human glomeruli, cultured human podocytes, and cultured human endothelial cells were analyzed for Ang1, Ang2, and Tie2 by using reverse transcription-PCR and Western blotting. Ang1 was detected in podocytes in normal glomeruli and, with VEGF, was concentrated in podocyte foot processes. Tie2 was demonstrated on glomerular capillary endothelial cells, particularly on the abluminal surface. Reverse transcription-PCR and Western blotting analyses confirmed the expression of Ang1 and Tie2 in glomeruli and of Ang1 in cultured podocytes. These findings suggest a role for Ang1 in the maintenance of the glomerular endothelium and make it a good candidate to be a regulator of the actions of VEGF on glomerular permeability, resisting angiogenesis while allowing the induction of high permeability to water and small solutes.
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Pedersen, M. Mau, J. Sandahl Christiansen, E. B. Pedersen, and C. E. Mogensen. "Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control." Clinical Science 83, no. 4 (October 1, 1992): 445–51. http://dx.doi.org/10.1042/cs0830445.
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1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intra-individual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 ± 8 years, duration of diabetes 9 ± 5 years, mean arterial blood pressure 90 ± 5 mmHg (means ± sd), urinary albumin excretion rate 5.4 × / ÷ 1.6 μg/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [125I]-iothalamate and 131I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control. 2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (σ = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [R2 with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002]. 3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants (R2 = 0.36, analysis of variance: P = 0.009). 4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin. 5. When compared with eight healthy control subjects, atrial natriuretic peptide was moderately increased in the diabetic patients [4.7(4.2–6.2) versus 3.9 (3.4–4.6) pmol/l, median (first and third quartile), 2P<0.05]. 6. In conclusion, the study identified individual changes in atrial natriuretic peptide, arginine vasopressin and long-term glycaemic control as factors associated with intra-individual variation in glomerular filtration rate. It is suggested that atrial natriuretic peptide is involved in the regulation of glomerular filtration rate and possibly specifically in diabetic hyperfiltration.
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Austin, S. M., J. S. Lieberman, L. D. Newton, M. Mejia, W. A. Peters, and B. D. Myers. "Slope of serial glomerular filtration rate and the progression of diabetic glomerular disease." Journal of the American Society of Nephrology 3, no. 7 (January 1993): 1358–70. http://dx.doi.org/10.1681/asn.v371358.
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Glomerular function was evaluated longitudinally over a 24- to 48-month period in 18 patients with diabetic glomerular disease (DGD) manifested by proteinuria. GFR was determined by iothalamate clearance at 4-month intervals. The patients were divided into two groups: Group 1 (N = 9) had subnephrotic proteinuria and an initially normal GFR of 91 +/- 8 mL/min. Group 2 (N = 9) had nephrotic-range proteinuria, and initial GFR was reduced to 53 +/- 5 mL/min. Serial GFR fluctuated over time in Group 1, but no trend towards hypofiltration was evident. In contrast, GFR declined linearly in Group 2 at 1.1 +/- 0.3 mL/min per month. The transglomerular sieving of uncharged dextrans of graded size was analyzed and initially revealed a uniform reduction in glomerular pore density and an enhancement of shuntlike pores. Pore density was initially reduced by 80% and declined further after 24 months in nephrotic Group 2; corresponding pore density in subnephrotic Group 1 was reduced by half but remained constant. Renal biopsy of four members of Group 1 revealed a 22% prevalence of global glomerulosclerosis. Remaining open glomeruli exhibited hypertrophy, excessive extracellular matrix, and deformation of epithelial podocytes. The latter abnormality appeared to be the predominant determinant of lowered ultrafiltration capacity. It was inferred that trials of therapy to attenuate the progression of DGD should be initiated at a functional level similar to that in subnephrotic Group 1. Because GFR is unlikely to decline over a 2- to 4-yr period, it is suggested that such trials be extended for longer periods. Alternatively, morphometric analysis of serial renal biopsies may shorten the time needed to demonstrate effective renoprotection in DGD.
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Ferro, Charles J., James Hodson, Jason Moore, Mark McClure, Charles R. V. Tomson, Peter Nightingale, and Richard Borrows. "Bayesian Analysis of Glomerular Filtration Rate Trajectories in Kidney Transplant Recipients." Transplantation 99, no. 3 (March 2015): 533–39. http://dx.doi.org/10.1097/tp.0000000000000377.
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Myers, B. D., A. Chagnac, H. Golbetz, L. Newton, S. Strober, and R. K. Sibley. "Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis." American Journal of Physiology-Renal Physiology 260, no. 5 (May 1, 1991): F717—F727. http://dx.doi.org/10.1152/ajprenal.1991.260.5.f717.
