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Background: A renal biopsy is essential for the identification and management of renal disorders. Although considered an invasive operation, it is necessary for a definitive diagnosis and treatment of many renal diseases. The primary goal of this study was to assess the clinicopathological aspect of renal diseases undergoing biopsy in children receiving tertiary care.Patients and Methods: Children (≤18 years) hospitalized with nephrotic syndrome were the subjects of this cross-sectional study, and comprehensive assessments confirmed the need for a kidney biopsy. Included were 277 children who met the inclusion and exclusion criteria. Data on patient outcomes, biopsy indications, complications, histopathologic results, and demographic information were documented.Results: Of the 277 patients who underwent renal biopsy, 63.2% were male, and 36.8% were female. Average age of the patients was 15 ± 2.9 years, with age distribution ranging from 3 to 18 years. The most frequent indication for renal biopsy was atypical age of <1 and >10-years-old (91.7%), steroid-resistant (5.1%), asymptomatic hematuria (21.3%), abnormal glomerular filtration rate (16.2%), and proteinuria (14.8%). The most common histopathological findings were focal segmental glomerulosclerosis (FSGS) (36.5%), followed by minimal change disease (MCD) (13.4%), membranoproliferative glomerulonephritis (MPGN) (10.5%), membranous glomerulonephritis (MGN) (7.94%), IgA nephropathy (IGAN) (7.58%), non-proliferative glomerulonephritis (NPGN) (7.58%), diffuse proliferative glomerulonephritis (DPGN) (6.9%), crescentic GN (5.8%), and systemic lupus erythematosus (SLE) (3.97%). The high frequency of positive samples was seen in SLE, followed by DPGN, MPGN, IGAN, and MGN. In contrast, MCD, crescentic GN, and NPGN showed negativity in all differential item functioning (DIF) parameters.Conclusion: Renal biopsy is a safe and effective procedure in the diagnosis and treatment of in children with nephrotic syndrome. FSGS had the highest frequency in examined biopsies.
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Rim , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/patologia , Feminino , Masculino , Criança , Adolescente , Biópsia , Pré-Escolar , Estudos Transversais , Rim/patologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/diagnósticoRESUMO
Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria, has a high risk of progression to end-stage renal disease (ESRD). Meanwhile, the recurrence of FSGS after renal transplantation is one of the main causes of graft loss. The diagnosis of recurrent FSGS is mainly based on renal puncture biopsy transplants, an approach not widely consented by patients with early mild disease. Therefore, there is an urgent need to find definitive diagnostic markers that can act as a target for early diagnosis and intervention in the treatment of patients. In this review, we summarize the domestic and international studies on the pathophysiology, pathogenesis and earliest screening methods of FSGS and describe the functions and roles of specific circulating factors in the progression of early FSGS, in order to provide a new theoretical basis for early diagnosis of FSGS recurrence, as well as aid the exploration of therapeutic targets.
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Biomarcadores , Glomerulosclerose Segmentar e Focal , Recidiva , Humanos , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/sangue , Biomarcadores/sangue , Transplante de Rim , Diagnóstico PrecoceRESUMO
AIM: To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. MATERIALS AND METHODS: 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. RESULTS: At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; Ñ=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; Ñ=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; Ñ=0.039) were associated with the CKD progression. CONCLUSION: In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.
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Taxa de Filtração Glomerular , Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Humanos , Masculino , Glomerulonefrite Membranosa/fisiopatologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Feminino , Pessoa de Meia-Idade , Glomerulosclerose Segmentar e Focal/fisiopatologia , Glomerulosclerose Segmentar e Focal/diagnóstico , Adulto , Estudos Retrospectivos , Prognóstico , Progressão da Doença , Federação Russa/epidemiologia , Rim/patologia , Rim/fisiopatologia , Biópsia , Proteinúria/etiologia , Proteinúria/diagnóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologiaRESUMO
Patients with nephrotic syndrome (NS) present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. In children, the most common causes are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS). In adults, FSGS and membranous nephropathy (MN) are the most common primary causes. There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections. In addition to confirming the diagnosis of NS by measuring proteinuria and serum albumin and lipid levels, evaluation should assess for secondary causes. In children, most cases are due to minimal change disease, which is responsive to steroid treatment. A glucocorticoid should be prescribed for children younger than 12 years. If the patient improves with steroid treatment, no biopsy is needed. If the patient does not improve, genetic testing and kidney biopsy are warranted to determine the diagnosis. In adults, biopsy typically is indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies. This is diagnostic of MN. For patients with NS, management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids. Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies. Steroid-resistant NS also requires use of alternative therapies. Long-term NS management includes dietary sodium restriction, edema management, and blood pressure control. Thromboembolism prophylaxis should be considered for patients with NS and high risk of thromboembolism, particularly those with MN.
