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M. O. Ryznychuk y V. P. Pishak. "Clinical characteristic and genetic polymorphism of hereditary kidney disease. Communication 1". Bukovinian Medical Herald 17, n.º 1 (65) (2 de febrero de 2013): 169–73. http://dx.doi.org/10.24061/2413-0737.xvii.1.65.2013.40.
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WASIELEWSKA, MAŁGORZATA, IWONA SZATKOWSKA, EWA CZERNIAWSKA–PIĄTKOWSKA y DANIEL ZABORSKI. "Molecular background of hereditary nephropathies in spaniel dogs". Medycyna Weterynaryjna 75, n.º 12 (2019): 6330–2019. http://dx.doi.org/10.21521/mw.6330.
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The molecular background of hereditary nephropathies in English Cocker Spaniels and Springer Spaniels remained unclear until the beginning of the 21st century. It was only the discovery of an association between these diseases and Alport syndrome in humans that made it possible to identify the genes potentially responsible for nephropathies in dogs. Eventually, two mutations were identified in the COL4A4 gene coding for the alpha chains of collagen IV, the main component of the glomerular basement membrane (GBM). This review presents the molecular mechanism resulting from the aforementioned mutations, the signs of disease, functions of the GBM, and breeding aspects.
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Arant, Billy S. "Prevention of hereditary nephropathies by antenatal interventions". Pediatric Nephrology 1, n.º 3 (septiembre de 1987): 553–60. http://dx.doi.org/10.1007/bf00849269.
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Dufier, J. L., D. Orssaud, P. Dhermy, M. C. Gubler, M. F. Gagnadoux y M. Broyer. "Ocular changes in some progressive hereditary nephropathies". Pediatric Nephrology 1, n.º 3 (1987): 525–30. http://dx.doi.org/10.1007/bf00849264.
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Fuentes Milián, Yangel, Danyer Daniel Tamayo Ribeaux, Anabel Cepero Rodríguez y Bárbara Martínez Pérez. "Screening and diagnostic algorithm of hereditary metabolic nephropathies in newborns". Multidisciplinar (Montevideo) 2 (1 de enero de 2024): 67. http://dx.doi.org/10.62486/agmu202467.
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Introduction: inborn errors of metabolism expressed as hereditary nephropathies, entail various biochemical abnormalities that facilitate their screening and diagnosis in the newborn.Objective: to offer a useful, ideal, simple and reliable screening alternative as a tool for the diagnosis of hereditary metabolic nephropathies in newborns.Methods: an observational and cross-sectional study was carried out during the period September 2021-February 2023, at the Abel Santamaría Cuadrado General Teaching Hospital, Pinar del Río province, Cuba. The universe consisted of 90 patients and a representative sample of 63 was taken. The variables were studied: glycemia, lactinemia, ammonemia, arterial hemogasometry, urinalysis, hyperazotemia, heel test and perinatal risk factors associated with hyperazotemia. Empirical, theoretical and statistical methods were used. Medical ethics were respected.Results: the correlation predominated hypoglycemia, hyperlactinemia and hyperammonemia with an incidence of 55.56% and patients with metabolic acidosis in 49.21%. A greater frequency was observed in the correlation of patients with alterations in the urinary supernatant and hyperazoemia, for 33.33% of the sample. The number of patients with negative neonatal screening was higher, at 87%. Low birth weight and prematurity were the perinatal risk factors most associated with hyperazoemia in the patients treated, 36.51% and 33.33% respectively.Conclusions: the results obtained show high sensitivity and low specificity, but they still give us a reliable parameter and a tool to help diagnose hereditary metabolic nephropathies
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Zerres, Klaus y Sabine Rudnik-Schöneborn. "Current Status of DNA Diagnosis for Hereditary Nephropathies". Kidney and Blood Pressure Research 19, n.º 3-4 (1996): 209–14. http://dx.doi.org/10.1159/000174076.
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Niaudet, Patrick. "Living donor kidney transplantation in patients with hereditary nephropathies". Nature Reviews Nephrology 6, n.º 12 (28 de septiembre de 2010): 736–43. http://dx.doi.org/10.1038/nrneph.2010.122.
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Picut, C. A. y R. M. Lewis. "Comparative pathology of canine hereditary nephropathies: An interpretive review". Veterinary Research Communications 11, n.º 6 (1987): 561–81. http://dx.doi.org/10.1007/bf00396371.
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Yanus, G. A., A. G. Iyevleva, E. N. Suspitsin, A. V. Tumakova, E. V. Belogubova, S. N. Aleksakhina, A. V. Togo y E. N. Imyanitov. "Hereditary predisposition to kidney cancer: cancer syndromes, multisystemic disorders, and nephropathies". Sechenov Medical Journal 14, n.º 2 (14 de agosto de 2023): 5–20. http://dx.doi.org/10.47093/2218-7332.2023.14.2.5-20.
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Kidney cancer (KC) is a common disease characterized by extreme heterogeneity. There are nine known monogenic diseases associated with a significantly elevated KC risk: von Hippel-Lindau disease, MET-associated papillary renal cancer, familial multiple leiomyomatosis and renal cell cancer, SDHx-associated familial pheochromocytoma/ paraganglioma, Birt-Hogg-Dube syndrome, tuberous sclerosis, Cowden syndrome, BAP1- and MITF-associated melanoma-KC predisposition. These syndromes differ in the degree of cancer risk, the quantity, growth and progression rates of associated precancerous lesions, the morphology, and clinical presentations of malignancy itself, and in the response to therapy. Identification of causative germline lesion allows planning the surveillance of a mutation carrier, choosing the right time and extent of surgery, and optimizing treatment regimen. Hereditary KC research often brings forward novel approaches to the management of sporadic “phenocopies” of hereditary syndromes, i.e. sporadic cancers with somatic mutations in similar genes. The main directions for further study of genetic factors of KC are to find novel KC genes, to study risk modifiers in carriers of highly penetrant mutations, to clarify the involvement of hereditary nephropathies in the occurrence of renal cancers.
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Minkus, G., W. Breuer, R. Wanke, C. Reusch, G. Leuterer, G. Brem y W. Hermanns. "Familial Nephropathy in Bernese Mountain Dogs". Veterinary Pathology 31, n.º 4 (julio de 1994): 421–28. http://dx.doi.org/10.1177/030098589403100403.
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Between January 1988 and March 1992 nephropathies were frequently diagnosed in Bernese Mountain Dogs. During this period, 20 animals (16 females, four males), ages 2–5 years (average age at time of diagnosis = 3.3 years) presented with clinically renal insufficiency. Morphologic diagnosis of the renal lesions was identical in all cases, i.e., membranoproliferative glomerulonephritis (MPGN) with concomitant interstitial nephritis. Deposits of immunoglobulin-M (IgM) and of the third complement component were regularly demonstrated immunohistochemically in the glomeruli; deposits of immunoglobulin-A (IgA) and immunoglobulin-G (IgG) were found only in isolated cases. Reduplication of glomerular basement membranes, mesangial interposition, and subendothelial deposits of the immunocomplex type were also detected by electron microscopy. A pedigree analysis indicated that the MPGN in these 20 Bernese Mountain Dogs of approximately the same age was of hereditary genesis. Thus, MPGN should be allocated to the group of familial nephropathies. Serologically, high IgG titers against Borrelia burgdorferi were found in 17 dogs. These findings are discussed in relation to familial nephropathies in humans.
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Carriazo, Sol M., Maria Dolores Sanchez-Nino, Laura J. Castañeda Infante y Alberto Ortiz. "Is There a Contribution of Genes Involved in Hereditary Nephropathies to AKI?" Journal of the American Society of Nephrology 31, n.º 10S (octubre de 2020): 523–24. http://dx.doi.org/10.1681/asn.20203110s1523d.
