Adult-onset Nephrotic Syndrome Research Articles

The diversity of peripheral blood T cells and myeloid-derived suppressor cells in patients with idiopathic membranous nephropathy.

Membranous nephropathy is a leading cause of adult-onset nephrotic syndrome. Peripheral T cells and myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, while their exact roles and interaction in these processes are unclear. Here, we studied the roles of T cells, MDSCs, and their subsets in patients with idiopathic membranous nephropathy (IMN). 35 IMN patients and 30 healthy controls were included in this retrospective study. Flow cytometry was performed to determine the phenotype of human T cells and MDSCs in peripheral blood mononuclear cells (PBMCs). Anti-PLA2R was measured by ELISA. Values ≥ 20 RU/mL were defined as positive and < 14 RU/mL as negative. A higher ratio of CD4/CD8 T cells with a lower proportion of Tregs, a remarkably lower proportion of G-MDSCs (but not M-MDSCs), lower frequency of PD-L2+G-MDSCs, and higher frequency of PD-L1+M-MDSCs were found in IMN patients compared to healthy controls. The ratio of CD4/CD8 T cells was higher, and the frequencies of PD-1+CD4+ T cells, CTLA-4+CD4+ T cells, PD-1+Tregs, and CTLA-4+Tregs were lower in PBMCs of PLA2R-positive IMN patients compared to PLA2R-negative IMN patients. Tregs and G-MDSCs were reduced in the circulation of the IMN patients, which may promote understanding of the crucial functions that are mediated by these cells in the pathogenesis of IMN.

Causal effects of rheumatoid arthritis or ankylosing spondylitis on membranous nephropathy: a two-sample Mendelian randomization study.

Membranous nephropathy (MN) is the leading cause of adult-onset nephrotic syndrome, with primary MN of unclear cause accounting for 80% of cases. Retrospective clinical research reported that MN occurring in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients was triggered by nephrotoxic drugs or of unknown cause. However, whether RA or AS itself increases the risk of developing MN is unknown. We conducted mendelian randomization (MR) analysis to evaluate the causal effects of RA or AS on MN using genome-wide association study (GWAS) statistics. The inverse variance weighted (IVW) method was the primary analysis, and several supplementary analyses and sensitivity analyses were performed to test the causal estimates. We obtained 30 valid instrumental variables (IVs) of RA and 16 valid IVs of AS from large-scale open-access GWASs. The genetically predicted RA significantly increased the risk of MN [IVW odds ratios (OR)=1.327, 95% confidence interval (CI)=(1.124, 1.565), P=8.051×10-4]. Three supplementary MR analyses provided the consistent positive causal effect of RA on MN (all P<0.05). No horizontal pleiotropy was detected by MR Egger intercept analysis (P=0.411). However, the genetically predicted AS had no causal effect on MN by IVW and supplementary analysis (all P>0.05). Genetically predicted RA could increase the risk of MN, but genetically predicted AS was not associated with MN. Screening for kidney involvement in RA patients should be noted, and active treatment of RA will reduce the public health burden of MN.

Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment.

Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causing in situ immune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidney-limited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009. Further utilization of mass spectrometry on immunoprecipitated glomerular extracts and laser micro dissected glomeruli has allowed the rapid discovery of other antigens (thrombospondin type-1 domain-containing protein 7A, neural epidermal growth factor-like 1 protein, semaphorin 3B, protocadherin 7, high temperature requirement A serine peptidase 1, netrin G1) targeted by autoantibodies in PMN. Despite these major advances in our understanding of the pathophysiology of PMN, treatments remain non-specific, often ineffective, or toxic. In this review, we summarize our current understanding of the immune mechanisms driving PMN from animal models and clinical studies, and the implications on the development of future targeted therapeutic strategies.

To Study the Association of Bone Mineral Density With Clinical Activity in Adult-Onset Nephrotic Syndrome

To Study the Association of Bone Mineral Density With Clinical Activity in Adult-Onset Nephrotic Syndrome

Molecular Characterization of Membranous Nephropathy.