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Síndrome Nefrótica , Humanos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapia , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/terapia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/terapia , Glucocorticoides/uso terapêutico , Adulto , Criança , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/terapia , Proteinúria/diagnóstico , Proteinúria/etiologiaAssuntos
Glomerulonefrite por IGA , Glomerulosclerose Segmentar e Focal , Humanos , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/classificação , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/classificação , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomérulos Renais/patologia , BiópsiaRESUMO
Primary glomerular disease (PGD) is an idiopathic cause of renal glomerular lesions that is characterized by proteinuria or hematuria and is the leading cause of chronic kidney disease (CKD). The identification of circulating biomarkers for the diagnosis of PGD requires a thorough understanding of the metabolic defects involved. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry was performed to characterize the amino acid (AA) profiles of patients with pathologically diagnosed PGD, including minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), membranous nephropathy, and immunoglobulin A nephropathy. The plasma concentrations of asparagine and ornithine were low, and that of aspartic acid was high, in patients with all the pathologic types of PGD, compared to healthy controls. Two distinct diagnostic models were generated using the differential plasma AA profiles using logistic regression and receiver operating characteristic analyses, with areas under the curves of 1.000 and accuracies up to 100.0% in patients with MCD and FSGS. In conclusion, the progression of PGD is associated with alterations in AA profiles, The present findings provide a theoretical basis for the use of AAs as a non-invasive, real-time, rapid, and simple biomarker for the diagnosis of various pathologic types of PGD.
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Aminoácidos , Biomarcadores , Metabolômica , Humanos , Feminino , Masculino , Aminoácidos/sangue , Adulto , Metabolômica/métodos , Pessoa de Meia-Idade , Biomarcadores/sangue , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/diagnóstico , Nefrose Lipoide/sangue , Nefrose Lipoide/diagnóstico , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/diagnóstico , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/diagnóstico , Glomérulos Renais/metabolismo , Glomérulos Renais/patologiaRESUMO
BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.
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Glomerulosclerose Segmentar e Focal , Transplante de Rim , Síndrome Nefrótica , Recidiva , Humanos , Transplante de Rim/efeitos adversos , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/terapia , Glomerulosclerose Segmentar e Focal/cirurgia , Glomerulosclerose Segmentar e Focal/diagnóstico , Criança , Masculino , Síndrome Nefrótica/tratamento farmacológico , Feminino , Adolescente , Pré-Escolar , Resultado do Tratamento , Fatores de Risco , Estudos Retrospectivos , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Sobrevivência de Enxerto/efeitos dos fármacos , Indução de Remissão , Estados Unidos/epidemiologia , LactenteRESUMO
Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.
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Biomarcadores , Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Podócitos , Proteômica , Humanos , Síndrome Nefrótica/sangue , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/metabolismo , Proteômica/métodos , Adulto , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/patologia , Feminino , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/metabolismo , Masculino , Podócitos/metabolismo , Podócitos/patologia , Biomarcadores/sangue , Proteoma/análise , Pessoa de Meia-Idade , Estudos de Coortes , Curva ROCRESUMO
BACKGROUND: Alport syndrome is a genetically heterogenous disorder resulting from variants in genes coding for alpha-3/4/5 chains of Collagen IV, which results in defective basement membranes in the kidney, cochlea and eye. The syndrome has different inheritance patterns and historically, was thought of as a disease affecting solely males. CASE: A 15-year-old female presented with pedal oedema, hypertension and proteinuria. She underwent a kidney biopsy which showed findings in keeping with focal segmental glomerulosclerosis. Her condition was refractory to steroids. Steroid-resistant nephrotic syndrome genetics were sent, revealing a rare pathogenic variant in the COL4A5 gene. CONCLUSION: Heterozygous females with X-linked Alport syndrome can develop chronic kidney disease and hearing loss. Clinicians should be mindful when reviewing kidney histology to include Alport syndrome as a differential for female patients. COL4A3-5 genes should be included in all steroid-resistant nephrotic syndrome genetic panels.