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Riedhammer, Korbinian M., Matthias C. Braunisch, Roman Günthner, Matias Wagner, Clara Hemmer, Tim M. Strom, Christoph Schmaderer et al. "Exome Sequencing and Identification of Phenocopies in Patients With Clinically Presumed Hereditary Nephropathies". American Journal of Kidney Diseases 76, n.º 4 (octubre de 2020): 460–70. http://dx.doi.org/10.1053/j.ajkd.2019.12.008.
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Dimitrijevic, Jovan, Vera Todorovic, Anastasija Aleksic, Dijana Jovanovic, Dijana Pilcevic, Sanja Vignjevic, Sava Micic et al. "Alport’s syndrome and benign familial haematuria: Light and electron microscopic studies of the kidney". Srpski arhiv za celokupno lekarstvo 136, Suppl. 4 (2008): 275–81. http://dx.doi.org/10.2298/sarh08s4275d.
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INTRODUCTION. Hereditary nephropathy is clinically characterized by the familial occurrence in successive generations of progressive haematuric nephritis and neural hearing loss. Hereditary nephropathy of Alport?s syndrome (AS) and benign familial (recurrent) haematuria (BFH) are morphologically characterized by specific and diagnostically important thickening and splitting of lamina densa of the glomerular basement membranes. Those lesions can be recognized only by electron microscopy. Hereditary nephritis is usually present clinically with haematuria, and new mutations without a family history of haematuria. It is therefore important to differentiate hereditary nephritis from BFH and no familial haematuria. Thus, electron microscopy is essential in diagnosis of haematuria. OBJECTIVE. The aim of this study was to describe, by light microscopy, constellation of renal alterations by which hereditary nephropathy can be recognized with high probability as well as to compare the diagnostic validity of the findings observed by light and electron microscopy in AS and BFH. METHOD. We examined 48 renal biopsies of the patients with hereditary nephoropathies by light and electron microscopy. Tissue samples were fixed in buffered paraformaldehyde and embedded in paraffin for long-term preservation. For the electron microscopy analysis, the following fixation in 4% glutaraldehyde tissue was postfixed in 1% osmium tetroxide. Thereafter, the following dehydration procedure tissue slices were embedded in epon. RESULTS. Our results demonstrated that the interstitial foam cells, foetal-like glomeruli, minimal glomerular abnormalities with stain less intense in basement membranes, mild irregular mesangial widening, focal thickening of Bowman?s capsule, foci of dilatation tubules, tubular ectasia and atrophy, erythrocyte tubules casts were present in hereditary nephritis. Additionally, light microscopic biopsy findings in patients with BFH were either normal or revealed minor changes (e.g. increased mesangial matrix). All biopsies were reevaluated by electron microscopy and ultrastructural findings confirmed the diagnosis of hereditary nephropathies. CONCLUSION. The findings observed by light microscopy represent an important step that leads to a definitive diagnosis of AS and BFH. The definitive diagnosis, however, depends on electron microscopy.
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Sementilli, Angelo, Luiz Antonio Moura y Marcello Fabiano Franco. "The role of electron microscopy for the diagnosis of glomerulopathies". Sao Paulo Medical Journal 122, n.º 3 (mayo de 2004): 104–9. http://dx.doi.org/10.1590/s1516-31802004000300006.
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CONTEXT: Electron microscopy has been used for the morphological diagnosis of glomerular diseases for more than three decades and its value has been widely emphasized. However, recent reports have analyzed the routine use of electron microscopy critically. Its use in other areas of diagnosis such as tumor diseases has declined considerably; in addition, in view of the unavoidable financial pressure for the reduction of costs due to investigations and diagnostic routines, the selection of cases for electron microscopy has been quite rigorous. OBJECTIVE: To identify the glomerular diseases that depend on electron microscopy for a final diagnosis, by means of reviewing renal biopsies performed over a 12-year period. DESIGN: Prospective SETTING: Hospital Ana Costa, Hospital Guilherme Álvaro and Serviço de Anatomia Patológica de Santos, Santos, São Paulo, Brazil. PARTICIPANTS: 200 consecutive renal biopsies obtained from private hospitals and the teaching hospital from 1979 to 1991 were studied. MAIN MEASUREMENTS: All cases were analyzed via light microscopy, immunofluorescence and electron microscopy. The diagnosis was first made via light microscopy plus immunofluorescence and then via electron microscopy. RESULTS: Electron microscopy was diagnostic or essential for diagnosis in 10.0% of the cases, corresponding to 3.4% of primary glomerulopathies and 100% of hereditary glomerulopathies. Electron microscopy was contributory (useful) to the diagnosis in 5.5% of the cases, confirming the preliminary diagnosis formulated on the basis of clinical and laboratory data and light microscopy plus immunofluorescence findings. We obtained a 7.5% rate of discordant immunofluorescence, which was considered as such when negative immunofluorescence findings were not confirmed by electron microscopy. The final diagnosis with the use of light microscopy plus immunofluorescence alone was 77.0%. CONCLUSIONS: It was possible to diagnose with certainty a great percentage of glomerulopathies (82.5-90% of the cases) based on the light microscopy and immunofluorescence findings alone. Electron microscopy was essential for the diagnosis of hereditary nephropathies.
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Fatima, Rana, Rakesh Kumar, Amitesh Goud, Srikanth Muddhasani, Satish Reddy, Gouri shankar Swarnalatha y Meenakshi Swain. "Biopsy Proven Kidney Disease From A Rural Tertiary Care Centre — A Social And Epidemiological Perspective". Perspectives in Medical Research 9, n.º 3 (6 de enero de 2022): 68–71. http://dx.doi.org/10.47799/pimr.0903.16.
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Abstract The prevalence of chronic kidney disease (CKD) is rising in rural areas. Screening of high risk cases, early detection and referral by the physicians reduces the prevalence of kidney disease in the population. Hereditary disorders, Glomerular diseases, Obstructive nephropathies are common causes in CKD in rural areas. Kidney biopsy is an essential diagnostic tool in to diagnose glomerular diseases. This prospective study done at tertiary care teaching hospital between 2017 and 2020 to understand the profile of glomerular diseases in rural area. Forty patients were included in the Study. Primary glomerular disease (PGD) was present in 26 patients and Secondary glomerular disease (SGD) in 10 and primary tubulointerstitial pathology in 4 patients. The most common Secondary glomerular disease was lupus. Glomerular diseases are amenable to immunomodulatory therapy leading to change in clinical outcome of the disease. However, Kidney biopsy is underutilized particularly in elderly patients, hypertensive nephropathy patients, suspected non diabetic kidney disease and lupus patients. Financial and social issues play dominant role in the treatment plan of chronic diseases in rural areas. Regional registry of kidney biopsy of urban and rural areas separately helps in paving a way of understanding the profile of glomerular diseases and its prevention.
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Hopfer, H. y M. J. Mihatsch. "Hereditäre Nephropathien". Der Nephrologe 5, n.º 6 (18 de septiembre de 2010): 508–16. http://dx.doi.org/10.1007/s11560-009-0381-x.
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Vyalkova, Albina A., Svetlana A. Chesnokova, Oksana O. Ustinova y Larisa A. Gaikova. "Сhronic kidney disease in children: principles of ambulatory management". Russian Pediatric Journal 24, n.º 2 (14 de mayo de 2021): 122–29. http://dx.doi.org/10.46563/1560-9561-2021-24-2-122-129.
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Introduction. The term «chronic kidney disease» (CKD) is used to define the outcomes of various forms of chronic progressive kidney disease, characterized by kidney damage, or a decrease in their function for three months or more, regardless of the nosological diagnosis. The aim of the work was to determine the frequency, structure, and clinical and paraclinical features of CKD in children to substantiate the principles of its management in primary health care. Results. In CKD patients, tubulointerstitial renal lesions were established to prevail (80%). Associated with congenital malformations of the urinary system, reflux uropathy, and urolithiasis in 98% of cases tubulointerstitial renal lesions are complicated by renal infection. In 8.9% of children, CKD was formed as an outcome of glomerulopathies; in 6.7% of children - with congenital and hereditary nephropathies; in 4.4% of children an outcome of a hemolytic uremic syndrome. The observed children dominated by I-II (74.3%), less often III and IV (25.7%) stages of CKD. The revealed clinical and paraclinical features of CKD in children are presented. The modern principles of early diagnosis of CKD in children and the identification of risk factors for the progression of nephropathy have been substantiated. For the diagnosis of CKD in childhood there has been created a. n algorithm, including at the outpatient stage. Authors suggested a set of measures for the prevention of nephropathy. Conclusion. For early diagnosis of CKD in childhood there was developed an algorithm based on the analysis of a complex of clinical and paraclinical, structural and functional parameters of the kidneys in combination with the parameters of endothelial function and cytokine status.