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Patients with diffuse, proliferative lupus nephritis (DPLN) were subjected to differential solute clearances (n = 22) and serial renal biopsy (n = 11) before and again after 6-12 mo of immunosuppressive therapy. Glomerular sieving of dextrans of graded size was analyzed with a heteroporous membrane model. This revealed active DPLN to be associated with 1) a reduction of overall pore density accompanied by a 53% depression of glomerular filtration rate (GFR), and 2) appearance of a subset of large, nondiscriminatory pores, which accounted for the observed nephrotic level of proteinuria. Morphometric analysis of biopsy tissue provided evidence of reduced filtration surface area due to global or segmental occlusion of capillary loops in glomerular tufts. Activity of DPLN resolved posttreatment. A computed increase in pore density was associated with a 24% increment in GFR; a marked reduction in the fraction of shuntlike pores was accompanied by a parallel reduction of proteinuria into a subnephrotic range. Repeat biopsy revealed diminished glomerular cellularity, fewer immune deposits, and an ensuing increase in the fraction of tuft area occupied by patent loops. Epithelial filtration slit frequency also increased. Neither functional nor structural recovery was complete, however. Residual pore density approximated only 23-35% of that in healthy controls, and corresponding shuntlike pores were threefold more prominent. We conclude that severe DPLN is only partially reversible by current modalities of treatment and that the ensuing residual injury is far more severe than suggested by conventional tests of renal function.
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LAFAYETTE, RICHARD A., TAHIRA MALIK, MAURICE DRUZIN, GERALDINE DERBY, and BRYAN D. MYERS. "The Dynamics of Glomerular Filtration after Caesarean Section." Journal of the American Society of Nephrology 10, no. 7 (July 1999): 1561–65. http://dx.doi.org/10.1681/asn.v1071561.
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Abstract. The objective of this study was to determine whether the glomerular hyperfiltration of pregnancy is maintained even after Caesarean section and, if so, to define the responsible hemodynamics. The dynamics of glomerular filtration were evaluated in 12 healthy women who had just completed an uncomplicated pregnancy and were delivered by Caesarean section. Age-matched but non-gravid female volunteers (n = 22) served as control subjects. GFR in postpartum women was elevated above control values by 41%; 149 ± 10 versus 106 ± 3 ml/min per 1.73 m2, respectively (P < 0.001). In contrast, corresponding renal plasma flow was the same in the two groups, such that the postpartum filtration fraction was significantly elevated by 20%. Computation of glomerular intracapillary oncotic pressure (πGC) from knowledge of plasma oncotic pressure and the filtration fraction revealed this quantity to be significantly reduced in postpartum women, 20.6 ± 1.7 versus 26.1 ± 2.0 mmHg in control subjects (P < 0.001). A theoretical analysis of glomerular ultrafiltration suggests that depression of πGC, the force opposing the formation of filtrate, is predominantly or uniquely responsible for the observed postpartum hyperfiltration.
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Lundqvist, S., S. O. Hietala, C. Berglund, and K. Karp. "Simultaneous Urography and Determination of Glomerular Filtration Rate." Acta Radiologica 35, no. 4 (July 1994): 391–95. http://dx.doi.org/10.1177/028418519403500415.
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The total plasma clearance of iohexol at urography and 51Cr-EDTA was compared in 31 patients with di- or tetraparesis. A reference 51Cr-EDTA clearance was also performed 24 hours prior to the urography. The GFR was calculated from one, 2 or 4 plasma samples collected 180, 210, 240 and 270 min after the injection. An X-ray fluorescence analyzer was used for the analysis of iohexol in plasma as well as the contrast medium clearance calculations. It was shown that single or multiple sample clearance of iohexol and 51Cr-EDTA were equivalent methods for measurement of the GFR. The GFR was not affected by iohexol in a dose routinely used for urography. It was concluded that the patient comfort is improved if 51Cr-EDTA clearance is replaced by contrast medium clearance in association with urography.
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Koehler, Sybille, Alexander Kuczkowski, Lucas Kuehne, Christian Jüngst, Martin Hoehne, Florian Grahammer, Sean Eddy, et al. "Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis." Journal of the American Society of Nephrology 31, no. 3 (February 11, 2020): 544–59. http://dx.doi.org/10.1681/asn.2019030312.
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BackgroundUnderstanding podocyte-specific responses to injury at a systems level is difficult because injury leads to podocyte loss or an increase of extracellular matrix, altering glomerular cellular composition. Finding a window into early podocyte injury might help identify molecular pathways involved in the podocyte stress response.MethodsWe developed an approach to apply proteome analysis to very small samples of purified podocyte fractions. To examine podocytes in early disease states in FSGS mouse models, we used podocyte fractions isolated from individual mice after chemical induction of glomerular disease (with Doxorubicin or LPS). We also applied single-glomerular proteome analysis to tissue from patients with FSGS.ResultsTranscriptome and proteome analysis of glomeruli from patients with FSGS revealed an underrepresentation of podocyte-specific genes and proteins in late-stage disease. Proteome analysis of purified podocyte fractions from FSGS mouse models showed an early stress response that includes perturbations of metabolic, mechanical, and proteostasis proteins. Additional analysis revealed a high correlation between the amount of proteinuria and expression levels of the mechanosensor protein Filamin-B. Increased expression of Filamin-B in podocytes in biopsy samples from patients with FSGS, in single glomeruli from proteinuric rats, and in podocytes undergoing mechanical stress suggests that this protein has a role in detrimental stress responses. In Drosophila, nephrocytes with reduced filamin homolog Cher displayed altered filtration capacity, but exhibited no change in slit diaphragm structure.ConclusionsWe identified conserved mechanisms of the podocyte stress response through ultrasensitive proteome analysis of human glomerular FSGS tissue and purified native mouse podocytes during early disease stages. This approach enables systematic comparisons of large-scale proteomics data and phenotype-to-protein correlation.
