Focal And Segmental Glomerulosclerosis Research Articles

Incidence of pediatric glomerular diseases in Arab world: A systematic review

Despite the high number of Arab children, there are a scanty available data about different types of pediatric glomerular diseases in all Arab countries. Very few Arab countries have a national renal biopsy registry. In this review, we performed a systematic review analyzing the incidence of pediatric glomerular disease in all Arab countries. Relevant manuscripts in all 22 Arab countries found through searches of Medline, Science Direct, Embase and Google Scholar were evaluated. The period was from January 1990 to March 2018. A total of 17 manuscripts containing 3083 renal biopsies from seven countries were analyzed. Male-to-female ratio was 1.3:1. Saudi Arabia revealed the most published studies with seven papers. The average period of the study was 8.63 years. Retrospective studies represent 94.12%. Minimal change disease (MCD) (29.25%), focal and segmental glomerulosclerosis (FSGS) (22.34%), mesangioproliferative glomerulonephritis (14.78%), membranoproliferative glomerulonephritis (6.9%), IgA nephropathy (3.98%), and membranous glomerulopathy (2.65%) were the top types of primary glomerular diseases. The most common types of secondary glomerular diseases were lupus nephritis (36.1%), postinfectious glomerulonephritis (17.62%), congenital nephrotic syndrome (6.08%), Alport syndrome (4.71%), Henoch-Schönlein purpura (1.49%), and amyloidosis (1.36%). In conclusion, MCD and lupus nephritis are, respectively, the most common types of primary and secondary glomerular diseases in children of all evaluated Arab countries. FSGS is the predominant pattern of primary glomerular diseases in Asian Arab countries. The trend of all types of glomerular diseases has not changed in the past 28 years except a noted significant reduction in FSGS. Arab countries are strongly recommended to establish a renal biopsy registry.

Pattern of biopsy-proven kidney diseases: experience of a teaching hospital in Bahawalpur, Pakistan.

This descriptive observational study was conducted at the Department of Nephrology, Bahawal Victoria Hospital, Bahawalpur, Pakistan, from January 2012 to April 2018, to study the pattern of biopsy-proven kidney diseases in that region as a part to establish a national renal biopsy registry. All adult patients who underwent renal biopsy at the Bahawal Victoria Hospital, Bahawalpur, Pakistan, from January 2012 to April 2018, were included in the study. All the biopsies were evaluated by light microscopy and immunofluorescence. All the patients underwent urine dipstick, microscopic examination, and quantification of proteinuria. Hepatitis B surface antigen, anti-hepatitis C virus, human immunodeficiency virus, and serology (antinuclear antibody, anti-ds DNA, and C3 and C4) were checked in all the patients. There were a total of 195 patients, with a mean age of 30.5 ± 12.8 years. Females were comparatively younger than males (P = 0.0154). Primary glomerulonephritis (GN) accounted for 77% (155) of all the patients, whereas secondary GN contributed 15.8%. Focal and segmental glomerulosclerosis (FSGS) was the most common diagnosis (28.2%) followed by membranous nephropathy (MN) (18.9%). Lupus nephritis was the third-most common pathology, and it predominated among females (P= 0.0026). Out of the eight diabetic patients, one each had FSGS and crescentic GN. In conclusion, primary glomerular diseases were the predominant biopsy-proven kidney diseases, and FSGS and MN were the most common glomerular diseases. This pattern in South Punjab closely resembles that in southern and northern parts of the country.

Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: Role of NADPH oxidases and Src family tyrosine kinases

The soluble urokinase receptor (suPAR) has been implicated in the pathogenesis of chronic kidney diseases (CKD) and may function as a circulating “permeability factor” driving primary focal and segmental glomerulosclerosis (FSGS). Here we examined the mechanisms whereby suPAR causes mobilization and increased activation of Ca2+-permeable TRPC6 channels, which are also implicated in FSGS. Treatment of immortalized mouse podocytes with recombinant suPAR for 24 h caused a marked increase in cytosolic reactive oxygen species (ROS) that required signaling through integrins. This effect was associated with increased assembly of active cell surface NADPH oxidase 2 (Nox2) complexes and was blocked by the Nox2 inhibitor apoycynin. Treatment with suPAR also evoked a functionally measurable increase in TRPC6 channels that was blocked by concurrent treatment with the ROS-quencher TEMPOL as well as by inhibition of Rac1, an essential component of active Nox2 complexes. Elevated ROS evoked by exposing cells to suPAR or H2O2 caused a marked increase in the abundance of tyrosine-phosphorylated proteins including Src, and suPAR-evoked Src activation was blocked by TEMPOL. Moreover, mobilization and increased activation of TRPC6 by suPAR or H2O2 was blocked by concurrent exposure to PP2, an inhibitor of Src family tyrosine kinases. These data suggest that suPAR induces oxidative stress in podocytes that in turn drives signaling through Src family kinases to upregulate TRPC6 channels. The combination of oxidative stress and altered Ca2+ signaling may contribute to loss of podocytes and progression of various forms of CKD.

Rituximab does not Prevent Focal and Segmental Glomerulosclerosis Recurrence after Renal Transplantation in Patients at Risk

SENTRA-GLOSEN. Introduction Recurrence of focal and segmental glomerulosclerosis (FSGS) after renal transplantation is a characteristic complication of the disease that occurs in one third of the cases and has an important detrimental influence on graft survival. Different characteristics have been proposed as risk factors for recurrent disease although there is no general agreement on their importance and significance. Some studies have suggested that rituximab, administered at the time of transplantation, may be effective in preventing recurrence, but such efficacy has not been corroborated. Materials and Methods We perform a multicenter retrospective cohort study including 93 kidney transplants between years 2000 and 2014 in 87 patients [6 patients received a second transplant] with biopsy-proven FSGS as the underlying primary disease; patients with genetic or secondary causes were excluded. The aims of the study are to identify those factors that predict proteinuria recurrence and to analyze the efficacy of rituximab as preventive treatment in patients at risk. We also evaluate remission after recurrence treatment and the impact of recurrence on the graft survival. Results Fifteen patients (16.1%) presented a FSGS recurrence. When the analysis was restricted to those patients presenting with nephrotic syndrome at baseline, the incidence of recurrence increased to 44.1%. A younger age at diagnosis, a lower serum albumin and higher amount of proteinuria at baseline, more frequent immunosuppressive treatments at baseline, a higher number of relapses in previous transplants and a lower age at the time of transplantation were associated with the risk of recurrence. By multivariate analysis, the only risk factor for FSGS recurrence was the value of serum albumin at baseline. RTX (1g at induction and 1g two weeks after transplantation) was used as a potential prophylactic treatment in 12 of the 34 patients considered at risk for FSGS recurrence (hypoalbuminemia and nephrotic proteinuria at baseline). Clinical and analytical characteristics, both at baseline and at transplantation, were similar in both groups. No differences were found in the number of recurrences: 6/12 (50%) among RXT-treated patients and 9/22 (40.9%) versus non-treated patients (p = 0.610). Proteinuria remission after different treatments, most of them including plasmapheresis, was observed in 71.4% of patients. The addition of RTX to plasmapheresis did not increase efficacy. FSGS recurrence had a remarkable impact on graft survival, with 53% functioning grafts at the end of follow-up among patients who had suffered recurrence versus 88,5% in those who did not (p = 0.004); graft survival of FSGS recurrent patients achieving proteinuria remission after treatment was similar to that of patients without recurrence. Discussion In conclusion, the presence of hypoalbuminemia at the onset of the disease is the main predicting factor for FSGS recurrence. Rituximab does not prevent FSGS recurrence in patients at risk.

Molecular and Cellular Mechanisms for Proteinuria in Minimal Change Disease.