Molecular characterization of nephropathies may facilitate pathophysiologic insight, development of targeted therapeutics, and transcriptome-based disease classification. Although membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome, the molecular pathways of kidney damage in MN require further definition. We applied a machine-learning framework to predict diagnosis on the basis of gene expression from the microdissected kidney tissue of participants in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. We sought to identify differentially expressed genes between participants with MN versus those of other glomerulonephropathies across the NEPTUNE and European Renal cDNA Bank (ERCB) cohorts, to find MN-specific gene modules in a kidney-specific functional network, and to identify cell-type specificity of MN-specific genes using single-cell sequencing data from reference nephrectomy tissue. Glomerular gene expression alone accurately separated participants with MN from those with other nephrotic syndrome etiologies. The top predictive classifier genes from NEPTUNE participants were also differentially expressed in the ERCB participants with MN. We identified a signature of 158 genes that are significantly differentially expressed in MN across both cohorts, finding 120 of these in a validation cohort. This signature is enriched in targets of transcription factor NF-κB. Clustering these MN-specific genes in a kidney-specific functional network uncovered modules with functional enrichments, including in ion transport, cell projection morphogenesis, regulation of adhesion, and wounding response. Expression data from reference nephrectomy tissue indicated 43% of these genes are most highly expressed by podocytes. These results suggest that, relative to other glomerulonephropathies, MN has a distinctive molecular signature that includes upregulation of many podocyte-expressed genes, provides a molecular snapshot of MN, and facilitates insight into MN's underlying pathophysiology.

Posttransplant membranous nephropathy - A case report

Primary membranous nephropathy (PMN) is a common cause of adult-onset nephrotic syndrome. Anti-M-type phospholipase A2 receptor (PLA2R) antibodies are pathogenic and correlate with clinical outcomes. The role of anti-PLA2R in recurrent PMN is unclear. In the present manuscript, we report five cases of PMN who underwent kidney transplantation (KT) with varying titers of anti-PLA2R pre-kidney transplantation (KT). Two patients with anti-PLA2R in the second and third tertiles had a recurrence of PMN, whereas patients with a negative or anti-PLA2R in the first tertile had no recurrence. The report signals a heightened risk of PMN recurrence in patients with elevated anti-PLA2R antibody titer at KT.

Adult-onset nephrotic syndrome following coronavirus disease vaccination.

ABSTRACTA 22-year-old healthy man was admitted for oedema 15 days after the first injection of the COVISHIELD coronavirus disease 2019 (COVID-19) vaccine (Oxford AstraZeneca) vaccine. Nephrotic syndrome was diagnosed and a kidney biopsy showed minimal change disease. Oral prednisolone was started at 1 mg/kg/day resulting in complete remission within 1 week.

Primary membranous glomerulonephritis with negative serum PLA2R in haemophilia A successfully managed with rituximab \u2013 case report and review of the literature

BackgroundHepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause a wide range of glomerular pathologies. In people with haemophilia, transfusion-associated infections with these viruses are common and definitive pathological diagnosis in this population is complicated by the difficulty of safely obtaining a renal biopsy. Membranous nephropathy (MN) is a common cause of adult onset nephrotic syndrome occurring in both primary and secondary forms. Primary MN is associated with podocyte autoantibodies, predominantly against phospholipase A2 receptor (PLA2R). Secondary disease is often associated with viral infection; however, infrequently with HIV or HCV. Distinguishing these entities from each other and other viral glomerular disease is vital as treatment strategies are disparate.Case presentationWe present the case of a 48-year-old man with moderate haemophilia A and well-controlled transfusion-associated HCV and HIV coinfection who presented with sudden onset nephrotic range proteinuria. Renal biopsy demonstrated grade two membranous nephropathy with associated negative serum PLA2R testing. Light and electron microscopic appearances were indeterminant of a primary or secondary cause. Given his extremely stable co-morbidities, treatment with rituximab and subsequent angiotensin receptor blockade was initiated for suspected primary MN and the patient had sustained resolution in proteinuria over the following 18 months. Subsequent testing demonstrated PLA2R positive glomerular immunohistochemistry despite multiple negative serum results.ConclusionsPursuing histological diagnosis is important in complex cases of MN as the treatment strategies between primary and secondary vary significantly. Serum PLA2R testing alone may be insufficient in the presence of multiple potential causes of secondary MN.