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Colágeno Tipo IV , Nefrite Hereditária , Síndrome Nefrótica , Humanos , Feminino , Adolescente , Síndrome Nefrótica/genética , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/complicações , Síndrome Nefrótica/tratamento farmacológico , Colágeno Tipo IV/genética , Nefrite Hereditária/genética , Nefrite Hereditária/complicações , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/patologia , Biópsia , Rim/patologia , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , MutaçãoRESUMO
Incorporating genetic testing in routine outpatient nephrology clinic can improve on chronic kidney disease (CKD) diagnosis and utilization of precision medicine. We sent a genetic test on patients with atypical presentation of common kidney diseases, electrolytes derangements, and cystic kidney diseases. We were able to identify a gene variant contributing to patients' kidney disease in more than half of our cohort. We then showed that patients with ApoL1 risk allele have likely worse kidney disease, and we were able to confirm genetic focal segmental glomerulosclerosis (FSGS) in 2 patients and avoid unnecessary immunosuppression. Genetic testing has also improved our operation to establish a polycystic kidney disease excellence center by confirming our diagnosis, especially in patients without a well-defined family history. In conclusion, utilizing genetic testing in a routine outpatient renal clinic did not cause any burden to either patients or nephrologists, with minimal administrative effort and no financial cost to our patients. We expect that genetic testing in the right setting should become routine in nephrology to achieve a patient-centered precision medicine with less invasive means of kidney disease diagnosis.
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Testes Genéticos , Humanos , Testes Genéticos/métodos , Masculino , Feminino , Apolipoproteína L1/genética , Adulto , Pessoa de Meia-Idade , Predisposição Genética para Doença , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/diagnóstico , Nefrologia , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/diagnóstico , Instituições de Assistência Ambulatorial , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/diagnósticoRESUMO
INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a common glomerulopathy with an unclear mechanism. The demand for FSGS clinical diagnostic biomarkers has not yet been met. Circular RNA (circRNA) is a novel non-coding RNA with multiple functions, but its diagnostic value for FSGS remains unexplored. This study aimed to identify circRNAs that could aid in early clinical diagnosis and to investigate their mechanisms in podocyte injury. METHODS: The signature of plasma circRNAs for FSGS was identified by circRNA microarray. The existence of circRNAs was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR), RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by the receiver operating characteristic curve. The circRNA-miRNA-mRNA network was built with Cytoscape 7.3.2. Statistically significant differences were calculated by the Mann-Whitney U test. RESULTS: A total of 493 circRNAs (165 upregulated, 328 downregulated) were differentially expressed in the plasma of FSGS patients (n = 3) and normal controls (n = 3). Eight candidate circRNAs were demonstrated to be circular and stable transcripts. Among them, hsa_circ_0001230 and hsa_circ_0023879 were significantly upregulated in FSGS patients (n = 29) compared to normal controls (n = 51). The areas under the curve value of hsa_circ_0001230 and hsa_circ_0023879 were 0.668 and 0.753, respectively, while that of the two-circRNA panel was 0.763. The RNA pull-down analysis revealed that hsa_circ_0001230 and hsa_circ_0023879 could sponge hsa-miR-106a. Additionally, hsa_circ_0001230 and hsa_circ_0023879 positively regulated hsa-miR-106a target genes phosphatase and tensin homolog (PTEN) and Bcl-2-like protein 11 (BCL2L11) in podocytes. CONCLUSION: hsa_circ_0001230 and hsa_circ_0023879 are novel blood biomarkers for FSGS. They may regulate podocyte apoptosis by competitively binding to hsa-miR-106a.
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Biomarcadores , Glomerulosclerose Segmentar e Focal , MicroRNAs , RNA Circular , RNA Mensageiro , Humanos , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/diagnóstico , RNA Circular/sangue , RNA Circular/genética , Biomarcadores/sangue , MicroRNAs/sangue , MicroRNAs/genética , RNA Mensageiro/sangue , RNA Mensageiro/genética , Podócitos/metabolismo , Podócitos/patologia , Masculino , Feminino , Adulto , Redes Reguladoras de GenesRESUMO
BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.
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Anuria , Glomerulosclerose Segmentar e Focal , Nefropatias , Transplante de Rim , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Calcineurina/toxicidade , Creatinina , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , RecidivaRESUMO
RATIONALE & OBJECTIVE: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). PREDICTORS: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. OUTCOME: Progression to ESKD. ANALYTICAL APPROACH: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log2 transformed to approximate normal distribution and normalized to urinary creatinine (Log2uPlasminogen/cr, Log2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression. RESULTS: Adjusted Log2uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log2 uPlasminogen/cr, Log2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1). LIMITATIONS: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. CONCLUSIONS: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. PLAIN-LANGUAGE SUMMARY: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.
