Clinical and histological features in pediatric and adolescent/young adult patients with renal disease: a cross-sectional analysis of the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: Only a few studies have investigated epidemiological and clinicopathological information regarding pediatric and adolescent and young adult (AYA) patients with renal disease. The purpose of this study was to clarify the differences and relationship of clinicopathological findings between pediatric and AYA patients using the Japan Renal Biopsy Registry (J-RBR). METHODS: This cross-sectional study analyzed data from patients registered in the J-RBR between 2007 and 2017. Clinicopathological findings at diagnosis were analyzed for 3,463 pediatric (age < 15 years) and 6,532 AYA (age 15-30 years) patients. RESULTS: Although chronic nephritic syndrome was the most common clinical diagnosis at age > 5 years, nephrotic syndrome was the most frequent diagnosis at age < 4 years. The most common pathological diagnosis as classified by pathogenesis in pediatric patients was primary glomerular disease (except IgA nephropathy), whereas IgA nephropathy was increased in AYA patients. Mesangial proliferative glomerulonephritis was the most common pathological diagnosis as classified by histopathology in both pediatric and AYA patients. Minor glomerular abnormalities were the most frequent histopathologic diagnoses of nephrotic syndrome in childhood, but their frequency decreased with age. CONCLUSION: To the best of our knowledge, this is the first report of clinicopathological features of pediatric and AYA patients in a large nationwide registry of renal biopsy. There were differences of clinical, pathological and histopathologic findings between pediatric and AYA patients.

Clinical and pathological analysis of renal biopsies of elderly patients in Northeast China: a single-center study.

PURPOSE: To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China. METHODS: We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age: below 60 years (non-elderly group, n = 5923) and at least 60 years (elderly group, n = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the t-test and chi-square test. RESULTS: Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders (p < .05). The incidence of IgA nephropathy, mesangial proliferative glomerulonephritis, and lupus nephritis was significantly lower in elderly patients than in non-elderly patients. The incidence of membranous nephropathy, membranoproliferative glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, systemic vasculitis-associated renal damage, and amyloid nephropathy was significantly higher in elderly patients than in non-elderly patients (p < .05). The incidence of perinephric hematoma (≥4 cm2) in elderly patients with renal biopsy was lower than that in non-elderly patients. We noted that 79.9% of primary glomerulonephritis patients who received immunosuppressive therapy showed a remission rate of 83.5%. CONCLUSION: The spectrum of kidney disease in the elderly is different from that in the younger population.

Outcomes of immunoglobulin-associated mesangiocapillary glomerulonephritis: A South African experience.

AIM: Immunoglobulin-associated mesangiocapillary glomerulonephritis is currently the most common biopsy-confirmed glomerulonephritis in Cape Town, South Africa. We aimed to determine the outcome of patients with a biopsy-confirmed diagnosis of immunoglobulin-associated mesangiocapillary glomerulonephritis at our centre. METHODS: A retrospective cohort study of adult patients was conducted from January 1, 2000 to December 31, 2016. The endpoint was a composite of doubling of creatinine and/or end-stage renal disease and/or death. Cox univariable and multivariable proportional hazards models were used to examine the association between the composite endpoint and predictor variables. Survival curves were made with the use of Kaplan-Meier estimates. RESULTS: A total of 70 patients were included in the study and their median duration of follow-up was 30.4 months. Forty-eight (68.6%) patients reached the composite endpoint. The proportion reaching this endpoint at 1, 3 and 5 years were 37.5%, 64.6% and 81.3%, respectively. Cox multivariable proportional hazards model identified a serum creatinine concentration > 200 µmol/L at the time of biopsy, moderate to severe interstitial fibrosis, ≥50% crescents and cyclophosphamide therapy as predictors of the composite endpoint. CONCLUSION: Immunoglobulin-associated mesangiocapillary glomerulonephritis remains a common glomerular pathological diagnosis in our setting and has poor outcomes. This may partially be explained by late presentation. Future research needs to focus on identifying the possible cause(s) of this common glomerular disease so that more targeted therapeutic approaches can be offered.

A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease.