Minimal Change Disease (MCD) is a clinical condition characterized by acute nephrotic syndrome, no evident renal lesions at histology and good response to steroids. However, frequent recurrence of the disease requires additional therapies associated with steroids. Such multi-drug dependence and frequent relapses may cause disease evolution to focal and segmental glomerulosclerosis (FSGS) over time. The differences between the two conditions are not well defined, since molecular mechanisms may be shared by the two diseases. In some cases, genetic analysis can make it possible to distinguish MCD from FSGS; however, there are cases of overlap. Several hypotheses on mechanisms underlying MCD and potential molecular triggers have been proposed. Most studies were conducted on animal models of proteinuria that partially mimic MCD and may be useful to study glomerulosclerosis evolution; however, they do not demonstrate a clear-cut separation between MCD and FSGS. Puromycin Aminonucleoside and Adriamycin nephrosis are models of glomerular oxidative damage, characterized by loss of glomerular basement membrane polyanions resembling MCD at the onset and, at more advanced stages, by glomerulosclerosis resembling FSGS. Also Buffalo/Mna rats present initial lesions of MCD, subsequently evolving to FSGS; this mechanism of renal damage is clearer since this rat strain inherits the unique characteristic of overexpressing Th2 cytokines. In Lipopolysaccharide nephropathy, an immunological condition of renal toxicity linked to B7-1(CD80), mice develop transient proteinuria that lasts a few days. Overall, animal models are useful and necessary considering that they reproduce the evolution from MCD to FSGS that is, in part, due to persistence of proteinuria. The role of T/Treg/Bcells on human MCD has been discussed. Many cytokines, immunomodulatory mechanisms, and several molecules have been defined as a specific cause of proteinuria. However, the hypothesis of a single cell subset or molecule as cause of MCD is not supported by research and an interactive process seems more logical. The implication or interactive role of oxidants, Th2 cytokines, Th17, Tregs, B7-1(CD80), CD40/CD40L, c-Mip, TNF, uPA/suPAR, Angiopoietin-like 4 still awaits a definitive confirmation. Whole genome sequencing studies could help to define specific genetic features that justify a definition of MCD as a “clinical-pathology-genetic entity.”

Trpc6 inactivation confers protection in a model of severe nephrosis in rats

Mutations in canonical transient receptor potential-6 (TRPC6) channels give rise to rare familial forms of focal and segmental glomerulosclerosis (FSGS). Here we examined a possible role for TRPC6 in the progression of chronic puromycin aminonucleoside (PAN) nephrosis in Sprague-Dawley rats, a classic model of acquired nephrotic syndromes. We used CRISPR/Cas9 technology to delete a 239-bp region within exon 2 of the Trpc6 gene (Trpc6del allele). Trpc6del/del rats expressed detectable Trpc6 transcripts missing exon 2, and TRPC6 proteins could be detected by immunoblot of renal cortex. However, the abundance of Trpc6 transcripts and TRPC6 protein in renal cortex was much lower than in Trpc6wt/wt littermates, and functional TRPC6 channels could not be detected in whole-cell recordings from glomerular cells cultured from Trpc6del/del animals, possibly because of disruption of ankyrin repeats 1 and 2. During the chronic phase of PAN nephrosis, Trpc6del/del rats had reduced urine albumin excretion, reduced serum cholesterol and triglycerides, and improved azotemia compared to wild-type Trpc6wt/wt littermates. Glomerulosclerosis was severe during chronic PAN nephrosis in Trpc6wt/wt rats but was markedly reduced in Trpc6del/del littermates. Trpc6del/del animals also had less severe tubulointerstitial fibrosis as assessed by several biochemical and histological analyses, as well as reduced foot process effacement and glomerular basement thickening compared to Trpc6wtt/wt controls. None of the manipulations in this study affected the abundance of TRPC5 channels in renal cortex. TRPC3 was increased in PAN nephrosis and in Trpc6del/del rats. These data support a role for TRPC6 channels in driving an acquired form of secondary FSGS.Key messagesWe examined aminonucleoside nephrosis in rats with wild type and inactivated TRPC6.TRPC6 channels were inactivated by CRISPR/Cas9 editing of the Trpc6 gene.TRPC6 inactivation reduced albuminuria in the chronic but not the acute phase.TRPC6 inactivation reduced glomerulosclerosis and ultrastructural changes.TRPC6 inactivation also reduced interstitial changes and renal fibrosis.