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Sreelatha, Souparnika, Benedicta D'souza y Vivian D'souza. "Matrix metalloproteinases in nephrotic syndrome; a vital but obscure field of research". Journal of Nephropathology 8, n.º 3 (7 de agosto de 2019): 33. http://dx.doi.org/10.15171/jnp.2019.33.
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Context: Matrix metalloproteinases (MMPs) are involved in the remodelling of the glomerular basement membrane (GBM) by tightly regulating the metabolism of extracellular matrix (ECM) of the GBM. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO, Scopus and Web of Science have been searched. Results: Gelatinases (MMP-2 and MMP-9) are mainly found involved in the remodelling of GBM and therefore this review focuses on these two MMPs and their action in nephrotic syndrome (NS), which is a protein losing enteropathy occurring due to the loss of integrity of GBM. In addition to the blood corpuscles, glomerular epithelial cells and mesangium are also expressing MMPs, and various cytokines and growth factors are involved in addition to tissue inhibitors of metalloproteinases (TIMPs) in regulating the metabolism of ECM via MMPs. While examining the results of MMP activity and expression in NS, except diabetic nephropathy (DN), membranoproliferative glomerulonephritis (MPGN) and hereditary NS where there was a clear down-regulation of MMP, all the other types of NS showed conflicting results. Both suppression and induction of MMPs are finally leading to GBM thickening, loss of integrity and proteinuria. Enhanced MMP activity leads to increase in matrix turnover and accumulation of ECM remnants and apoptotic cells leading to fibrosis. On the other hand, diminished expression of MMPs prevents the normal ECM turnover and matrix accumulation. The review compiled the mechanisms of action of both downregulation and upregulation of MMPs. Conclusions: Imbalance of ECM metabolism due to varied expression levels and activities of MMPs in different types of primary NS might contribute to the progression of nephropathies. Further studies are required to identify the potential and usage of MMPs as a diagnostic/prognostic/ therapeutic tool.
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Lhotta, K. "Pathogenese und Klinik hereditarer Nephropathien". Acta Medica Austriaca 28, n.º 3 (julio de 2001): 78–80. http://dx.doi.org/10.1046/j.1563-2571.2001.01018.x.
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Severova-Andreevska, Galina, Ladislava Grcevska, Gordana Petrushevska, Koco Cakalaroski, Aleksandar Sikole, Olivera Stojceva–Taneva, Ilina Danilovska y Ninoslav Ivanovski. "The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study". Open Access Macedonian Journal of Medical Sciences 6, n.º 4 (30 de marzo de 2018): 606–12. http://dx.doi.org/10.3889/oamjms.2018.162.
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INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR).AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function.MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun” were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used.RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a “mixed” rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR + IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease.CONCLUSION: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.
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Moiseev, Sergey V. y Eugene M. Shilov. "Kidney involvement in rare hereditary diseases". Terapevticheskii arkhiv 96, n.º 6 (7 de julio de 2024): 559–64. http://dx.doi.org/10.26442/00403660.2024.06.202722.
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Various rare inherited disorders can be associated with kidney involvement, including glomerulopathies, tubulopathies, multiple cysts, congenital anomalies of the kidneys and urinary tract, urolithiasis, malignant and benign tumors. Genetic nephropathy should be always considered in children, adolescents and young patients with the kidneys or urinary tract disorders and/or patients with positive family anamnesis. Extrarenal manifestations can be a valuable clue for diagnosis of certain hereditary diseases, e.g. neurosensory deafness in Alport syndrome or photofobia in nephropathic cystinosis. Diagnosis of monogenic inherited diseases should be verified by genetic testing. Specific drugs are available for treatment of certain hereditary diseases involving kidney, e.g. Fabry disease, cystinosis, primary hyperoxaluria I type and atypical hemolytic uremic syndrome.
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Persey, Malcolm R., David R. Booth, Susanne E. Booth, Raul van Zyl-Smit, Bruce K. Adams, Abe B. Fattaar, Glenys A. Tennent, Philip N. Hawkins y Mark B. Pepys. "Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I". Kidney International 53, n.º 2 (febrero de 1998): 276–81. http://dx.doi.org/10.1046/j.1523-1755.1998.00770.x.
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Janssens, Virginie, Héloïse P. Gaide Chevronnay, Sandrine Marie, Marie-Françoise Vincent, Patrick Van Der Smissen, Nathalie Nevo, Seppo Vainio et al. "Protection of Cystinotic Mice by Kidney-Specific Megalin Ablation Supports an Endocytosis-Based Mechanism for Nephropathic Cystinosis Progression". Journal of the American Society of Nephrology 30, n.º 11 (23 de septiembre de 2019): 2177–90. http://dx.doi.org/10.1681/asn.2019040371.
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BackgroundDeletions or inactivating mutations of the cystinosin gene CTNS lead to cystine accumulation and crystals at acidic pH in patients with nephropathic cystinosis, a rare lysosomal storage disease and the main cause of hereditary renal Fanconi syndrome. Early use of oral cysteamine to prevent cystine accumulation slows progression of nephropathic cystinosis but it is a demanding treatment and not a cure. The source of cystine accumulating in kidney proximal tubular cells and cystine’s role in disease progression are unknown.MethodsTo investigate whether receptor-mediated endocytosis by the megalin/LRP2 pathway of ultrafiltrated, disulfide-rich plasma proteins could be a source of cystine in proximal tubular cells, we used a mouse model of cystinosis in which conditional excision of floxed megalin/LRP2 alleles in proximal tubular cells of cystinotic mice was achieved by a Cre-LoxP strategy using Wnt4-CRE. We evaluated mice aged 6–9 months for kidney cystine levels and crystals; histopathology, with emphasis on swan-neck lesions and proximal-tubular-cell apoptosis and proliferation (turnover); and proximal-tubular-cell expression of the major apical transporters sodium-phosphate cotransporter 2A (NaPi-IIa) and sodium-glucose cotransporter-2 (SGLT-2).ResultsWnt4-CRE–driven megalin/LRP2 ablation in cystinotic mice efficiently blocked kidney cystine accumulation, thereby preventing lysosomal deformations and crystal deposition in proximal tubular cells. Swan-neck lesions were largely prevented and proximal-tubular-cell turnover was normalized. Apical expression of the two cotransporters was also preserved.ConclusionsThese observations support a key role of the megalin/LRP2 pathway in the progression of nephropathic cystinosis and provide a proof of concept for the pathway as a therapeutic target.
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Veys, Koenraad R. P., Mohamed A. Elmonem, Maria Van Dyck, Mirian C. Janssen, Elisabeth A. M. Cornelissen, Katharina Hohenfellner, Giusi Prencipe, Lambertus P. van den Heuvel y Elena Levtchenko. "Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis". Journal of the American Society of Nephrology 31, n.º 5 (9 de abril de 2020): 1092–106. http://dx.doi.org/10.1681/asn.2019080774.