A Novel Model for Nephrotic Syndrome Reveals Associated Dysbiosis of the Gut Microbiome and Extramedullary Hematopoiesis

Glomerular kidney disease causing nephrotic syndrome is a complex systemic disorder and is associated with significant morbidity in affected patient populations. Despite its clinical relevance, well-established models are largely missing to further elucidate the implications of uncontrolled urinary protein loss. To overcome this limitation, we generated a novel, inducible, podocyte-specific transgenic mouse model (Epb41l5fl/fl*Nphs1-rtTA-3G*tetOCre), developing nephrotic syndrome in adult mice. Animals were comprehensively characterized, including microbiome analysis and multiplexed immunofluorescence imaging. Induced knockout mice developed a phenotype consistent with focal segmental glomerular sclerosis (FSGS). Although these mice showed hallmark features of severe nephrotic syndrome (including proteinuria, hypoalbuminemia and dyslipidemia), they did not exhibit overt chronic kidney disease (CKD) phenotypes. Analysis of the gut microbiome demonstrated distinct dysbiosis and highly significant enrichment of the Alistipes genus. Moreover, Epb41l5-deficient mice developed marked organ pathologies, including extramedullary hematopoiesis of the spleen. Multiplex immunofluorescence imaging demonstrated red pulp macrophage proliferation and mTOR activation as driving factors of hematopoietic niche expansion. Thus, this novel mouse model for adult-onset nephrotic syndrome reveals the significant impact of proteinuria on extra-renal manifestations, demonstrating the versatility of this model for nephrotic syndrome-related research.

Reversal of endothelial dysfunction post-immunosuppressive therapy in adult-onset podocytopathy and primary membranous nephropathy

Background and aimsThe effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. MethodsNewly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4+CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. ResultsFifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC (p = 0.002) while PWV (p = 0.007), E-selectin (p < 0.001) and CD4+CD28null T cells (p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% (p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s (p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml (p = 0.002) while the CD4+CD28null T cell population reduced from 5.20 to 3.70% (p = 0.032) of total CD4+ cells. In the PMN cohort, despite significant reduction, E-selectin and CD4+CD28null T cells at follow-up remained higher than in healthy controls. ConclusionImmunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN.

SAT-009 Exploring novel biomarkers in Membranous Nephropathy using protein array platform

Membranous nephropathy (MN) is the leading cause of adult-onset nephrotic syndrome. Autoantibody biomarkers for MN include the landmark discovery of Anti-PLA2R antibody against phospholipase A2 receptor (PLA2R) with a prevalence of 50-70% followed by Thrombospondin Type-1 Domain-Containing 7A (THSD7A), with a prevalence of 2-3%. It is believed that yet undiscovered autoantibodies might be involved in the remaining 20-25% of MN patients. In this pilot study, we sought to identify a panel of candidate protein biomarkers in MN using the Sengenics™ Immunome protein array Single-center cohort study of 10 patients with biopsy proven MN (cases) and 10 individuals with biopsy proven minor glomerular abnormalities (controls), recruited at the Department of Renal Medicine of the Singapore General Hospital (SGH) between 1st January 2016 and 31st March 2017. Scientific Methods: After hybridizing the 20 serum samples on the Sengenics Immunome™ protein microarray slides, signals were detected using a microarray laser scanner at a 10μm resolution. The penetrance-based fold change (pFC) analysis method was implemented for the identification of antibodies against the proteins in each case sample, thus eliminating false positive signals from the data by setting a protein-specific threshold which was calculated on a per-protein basis via the mean +2 standard deviation intensity of the signal for each specific protein measured for the matched healthy control samples. Bioinformatics analyses were performed to identify and rank the biomarkers based on their sensitivity and specificity. Cases were 50% male, with 20% diabetic and 60% hypertensive, median age of 52.5years (IQR 48.5, 68.5), 90% Chinese, with median eGFR 76.5 (IQR 61.2, 111.7) and median proteinuria 5.61g (IQR 4.0, 7.4). Controls were race and gender matched with 50% male, 90% Chinese, with 40% diabetic and 80% hypertensive, median age of 53.5years (IQR 45.8, 59.8), median eGFR 74.3 (IQR 44.5, 100.8), median proteinuria 1.67g (IQR 0.6, 4.1). Both groups were comparable except for median proteinuria (p=0.035). A total of 328 biomarkers were identified and the top 15 are listed in Table 1. The top 5 biomarkers in our study show high differential expression in MN serum when compared to controls (see table 1). Mx1, a GTPase commonly involved downstream of the type I IFN pathway and associated with antiviral activity, has been found to be upregulated in lupus nephritis and its association with MN warrants further investigation. The presence of EEF1G in MN patients correlate to MN murine mice model studies that have shown differential expression of EEF1G, specifically subunit alpha, in MN kidney tissue when compared with normal kidneys. GSK3B, which has been found to be associated with diabetic nephropathy through microRNA and haplotype association studies, was prominently elevated in MN patients with diabetes versus diabetes alone and may be useful in the stratification between membranous nephropathy and diabetic nephropathy. From this pilot study, we have found a panel of potential candidate proteins that can be further studied in a larger scale protein profiling study which can eventually lead to the discovery of more specific biomarkers which can act as a management adjunct by accurately diagnosing, prognosticating and aid in treatment of MN.

Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children

Heterozygous PAX2 mutations cause renal coloboma syndrome (RCS) [OMIM no. 120330]. RCS is a renal syndromic disease encompassing retinal coloboma and sensorineural hearing loss. Recently, a causative role for PAX2 was reported in adult-onset nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS). However, the prevalence of PAX2 mutations among large cohort of children with steroid-resistant nephrotic syndrome (SRNS) and FSGS has not been systematically studied. We employed whole-exome sequencing (WES) to identify the percentage of SRNS cases explained by monogenic mutations in known genes of SRNS/FSGS. As PAX2 mutations are not an established cause of childhood FSGS, we evaluated a cohort of 215 unrelated families with SRNS, in whom no underlying genetic etiology had been previously established. Using WES, we identified 3 novel causative heterozygous PAX2 mutations in 3 out of the 215 unrelated index cases studied (1.3%). All three cases were detected in individuals from families with more than one affected and compatible with an autosomal dominant mode of inheritance (3/57 familial cases studied (5.2%)). The clinical diagnosis in three out of four pediatric index patients was done during routine medical evaluation. Our findings demonstrate high frequency of PAX2 mutations in familial form of SRNS (5.2%) and further expand the phenotypic spectrum of PAX2 heterozygous mutations to include autosomal dominant childhood-onset FSGS. These results highlight the importance of including PAX2 in the list of genes known to cause FSGS in children.

Loss of Subpodocytic Space Predicts Poor Response to Tacrolimus in Steroid-Resistant Calcineurin Inhibitor-Naïve Adult-Onset Primary Focal Segmental Glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult-onset nephrotic syndrome, but its pathophysiology is poorly understood. The question as to why only a subset of patients responds to treatment in unanswered. In the past few years, change of podocytic phenotype from stationary type in health to migratory type in disease has been described, of which loss of subpodocytic space is a surrogate marker. Diagnostic biopsies of adult-onset steroid-resistant calcineurin inhibitor-naïve primary FSGS cases, which were subsequently treated with tacrolimus were included in this retrospective study conducted from 2011 to 2013. The ultrastructure of all cases was studied in detail, especially in context to the presence or absence of subpodocytic space. In the present study, we have compared presence or absence of subpodocytic space in tacrolimus-responsive versus tacrolimus-resistant cases to identify potential electron microscopic features predictive of response to treatment, of which loss of subpodocytic space indicating migratory phenotype is the most important and consistent feature. The present series included 7 tacrolimus responsive cases (includes two cases with partial response) and seven tacrolimus-resistant cases. The tacrolimus-resistant patients were of older age, had a longer duration of illness, and a lower eGFR as compared to tacrolimus responsive cases. The subpodocytic space was preserved in patients on tacrolimus with complete remission and lost in patients with partial response and tacrolimus-resistant cases.

Therapeutic efficacy of rituximab for the management of adult-onset steroid-dependent nephrotic syndrome: a retrospective study.