Advances in molecular diagnosis and therapeutics in nephrotic syndrome and focal and segmental glomerulosclerosis.

The widespread adoption of next-generation sequencing by research and clinical laboratories has begun to uncover the previously unknown genetic basis of many diseases. In nephrology, one of the best examples of this is seen in focal and segmental glomerulosclerosis (FSGS) and nephrotic syndrome. We review advances made in 2017 as a result of human and molecular genetic studies as it relates to FSGS and nephrotic syndrome. There are more than 50 monogenic genes described in steroid-resistant nephrotic syndrome and FSGS, with seven reported in 2017. In individuals presenting with FSGS or nephrotic syndrome before or at the age of 18 years, the commonest genes in which a mutation is found continues to be limited to only a few including NPHS1 and NPHS2 based on multiple studies. For FSGS or nephrotic syndrome that presents after 18 years, mutations in COl4A3/4/5, traditionally associated with Alport syndrome, are increasingly being reported. Despite the extensive genetic heterogeneity in FSGS, there is evidence that some of these genes converge onto common pathways. There are also reports of in-vivo models exploring apolipoprotein 1 biology, variants in which account for part of the increased risk of nondiabetic kidney disease in African-Americans. Finally, genetic testing has several clinical uses including clarification of diagnosis and treatment; identification of suitable young biologic relatives for kidney donation; and preimplantation genetic diagnosis. CRISPR gene editing is currently an experimental tool only, but the recent reports of excising mutations in embryos could be a therapeutic option for individuals with any monogenic disorder in the future. Sequencing efforts are bringing novel variants into investigation and directing the efforts to understand how these lead to disease phenotypes. Expanding our understanding of the genetic basis of health and disease processes is the necessary first step to elaborate the repertoire of therapeutic agents available for patients with FSGS and nephrotic syndrome.

A six-year survey of the spectrum of renal disorders on native kidney biopsy results in Central Iran and a review of literature.

Native kidney biopsy reports in previous studies that are mostly originated in Western countries show various results in different parts of the world. In this study, we aimed to determine the prevalence of renal biopsy disorders in Iran and compare it with that of other studies in the world. This cross-sectional study evaluated consecutive native kidney biopsies performed in four centers in Isfahan, Iran, from 2009 to 2014. We also reviewed other relevant studies in Iran and the world. Overall, 1547 renal biopsies were reviewed; 493 cases were excluded (transplant or re-biopsy cases) and 1054 cases (43.3% female) were included in our study with a mean (±standard deviation) age of 33.1 (±18.5) years. The first three most prevalent diagnoses were focal and segmental glomerulosclerosis (FSGS) (24.8%), minimal change disease (MCD) (14.2%), and membranous glomerulonephritis (MGN) (9.6%). IgA nephropathy (IgAN) was more prevalent among men, whereas lupus nephritis had a higher prevalence among women. In three out of six previous studies conducted in Iran, the most prevalent pathological diagnosis was MGN; in two others, MCD predominated; and in the third study, FSGS had the highest prevalence. In Europe and Western Pacific Region, IgAN was by far the most prevalent GN, while studies in other parts of the world show conflicting results. The most prevalent diagnosis in our study was FSGS, which was consistent with previous studies in Iran, which seems to have an increasing prevalence. It is recommended that having a national registry is crucial to determine the current status and for better planning and management of renal disorders.

Spectrum of glomerular diseases in Arab countries: A systematic review.

According to the best of our knowledge, there is no review compiling incidence of glomerular disease in all Arab countries. Most of the Arab countries do not have a national renal biopsy registry. In addition, there is scanty data available on the epidemiology of glomerular diseases in Arab countries. In this review, we performed a systematic review analyzing the incidence of glomerular disease in all Arab countries. Relevant manuscripts in all 22 Arab countries found through searches of Medline, Science Direct, Embase, and Google Scholar were evaluated. The time was from January 1990 to March 2018. A total of 36 manuscripts containing 10,727 biopsies from 11 countries were analyzed. The male-to-female ratio was 1.2:1. Saudi Arabia had the largest number of published studies with 14 papers followed equally by Iraq, Jordan, and Sudan with three papers each. The average period of study was 8.17 years. Retrospective studies represented 86.11%. Focal and segmental glomerulosclerosis (FSGS) (27%), minimal change disease (14%), membranoproliferative glomerulonephritis (13%), mesangioproliferative glomerulonephritis (13%), and membranous glomerulopathy (11%) were the main types of primary glomerular diseases. The most common types of secondary glomerular diseases were lupus nephritis (LN) (58%), amyloidosis (10.19%), diabetic nephropathy (9.89%), hypertension (4.84%) and poststreptococcal glomerulonephritis (2.72%). In conclusion, FSGS and LN are the most common types of primary and secondary glomerular diseases, respectively, in all evaluated Arab countries. The trend of all types of glomerular diseases has not changed in the last three decades. We strongly recommend that each Arab country should have its own renal biopsy registry.

Changes in podocyte TRPC channels evoked by plasma and sera from patients with recurrent FSGS and by putative glomerular permeability factors

Primary forms of focal and segmental glomerulosclerosis (FSGS) are driven by circulating factors that cause dysfunction or loss podocytes. Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca2+-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains. Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus. These effects were mimicked by the soluble urokinase receptor (suPAR) and by tumor necrosis factor (TNF), circulating factors implicated in nephrotic syndromes. Most but not all of the recurrent FSGS plasma samples that we examined also caused a loss of podocin over a period of several hours. The loss of podocin was also seen following exposure to suPAR but not TNF. However, TNF increased the effects of suPAR on TRPC6 and podocin, and TNF and suPAR are required for the full effects of one of the recurrent FSGS plasma samples. The actions of FSGS plasma, suPAR and TNF on surface abundance of TRPC6 were blocked by cilengitide, an inhibitor of αvβ3-integrin signaling. These data suggest that primary FSGS is a heterogeneous condition mediated by multiple circulating factors, and support TRPC6 and αvβ3-integrin as potential therapeutic targets.

Available and incoming therapies for idiopathic focal and segmental glomerulosclerosis in adults.

Focal and segmental glomerulosclerosis (FSGS) is a histological pattern clinically characterized by nephrotic proteinuria, hypoalbuminemia, edema and dyslipidemia. Approximately 50% of patients progress to end-stage renal disease within 5-10 years, particularly those not responding to the therapies. FSGS pathogenesis is largely unknown and therapy is symptomatic and unspecific. The podocyte is considered as the pathogenetic main target and FSGS is now categorized as a podocytopathy together with minimal change disease, diffuse mesangial proliferation and collapsing glomerulonephritis. This paper provides an overview on the treatment of idiopathic FSGS in adults, citing the latest published trials and the most reliable pathogenetic hypotheses of the disease. A large part of the review then focuses on emerging therapies, specifying for each new drug the assumed mechanism of action and the data available in the literature on the drug's use in experimental animals and humans.

Reporting renal biopsies from Cyprus: a systematic approach.