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Buckheit, J. B., R. A. Olshen, K. Blouch, and B. D. Myers. "Modeling of progressive glomerular injury in humans with lupus nephritis." American Journal of Physiology-Renal Physiology 273, no. 1 (July 1, 1997): F158—F169. http://dx.doi.org/10.1152/ajprenal.1997.273.1.f158.
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We studied glomerular function longitudinally for 36-120 mo in 21 patients undergoing treatment for diffuse, proliferative lupus nephritis. We determined glomerular filtration rate (GFR) and glomerular oncotic pressure (IIGC) and computed the two-kidney ultrafiltration coefficient (Kf) at 6- to 12-mo intervals. The relationships and cross talk among the three variables over time were then analyzed by eigenfunction regression and canonical correlations. We also performed a morphometric analysis of serial biopsies and computed single-nephron Kf in patent glomeruli at baseline and after 36-94 mo of follow-up. Patients were divisible into progressors (n = 12) or nonprogressors (n = 9) according to the presence or absence, respectively, of an irrevocable decline in GFR over time. Examination of longitudinal variables revealed GFR to be strongly related to Kf in all patients and inversely related to IIGC in progressors. By serial morphometric analysis we observed a threefold increase in the prevalence of global sclerosis in progressors but unchanged prevalence in nonprogressors. Whereas single-nephron Kf of remnant glomeruli increased to supernormal levels in nonprogressors, the absence of this compensatory phenomenon in progressors permitted GFR and Kf to decline in parallel with the declining number of functional glomeruli.
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Nishad, Rajkishor, Prajakta Meshram, Ashish Kumar Singh, G. Bhanuprakash Reddy, and Anil Kumar Pasupulati. "Activation of Notch1 signaling in podocytes by glucose-derived AGEs contributes to proteinuria." BMJ Open Diabetes Research & Care 8, no. 1 (June 2020): e001203. http://dx.doi.org/10.1136/bmjdrc-2020-001203.
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IntroductionAdvanced glycation end-products (AGEs) are implicated in the pathogenesis of diabetic nephropathy (DN). Previous studies have shown that AGEs contribute to glomerulosclerosis and proteinuria. Podocytes, terminally differentiated epithelial cells of the glomerulus and the critical component of the glomerular filtration barrier, express the receptor for AGEs (RAGE). Podocytes are susceptible to severe injury during DN. In this study, we investigated the mechanism by which AGEs contribute to podocyte injury.Research design and methodsGlucose-derived AGEs were prepared in vitro. Reactivation of Notch signaling was examined in AGE-treated human podocytes (in vitro) and glomeruli from AGE-injected mice (in vivo) by quantitative reverse transcription-PCR, western blot analysis, ELISA and immunohistochemical staining. Further, the effects of AGEs on epithelial to mesenchymal transition (EMT) of podocytes and expression of fibrotic markers were evaluated.ResultsUsing human podocytes and a mouse model, we demonstrated that AGEs activate Notch1 signaling in podocytes and provoke EMT. Inhibition of RAGE and Notch1 by FPS-ZM1 (N-Benzyl-4-chloro-N-cyclohexylbenzamide) and DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenyl glycine t-butylester), respectively, abrogates AGE-induced Notch activation and EMT. Inhibition of RAGE and Notch1 prevents AGE-induced glomerular fibrosis, thickening of the glomerular basement membrane, foot process effacement, and proteinuria. Furthermore, kidney biopsy sections from people with DN revealed the accumulation of AGEs in the glomerulus with elevated RAGE expression and activated Notch signaling.ConclusionThe data suggest that AGEs activate Notch signaling in the glomerular podocytes. Pharmacological inhibition of Notch signaling by DAPT ameliorates AGE-induced podocytopathy and fibrosis. Our observations suggest that AGE-induced Notch reactivation in mature podocytes could be a novel mechanism in glomerular disease and thus could represent a novel therapeutic target.
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Verma, Neena, Chandra Shekhar Lal, Vidyanand Rabidas, Krishna Pandey, Dharmendra Singh, Sanjay Kumar, Rakesh Bihari Verma, and Pradeep Das. "Microalbuminuria and Glomerular Filtration Rate in Paediatric Visceral Leishmaniasis." BioMed Research International 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/498918.
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Visceral leishmaniasis, caused byLeishmania donovani, is a serious form of leishmaniasis and fatal if untreated. Nearly half of the VL cases are children. There are very few studies of renal function in pediatric visceral leishmaniasis. The aim of this study was to evaluate renal dysfunction by studying glomerular filtration rate (GFR), microalbuminuria, and microscopic examination of urine. Laboratory analysis was performed on blood and urine samples of 40 parasitologically confirmed pediatric VL cases. Laboratory data of urine examination showed albuminuria in 10% (4/40), white blood cells in 20% (8/40), hematuria in 10% (4/40), microalbuminuria in 37.5% (15/40), and decreased GFR in 27.5% (11/40). Renal involvement was manifested in most of the pediatric VL cases. These findings may help clinicians in decision making for safe and suitable antileishmanial treatment particularly in childhood VL.