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BackgroundNephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis. Because macrophage-mediated inflammation plays an important role in the pathogenesis of cystinosis, biomarkers of macrophage activation could have potential for the therapeutic monitoring of cystinosis.MethodsWe conducted a 2-year prospective, longitudinal study in which 61 patients with cystinosis who were receiving cysteamine therapy were recruited from three European reference centers. Each regular care visit included measuring four biomarkers of macrophage activation: IL-1β, IL-6, IL-18, and chitotriosidase enzyme activity.ResultsA multivariate linear regression analysis of the longitudinal data for 57 analyzable patients found chitotriosidase enzyme activity and IL-6 to be significant independent predictors for white blood cell cystine levels in patients of all ages with cystinosis; a receiver operating characteristic analysis ranked chitotriosidase as superior to IL-6 in distinguishing good from poor therapeutic control (on the basis of white blood cell cystine levels of <2 nmol 1/2 cystine/mg protein or ≥2 nmol 1/2 cystine/mg protein, respectively). Moreover, in patients with at least one extrarenal complication, chitotriosidase significantly correlated with the number of extrarenal complications and was superior to white blood cell cystine levels in predicting the presence of multiple extrarenal complications.ConclusionsChitotriosidase enzyme activity holds promise as a biomarker for use in therapeutic monitoring of nephropathic cystinosis.
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Moiseev, S., N. Chebotareva, N. Bulanov y E. M. Shilov. "Rare inherited diseases with kidney involvement: approaches to diagnosis and treatment". Clinical pharmacology and therapy 38, n.º 3 (2 de septiembre de 2023): 6–18. http://dx.doi.org/10.32756/0869-5490-2023-3-6-18.
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Many rare inherited disorders can be associated with the various types of kidney involvement, including glomerular disease, tubulopathies, congenital anomalies of the kidneys and urinary tract, urolithiasis, multiple cysts, malignant and benign tumors. Hereditary nephropathy should be always considered in children, adolescents and young patients with the kdineys or urinary tract disorders and/or patients with positive family anamnesis although certain genetic diseases can manifest in adult or even in the elderly whereas proband family members frequently show no signs of the disease. Extrarenal manifestations can be a valuable clue for diagnosis of various genetic disorders, e.g. neurosensory deafness in Alport syndrome, cornea verticillata and angiokeratoma in Fabry disease, photofobia in nephropathic cystinosis. Genetic tests are essential for verification of monogenic inherited diseases. In the nearest future, whole-exome or genome sequencing at constantly decreasing cost may replace targeted sequencing of the known causal gene(s) or gene panels, particularly when various inherited disorders present with the similar clinical phenotypes.
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Alsultan, Mohammad Khaled, Zeina Nizar Bdeir, Qussai Hassan y Tahani Ali. "Successful Kidney Transplant for Nephropathic Cystinosis in a Patient with Von Willebrand Disease Type III: The First Case Report". Case Reports in Nephrology and Dialysis 11, n.º 3 (30 de noviembre de 2021): 362–66. http://dx.doi.org/10.1159/000520794.
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Nephropathic cystinosis (NC) is a rare autosomal recessive disease, which causes cysteine-crystals accumulation with progression to end-stage renal disease (ESRD). Von willebrand disease (VWD) type III is a rare subtype of von willebrand factor (VWF) abnormality, which is characterized by severe reduction of VWF and factor VIII activity. A 16-year-old patient with NC and VWD type III presented with uremic symptoms due to ESRD. Dialysis access was inserted and followed by hemodialysis (HD) for 4 months with a proper infusion of blood products. While renal transplant remains the treatment of choice of NC and superior to chronic HD, bleeding complications were a major concern in this case with coexisting VWD type III. However, with the meticulous implementation of the Hematology team’s daily recommendations, renal transplantation was successfully performed. This is the first case that mentions a new association between two inherited rare disorders, NC and VWD type III, and this entity has not been reported before. Moreover, successful kidney transplantation in our patient supports the possibility of these procedures in hereditary clotting disorders.
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Tavares, Isabel, Luísa Lobato, Carlos Matos, Josefina Santos, Paul Moreira, Maria João Saraiva y António Castro Henriques. "Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The First Report". Case Reports in Nephrology 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/919763.
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Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val) mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated byClostridium difficilecolitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val) fibrinogen A alpha-chain amyloidosis.
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Génevaux, Franziska, Ajla Barucija, Kilian Hierdeis, Louisa Hock y Stefan Eber. "Hämatologie in der pädiatrischen Praxis". Kinder- und Jugendmedizin 24, n.º 01 (febrero de 2024): 39–49. http://dx.doi.org/10.1055/a-2220-1397.
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ZUSAMMENFASSUNGAnämien sind heterogen und vielfältig, daher werden besonders seltene Anämieformen häufig unterdiagnostiziert. Eine ausführliche Diagnostik im klinischen Alltag ist deshalb notwendig. Zum Ausschluss häufiger Anämieursachen sollten immer eine eingehende klinische Anamnese und Diagnostik mit der Suche nach Infektionen oder Tumoren, Hämolysezeichen und Coombs-Test erfolgen. Als Differenzialdiagnose bei verändertem Blutbild muss auch an ein malignes Geschehen gedacht werden. Nur durch das Ausschließen zahlreicher Differenzialdiagnosen lassen sich seltene Anämien detektieren und adäquat behandeln.Die Eisenmangelanämie ist die häufigste Anämieform, die sich mit einer mikrozytären, hypochromen Anämie im Blutbild präsentiert. Ursache ist entweder eine zu geringe Zufuhr, eine schwache Absorption (zum Beispiel bei Zöliakie) oder eine vermehrte Ausscheidung von Eisen. Therapeutisch kann eine orale Therapie mit Fe2+ (Ferrosanol-Tropfen/Kapseln) eingeleitet werden und bei schwerer, therapieresistenter Eisenmangelanämie sollte eine Eisentransfusion in Erwägung gezogen werden.Bei der Sichelzellerkrankung kommt es zu mehr oder weniger schweren Gefäßverschlüssen, chronischer Hämolyse und Infektbereitschaft durch funktionelle Asplenie. Eine Prophylaxe mit Hydroxycarbamid kann Sichelzellkrisen vorbeugen, die einzig kausale Therapie ist die allogene Stammzellentransplantation.Die hereditäre Sphärozytose und der Pyruvatkinase-Mangel sind in Mitteleuropa die häufigsten, genetisch bedingten chronischen hämolytischen Anämien. Bei diesen beiden Erkrankungen ist durch einfache hämatologische Untersuchungen eine Unterteilung in verschiedene Schweregrade der Erkrankung möglich. Diese Einteilung erlaubt eine prognostische Aussage über den zu erwartenden klinischen Verlauf und die Einleitung einer adäquaten Therapie. Als erste kongenitale hämolytische Anämie kann der Pyruvatkinase-Mangel molekular durch Mitapivat behandelt werden. Dieser Therapieversuch sollte vor der Splenektomie erfolgen. Bei der Sphärozytose sollte eine nahezu totale Splenektomie (NTS) der vollständigen Splenektomie vorgezogen werden, da dadurch die immunologische Milzfunktion erhalte werden kann.Weitere wichtige Anämien sind die Autoimmunhämolytischen Anämien (AIHA). Sie werden durch eine Bildung von Antikörpern gegen Antigene auf autologen Erythrozyten charakterisiert. Die zwei häufigsten Vertreter sind die durch Wärme- und Kälteantikörper ausgelösten AIHA. Therapeutisch können Steroide und bei Steroidresistenz Immunsuppressiva angewandt werden.Renale Anämien sind sehr selten und treten bei Kindern mit chronischem Nierenversagen, meist als Folge kongenitaler Nephropathien, auf. Es sollten einerseits die Verbesserung der Nierenfunktion, andererseits die Stimulation der Erythropoese als therapeutische Ansätze erwogen werden.
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Carriazo, Sol, Maria Dolores Sanchez-Nino, Maria Vanessa Perez Gomez, Laura Castañeda-Infante, Teresa Stock da Cunha, Guillermo Gonzalez-Martin, Alejandro Avello et al. "P0054ACQUIRED DIFFERENTIAL EXPRESSION IN ACUTE KIDNEY INJURY OF GENES RESPONSIBLE FOR HEREDITARY NEPHROPATHIES". Nephrology Dialysis Transplantation 35, Supplement_3 (1 de junio de 2020). http://dx.doi.org/10.1093/ndt/gfaa142.p0054.