In April 2012, a group of nephrologists organized a consensus conference in Cambridge (UK) on type II membranoproliferative glomerulonephritis and decided to use a new terminology, "C3 glomerulopathy" (C3 GP). Further knowledge on the complement system and on kidney biopsy contributed toward distinguishing this disease into three subgroups: dense deposit disease (DDD), C3 glomerulonephritis (C3 GN), and the CFHR5 nephropathy. The persistent presence of microhematuria with or without light or heavy proteinuria after an infection episode suggests the potential onset of C3 GP. These nephritides are characterized by abnormal activation of the complement alternative pathway, abnormal deposition of C3 in the glomeruli, and progression of renal damage to end-stage kidney disease. The diagnosis is based on studying the complement system, relative genetics, and kidney biopsies. The treatment gap derives from the absence of a robust understanding of their natural outcome. Therefore, a specific treatment for the different types of C3 GP has not been established. Recommendations have been obtained from case series and observational studies because no randomized clinical trials have been conducted. Current treatment is based on corticosteroids and antiproliferative drugs (cyclophosphamide, mycophenolate mofetil), monoclonal antibodies (rituximab) or complement inhibitors (eculizumab). In some cases, it is suggested to include sessions of plasma exchange.

Pattern of renal diseases and the need for establishment of renal biopsy registry in Saudi Arabia.

Renal disease is a common medical problem in Saudi Arabia. Varieties of renal lesions if not treated properly or not discovered early will lead to a chronic kidney disease. Identifying the types of renal lesions can help in identifying the high-risk patients and appropriate treatment can be provided. Glomerulonephritis (GN) is considered one of the leading causes of end-stage renal disease in Saudi Arabia. The prevalence of different renal lesions were identified by different reports; however, these reports showed inconsistency. One important reason for such differences is related to the lack of unified methods in diagnosing and processing renal tissues and to the fact that different reports were reported by different pathologists. In addition, the differences in the reported results may reflect patient selection biases for renal biopsy or to the different policies and protocols adopted by different nephrologists. This is a prospective, multicenter study that involves different patients from different institutes and from different regions in Saudi Arabia to delineate the pattern of renal diseases based on renal biopsies. Four hundred and five cases were selected and studied over two years. This preliminary report shows that the most common primary renal lesion in Saudi Arabia is focal segmental glomerulosclerosis in 24.1%, followed by IgA nephropathy (15.2%), mesangioproliferative non-IgA, (13.2%), and membranoproliferative GN (12.4%). Lupus nephritis was the most common cause of secondary GN in 66% of the secondary causes.

Changes in primary glomerulonephritis in Singapore over four decades
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This review of 3,289 native kidney biopsies over the past four decades in Singapore documents the changing pattern of biopsy-proven glomerulonephritis (GN)from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative GN was the most common form of primary GN, similar to the Asian region. In the 2nd decade, the percentage of mesangial proliferative GN decreased, but membranous GN became more common, as was seen in China and Thailand. In the 3rd decade, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy continued to rise, but it was only recently, in the 4th decade, that FSGS prevalence increased dramatically, although membranous nephropathy continues to increase in some Asian countries. In the last decade in Singapore, Malaysia, and Japan, prevalence of IgA nephritis has decreased but remains the most common GN. The percentage of FSGS continues to increase in many countries like in Italy, United States of America, United Kingdom, China, and Malaysia. We surmise that socioeconomic factors play significant roles in the evolution of the renal biopsy pattern.
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C3 glomerulopathy in children: Is there still a place for anti-cellular immunosuppression?

AIM: To contribute additional clinical experience to the paucity of reports on C3 glomerulopathy (C3GP) in children, we are reporting our cohort of 11 children with C3GP, emphasizing the therapeutic options in this peculiar entity. METHODS: We describe the incidence, manifestation, histopathology findings, follow-up, treatment and outcome of C3GP in 11 children with C3GP by retrospectively analyzing their clinical charts and renal biopsy reports. RESULTS: Eleven C3GP patients were identified among 240 children who had undergone renal biopsy, accounting for a 4.6% incidence of C3GP. A light microscopy examination showed a membranoproliferative pattern (n = 8), mesangial proliferation (n = 1), a mesangial/membranoproliferative pattern (n = 1) and endocapillary proliferation (n = 1). All children presented with proteinuria of varying degrees, the majority of them with additional hematuria, three with full-blown nephrotic-nephritic syndrome, and two with renal insufficiency at presentation. Very diverse treatments were applied in our cohort of patients, from no specific treatment to different mono or combined anti-cellular immunosuppression treatments, as well as a trial of plasma therapy or eculizumab. Our results are in to some extend in concordance with other studies revealing that an optimal therapy for C3GP is still unknown, but we believe that a trial of classical immunosuppression before eculizumab is still worth trying, while eculizumab can have a beneficial effect, but not in all patients. CONCLUSION: A diverse histological pattern and clinical picture and no known optimal therapy are a hallmark of C3GP.

Descriptive analysis of glomerulonephritis by histological type and their progression among adults in a tertiary care center in Sri Lanka.

Prevalence of different glomerulonephritides and their clinical course vary geographically. Our objectives are to assess the prevalence of different histological types of glomerulonephritis (GN) based on the light microscopic histology and to assess their progression according to histological type. A retrospective cross-sectional study was carried out among adult patients (>18 years) with a histological diagnosis of GN at the University Professorial Unit over a period of six months. Information including demographic data, renal biopsy findings, and progression of the disease through serum creatinine (SCr) level were collected through existing clinic records of consenting patients. Data were analyzed by Statistical Package for the Social Sciences. There were 109 patients (females = 90) with a mean age of 40.32 ± 15.24 years. The most common histological type was focal segmental glomerulosclerosis (FSGS) in 27 (24.8%) followed by minimal change disease in 25 (22.9%), mesangioproliferative glomerulonephritis (MesPGN) in 18 (16.5%), membranoproliferative glomerulonephritis in six (5.5%), membranous glomerulonephritis in three patients (2.8%), and crescentic GN in one patient (0.9%). There was a statistically significant rise in SCr level at seven years from the initial presentation in the histological types; FSGS [P = 0.04; 95% confidence interval (CI) = 0.06-1.0] and MesPGN (P = 0.03; 95% CI = 0.3-0.9). Focal segmental glomerulosclerosis was the most common histology type in the population studied. There was a statistically significant progression of FSGS and MesPGN.

C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy.

C3 glomerulonephritis (C3GN) and dense deposit disease comprise the two classes of C3 glomerulopathy. Studies from Europe and Asia have aided our understanding of this recently defined disorder, but whether these data apply to a diverse United States patient population remains unclear. We, therefore, reviewed clinical and histopathological data, including generation of a C3 Glomerulopathy Histologic Index to score biopsy activity and chronicity, to determine predictors of progression to end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) in 111 patients (approximately 35% non-white) with C3 glomerulopathy: 87 with C3GN and 24 with dense deposit disease. Complement-associated gene variants and autoantibodies were detected in 24% and 35% of screened patients, respectively. Our C3 Glomerulopathy Histologic Index denoted higher activity in patients with C3GN and higher chronicity in patients with dense deposit disease. Over an average of 72 months of follow-up, remission occurred in 38% of patients with C3GN and 25% of patients with dense deposit disease. Progression to late-stage CKD and ESRD was common, with no differences between C3GN (39%) and dense deposit disease (42%). In multivariable models, the strongest predictors for progression were estimated glomerular filtration rate at diagnosis (clinical variables model) and tubular atrophy/interstitial fibrosis (histopathology variables model). Using our C3 Glomerulopathy Histologic Index, both total activity and total chronicity scores emerged as the strongest predictors of progression. Thus, in a large, diverse American cohort of patients with C3 glomerulopathy, there is a high rate of progression to CKD and ESRD with no differences between C3GN and dense deposit disease.

Clinicopathological study of nondiabetic renal disease in type 2 diabetic patients: A single center experience from India.

Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM), leading to chronic kidney disease/end-stage renal disease. Wide spectrum of nondiabetic renal diseases (NDRD) is reported in type-2 diabetes (type-2 DM). We carried out this single-center study to find clinical, laboratory, and histological features of NDRD in type-2 DM patients and to assess the prevalence of NDRD in India. A single-center retrospective study which included analysis of renal biopsies from patients with type-2 DM, performed between January 2008 and September 2016. Biopsy findings were categorized into three groups, Group-I (isolated NDRD); Group-II (NDRD superimposed on underlying DN); and Group-III (isolated DN). Out of 152 diabetic patients (111 males and 41 females), 35 (23.03%) patients were of Group-I (isolated NDRD), 35 (23.03%) of Group-II (NDRD superimposed on underlying DN), and 82 (53.95%) of Group-III (isolated DN). The mean age (in years) was 55.08 ± 10.71, 55.65 ± 8.71, and 54.45 ± 9.01 respectively in Group-I, II, and III. Nephrotic syndrome (NS) was the most common clinical presentation in all groups. Duration of DM was significantly shorter in Group-I than in Group-II. Diabetic retinopathy was absent in Group-I. Proteinuria was more in Group-III than Group-I. Low serum C3 and/or C4 levels was observed in five (14.29%) cases of Group-I and Group-II each and two (2.43%) cases of Group-III. Nearly, 70 (46.05%) patients were found to have NDRD either in isolated form or as combined lesions. The most common histological types of NDRD were acute tubulointerstitial nephritis (38.57%) followed by benign nephrosclerosis (15.72%), membranous nephropathy (10%), IgA nephropathy (7.14%), and membranoproliferative glomerulonephritis (7.14%). The incidence of NDRD (with/without DN) in type-2 DM is very high. Shorter duration of diabetes, hematuria, absence of retinopathy, low serum complement levels, and nephrotic range proteinuria are predictors of NDRD.

Patterns of renal disease in South Korea: a 20-year review of a single-center renal biopsy database.

BACKGROUND: Several registries and centers have reported the results of renal biopsies from different parts of the world. As there are few data regarding the epidemiology of glomerulonephritis (GN) in South Korea, we conducted this study on renal biopsy findings during the last 20 years from a single center. METHODS: Data for 818 patients who underwent renal biopsy at our center between 1992 and 2011 were collected retrospectively. All kidney specimens were examined with light microscopy (LM) and immunofluorescent microscopy (IF). RESULTS: There were 818 cases of native kidney biopsies. In cases of primary GN, the most frequent type of renal pathology in adults (18-59 years) was mesangial proliferative GN (MsPGN, 34.5%) followed by IgA nephropathy (IgAN, 33.3%) and membranous GN (MGN, 8.8%). Indications in adults (18-59 years) were asymptomatic urinary abnormalities (75.3%) followed by nephrotic syndrome (19.8%) and acute kidney injury (AKI, 3.4%). CONCLUSIONS: Among 818 renal biopsy specimens, MsPGN and IgAN were the most frequent biopsy-proven renal diseases. MGN was the third most common cause of primary GN and lupus nephritis (LN) was the most common secondary glomerular disease. Our data contribute to the epidemiology of renal disease in South Korea.

Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986-2015.

BACKGROUND AND OBJECTIVES: Large-scale, contemporary studies exploring glomerular disease epidemiology in the United States are lacking. We aimed to determine 30-year temporal and demographic trends in renal biopsy glomerular disease diagnosis frequencies in the southeastern United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional, observational study, we identified all patients with a native kidney biopsy specimen showing one of 18 widely recognized glomerular disease diagnoses referred to the University of North Carolina Chapel Hill Division of Nephropathology between 1986 and 2015. Biopsy era (1986-1995, 1996-2005, and 2006-2015) and demographics (age, sex, and race) were our primary and secondary predictors, respectively, and the relative frequency of each glomerular disease diagnosis was our primary outcome. RESULTS: Among 21,374 patients (mean age =48.3±18.3 years old; 50.8% men; 56.8% white; 38.3% black; 2.8% Latino; 1.4% Asian; 0.8% other), the frequency of diabetic glomerulosclerosis in renal biopsy specimens increased dramatically over the three decades (5.5%, 11.4%, and 19.1% of diagnoses, respectively; P for trend <0.001). The frequency of FSGS initially increased but then declined (22.6%, 27.2%, and 24.7%, respectively; P for trend =0.64). The frequencies of other common glomerular disease subtypes remained stable (IgA nephropathy and ANCA/pauci-immune GN) or declined (minimal change disease, membranous nephropathy, membranoproliferative GN, and lupus nephritis). These temporal trends were largely preserved within all demographic subgroups, although cross-sectional frequency distributions differed according to age, sex, and race. CONCLUSIONS: We identified significant changes in relative renal biopsy frequencies of many glomerular disease subtypes over three decades. Temporal trends were consistently observed within all major demographic groups, although relative predominance of individual glomerular disease subtypes differed according to patient age, sex, and race. We propose that exploration of behavioral and environmental exposures that likely underlie these findings should be the focus of future hypothesis-driven research.