Recent reports have described the efficacy of rituximab in treating steroid-dependent nephrotic syndrome (SDNS) in pediatric patients. However, few reports describe data regarding adult-onset SDNS. We investigated the efficacy of rituximab for the management of adult-onset SDNS. We performed a retrospective cohort study investigating eight patients with adult-onset SDNS who were treated with rituximab. Clinical data were obtained at the initiation of rituximab therapy. The primary outcomes evaluated were successful suppression of relapses and CD19+ cells after rituximab treatment. The corticosteroid- and immunosuppressant-sparing effect and adverse events were additionally evaluated. All eight patients were diagnosed with minimal change nephrotic syndrome and received immunosuppressants in addition to corticosteroid. Total number of relapses was 10.5 times as a median value. Rituximab administration was repeated in two patients, whereas six received single-dose rituximab. Three of eight (37.5%) patients showed relapse after rituximab therapy. A rituximab-induced depletion in CD19+ cells noted initially was followed by their reappearance in all patients. There were cases with no relapse after the reappearance of CD19+ cells. The median relapse time pre- and post-rituximab therapy showed a decrease from 1time/year (interquartile range [IQR] 1-3times/year) to 0time/year (IQR 0-1time/year). Rituximab treatment induced a significant reduction in the required doses of corticosteroid and cyclosporine (P < 0.01). No serious adverse events were observed. Rituximab treatment was effective not only in childhood-onset but also in adult-onset SDNS. Further studies are needed to establish optimal treatment regimens.

Histopathological study of nephrotic syndrome in adults: A Moroccan report.

The reported causes of nephrotic syndrome (NS) varies between different countries. In this retrospective study, we aimed to evaluate the underlying causes of NS in adult patients who underwent renal biopsy in a region of Morocco and we also determined the distribution of histopathological diagnoses with regard to the age subgroups and genders from January 2007 to December 2016. Patients were divided into four groups according to age at the time of renal biopsy. A total of the 257 patients with NS were included in this study. The mean age of the patients was 40.9 ± 16.7 years; male gender was preponderant (61.9%). One hundred and sixty-six (64.6 %) and 81 (35.4%) patients were diagnosed as primary and secondary glomerulonephritis, respectively. The most common diagnosis in NS was membranous nephropathy (MN) (22.2%), followed by minimal change disease (MCD) (20.6%), and lupus nephritis (LN) (13.6%). Among the patients aged 15-30, 31-45, 46-60, and >61 years, the most common cause of NS was MCD (32.1%), MN (29.6 %), MN (26.1%), and amyloidosis (AM) (28.2%), respectively. The proportion of patients with MCD and LN decreased in parallel with patient age and the proportion of patients with renal AM increased in parallel with patient age. Among the female patients aged 15-30 and 31-45 years, LN was the leading cause of NS (41.5 and 36.7%, respectively). Among the male patients aged 15-30 years, MCD was the leading cause of NS (43.2%). Our study over 10 years represents an important data of regional variations of glomerular diseases presenting with adult-onset NS.

Glomerular Diseases in Children.

Unique challenges exist in the diagnosis and treatment of glomerular diseases with their onset during childhood. Mounting evidence supports the notion that earlier onset cases occur due to larger numbers of genetic risk alleles. Nearly all causes of adult-onset glomerulonephritis, nephrotic syndrome, and thrombotic microangiopathy have also been described in children, although the prevalence of specific causes differs. Postinfectious glomerulonephritis, Henoch-Schönlein purpura nephritis, and minimal change disease remain the most common causes of glomerular disease in younger children in the United States and can be diagnosed clinically without need for biopsy. IgA nephropathy is the most common pediatric glomerular disease diagnosed by kidney biopsy and is considered the most common chronic glomerulopathy worldwide. In both developing and developed countries, there is a strong relationship between infectious diseases and nephritis onset or relapse. Although research has led to a better understanding of how to classify and manage glomerular diseases in children, the need for disease-specific biomarkers of activity and chronicity remains a hurdle. The strength of the immune system and the growth and maturation that occurs during adolescence are unique and require age-specific approaches to disease management.

P256 Hypogammaglobulinemia as presenting sign of nephrotic syndrome

Secondary hypogammaglobulinemia has been described. We report a case of severe rapid-onset hypogammaglobulinemia presenting as adult onset nephrotic syndrome.