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Abstract Background and Aims Gene sequencing is becoming an important diagnostic tool in a great number of medical specialties. Despite its interpretation is still a challenge, allows the identification of genes related to hereditary diseases and bild a base for the study of acquired nephropathies. We hypothesize that those genes responsible for hereditary nehpropathies could contribute to the pathogenesis of acquired nephropathies. Method In a murine model of acute kidney disease induced by folic acid, we analyzed the kidney transcriptomic after 24 hours of damage. In this database we evaluated if 625 genes described as responsible for hereditary nephropathies were expressed significantly. Later, we evaluated the correlation between diferentially expressed genes and glomerular filtration, using transcriptomic databases of human nephropathies (Nephroseq), so that, we could identify those relevant in acquired human nephropathies and in experimental settings. A functional enrichment analysis was done using the software Gorilla, and some of the genes were validated in our laboratory using RT-PCR. Results In acute kidney disease, the renal expression of 3906/25051 (15.59%) genes increased and the expression of 3537 (14.11%) decreased significantly (p<0.05). The percentage of genes expressed diferentially was higher when analysing the 625 genes responsible of familiar nephropathies. We identified 615 of those in the murine model and 105/615 (17.07%) increased it expression, and 155 (25.20%), decreased it (p<0.05 when compared with the database with 25051 genes). 241 of those 260 diferentially expressed genes (92.69%) where associated significantly with glomerular filtration rate in human nephropathies. The most enriched GO process were “complement activation", "protein activation cascade", "activation of immune response" and "RNA processing”. We have validated the expression of 7 of the genes in acute kidney injury (SLC34A1, SLC34A3, Klotho, MAGED2, NLRP3, FN1, COL4A1), which supports the relevance of the transcriptomic results. Conclusion Genes involved in familiar nephropathies are overexpressed between genes diferentially expressed in acquired nephropathies, suggesting that they could play a role in the pathogenesis of the last, throught the regulation of the RNA processing, protein activation or immune response and complement regulation. The analysis of the functioning of genes responsible for familiar nephropathies in acquired nephropaties could identify new therapeutic targets in kidney damage.
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Stippel, Michaela, Korbinian M. Riedhammer, Bärbel Lange-Sperandio, Michaela Geßner, Matthias C. Braunisch, Roman Günthner, Martin Bald et al. "Renal and Skeletal Anomalies in a Cohort of Individuals With Clinically Presumed Hereditary Nephropathy Analyzed by Molecular Genetic Testing". Frontiers in Genetics 12 (26 de mayo de 2021). http://dx.doi.org/10.3389/fgene.2021.642849.
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Background: Chronic kidney disease (CKD) in childhood and adolescence occurs with a median incidence of 9 per million of the age-related population. Over 70% of CKD cases under the age of 25 years can be attributed to a hereditary kidney disease. Among these are hereditary podocytopathies, ciliopathies and (monogenic) congenital anomalies of the kidney and urinary tract (CAKUT). These disease entities can present with a vast variety of extrarenal manifestations. So far, skeletal anomalies (SA) have been infrequently described as extrarenal manifestation in these entities. The aim of this study was to retrospectively investigate a cohort of individuals with hereditary podocytopathies, ciliopathies or CAKUT, in which molecular genetic testing had been performed, for the extrarenal manifestation of SA.Material and Methods: A cohort of 65 unrelated individuals with a clinically presumed hereditary podocytopathy (focal segmental glomerulosclerosis, steroid resistant nephrotic syndrome), ciliopathy (nephronophthisis, Bardet-Biedl syndrome, autosomal recessive/dominant polycystic kidney disease), or CAKUT was screened for SA. Data was acquired using a standardized questionnaire and medical reports. 57/65 (88%) of the index cases were analyzed using exome sequencing (ES).Results: 8/65 (12%) index individuals presented with a hereditary podocytopathy, ciliopathy, or CAKUT and an additional skeletal phenotype. In 5/8 families (63%), pathogenic variants in known disease-associated genes (1x BBS1, 1x MAFB, 2x PBX1, 1x SIX2) could be identified.Conclusions: This study highlights the genetic heterogeneity and clinical variability of hereditary nephropathies in respect of skeletal anomalies as extrarenal manifestation.
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Corsello, Antonio, Chiara Maria Trovato, Valeria Dipasquale, Emanuele Proverbio, Gregorio Paolo Milani, Antonella Diamanti, Carlo Agostoni y Claudio Romano. "Malnutrition management in children with chronic kidney disease". Pediatric Nephrology, 2 de julio de 2024. http://dx.doi.org/10.1007/s00467-024-06436-z.
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AbstractChronic kidney disease (CKD) encompasses diverse conditions such as congenital anomalies, glomerulonephritis, and hereditary nephropathies, necessitating individualized nutritional interventions. Early detection is pivotal due to the heightened risk of adverse outcomes, including compromised growth and increased healthcare costs. The nutritional assessment in pediatric CKD employs a comprehensive, multidisciplinary approach, considering disease-specific factors, growth metrics, and dietary habits. The prevalence of malnutrition, as identified through diverse tools and guidelines, underscores the necessity for regular and vigilant monitoring. Nutritional management strategies seek equilibrium in calorie intake, protein requirements, and electrolyte considerations. Maintaining a well-balanced nutritional intake is crucial for preventing systemic complications and preserving the remaining kidney function. The nuanced landscape of enteral nutrition, inclusive of gastrostomy placement, warrants consideration in scenarios requiring prolonged support, with an emphasis on minimizing risks for optimized outcomes. In conclusion, the ongoing challenge of managing nutrition in pediatric CKD necessitates continuous assessment and adaptation. This review underscores the significance of tailored dietary approaches, not only to foster growth and prevent complications but also to enhance the overall quality of life for children grappling with CKD. Graphical abstract
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Zellner, Alicia, Christian Schaaf, Maike Buettner-Herold, Peer-Hendrik Kuhn, Matthias Braunisch, Jasmina Ćomić, Lutz Renders et al. "#4876 CLASSIFICATION OF BIOPSY FINDINGS IN INDIVIDUALS WITH NEPHROPATHIES USING MOLECULAR GENETIC TESTING AND PROTEOMICS". Nephrology Dialysis Transplantation 38, Supplement_1 (junio de 2023). http://dx.doi.org/10.1093/ndt/gfad063c_4876.