Profile of glomerular diseases associated with hepatitis B and C: A single-center experience from India.

Hepatitis B and C are known to affect kidneys in a number of ways. Glomerular diseases associated with hepatitis B and C include membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis, immunoglobulin A nephropathy, rarely amyloidosis, and fibrillary and immunotactoid glomerulopathy. In a retrospective analysis of kidney biopsy of 534 patients, we found 16 (2.9%) patients of hepatitis B and 11 (2.05%) patients of hepatitis C with glomerular disease. The most common form of glomerulonephritis in hepatitis B patient was MN and in hepatitis C patient was MPGN.

Epidemiology of Glomerular Disease in Southern Arizona: Review of 10-Year Renal Biopsy Data.

Glomerulonephritis stands third in terms of the etiologies for end-stage kidney disease in the USA. The aim of this study was to look at the patterns of biopsy-proven glomerulonephritis based on data from a single center.Kidney biopsy specimens of all patients above the age of 18 years, over a 10-year period, who had diagnosis of nondiabetic glomerular disease, were selected for the study.The most common histopathological diagnosis was focal and segmental glomerulosclerosis (FSGS) (22.25%, 158/710) followed by membranous nephropathy (20.28%, 144/710) and immunoglobulin (Ig)A nephropathy (19.71%, 140/710). There was male preponderance in all histological variants except IgA nephropathy, lupus nephritis, and pauci-immune glomerulonephritis. The race distribution was uneven, and all histological variants, except minimal change disease and lupus nephritis, were more commonly seen in whites. In a separate analysis of the histological pattern in Hispanics, lupus nephritis was the most common pathology (28.70%, 62/216) followed by FSGS (18.05%, 39/216). In American Indian population, the most common pathology was IgA nephropathy (33.33%, 8/24) followed by FSGS (16.67%, 4/24).This study highlights the histopathological patterns of glomerular disease in southern Arizona. The data suggest regional and ethnic variations in glomerular disease that may point towards genetic or environmental influence in the pathogenesis of glomerular diseases.

Differences in clinical findings, pathology, and outcomes between C3 glomerulonephritis and membranoproliferative glomerulonephritis.

BACKGROUND: To clarify the clinical manifestations of pediatric complement component C3 glomerulonephritis (C3GN), we retrospectively evaluated differences in the clinicopathological findings and prognosis between C3GN and immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). METHODS: Thirty-seven patients diagnosed with "idiopathic MPGN" were enrolled in this retrospective study. The patients were divided into two groups, with Group 1 consisting of 19 patients diagnosed with IC-MPGN and Group 2 consisting of 18 patients diagnosed with C3GN. The clinical findings and the prognosis were investigated for both groups. RESULTS: Thirteen patients in Group 2 were identified by mandatory annual school screening for urinary abnormalities. The incidence of macro-hematuria and the frequency of low serum C4 values were lower in Group 2 patients than in Group 1 patients. At the time of the second renal biopsy, urinary protein excretion, incidence of hematuria, frequency of low serum C3 values, and scores for mesangial proliferation, glomerular sclerosis, and interstitial fibrosis were higher in Group 2 patients than in Group 1 patients. At the most recent follow-up examination, the number of patients categorized as non-responding or with end-stage renal disease was higher in Group 2 patients than in Group 1 patients. CONCLUSIONS: Our results suggest that the treatment response and prognosis of patients with C3GN are worse than those of patients with IC-mediated MPGN. Therefore, in the clinical context regarding treatment options and prognosis, it may be useful to classify idiopathic MPGN as C3GN or IC-MPGN. In addition, long-term follow-up of C3GN is necessary.

Hypertension, end-stage renal disease and mesangiocapillary glomerulonephritis in methamphetamine users.