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Wu, Jingyang, Jin Geng, Limin Liu, Weiping Teng, Lei Liu, and Lei Chen. "The Relationship between Estimated Glomerular Filtration Rate and Diabetic Retinopathy." Journal of Ophthalmology 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/326209.
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Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness in working-aged people. Several studies have suggested that glomerular filtration rate (GFR) was correlated with DR. This is a hospital-based study and the aim of it was to examine the relationship between the GFR and DR in patients with type 2 diabetes mellitus (T2DM). We used CKD-EPI equation to estimate GFR and SPSS 19.0 and EmpowerStats software to assess their relationship. Among the 1613 participants (aged 54.75 ± 12.19 years), 550 (34.1%) patients suffered from DR. The multivariate analysis revealed that the risk factors for DR include age (P<0.001, OR = 0.940), duration of diabetes (P<0.001, OR = 1.163), hemoglobin A1c (P=0.007, OR = 1.224), systolic blood pressure (P<0.001, OR = 1.032), diastolic blood pressure (P=0.007, OR = 0.953), high density lipoprotein cholesterol (P=0.024, OR = 3.884), and eGFR (P=0.010, OR = 0.973). Through stratified analysis and saturation effect analysis, our data suggests that eGFR of 99.4 mL/min or lower might imply the early stage of DR in diabetic patients. Thus, the evaluation of eGFR has clinical significance for the early diagnosis of DR.
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Remuzzi, A., B. M. Brenner, V. Pata, G. Tebaldi, R. Mariano, A. Belloro, and G. Remuzzi. "Three-dimensional reconstructed glomerular capillary network: blood flow distribution and local filtration." American Journal of Physiology-Renal Physiology 263, no. 3 (September 1, 1992): F562—F572. http://dx.doi.org/10.1152/ajprenal.1992.263.3.f562.
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We developed a mathematical model to simulate blood flow and filtration in individual capillary segments of a glomerular network reconstructed from a normal Munich-Wistar (MW) rat. Three-dimensional geometric reconstruction was obtained by semithin serial sections (1 micron) of one glomerulus after perfusion fixation of kidney. Photomicrographs of each section were digitized and processed, using a computer-based image-analysis system, to derive the topological organization of the capillary network and mean diameter and length of individual capillary segments. Blood flow rate in capillary segments was calculated using a theoretical model that considers apparent viscosity of blood in small capillaries as a function of local rheological parameters, partition of cells at bifurcations, and local filtration dependent on transmembrane hydraulic and oncotic pressure gradients along the network. In accord with previous observations, the topological organization of the capillary network disclosed a three-lobular structure. The ultrafiltration coefficient (Kf) calculated for the euvolemic MW rat with the present network approach was compared with that derived from a theoretical model that assumes identical capillaries in parallel. The latter model is shown to underestimate Kf, particularly under conditions in which filtration pressure equilibrium is approached. Calculation of local blood flow and filtration along the network indicates a heterogeneous distribution of these parameters and that some parts of the capillary network operate at filtration pressure equilibrium even if the overall network operates at filtration disequilibrium.
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Hanke, Nils, Lynne Staggs, Patricia Schroder, Jennifer Litteral, Susanne Fleig, Jessica Kaufeld, Cornelius Pauli, Hermann Haller, and Mario Schiffer. "“Zebrafishing” for Novel Genes Relevant to the Glomerular Filtration Barrier." BioMed Research International 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/658270.
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Data for genes relevant to glomerular filtration barrier function or proteinuria is continually increasing in an era of microarrays, genome-wide association studies, and quantitative trait locus analysis. Researchers are limited by published literature searches to select the most relevant genes to investigate. High-throughput cell cultures and otherin vitrosystems ultimately need to demonstrate proof in anin vivomodel. Generating mammalian models for the genes of interest is costly and time intensive, and yields only a small number of test subjects. These models also have many pitfalls such as possible embryonic mortality and failure to generate phenotypes or generate nonkidney specific phenotypes. Here we describe anin vivozebrafish model as a simple vertebrate screening system to identify genes relevant to glomerular filtration barrier function. Using our technology, we are able to screen entirely novel genes in 4–6 weeks in hundreds of live test subjects at a fraction of the cost of a mammalian model. Our system produces consistent and reliable evidence for gene relevance in glomerular kidney disease; the results then provide merit for further analysis in mammalian models.
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Chen, Sheng-Pyng, Chi-Rong Li, Huan-Cheng Chang, Yu-Ling Li, and Hsiang-Chu Pai. "Relationship Between Metabolic Syndrome Severity and Kidney Function as Related to Gender: A Population-Based Longitudinal Study." Clinical Nursing Research 29, no. 6 (April 26, 2018): 355–62. http://dx.doi.org/10.1177/1054773818773385.
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The purpose of this study was to explore the relationship between the metabolic syndrome severity Z-score and kidney function by gender. We also examined the estimated glomerular filtration rate in relation to other known risk factors. The study used was a population-based prospective longitudinal research design. A total of 4,838 participants (2,683 females and 2,155 males) included individuals aged >30 years who were undergoing a health examination from 2006 to 2014 in Pingzhen City, Taiwan. In the initial generalized estimated equation model analysis, which included the covariates of age of first visit, period between the first and current visit, and metabolic syndrome severity Z-score, the results indicated that the interaction between age and metabolic syndrome severity Z-score is significantly related to the estimated glomerular filtration rate for males ( p = .040). For females, the interaction between age and metabolic syndrome severity Z-score was not significant, but a higher metabolic syndrome severity Z-score was significantly associated with lower estimated glomerular filtration rate ( p = .001). After controlling for the confounders, unhealthy behaviors, and comorbidities, the metabolic syndrome severity Z-score was still a negative predictor of estimated glomerular filtration rate in both the male ( p = .005) and female ( p = .023) models.
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Remuzzi, A., C. Battaglia, L. Rossi, C. Zoja, and G. Remuzzi. "Glomerular size selectivity in nephrotic rats exposed to diets with different protein content." American Journal of Physiology-Renal Physiology 253, no. 2 (August 1, 1987): F318—F327. http://dx.doi.org/10.1152/ajprenal.1987.253.2.f318.
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Glomerular size-selective properties in animals made nephrotic by adriamycin (ADR) injection and fed standard (20% protein) or high-protein (35% protein) diets were investigated using dextran fractional clearances. To interpret filtration and dextran-sieving data, a theoretical approach previously developed for analysis of experimental data in healthy and nephrotic humans was used. Four types of hypothetical pore-radius distributions were compared in order to establish the best tool for describing membrane pore structure in normal and nephrotic rats. This analysis revealed that a spread distribution of pores, the lognormal probability distribution, is the most adequate in representing membrane intrinsic characteristics. ADR animals on standard diet developed massive proteinuria and a lower glomerular filtration rate (GFR) than control animals. High-protein feeding in ADR rats induced a further increase in urinary protein excretion and in GFR. Dextran fractional clearance was more elevated for larger dextran fractions (greater than 46 A) in ADR animals on the standard diet than in control rats. No differences were observed in dextran-sieving curves between ADR rats on the standard and high-protein diet. Theoretical analysis of filtration and fractional clearance data revealed comparable changes in the intrinsic parameters of glomerular size selectivity in the two groups of nephrotic animals. These observations indicate that increased traffic of plasma proteins through the glomerular capillary wall does not imply, in our experimental condition, a further loss of glomerular size-selective properties. The greater urinary protein excretion of ADR animals on high-protein diet than ADR animals on a standard diet cannot be explained by further impairment of glomerular size selectivity but more likely reflects hemodynamic changes.
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Jerebtsova, Marina, Namita Kumari, Yuri Obuhkov, and Sergei Nekhai. "Adenoviral E4 Gene Stimulates Secretion of Pigmental Epithelium Derived Factor (PEDF) that Maintains Long-term Survival of Human Glomerulus-derived Endothelial Cells." Molecular & Cellular Proteomics 11, no. 11 (August 21, 2012): 1378–88. http://dx.doi.org/10.1074/mcp.m112.020313.
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Renal glomerular endothelial cells are specialized cells with an important role in physiological filtration and glomerular disease. However, maintenance of human primary endothelial cells requires stimulation with serum and growth factors that often results in modification of the cells properties. Previously, expression of early adenovirus region E4 was shown to help maintaining long-term survival of human endothelial cells in serum free media without addition of growth factors. In the current study, we showed that media conditioned with human epithelial cells stably transfected with Ad E4 region also supported survival of human glomerulus-derived endothelial cells in serum-free media. Mass-spectrometry analysis of the conditioned media identified pigmental epithelium derived factor (PEDF) as a major component of the conditioned media. PEDF expression in 293-E4 cells was validated by RT-PCR, Western blot and ELISA analysis. PEDF expression was detected in mouse glomeruli. Supplementation with recombinant PEDF supported survival of primary endothelial cells and the cells transformed with SV40 large T antigen in serum-free media, and extended the life-span of both cell cultures. PEDF did not inhibit FGF-2 stimulated growth and tubulogenesis of endothelial cells. Thus we demonstrated that adenoviral E4 region stimulated expression and secretion of PEDF by human renal epithelial cells that acted as a survival factor for glomerulus-derived endothelial cells.
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Chagnac, Avry, Talia Weinstein, Asher Korzets, Edward Ramadan, Judith Hirsch, and Uzi Gafter. "Glomerular hemodynamics in severe obesity." American Journal of Physiology-Renal Physiology 278, no. 5 (May 1, 2000): F817—F822. http://dx.doi.org/10.1152/ajprenal.2000.278.5.f817.
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Differential solute clearances were used to characterize glomerular function in 12 nondiabetic subjects with severe obesity (body mass index >38). Nine healthy subjects served as the control group. In the obese group, glomerular filtration rate (GFR) and renal plasma flow (RPF) exceeded the control value by 51 and 31%, respectively. Consequently, filtration fraction increased. The augmented RPF suggested a state of renal vasodilatation involving, mainly or solely, the afferent arteriole. Albumin excretion rate and fractional albumin clearance increased by 89 and 78%, respectively. Oral glucose tolerance tests were suggestive of insulin resistance. Insulin resistance was positively correlated with GFR ( r = 0.88, P < 0.001) and RPF ( r = 0.72, P < 0.001). Mean arterial pressure was higher than in the control group. Fractional clearances of dextrans of broad size distribution tended to be lowered. The determinants of the GFR were estimated qualitatively by using a theoretical model of dextran transport through a heteroporous membrane. This analysis suggests that the high GFR in very obese subjects may be the result of an increase in transcapillary hydraulic pressure difference (ΔP). An abnormal transmission of increased arterial pressure to the glomerular capillaries through a dilated afferent arteriole could account for the augmentation in ΔP.
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Corbett, Mark, Ana Duarte, Alexis Llewellyn, James Altunkaya, Melissa Harden, Martine Harris, Simon Walker, Stephen Palmer, Sofia Dias, and Marta Soares. "Point-of-care creatinine tests to assess kidney function for outpatients requiring contrast-enhanced CT imaging: systematic reviews and economic evaluation." Health Technology Assessment 24, no. 39 (August 2020): 1–248. http://dx.doi.org/10.3310/hta24390.
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Background Patients with low estimated glomerular filtration rates may be at higher risk of post-contrast acute kidney injury following contrast-enhanced computed tomography imaging. Point-of-care devices allow rapid measurement of estimated glomerular filtration rates for patients referred without a recent estimated glomerular filtration rate result. Objectives To assess the clinical effectiveness and cost-effectiveness of point-of-care creatinine tests for outpatients without a recent estimated glomerular filtration rate measurement who need contrast-enhanced computed tomography imaging. Methods Three systematic reviews of test accuracy, implementation and clinical outcomes, and economic analyses were carried out. Bibliographic databases were searched from inception to November 2018. Studies comparing the accuracy of point-of-care creatinine tests with laboratory reference tests to assess kidney function in adults in a non-emergency setting and studies reporting implementation and clinical outcomes were included. Risk of bias of diagnostic accuracy studies was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Probabilities of individuals having their estimated glomerular filtration rates correctly classified were estimated within a Bayesian framework and pooled using a fixed-effects model. A de novo probabilistic decision tree cohort model was developed to characterise the decision problem from an NHS and a Personal Social Services perspective. A range of alternative point-of-care testing approaches were considered. Scenario analyses were conducted. Results Fifty-four studies were included in the clinical reviews. Twelve studies reported diagnostic accuracy for estimated glomerular filtration rates; half were rated as being at low risk of bias, but there were applicability concerns for most. i-STAT (Abbott Point of Care, Inc., Princeton, NJ, USA) and ABL (Radiometer Ltd, Crawley, UK) devices had higher probabilities of correctly classifying individuals in the same estimated glomerular filtration rate categories as the reference laboratory test than StatSensor® devices (Nova Biomedical, Runcorn, UK). There was limited evidence for epoc® (Siemens Healthineers AG, Erlangen, Germany) and Piccolo Xpress® (Abaxis, Inc., Union City, CA, USA) devices and no studies of DRI-CHEM NX 500 (Fujifilm Corporation, Tokyo, Japan). The review of implementation and clinical outcomes included six studies showing practice variation in the management decisions when a point-of-care device indicated an abnormal estimated glomerular filtration rate. The review of cost-effectiveness evidence identified no relevant studies. The de novo decision model that was developed included a total of 14 strategies. Owing to limited data, the model included only i-STAT, ABL800 FLEX and StatSensor. In the base-case analysis, the cost-effective strategy appeared to be a three-step testing sequence involving initially screening all individuals for risk factors, point-of-care testing for those individuals with at least one risk factor, and including a final confirmatory laboratory test for individuals with a point-of-care-positive test result. Within this testing approach, the specific point-of-care device with the highest net benefit was i-STAT, although differences in net benefit with StatSensor were very small. Limitations There was insufficient evidence for patients with estimated glomerular filtration rates < 30 ml/minute/1.73 m2, and on the full potential health impact of delayed or rescheduled computed tomography scans or the use of alternative imaging modalities. Conclusions A three-step testing sequence combining a risk factor questionnaire with a point-of-care test and confirmatory laboratory testing appears to be a cost-effective use of NHS resources compared with current practice. The risk of contrast causing acute kidney injury to patients with an estimated glomerular filtration rate of < 30 ml/minute/1.73 m2 is uncertain. Cost-effectiveness of point-of-care testing appears largely driven by the potential of point-of-care tests to minimise delays within the current computed tomography pathway. Future work Studies evaluating the impact of risk-stratifying questionnaires on workflow outcomes in computed tomography patients without recent estimated glomerular filtration rate results are needed. Study registration This study is registered as PROSPERO CRD42018115818. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 39. See the NIHR Journals Library website for further project information.
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Faridz, Siska Monika, Syuhada Syuhada, and Akhmad Kheru. "KORELASI KADAR HEMOGLOBIN DENGAN LAJU FILTRASI GLOMERULUS PADA PASIEN GAGAL GINJAL KRONIK STADIUM 3 DAN 4." Jurnal Kebidanan Malahayati 7, no. 3 (July 31, 2021): 489–94. http://dx.doi.org/10.33024/jkm.v7i3.4113.
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Background Chronic kidney disease was one of the 18 causes of death in 2010. Anemia is a complication of CKD that often occurs even earlier than other complications. Renal dysfunction results in reduced creatinine filtration ability and an increase in serum creatinine.Purpose of this study was to determine the correlation between hemoglobin levels and glomerular filtration rate in patients with stage 3 and 4 chronic kidney failure at Abdul Moeloek Hospital in Bandar Lampung in 2020.Methods This type of research is quantitative with retrospective analytical methods. The research was conducted at the Medical Records section of the Abdul Moeloek Hospital Bandar Lampung from December 2020 to completion. The number of samples as many as 36 people using the person correlation statistical test. Result Based on the results of the Pearson correlation analysis between hemoglobin levels and glomerular filtration rate in patients with stage 3 and 4 chronic kidney failure at Abdul Moeloek Hospital, Bandar Lampung, 2020 shows a relationship with r (correlation coefficient) of, 688. This data shows that there is a positive relationship between hemoglobin levels and glomerular filtration rate in patients with stage 3 and 4 chronic renal failure at Abdul Moeloek Hospital, Bandar Lampung in 2020, the relationship is categorized as a strong relationship (0.61-0.80). . The P-value = 0,000 indicates a significant relationship between hemoglobin levels and glomerular filtration rate in patients with stage 3 and 4 chronic renal failure at Abdul Moeloek Hospital Bandar Lampung in 2020. Conclusion There is a correlation between hemoglobin levels and glomerular filtration rate in patients with stage chronic renal failure. 3 and 4 at Abdul Moeloek Hospital in Bandar Lampung in 2020Suggestions for the Community The community is expected to seek information regarding the prevention of kidney failure and then start living a healthy lifestyle to avoid kidney failure. For patients with kidney failure, they should regularly check themselves to the nearest health facility and check creatinine and hemoglobin levels. Keywords: Chronic renal failure, Creatinine, Hemoglobin, Glumerular Filtration Rate ABSTRAK Latar Belakang Penyakit ginjal kronik salah satu penyebab kematian ke-18 pada tahun 2010. Anemia merupakan salah satu komplikasi PGK yang sering terjadi bahkan terjadi lebih awal dari komplikasi lainnya. Disfungsi ginjal mengakibatkan kemampuan filtrasi kreatinin akan berkurang dan akan terjadi peningkatan pada kreatinin serum.Tujuan penelitian ini untuk mengetahui korelasi antara kadar hemoglobin dengan laju filtrasi glomerulus pada pasien gagal ginjal kronik stadium 3 dan 4 di Rumah Sakit Abdul Moeloek Bandar Lampung Tahun 2020.Metode Jenis penelitian ini adalah kuantitatif dengan metode analitik retrospektif. Penelitian dilakukan di bagian Rekam Medik Rumah Sakit Abdul Moeloek Bandar Lampung pada bulan Desember 2020 hingga selesai. jumlah sampel sebanyak 36 orang menggunakan uji statistic korelasi person. Berdasarkan hasil analisi korelasi Pearson antara kadar hemoglobin dengan laju filtrasi glomerulus pada pasien gagal ginjal kronik stadium 3 dan 4 di Rumah Sakit Abdul Moeloek Bandar Lampung Tahun 2020 menunjukan adanya hubungan dengan r (koefisien korelasi) sebesar ,688.Hasil Data ini menunjukan bahwa terdapat hubungan positif antara kadar hemoglobin dengan laju filtrasi glomerulus pada pasien gagal ginjal kronik stadium 3 dan 4 di Rumah Sakit Abdul Moeloek Bandar Lampung Tahun 2020 hubunganya dikategorikan sebagai hubungan yang kuat (strong) (0,61-0,80). Nilai P-value = 0,000 menunjukan hubungan signifikan antara kadar hemoglobin dengan laju filtrasi glomerulus pada pasien gagal ginjal kronik stadium 3 dan 4 di Rumah Sakit Abdul Moeloek Bandar Lampung Tahun 2020.Kesimpulan Terdapat korelasi antara kadar hemoglobin dengan laju filtrasi glomerulus pada pasien gagal ginjal kronik stadium 3 dan 4 di Rumah Sakit Abdul Moeloek Bandar Lampung Tahun 2020.Saran Bagi Masyarakat Masyarakat diharapkan mencari informasi terkait penegahan penyakit gagal ginjal kemudian mulai menjalani gaya hidup sehat agar terhindar dari penyakit gagal ginjal. Bagi penderita gagal ginjal agar rutin memeriksanakn diri ke fasilitas kesehatan terdekat dan memeriksakan kadar kreatinin serta hemoglobin. Kata Kunci : Gagal ginjal kronik, Kreatinin, Hemoglobin, Laju Filtrasi Glumerulus
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AMADOR, Victoria Araujo Ganzaroli, Ana Tereza Vaz de Sousa FREITAS, Alessandra Vitorino NAGHETTINI, Edna Regina Silva PEREIRA, and Maria do Rosário Gondim PEIXOTO. "Anthropometric measurements and markers of renal function in adults and older adults." Revista de Nutrição 29, no. 2 (April 2016): 199–209. http://dx.doi.org/10.1590/1678-98652016000200005.