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Abstract Background and Aims In approximately 10% of adults with chronic kidney disease, a hereditary cause can be identified. Important representatives are Alport syndrome and inherited podocytopathies, which often show the histological picture of focal segmental glomerulosclerosis (FSGS). FSGS is a histological finding of various etiologies (primary, hereditary, secondary). Especially in suspected glomerular kidney disease, kidney biopsy is the diagnostic gold standard. The aim of this study was to evaluate a cohort of individuals with genetically confirmed inherited nephropathy and previous kidney biopsy to determine whether the histological examination can provide a clue to the underlying inherited kidney disease. Biopsies were further investigated by proteomics via liquid-chromatography-mass spectrometry (LC-MS) to potentially elucidate the underlying protein defect. Method The cohort for this retrospective study consisted of 23 individuals with a genetically confirmed inherited nephropathy and a previously performed kidney biopsy. A systematic pathological secondary review of the 23 biopsies was carried out (genetic diagnosis unknown at secondary review). The findings of the biopsies were compared with the molecular genetic results. 9 proband and 9 control biopsies were additionally evaluated through LC-MS. Laser capture microdissection was used to extract glomeruli from the tissue samples, which were then further analyzed on alterations in protein expression secondary to the respective disease-causing variants. Results In the cohort, disease-causing variants were identified in the following genes: COL4A3 (n = 3), COL4A5 (n = 4), WT1 (n = 3), UMOD (n = 3), and each n = 1 for the genes INF2, DAAM2, MUC1, COQ8B, NPHP4, TRIM8, CD2AP, NPHS2, CLCN5, and PAX2. The biopsies showed predominantly segmental glomerulosclerosis and parenchymal scarring, as well as podocyte damage. Four individuals with the histological diagnosis of Alport syndrome were genetically confirmed as having X-chromosomal (n = 2; including one female carrier) and autosomal-recessive (n = 2) Alport syndrome. Proteomics showed heterogeneous results. Proband samples carried variants in COL4A3 (n = 3), COL4A5 (n = 3), ADCK4, NPHP4, and WT1 (the last three each n = 1). COL4A3 was detected in 6/9 of control samples and in 0/9 of proband samples; COL4A5 was detected in 5/9 of control samples and in 0/9 of proband samples. ADCK4, NPHP4, and WT1 could not be detected in this analysis, neither in control, nor in proband samples. Conclusion In this study, molecular genetic diagnostics allowed a more precise disease assignment and thus provided information on therapy, prognosis, recurrence in the transplant, possible extrarenal phenotypes, and inheritance. Histological findings can indicate an inherited disease and help to trigger genetic testing (e.g., Alport syndrome). However, genetic diagnostics can also classify cases for which there are no typical morphological criteria described or if severe scarring impairs morphological diagnosis. Numerous cases of a respective monogenic disease would have to be analyzed in order to establish common histopathological criteria, if present. This is a challenge due to the rapid discovery of new disease-associated genes and the rarity of the respective diseases. LC-MS-based proteomics from kidney biopsy samples showed to be of limited value in further characterizing changes associated with specific variants. Unlike the genome, which is consistent due to the stability of DNA, the proteome is influenced by various effects: Different stages of fibrosis depending on the time of biopsy and other factors like coexistent disease lead to varying protein intensities even in two separate samples that present identical genetic variants. The detected protein intensity patterns could not be sufficiently correlated with the genetic findings. Despite the detection of certain proteins of interest like type IV collagens, their intensity variation due to advanced tissue damage did not allow reliable conclusions on the underlying cause. Alternatively, molecular methods such as MALDI imaging could further visualize these changes.
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Monte Neto, José Tiburcio do y Gianna Mastroianni Kirsztajn. "The role of podocyte injury in the pathogenesis of Fabry disease nephropathy". Brazilian Journal of Nephrology 46, n.º 3 (septiembre de 2024). http://dx.doi.org/10.1590/2175-8239-jbn-2024-0035en.
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Abstract Renal involvement is one of the most severe morbidities of Fabry disease (FD), a multisystemic lysosomal storage disease with an X-linked inheritance pattern. It results from pathogenic variants in the GLA gene (Xq22.2), which encodes the production of alpha-galactosidase A (α-Gal), responsible for glycosphingolipid metabolism. Insufficient activity of this lysosomal enzyme generates deposits of unprocessed intermediate substrates, especially globotriaosylceramide (Gb3) and derivatives, triggering cellular injury and subsequently, multiple organ dysfunction, including chronic nephropathy. Kidney injury in FD is classically attributed to Gb3 deposits in renal cells, with podocytes being the main target of the pathological process, in which structural and functional alterations are established early and severely. This configures a typical hereditary metabolic podocytopathy, whose clinical manifestations are proteinuria and progressive renal failure. Although late clinical outcomes and morphological changes are well established in this nephropathy, the molecular mechanisms that trigger and accelerate podocyte injury have not yet been fully elucidated. Podocytes are highly specialized and differentiated cells that cover the outer surface of glomerular capillaries, playing a crucial role in preserving the structure and function of the glomerular filtration barrier. They are frequent targets of injury in many nephropathies. Furthermore, dysfunction and depletion of glomerular podocytes are essential events implicated in the pathogenesis of chronic kidney disease progression. We will review the biology of podocytes and their crucial role in regulating the glomerular filtration barrier, analyzing the main pathogenic pathways involved in podocyte injury, especially related to FD nephropathy.
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Khan, Muhammad Ali, Purba Nag, Anca Grivei, Kurt T. K. Giuliani, Xiangju Wang, Vishal Diwan, Wendy Hoy, Helen Healy, Glenda Gobe y Andrew J. Kassianos. "Adenine overload induces ferroptosis in human primary proximal tubular epithelial cells". Cell Death & Disease 13, n.º 2 (febrero de 2022). http://dx.doi.org/10.1038/s41419-022-04527-z.
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AbstractThe pathogenesis of crystal nephropathy involves deposition of intratubular crystals, tubular obstruction and cell death. The deposition of 8-dihydroxyadenine (DHA) crystals within kidney tubules, for instance, is caused by a hereditary deficiency of adenine phosphoribosyl transferase in humans or adenine overload in preclinical models. However, the downstream pathobiological patterns of tubular cell attrition in adenine/DHA-induced nephropathy remain poorly understood. In this study, we investigated: (i) the modes of adenine-induced tubular cell death in an experimental rat model and in human primary proximal tubular epithelial cells (PTEC); and (ii) the therapeutic effect of the flavonoid baicalein as a novel cell death inhibitor. In a rat model of adenine diet-induced crystal nephropathy, significantly elevated levels of tubular iron deposition and lipid peroxidation (4-hydroxynonenal; 4-HNE) were detected. This phenotype is indicative of ferroptosis, a novel form of regulated necrosis. In cultures of human primary PTEC, adenine overload-induced significantly increased mitochondrial superoxide levels, mitochondrial depolarisation, DNA damage and necrotic cell death compared with untreated PTEC. Molecular interrogation of adenine-stimulated PTEC revealed a significant reduction in the lipid repair enzyme glutathione peroxidase 4 (GPX4) and the significant increase in 4-HNE compared with untreated PTEC, supporting the concept of ferroptotic cell death. Moreover, baicalein treatment inhibited ferroptosis in adenine-stimulated PTEC by selectively modulating the mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) and thus, suppressing mitochondrial superoxide production and DNA damage. These data identify ferroptosis as the primary pattern of PTEC necrosis in adenine-induced nephropathy and establish baicalein as a potential therapeutic tool for the clinical management of ferroptosis-associated crystal nephropathies (e.g., DHA nephropathy, oxalate nephropathy).
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Del Águila García, María del Mar, Antonio M. Poyatos Andújar, Ana Isabel Morales García, Margarita Martínez Atienza, Susana García Linares y Rafael Jose Esteban de la Rosa. "MO046NGS PANEL PERFORMANCE IN THE DIAGNOSIS OF HEREDITARY RENAL DISEASE IN SOUTHERN SPAIN". Nephrology Dialysis Transplantation 36, Supplement_1 (1 de mayo de 2021). http://dx.doi.org/10.1093/ndt/gfab080.0018.
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Abstract Background and Aims Hereditary renal disease (HRD) is still underdiagnosed: although we know aspects related to autosomal dominant polycystic kidney disease (ADPKD), we know little about the incidence and prevalence of other entities such as Alport syndrome. Altogether, HRD can represent 15% of individuals undergoing renal replacement therapy (RRT) or could even be higher. The advancement of genetics at the healthcare level let to achieve accurate and early renal diagnoses, as well as the incorporation of genetic counseling to families, all of which will result in better management of the disease in its initial stages and the possibility of offering reproductive options that avoid transmission to offspring. Our objective is to know the performance offered by the implementation of the ERH panel through Next Generation Sequencing (NGS) in our healthcare area. Method Observational-descriptive study of 259 probands (141 men / 118 women), mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and suspected hereditary cause attended in the specialized consultation of our centers from October 2018 to October 2020. The DNA extracted from leukocytes obtained by venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA Genetics) according to the manufacturer's protocol. This panel covers the coding regions and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1). The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic analysis of the data and annotation of variants was performed using the SOPHiA DDM 5.8.0.3 software, and the revision of variants by consulting the main databases (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD). Results The panel was informative (pathogenic or probably pathogenic) in 80/259 patients (31%) and 56/259 cases (21.66%) of variants of uncertain significance (VSI) were detected. Autosomal dominant polycystic kidney disease accounted for 76.2% of the variants identified (56.2% PKD1, 20% PKD2), following Alport syndrome with 15% and the alterations in the PKHD1 gene associated with renal polycystic disease in its recessive form with about 4% (Figure 1). We have also identified a case of autosomal dominant tubulointerstitial kidney disease associated with the UMOD gene that was not suspected until the genetic study was performed. We highlight that 45% (36/80) of the variants identified as responsible for the renal disease are not yet described. Overall, the most prevalent type of mutation is that which produces displacement in the reading frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense. Conclusion Our NGS HRD panel a) offers an adequate diagnostic performance at the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the performance of many carrier studies among family members b) is able of diagnosing the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or poorly characterized cases, and c) opens the horizon for new diagnoses, all without increasing costs by outsourcing services. All this makes the genetic study of renal pathology a useful and efficient strategy. These results encourage us to enhance the resources in this area that we consider to be of strategic value.