BACKGROUND: Methamphetamine abuse has risen dramatically in South Africa. The chronic effects of abuse on the kidneys and blood pressure have not been documented. This study reviewed patients referred for evaluation of kidney disease and/or hypertension, who had been abusing methamphetamines. METHODS: The records of patients referred to the renal unit between 2005 and 2013 who had been using methamphetamines were retrospectively reviewed. Patient demographics, biophysical parameters, blood pressure, renal function, renal ultrasound and biopsy findings, complications of chronic kidney disease and comorbidities were recorded. RESULTS: Forty-seven patients were included in the study. Their mean age was 29 years. Hypertension was present in 42 (89.4%) of patients, with malignant hypertension in 21 (44.7%). Forty-five (95.7%) had chronic kidney disease (CKD), and 26 (55.3%) had end-stage renal disease. Renal biopsies were performed in 24 patients. Twelve (50.0%) of the biopsies showed hypertensive changes and 14 (58.3%) mesangiocapillary glomerulonephritis type 1, with deposition of IgM and C3 complement. CONCLUSION: Methamphetamine use is associated with severe hypertension, mesangiocapillary glomerulonephritis and CKD.

Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience.

BACKGROUND: C3 glomerulopathy (C3GP) is characterized by deposition of complement C3 with absence/traces of immunoglobulins in the glomeruli and categorized into dense deposit disease (DDD), C3 glomerulonephritis (C3GN), complement factor H related protein 5(CFHR5) nephropathy etc. Collaborative efforts of pathologists, complement biologists and nephrologists worldwide are expanding the histomorphological pattern and laboratory findings related to C3GP. Hence, we studied point prevalence and morphological spectrum of C3GP in Indian patients to correlate morphological patterns with standard therapies and outcome of the patients. METHODS: Retrospective analysis of renal biopsies (2007-2012,n-4565), which on immunofluorescence (IF) had C3 dominant deposits with absence or trace amount of immunoglobulin was carried out. Histopathology and electronmicroscopy (EM) were reviewed; cases were re-classified as DDD and C3GN. Histomorphological patterns of both groups were compared and correlated with treatment. Clinical details and follow up of patients were retrieved from the department of nephrology. RESULTS: There were 31 cases (0.7%) of C3GP sub-classified as DDD (n-13) and C3GN (n-14). It was difficult to sub-classify 4 cases since EM showed overlapping features. C3GN and DDD had distinct clinical characteristics and disease outcome, though pathological features were overlapping. Majority of C3GP patients were males and were in 2(nd) to 4(th) decade of life. Nephrotic syndrome in DDD and nephritic-nephrotic presentation in C3GN patients was more common. Hypertension and oliguria were more often observed in C3GN than DDD. Membranoproliferative pattern (MPGN) was commonest pattern in DDD; other patterns seen were mesangial proliferative, mesangial expansive/nodular, exudative and crescentic. C3GN also had all the above patterns, the predominant ones being MPGN and mesangial proliferative. Limited follow-up revealed response to therapy only in C3GN (33%). Progression to ESRD was 33% in DDD and 10% cases in C3GN. CONCLUSION: C3GP comprise 0.7% of all renal biopsies. MPGN pattern was the commonest morphological pattern in DDD whereas MPGN and mesangial proliferative pattern were equally dominant patterns in C3GN. EM of 4 cases (13%) showed intermediate features. Evaluation of alternate complement pathway must be done in all cases to identify the point of dysregulated alternate complement pathway and to confirm the diagnosis in ambiguous cases. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1730070964135632.

C1q nephropathy in India: a single-center study.

C1q nephropathy (C1qN) is defined by conspicuous C1q deposits in the glomerular mesangial regions of patients who do not have any evidence of systemic lupus erythematosus (SLE). We present our experience with C1qN over the last three years. In total, 1775 native renal biopsies were reviewed and dominant/co-dominant C1q mesangial deposits in patients with absence of clinical and/or serological evidence of SLE were considered as C1qN. Their clinical profile and renal function status were studied and correlated. C1qN was observed in 11 patients (0.61%), and included eight males and three females; the mean age was 36.6 years. The most common presentation was nephrotic syndrome. Hematuria was noted in eight patients (72%). The mean serum creatinine was 2.78 mg/dL. Hypertension was seen in two patients (18%). Mesangial proliferative glomerulonephritis (MePGN) was the most common histological pattern, followed by focal and segmental glomerulosclerosis and other lesions. The common codeposits along with C1q were IgM, followed by C3 and others. MePGN had better prognosis than others. To conclude, C1qN was noted in 0.61% of all renal biopsies with bimodal age distribution and may present as podocytopathy or non-podocytopathy. The prognosis depends on the morphological pattern and C1q deposits per se are not prognostic indicators.

Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. RESULTS: Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis. CONCLUSIONS: The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.