Genetic basis of adult-onset nephrotic syndrome and focal segmental glomerulosclerosis

Nephrotic syndrome (NS) is one of the most common glomerular diseases with signs of nephrosis, heavy proteinuria, hypoalbuminemia, and edema. Dysfunction of glomerular filtration barrier causes protein loss through the kidneys. Focal segmental glomerulosclerosis (FSGS) accounts for nearly 20% of NS among children and adults. Adult-onset FSGS/NS is often associated with low response to steroid treatment and immunosuppressive medication and poor renal survival. Several genes involved in NS and FSGS have been identified by linkage analysis and next-generation sequencing. Most of these genes encode proteins and are highly expressed in glomerular podocytes, which play crucial roles in slit-diaphragm signaling, regulation of actin cytoskeleton dynamics and maintenance of podocyte integrity, and cell-matrix interactions. In this review, we focus on the recently identified genes in the adult-onset NS and FSGS and discuss clinical significance of screening of these genes.

Histologic patterns of primary adult onset nephrotic syndrome and their clinical characteristics; a single center study from South India

Background: The histologic pattern causing nephrotic syndrome (NS) and their clinical outcome varies depending on age, sex, race, socioeconomic status and geographic location. There has been a changing trend in the histologic spectrum of NS in the last few decades, in India as well as worldwide. Objectives: The objective of the present study was to see the histologic spectrum of adult NS in our institution and to compare it with data from other centers. Patients and Methods: All adults (≥ 18 years) with nephrotic range proteinuria who underwent renal biopsy from August 2012 to February 2015, were consecutively included in this prospective study. NS caused by diabetes and other secondary glomerular diseases were excluded. Results: Eighty (65.4%) patients were males and 42 (34.4%) were females. The median age at the time of biopsy was 36 years (interquartile range [IQR]: 24.8–45). The most common lesions were minimal change disease (MCD) in 40.2%, membranous nephropathy (MN) in 24.6% and focal segmental glomerulosclerosis (FSGS) in 16.4% of the patients. MCD was observed mostly commonly in the age group 18-35 years and MN was seen mostly commonly in age group 36-55 years. Conclusions: MCD still continues to be leading cause of NS in south Indian adults as evidenced from previous studies from this region. Other common causes include MN and FSGS. The incidence of MPGN is on the decline.

Clinicopathological Analysis of Glomerular Disease of Adult Onset Nephrotic Syndrome in an Indian Cohort- A Retrospective Study.

Primary glomerular disease presenting with adult onset nephrotic syndrome are a major cause of chronic renal failure worldwide. The spectrum of renal disease presenting with nephrotic syndrome has undergone a gradual change globally over the course of time. However, there still exist regional differences in the incidence of primary glomerular diseases causing adult onset nephrotic syndrome. To observe the spectrum of renal diseases presenting with adult onset nephrotic syndrome with comparative analysis of changing trends over the last five decades with regards to Western and Indian literature. Subjects included patients with age of 18-80 years presenting with nephrotic syndrome. Renal biopsies with immunofluoroscence studies were performed in all patients. Baseline clinical parameters of serum urea, creatinine, albumin, globulin, cholesterol, 24 hour urine protein and urine microscopy were recorded. Descriptive statistics was used and results were expressed as frequencies, percentages, and mean±standard deviation. A total of 227 patients (72% males) were included for the study. Primary glomerular diseases formed 74.01% of total cases and majority of patients included males in the 4th decade. Minimal Change Disease (MCD) (15.8%) including its variants was the most common primary glomerular disease for adult onset of nephrotic syndrome followed by Mesangial proliferative Glomerulonephritis (MSGN) (13.2%). Membranous nephropathy and Type I Membranoproliferative Glomerulonephritis (MPGN) individually accounted for 12.3% of patients. Focal and Segmental Glomerulosclerosis (FSGS) accounted for only 11% of patients. Although, increased incidence of FSGS has been observed worldwide, there exist important regional differences in primary glomerular diseases in Indian population. MCD remains a major glomerular disease for adult onset nephrotic syndrome in different parts of India. Our study over three years represents important data of regional variations of primary glomerular diseases presenting with adult onset nephrotic syndrome.