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Tiwari, Vaibhav, Tarun Shikarwar y A. K. Bhalla. "#2003 Genetic association in patients with chronic kidney disease of unknown etiology: an observational study". Nephrology Dialysis Transplantation 39, Supplement_1 (mayo de 2024). http://dx.doi.org/10.1093/ndt/gfae069.1218.
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Abstract Background and Aims Chronic kidney disease (CKD), impacting over 850 million people worldwide, is a diverse group of inherited and acquired nephropathies. While only about 10% of adult CKD is hereditary, predominantly due to mutations in genes like PKD1, PKD2, and PKHD1, the etiology often remains unidentified, leading to challenges in management, especially in transplantation and genetic counseling contexts. This study used whole exome sequencing to investigate CKD of unknown origin, aiming to improve diagnostic yields and establish genetic associations. Our objective was to find the diagnostic yield of Whole exome sequencing in patients with CKD of unknown etiology and to establish genetic association for same. Method The study was conducted in the Department of Nephrology and the Institute of Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi. It was an observational cross-sectional analysis. All patients, both male and female of all age groups with Chronic Kidney Disease of unknown etiology who were willing to participate. All patients, both male and female of all age groups with Chronic Kidney Disease of known etiology were excluded as following: Results In the investigation of 56 chronic kidney disease samples with unknown etiology, genetic testing yielded 45 mutated gene variants in 37 subjects. The variants comprised 32 missense mutations, 8 deletions, 3 nonsense mutations, and 1 splice site mutation. Variant zygosity was as follows: 34 heterozygous, 6 homozygous, and 2 hemizygous. Pathogenic variants were detected in 9 patients (20%), likely pathogenic in 6 (13.33%), and variants of uncertain significance in 29 (64.44%). Eighteen subjects (32.14%) demonstrated no genetic mutations. A genetic diagnosis was established in 15 patients, representing a diagnostic yield of 26.78%. Stratified by disorder, the yield was 40% for glomerular, 100% for tubular, 50% for renal calculi, and 18.42% for undetermined CKD. Genetic testing facilitated a novel diagnosis or an alteration of the existing diagnosis in 6 patients (10.71%). Conclusion The results affirm the efficacy of genetic testing in elucidating the etiologies of chronic kidney disease where traditional diagnostic methods do not yield definitive causation. Genetic alterations were identified in a significant proportion of the patient population, indicating the presence of underlying genetic contributors to the disease. The identification of pathogenic and likely pathogenic variants highlights the potential of genetic testing to impact clinical decision-making and patient care.
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Thomé, Gustavo Gomes, Talissa Bianchini, Rafael Nazario Bringhenti, Pedro Guilherme Schaefer, Elvino José Guardão Barros y Francisco Veríssimo Veronese. "The spectrum of biopsy-proven glomerular diseases in a tertiary Hospital in Southern Brazil". BMC Nephrology 22, n.º 1 (diciembre de 2021). http://dx.doi.org/10.1186/s12882-021-02603-8.
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Abstract Background The prevalence and distribution of glomerular diseases differ among countries, and the indication to perform a kidney biopsy varies among centres. In this study, we assessed the prevalence of primary and secondary glomerulopathies based on histological diagnoses, and the correlation between glomerulopathies and demographic and clinical data was evaluated. Methods In this study, 1051 kidney biopsies were retrospectively reviewed between 2000 and 2018. Patient demographic, clinical and laboratory data were assessed. The prevalence of primary glomerulonephritis (PG) and secondary glomerulopathies (SG), as well as tubulointerstitial diseases (TIDs), hereditary nephropathies (HNs) and other diagnoses, were determined. The frequency of primary and secondary glomerulopathies was evaluated by age group, and the temporal variation in frequencies across three time periods (2000-2005, 2006-2011, and 2012-2018) was reported. Results The prevalence of SG predominated (52.4%), followed by PG (29.6%), other diagnoses (10.7%), TID (6.6%) and HN (1.1%). Among the primary forms of glomerular disease, focal segmental glomerulosclerosis (FSGS) was the most common (37.3%), followed by IgA nephropathy (IgAN, 24.4%), membranous nephropathy (MN, 18.6%) and minimal change disease (MCD, 8.4%). Lupus nephritis (LN, 41.1%) was most common in patients with SG, followed by diabetic kidney disease (DKD, 17.8%), systemic vasculitis (SV, 10.2%) and secondary FSGS (2nd FSGS, 10%). Nephrotic syndrome was the most common clinical presentation in patients with PG and also in patients with DRD and 2nd FSGS, whereas in patients with IgAN and SV, nephritic syndrome was the main presentation. For the age group between 18 and 50 years, LN, FSGS and IgAN predominated; for patients aged between 51 and 65 years, the proportion of DKD and 2nd FSGS increased, and SV was more common in patients > 65 years. The temporal variation in PG across the three time periods showed a statistically significant increase in IgAN (p = 0.001) and a reduction in FSGS over time (p < 0.001). In SG, there was a reduction in LN (p = 0.027) and an increase in DKD (p < 0.001) over time, with a tendency for 2nd FSGS to decrease over time (p = 0.053). Conclusions In the studied kidney biopsy registry, FSGS and IgAN were the most prevalent diagnoses in patients with PG, and LN and DKD were the most prevalent in patients with SG. Nephrotic syndrome was the major indication for biopsy. When comparing the temporal variation in glomerulopathies, there was a reduction in FSGS and an increase in IgAN in patients with PGs over time, and for patients with SGs, there was a reduction in LN with an increase in cases of DKD over time.
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Pandey, Prasant Kumar, Peerzada Owais Ahmad, Nomeeta Gupta y Amit Agarwal. "CLINICAL PROFILE AND OUTCOME OF PEDIATRIC MAINTENANCE HEMODIALYSIS A PROSPECTIVE, OBSERVATIONAL, HOSPITAL BASED STUDY." GLOBAL JOURNAL FOR RESEARCH ANALYSIS, 15 de noviembre de 2020, 1–9. http://dx.doi.org/10.36106/gjra/5901784.
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Introduction Dialysis forms the cornerstone of therapy for most patients with chronic kidney diseases stage V, End Stage Renal Disease (ESRD) and many patients with Acute Kidney Injury (AKI). Congenital disorders, including congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies, are responsible for about two thirds of all cases of CKD in developed countries, while glomerulonephritis in developing countries predominates as cause for CKD. Most paediatric patients continue to have haemodialysis till a source becomes available for renal transplant, some may die waiting kidney transplant due to complications and some might change dialysis centre at parents wish. Aims To identify the causes of Chronic Kidney Disease in children and to assess the outcome and impact of paediatric haemodialysis on Growth parameters and on laboratory parameters. Materials And Methods this study is Prospective observational hospital based study done at Pediatric hemodialysis centre at Department of Pediatrics and Neonatology, Batra Hospital and Medical Research Centre, New Delhi. Patients coming to Batra hospital for pediatric maintenance hemodialysis were study subjects. A total of 50 patients were taken up for study. Detailed history taking, clinical examination and relevant investigations of subjects were done. Dialysis had been performed with Fresenius 2008K machines and hollow fiberpolysulfone dialysis filters (Fresenius, Bad Homburg, Germany), using standard bicarbonate dialysis solution. Following hemodialysis procedure the child was followed till the end point. Results . Our study showed prevalence of CKD more in males. In our study out of 50 cases 27(54%) cases wer found to be having glomeruolnephritis as a cause of CKD. In our study out of 50 cases :30 (60%)cases were followed till the end of study 9 (18%)cases terminated dialysis on parent’s wish and dialysis may be continued at another centre.6 (12%)cases died during the study period And 5 (10%)cases underwent renal transplantation. Height improved on follow up and lab. Parameters like Hb,phosphate,crea also improved. Conclusion This study showed that in developing countries set up most common cause of CKD in paediatric age group is Glomerulonephritis followed by CAKUT and other congenital anomalies of urinary tract. Haemodialysis in children improves height, anemia, and other lab. Parameters like phosphate, creatinine and others. Most paediatric patients followed maintenance haemodialysis till end of study, some died, and some shifted to other haemodialysis centre while about 10% cases underwent kidney transplantation. There is a greater need for establishing multiple pediatric haemodialysis centres all over India, including rural set up for increasing the long term survival in pediatric patients with CKD ,ESRD and improving their quality of life.
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Da Costa, José Oliveira, Natália Marchão, Nadiesda Peres, Iolanda Godinho, Mónica Centeno, José António Lopes, Luisa Pinto y Estela Nogueira. "#2130 Pregnancy in patients with chronic kidney disease stage 3 to 5: what to expect?" Nephrology Dialysis Transplantation 39, Supplement_1 (mayo de 2024). http://dx.doi.org/10.1093/ndt/gfae069.1430.
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Abstract Background and Aims Chronic Kidney disease (CKD) has long been recognized as a risk factor for adverse pregnancy outcomes. Advanced CKD is also associated with decrease fertility, raising the importance of an early approach of pre- menopausal CKD women to discuss pregnancy planning and avoid long term kidney function deterioration or prematurity sequelae in their child-to-be. Method Retrospective analysis of maternal, obstetric and perinatal outcomes of patients with CKD stage 3 to 5, followed by the Nephro-obstetric clinical team between 2011 until 2023. Results We evaluated 31 gestations in 28 patients, with mean age of 32 years [19-43], 21 Caucasian and 7 African, 15 nulliparous, 21/28 with hypertension (HTN), 6/28 diabetic, 2/28 with HIV and 3/28 with systemic lupus erythematosus (SLE). CKD diagnosis occurred during pregnancy in 4/28 patients. Mean pre-pregnancy SCr was 2,1 ± 1 mg/dL [1,1-4,3] and mean proteinuria was 1535 ± 1874 mg/day [5 - 6000], and 11 patients had proteinuria >1 g/day. At gestation baseline, patients evaluated in each pregnancy were in CKD stage 3a (9/31), 3b (10/31), 4 (8/31) and 5 (4/31). CKD etiologies were heterogenous, with most common diagnosis being hereditary nephropathies (7/28), Diabetic nephropathy (6/28) and lupus nephritis (3/28). Exposure to teratogenic therapy occurred in 10/31 gestations (mean time of 11 weeks; 2 - 15), generally ACE/ARBs. Medical termination of pregnancy occurred in 3 gestations due to active SLE and severe growth restriction, 1 abortion at 16 weeks and 1 stillbirth due to cervical insufficiency. HTN aggravation occurred in 16/31 (52%) gestations and de novo proteinuria or proteinuria increase occurred in 7/31(22,5%) and 20/31 (64.5%) gestations, respectively due to pregnancy hyperfiltration, active lupus nephritis and preeclampsia. Considering pregnancies that progressed, renal function (RF) deterioration occurred 10/19 (53%) patients in CKD stage 3 with 20%/60%/20% with full/partial and no RF recovery, respectively. In CKD4 6/7 patients (86%) had RF aggravation with 17% and 83% with partial or no RF recovery. Of the 2 Patients in CKD stage 5 with gestation >20 weeks, 1 started dialysis during pregnancy and the other 4 months postpartum. Dialysis was initiated in 3 patients during pregnancy (2 CKD stage 4 and 1 CKD stage 5) due to urea level >100 mg/dL. RF deterioration was mainly due to pregnancy hyperfiltration and preeclampsia (11/26 gestations; 42%). Mean gestation age at delivery was 34 ± 4 weeks (28-41), with 73% and 53,8% pregnancies with gestational age <37 and 34 weeks, respectively. Mean birth weight was 1866 ± 707 g (555–3095 g), with 73% low birth weight (<2500 g). Mean Apgar 1/5/10 was 9/10/10, respectively. Cesarean was performed in 53,8% gestations and 61,5% newborns were admitted to the neonate care unit (NICU) due to prematurity Conclusion CKD patients with stage 3 to 5 are at increased risk of worse maternal outcomes, namely HTN aggravation (52%), de novo or increase proteinuria (87%) and RF deterioration (53% stage 3 and 86% stage 4) with significant permanent loss of kidney function. Obstetric and perinatal results were also significantly worse with a high incidence of preeclampsia (42%), prematurity (73%), low birth weight (73%) and the need of NICU (61.5%). It is of sum importance, that advanced CKD patients are previously counseled about those risks and are managed in a multidisciplinary feto- maternal clinic experienced in CKD pregnancy care that has a dialysis unit.
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Jabborov, O. O. "Features of Genetic Polymorphism in Population with Diabetic Nephropathia: Literature Review". Journal of Advances in Medicine and Medical Research, 8 de mayo de 2019, 1–7. http://dx.doi.org/10.9734/jammr/2019/v29i930123.
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The increasing prevalence of diabetes mellitus has led to a growing number of chronic complications including diabetic nephropathy (DN). In high prevalence of diabetes mellitus, DN is associated with high morbidity and mortality primarily due to cardiovascular diseases. Genetic factors play a significant role in the pathogenesis of DN and genetically susceptible individuals that can develop after being exposed to environmental parameters. DN is assumed to be a complex, polygenic disease. Genetic predisposition to diabetes is familial, and often with concomitant obesity. A number of detected polymorphisms in genes is a predisposing risk factor for the development of type 2 diabetes. Two main categories have been used to identify the genes associated with DN: (1) analysis of candidate genes, and (2) more recently genome-wide scan. A significant effort has been made to identify these main genes, whereas results are still inconsistent with different genes associated to a small effect in specific populations. A variety of genetic markers characteristic of different population groups confirms the special significance of the ethnic component for identifying hereditary risks, which determines the relevance and need for a detailed, comprehensive study of the genetic basis of type 2 diabetes.
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Souza, Kauê de Melo, Lucas Facco, Amanda Alves Fecury, Maria Helena Mendonça de Araújo, Euzébio de Oliveira, Carla Viana Dendasck, Keulle Oliveira da Souza y Claudio Alberto Gellis de Mattos Dias. "Number of cases of type 1 and 2 diabetes diagnosed in Amapá between 2007 and 2012". Revista Científica Multidisciplinar Núcleo do Conhecimento, 1 de diciembre de 2020, 18–26. http://dx.doi.org/10.32749/nucleodoconhecimento.com.br/health/diabetes-cases.
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Diabetes mellitus is a succession of different types of disorders in metabolism that are characterized by causing a high rate of blood sugar. Because it is a disease with genetic factors type 1 diabetes has as main risk factor heredity, while type 2 diabetes besides these factors, includes obesity, high blood pressure, poor food education and advancing age. This study aims to show the number of cases of type 1 and 2 diabetes diagnosed in Amapá with the variables gender, age group, sedentary lifestyle, overweight, smoking, between 2007 and 2012. The data for the research were taken from the computer department of SUS, DATASUS (http://datasus.saude.gov.br). Type 1 and 2 diabetes mellitus (DM1 and DM2) are diseases that are tied to disturbances in production or in the efficient use of insulin. Smoking, as well as sedentary lifestyle and overweight are important risk factors for the development of DM2. Type 2 diabetes mellitus provides the development of various organic nerve lesions. In addition, DM2, through its chronicity, enables the development of retinopathies, nephropathies and other conditions negative to the individual’s health.