Background: The etiology of renal disease varies in different parts of the world. In the Middle East, half of all patients reaching end-stage are categorised as either unknown etiology or hypertension-related nephropathy. Objectives: To report a renal biopsy series, in a reproducible format and manner, so that data can be compared directly among other series. Patients and Methods: Biopsies of native kidneys were performed in a 10-year period, at a tertiary referral hospital that provides the entire nephrology service for north Cyprus. Data are reported from 153 patients older than 17 years, who were either Turkish-Cypriot or from the Turkish mainland. Results: Mean biopsy rate was 48 per million population (pmp) per year. Mean age was 45.7 years (range 18-78). Overall, the sex distribution was similar (male 51%). The most common histopathological categories were primary glomerulonephritis (GN) (56%), secondary GN (27%), and tubulo-interstitial disease (14%). Of those with primary GN, 29% had secondary (2o) focal and segmental glomerulosclerosis (FSGS) (29%), followed by IgA nephropathy (24 %), membranous 18% and a further 11 patients with 1o FSGS (12%). The incidence of IgA nephropathy was 6.3 per pmp/year. When expressed as a percentage of the annual biopsy rate, 14% of all biopsies showed IgA nephropathy. Conclusions: To compare data among centres, they must be expressed in terms of the population (incidence pmp/year) and the biopsy rate. In our population, secondary FSGS is common and uncharacterised and we believe many will be caused by monogenic disease.

Diabetes, deafness and renal disease.

Deafness, kidney disease and diabetes are not a usual association, neither is a family history of these diseases. We present the case of a 47-year-old woman with non-nephrotic proteinuria, no haematuria, normal renal function, sensorineural hearing loss, recently diagnosed diabetes and maculopathy. There was a maternal family history of deafness, diabetes and renal disease. Renal biopsy revealed focal and segmental glomerulosclerosis (FSGS), leading to the pursuit of an m.3243A > G mitochondrial mutation and diagnosis of maternally inherited diabetes and deafness. The association of FSGS with mitochondrial diseases is not well known among nephrologists. Its timely diagnosis is important to avoid exposure to ineffective and unnecessary immunosuppression.

A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population.

BackgroundRecent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms.MethodsWe looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD). Two variants were genotyped in a cohort of well-studied adult TBMN patients from 19 Greek-Cypriot families, with a homogeneous genetic background. Patients were categorized as “Severe” or “Mild”, based on the presence or not of proteinuria, CRF and ESRD. A larger pooled cohort (HEMATURIA) of 524 patients, including IgA nephropathy patients, was used for verification. Additionally, three large general population cohorts [Framingham Heart Study (FHS), KORAF4 and SAPHIR] were used to investigate if the NEPH3-V353M variant has any renal effect in the general population.Results and conclusionsGenotyping for two high-scored variants in 103 TBMN adult patients with founder mutations who were classified as mildly or severely affected, pointed to an association with variant NEPH3-V353M (filtrin). This promising result prompted testing in the larger pooled cohort (HEMATURIA), indicating an association of the 353M variant with disease severity under the dominant model (p = 3.0x10-3, OR = 6.64 adjusting for gender/age; allelic association: p = 4.2x10-3 adjusting for patients’ kinships). Subsequently, genotyping 6,531 subjects of the Framingham Heart Study (FHS) revealed an association of the homozygous 353M/M genotype with microalbuminuria (p = 1.0x10-3). Two further general population cohorts, KORAF4 and SAPHIR confirmed the association, and a meta-analysis of all three cohorts (11,258 individuals) was highly significant (p = 1.3x10-5, OR = 7.46). Functional studies showed that Neph3 homodimerization and Neph3-Nephrin heterodimerization are disturbed by variant 353M. Additionally, 353M was associated with differential activation of the unfolded protein response pathway, when overexpressed in stressed cultured undifferentiated podocyte cells, thus attesting to its functional significance. Genetics and functional studies support a “rare variant-strong effect” role for NEPH3-V353M, by exerting a negative modifier effect on primary glomerular hematuria. Additionally, genetics studies provide evidence for a role in predisposing homozygous subjects of the general population to micro-albuminuria.

Clinical trials in minimal change disease.

Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS). Historically, cyclophosphamide, chlorambucil, mycophenolate and calcineurin inhibitors have been utilized with success in MCD; however, the chronic nature of the disease and the toxicity of long-term use of these medications has pushed the development of new therapies. Synthetic corticotropin (adrenocorticotropic hormone) and anti-CD20 monoclonal antibodies, for example, are currently under investigation in clinical trials. In addition, these new interventions have dramatically impacted our understanding of the mechanisms of the disease. Phase II-IV clinical trials targeting new mechanisms and/or molecules are in progress. The list is long and includes drugs blocking the adaptive immune system (abatacept and anti-CD40 antibodies), as well as retinoids and the sialic acid precursor N-acetyl-D-mannosamine (ManNAc), two agents that affect the sieving properties of the glomerular basement membrane. Other drugs are being tested against FSGS and, if successful, could also be utilized against MCD. Clinical trials currently in progress should furnish a proper solution to what appears to be a solvable problem.

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.

Renal Disease among HIV Positive Patients in Senegal

Introduction: Renal disease (RD) in human immunodeficiency virus (HIV) infection is a decisive turning point in the development and prognosis of this disease. In Africa, the prevalence varies between 2.5% and 48.6%. In Senegal, little data are available in the literature. The objective of our study was to describe the epidemiological, clinical, paraclinical, therapeutic and progressional aspects in patients living with HIV (PLWHIV). Patients and methods: This was a retrospective, descriptive and analytical study carried out over a 10-year period in the Department of Internal Medicine and Nephrology at the Aristide Le Dantec Hospital in Dakar, Senegal. We included all 15-year old and above PLHIV with available CD4 count and viral load. Results: Out of 248 PLHIV, 32 had kidney disease (KD), which means a hospital prevalence of 12.9%. The mean age was 51.22 ± 10 years (extremes of 36 and 77 years) with a sex ratio (male/female) of 1.28. Renal signs were dominated by glomerular nephropathy syndrome. It was present at 80%. Tubulo-interstitial nephropathy syndrome and chronic uremic syndrome accounted for 6.25% and 3.1% of cases, respectively. Renal function Impairment was present in 21 patients with 18 cases of acute kidney injury (85.7%) and 3 cases of chronic renal failure (14.3%), including 2 in stage 5 of chronic kidney disease. Renal biopsy (RB) was indicated and performed in 20 (62.5%) patients with glomerular signs in 12 patients (60%). Glomerular lesions were dominated by focal and segmental glomerulosclerosis (FSGS) in 6 cases, membraneous nephropathy (MN) in 4 cases and minimal change disease (MCD) in 2 cases. Tubulo-interstitial and vascular lesions were present in 45% and 12.5% of cases, respectively. In highly active antiretroviral therapy (HAART), 12 (37.5%) patients had total remission, 9 (28.12%) had partial remission. One (3.12%) death from severe metabolic acidosis on chronic renal failure was deplored. Conclusion: This study illustrates the high prevalence of RD in PLHIV in our exercise context.

Longterm Renal Outcome of Idiopathic Nephrotic Syndrome in Children

Objective: To study longterm renal outcome of Thai children with idiopathic nephrotic syndrome (INS). Methods: We retrospectively reviewed 75 INS children followed-up in a tertiary care, university hospital. Male to female ratio was 2:1. Mean age at diagnosis was 6.2 years, and 56.0% were less than 5 years old. 57.3% previously received prednisolone from other hospitals and 32 patients (42.7%) were steroid resistant nephrotic syndrome (SRNS). Initial short stature was found in 1.3%. Hypertension and hematuria was found in 34.7% and 14.7%, respectively. Renal biopsy performed in 40 patients (53.3%) revealed minimal changes disease in 17 (42.5%), focal and segmental glomerulosclerosis (FSGS) in 12 (30.0%), mesangial proliferative glomerulonephritis in 5 (12.5%), IgM nephropathy in 4 (10%), and IgA nephropathy in 2 (5%) patients. Immunosuppressive medications included Cyclophosphamide in 64.5%, Tacrolimus in 14.7%, Cyclosporin in 8.0% and Mycophenolate mofetil in 4.0%. Enalapril was given in 48.0%. Results: Mean follow-up time was 7.4 years. Complete remission was achieved in 77.3%. One patients (1.3%) had Chronic Kidney Disease stage 3 and 5 patients (6.7%) had End Stage Renal Disease (ESRD). One patient with ESRD died of severe respiratory tract infection. The factor associated with poor renal outcome was FSGS (p=0.032). Renal survival at 5,10, and 15 years were 95.3%, 85.7% and 57.2%, respectively. At last follow-up, short stature was found in 4.0% and hypertension in 20.0%. Other complications included cataract (29.3%), glaucoma (9.3%), diabetes mellitus (2.6%), septicemia (9.3%), other infections (10.6%). Conclusion: We suggest that although renal outcome in Thai children may be better than in caucasian, longterm follow up is still needed, especially in children with FSGS.

Rituximab use in adult primary glomerulopathy: where is the evidence?

Rituximab is a chimeric anti-CD20 antibody that results in depletion of B-cell lymphocytes. It is currently used in the treatment of a variety of autoimmune diseases, in addition to CD20-positive lymphomas. The use of rituximab in the treatment of the adult primary glomerular diseases has emerged recently, although not yet established as first-line therapy in international guidelines. In patients with steroid-dependent minimal change disease or frequently relapsing disease, and in patients with idiopathic membranous nephropathy (IMN), several retrospective and prospective studies support the use of rituximab to induce remission, whereas in idiopathic focal and segmental glomerulosclerosis (FSGS), the use of rituximab has resulted in variable results. Evidence is still lacking for the use of rituximab in patients with immunoglobulin A nephropathy (IgAN) and idiopathic membranoproliferative glomerulonephritis (MPGN), as only few reports used rituximab in these two entities. Randomized controlled trials (RCTs) are warranted and clearly needed to establish the definitive role of rituximab in the management of steroid-dependent and frequently relapsing minimal change disease, IMN, both as first-line and second-line treatment, and in MPGN. We await the results of an ongoing RCT of rituximab use in IgAN. Although current evidence for the use of rituximab in patients with idiopathic FSGS is poor, more RCTs are needed to clarify its role, if any, in the management of steroid-resistant or steroid-dependent FSGS.

Changing trends in pediatric renal biopsies: analysis of pediatric renal biopsies in national nephrology registry data

Renal biopsy is the gold standard method for determining the diagnosis, treatment, and prognosis in children with renal disease. This study aims to evaluate the histopathological features of pediatric renal biopsies obtained from the national nephrology registry in the last two decades. Data recorded in the Turkish Society of Nephrology Registry System (TSNRS) in 1991 as well as in between 2001 and 2010 were analyzed. A total of 3892 biopsies were recorded; with the least number in 1991 (total 103 biopsies from 17 centers) and the highest number in 2008 (total 654 biopsies from 23 centers). Glomerular diseases constituted the main group in the registry (62.64%), followed by systemic diseases (20.06%). Focal and segmental glomerulosclerosis (FSGS) and Henoch–Schönlein purpura (HSP) nephritis (IgA vasculitis) were the most common glomerular and systemic diseases, respectively. Overall prevalence of renal amyloidosis and membranous nephropathy (MN) was quite low (1.87% and 1.56%, respectively) in all periods. Compared to 1991, there was an increasing trend in the frequencies of certain disorders including hemolytic uremic syndrome (HUS), IgA nephropathy, and HSP nephritis; and there was a decrease in acute proliferative glomerulonephritis (GN) in 2008. As well as demonstrating the etiologies of renal diseases which can only be identified by renal biopsies, this study provides important information regarding the changing patterns of histopathological findings due to better management of pediatric renal diseases over the years in Turkey.