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Objective: To determine whether anthropometric indicators are associated with markers of renal function in adults and older adults. Methods: This cross-sectional study included 279 adults and older adults attending eight primary healthcare units in eastern Goiânia, Góias. Sociodemographic, lifestyle, and clinical data were collected using a standard questionnaire. Body mass index was categorized as overweight (≥25 kg/m²) or non-overweight. Waist circumference was classified as normal or high; chronic kidney disease was defined as a glomerular filtration rate below 60 mL/minutes/1.73 m²; micro/macroalbuminuria was defined as an albumin/creatinine ratio above 30 mg/g. The association between anthropometric indicators and renal function markers was assessed by multiple linear regression analysis. Results: Chronic kidney disease was present in 8.9% and micro/macroalbuminuria in 34.8% of the sample. The prevalence of overweight was 57.0%. Waist circumference and body mass index were positively associated with glomerular filtration rate, characterized as glomerular hyperfiltration. Microalbuminuria was positively associated with body mass index in women. Conclusion: The prevalences of chronic kidney disease and overweight were high in the study population. Overweight was positively associated with glomerular filtration rate.
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Herman, William H., Steven N. Emancipator, R. L. Patrick Rhoten, and Michael S. Simonson. "Vascular and glomerular expression of endothelin-1 in normal human kidney." American Journal of Physiology-Renal Physiology 275, no. 1 (July 1, 1998): F8—F17. http://dx.doi.org/10.1152/ajprenal.1998.275.1.f8.
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To understand better the function of endothelin-1 (ET-1) in renal physiology, we examined vascular and glomerular expression of ET-1 in normal human kidney and in lupus nephritis. Immunohistochemical analysis revealed that renal endothelium of glomeruli, arteries, veins, and capillaries expressed ET-1. Endothelial cells were the principal source of glomerular ET-1; positive immunostaining was detected only rarely in mesangial cells and vascular smooth muscle cells from normal kidney. However, mesangial staining for ET-1 was elevated in patients with lupus nephritis, suggesting that under certain conditions mesangial cells elaborate ET-1. Indeed cultured human mesangial cells from normal subjects secreted ET-1 peptide. ET-1 secretion was augmented by the protein kinase C activator phorbol ester and by transforming growth factor-β1 (TGF-β1), a cytokine implicated in the development of glomerulosclerosis. Transient transfection of cultured mesangial cells with a preproET-1 reporter construct showed that the preproET-1 promoter is transcriptionally active in mesangial cells and is stimulated by TGF-β1, phorbol ester, or ectopic expression of protein kinase β1. Cultured human mesangial cells have both ETA and ETB receptors that contribute to ET-1-stimulated mitogenesis. Taken together, these results demonstrate that ET-1 is expressed at sites where paracrine or autocrine signaling by ET-1 might control renal vasoconstriction, glomerular filtration rate, and remodeling of the glomerulus in renal disease.
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Gu, Liubao, Liji Huang, Haidi Wu, Qinglin Lou, and Rongwen Bian. "Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function." Diabetes and Vascular Disease Research 14, no. 3 (February 9, 2017): 221–25. http://dx.doi.org/10.1177/1479164116680318.
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Background: Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. Methods: In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. Results: In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. Conclusion: serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.
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Low, Serena, Xiao Zhang, Jiexun Wang, Lee Ying Yeoh, Yan Lun Liu, Keven Kue Loong Ang, Wern Ee Tang, et al. "Long-term prospective observation suggests that glomerular hyperfiltration is associated with rapid decline in renal filtration function: A multiethnic study." Diabetes and Vascular Disease Research 15, no. 5 (May 28, 2018): 417–23. http://dx.doi.org/10.1177/1479164118776465.
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Aim: Glomerular hyperfiltration usually occurs early in development of kidney complications in diabetes. To understand hyperfiltration as a marker of renal disease progression in type 2 diabetes mellitus, we aimed to examine association between glomerular hyperfiltration (estimated glomerular filtration rate ⩾ 120 mL/min/1.73 m2) and rapid renal decline (annual estimated glomerular filtration rate loss ⩾ 3 mL/min/1.73 m2). Methods: This was a prospective cohort comprising 1014 patients with type 2 diabetes mellitus attending a Diabetes Centre of a regional hospital in 2002–2014. A separate prospective cohort, comprising 491 patients who attended Diabetes Centre or primary-care polyclinics, was used for validation. We performed binary mediation analysis to examine role of hyperfiltration on relationship between baseline haemoglobin A1c and rapid renal decline. Results: Among patients in discovery cohort, 5.2% had baseline hyperfiltration. Over mean follow-up of 6 years, 22.9% had rapid glomerular filtration rate decline. Baseline hyperfiltration was significantly associated with greater odds of rapid renal decline after adjusting for demographics, diabetes duration and clinical covariates (odds ratio: 2.57; 95% confidence interval: 1.21–5.46; p = 0.014). Similar finding was found in validation cohort (odds ratio: 2.98; 95% confidence interval: 1.06–8.42; p = 0.034). Hyperfiltration significantly accounted for 35.3% of association between increasing baseline haemoglobin A1c and rapid renal decline. Conclusion: Glomerular hyperfiltration is an independent risk factor of rapid renal decline. It mediates the association between increasing haemoglobin A1c and rapid renal decline.