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Biomarcadores , Progressão da Doença , Falência Renal Crônica , Plasminogênio , Humanos , Masculino , Feminino , Biomarcadores/urina , Plasminogênio/urina , Plasminogênio/metabolismo , Pessoa de Meia-Idade , Adulto , Falência Renal Crônica/urina , Estudos de Coortes , Glomerulosclerose Segmentar e Focal/urina , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulonefrite por IGA/urina , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite Membranosa/urina , Glomerulonefrite Membranosa/diagnóstico , Fibrinolisina/urina , Fibrinolisina/metabolismoRESUMO
Genetic focal segmental glomerulosclerosis (FSGS) is an important but underestimated cause of inherited proteinuric chronic kidney disease (CKD) in adults. We discuss a case of familial CKD due to inverted formin 2 (INF2) gene mutation, where three siblings had disparate phenotypic presentations ranging from CKD with subnephrotic proteinuria to nephrotic-range proteinuria with collapsing FSGS on kidney biopsy over a period of 8 years. The youngest sibling was the index case. The family agreed to undergo genetic testing only after two more siblings were diagnosed with kidney disease. This case highlights how clinical heterogeneity, absence of family history in the index case, initial lack of specific biopsy-proven diagnosis and reluctance to undergo genetic testing can delay the diagnosis of genetic kidney disease in adults.
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Glomerulosclerose Segmentar e Focal , Insuficiência Renal Crônica , Adulto , Humanos , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/genética , Insuficiência Renal Crônica/genética , Rim , Biópsia , Proteinúria/genéticaAssuntos
Glomerulosclerose Segmentar e Focal , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/complicações , FemininoRESUMO
INTRODUCTION: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method. MATERIALS AND METHODS: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files. RESULTS: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD. DISCUSSION AND CONCLUSION: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.
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Complemento C4b , Glomerulosclerose Segmentar e Focal , Imuno-Histoquímica , Nefrose Lipoide , Humanos , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/diagnóstico , Nefrose Lipoide/metabolismo , Nefrose Lipoide/patologia , Nefrose Lipoide/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Adulto , Estudos Transversais , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Biópsia/métodos , Complemento C4b/metabolismo , Rim/patologia , Rim/metabolismo , Adulto Jovem , Adolescente , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/análise , Sensibilidade e Especificidade , Glomérulos Renais/patologia , Glomérulos Renais/metabolismoRESUMO
Between 15-20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases. We detected candidate diagnostic variants in genes associated with nephrotic syndrome and Focal Segmental Glomerulosclerosis (FSGS) in 29 out of 300 patients, solving about 10% of the probands. We also identified the same genetic cause of the disease (PAX2: c.1266dupC) in three family members with different clinical diagnoses. Interestingly we also found one female patient carrying a novel missense variant, c.1259C>A (p.Thr420Lys), in the GLA gene not previously associated with Fabry disease, which is in silico defined as a likely pathogenic and destabilizing, and associated with a mild alteration in GLA enzymatic activity. The identification of the specific genetic background may provide an opportunity to evaluate the risk of recurrence of the primary disease, especially among patient candidates living with a donor kidney transplant.
Assuntos
Doença de Fabry , Glomerulosclerose Segmentar e Focal , Nefropatias , Transplante de Rim , Humanos , Feminino , Transplante de Rim/efeitos adversos , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Doença de Fabry/patologia , Testes Genéticos , Nefropatias/patologia , Rim/patologia , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologiaRESUMO
A 6-year-old boy was diagnosed with chromosomal abnormalities (48,XYY, + 21[11]/46,XY[19]) at 4 months of age after a physical examination revealed an undescended testis and a dwarf penis. He also had mild renal dysfunction and severe proteinuria, and kidney biopsy at 2 years of age revealed focal segmental glomerulosclerosis. Genetic analysis to investigate suspected WT1 gene abnormalities revealed a novel variant in NM_024426.6:exon10:c.1506 T > A (p.(Asp502Glu)). His kidney function deteriorated rapidly, leading to the induction of peritoneal dialysis at 5 years of age. Although this variant had not been previously reported, bilateral nephrectomy was performed to prevent any progression of the tumor. Histopathology showed all the glomeruli observed within the observation area to be completely sclerotic, while also showing evidence of embryonal hyperplasia. This case was not a hot spot for Denys-Drash syndrome, but it had a similar phenotype and pathology that could have been derived from a WT1 gene abnormality.
Assuntos
Éxons , Glomerulosclerose Segmentar e Focal , Mutação de Sentido Incorreto , Proteínas WT1 , Humanos , Masculino , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/diagnóstico , Criança , Proteínas WT1/genética , Éxons/genética , Hiperplasia/patologia , Hiperplasia/genética , Nefrectomia , FenótipoRESUMO
INTRODUCTION: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. METHODS: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker. RESULTS: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively. CONCLUSION: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies.