Nephrotic Syndrome In Adults Research Articles

Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults.

The recent success achieved with the use of B cell-depleting agents in some patients with minimal change nephrotic syndrome (MCNS) suggests an unexpected role for B lymphocytes in the pathogenesis of this immune-mediated glomerular disease. Nevertheless, no extensive B-cell phenotyping analysis has ever been performed in untreated adult patients soon after MCNS diagnosis. We investigated the distribution of the different B-cell subpopulations in 22 untreated adult patients with biopsy-proven MCNS [MCNS relapse (MCNS-Rel)]. We compared these data with those for 24 healthy controls, 13 MCNS patients in remission (with no specific treatment) and 19 patients with idiopathic membranous nephropathy (IMN). Patients with MCNS-Rel or IMN had higher proteinuria and lower serum albumin and gammaglobulin levels (P < 0.0001 for all comparisons) than MCNS patients in remission. Plasmablasts were the only B-cell subsets present at significantly higher levels in MCNS-Rel patients than in the patients of the other three groups (P < 0.05 for all comparisons). The lower albumin levels and higher proteinuria levels were positively correlated with the percentage of circulating plasmablasts (Spearman test's ρ = -0.54, P = 0.01 and ρ = 0.65, P = 0.002, respectively). Similarly, the increase of immunoglobulin M (IgM) and the decrease of IgG levels were significantly associated with the percentage of plasmablasts in MCNS-Rel patients (Spearman's ρ = 0.36, P = 0.01 and Spearman's ρ = -0.60, P = 0.01, respectively). Increased production of interleukin (IL)-21, IL-6 and B-cell activating factor (BAFF) in the serum of MCNS-Rel patients was found significantly correlated with the percentage of plasmablasts (ρ = 0.72, P = 0.0002, ρ = 0.49, P = 0.04 and ρ = 0.62, P = 0.009, respectively). An increase in the proportion of circulating plasmablasts seems to be a hallmark of untreated MCNS in adult patients. Further studies are required to more precisely determine the phenotype and functions of these cells.

A National Registry Study of Patient and Renal Survival in Adult Nephrotic Syndrome

IntroductionWe aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS).MethodsWe conducted a national registry–based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014–2017. We linked the Scottish Renal Registry to death certificate data. We performed survival and Cox proportional hazards analyses, accounting for competing risks of death and ESKD. We compared mortality rates with those in the age- and sex-matched general population.ResultsA total of 372 patients had primary NS; 150 had secondary NS. Over a median follow-up of 866 days, 110 patients (21%) died. In patients with primary NS, observed versus population 3-year mortality was 2.1% (95% CI 0.0%–4.6%) versus 0.9% (0.8%–1.0%) in patients aged <60 years and 24.9% (18.4%–30.8%) versus 9.4% (8.3%–10.5%) in those aged ≥60 years. In secondary NS, this discrepancy was 17.1% (5.6%–27.2%) versus 1.1% (0.9%–1.2%) in <60-year-olds and 49.4% (36.6%–59.7%) versus 8.1% (6.6%–9.6%) in ≥60-year-olds. In primary NS, cardiovascular causes accounted for 28% of deaths, compared with 18% in the general population. Eighty patients (15%) progressed to ESKD. Incidence of ESKD by 3 years was 8.4% (95% CI 4.9%–11.7%) in primary and 35.1% (24.3%–44.5%) in secondary NS. Early remission of proteinuria and the absence of early acute kidney injury (AKI) were associated with lower rates of death and ESKD.ConclusionsAdults with NS have high rates of death and ESKD. Cardiovascular causes account for excess mortality in primary NS.

The Diagnostic and Prognosis Potential of B Cell Repertoire in Membranous Nephropathy

Background: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, which is an autoimmune glomerular disease. In current clinical practice, the diagnosis is dependent on renal tissue biopsy. A non-invasive method for diagnosis and prognosis surveillance is urgent need for patients. Methods: From 2017 to 2018 we recruited 66 MN patients before any treatment and 11 healthy controls. We analyzed multiple aspects of immunoglobulin heavy chain (IGH) repertoire between MN patients and healthy controls using high-throughput sequencing. Findings: We found that the frequency of IGHV3-66 in post-therapy patients is significantly lower than pre-therapy remarkably. Moreover, we found that IGHV3-38 gene is significantly related to PLA2R, which is the common used biomarker. The most important discovery was that in the patient before treatment we identified 24 IGHV genes had the potential to predict the therapeutic effect. Interpretation: Our study further demonstrates IGH repertoire can be a non-invasive biomarkers potentially for prognosis prediction of MN. The landscape of circulating B-lymphocyte repertoires shed new light on MN detection and surveillance. Funding Statement: This work was funded by grants from the National Natural Science Foundation of China (81972335) and Guangdong Provincial Science and Technology Plan (2017A020215185) and Guangdong Province Natural Science Funds for Distinguished Young Scholar (2016A030306050) and Science and Technology Innovation Platform in Foshan City (FS0AA-KJ218-1301-0007) and “Guangdong Te Zhi Program” youth science and technology talent project (2015TQ01R462) and Medical Scientific Research Foundation of Guangdong Province of China (B2017006). Declaration of Interests: The authors declare no financial or commercial conflicts of interest. Ethics Approval Statement: This study was approved by the ethics committee of the Affiliated Foshan Hospital of Sun Yat-Sen University.

A case of minimal change disease after the administration of anti receptor activator of nuclear factor kappa B ligand (RANKL) monoclonal antibody: a case report

BackgroundMinimal change disease (MCD) is one of the causes of idiopathic nephrotic syndrome in adults. The pathogenesis of proteinuria in MCD has not been fully understood. Recently, it has been reported that the receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) may contribute to the podocyte biology in kidney diseases. Denosumab is a human anti-RANKL monoclonal antibody used to treat osteoporosis. Here we report a case of MCD after denosumab administration.Case presentationA 59-year-old male without any episodes of proteinuria was given denosumab to treat osteoporosis. Two weeks after its administration, he noticed a foamy urine and bilateral pretibial edema. Laboratory tests revealed that he had severe proteinuria (15g/g Cr), hypoproteinemia (4.0g/dL), and hypoalbuminemia (1.5g/dL). Based on the results, he was diagnosed with nephrotic syndrome. The proteinuria selectivity index was 0.05, indicating selective proteinuria. Renal biopsy showed minor glomerular abnormality with less tubulointerstitial damage, and electron microscopy showed extensive foot process effacement, indicating MCD. With all these results, glucocorticoid therapy of 50mg/day prednisolone was started. After 4weeks of treatment, the urinary protein level remains high (3.1g/g Cr). Prednisolone therapy was continued, and the levels of proteinuria decreased gradually to the range of partial remission (1.2g/g Cr) with another 7weeks of prednisolone treatment, but complete remission was not achieved.ConclusionsThis might be a case wherein RANKL inhibition is associated with the pathogenesis of MCD. Further studies will be needed to elucidate the causal relationship of RANK-RANKL signaling to the pathogenesis of MCD.

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Usefulness of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset minimal change disease.

BackgroundMinimal change disease (MCD) is a common form of nephrotic syndrome in adults. However, the molecular mechanism underlying the pathogenesis of MCD remains incompletely understood. In this study, we aimed to investigate the role of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset MCD patients.MethodsThe lymphocyte subsets, 34 cytokine levels of Th1/Th2/Th17, serum and urine concentrations of CD80, and expression of CD80 in glomeruli were analyzed in 28 cases (15 males and 13 females; average age: 34.1 years, age range: 18–56 years), including 10 patients with MCD in relapse, nine patients with MCD in remission and nine healthy controls.ResultsThere was no significant difference of CD3+CD4+ cells proportion among patients with MCD in relapse, MCD in remission and healthy controls (P = 0.802). The cytokine levels of GM-CSF and tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) in patients with MCD in relapse increased 1.5 times higher than those in remission. An evident increase in the excretion of urinary CD80 was found in patients with relapsed MCD compared with those in remission (598.4 ± 115.8 vs 81.78 ± 7.04 ng/g creatinine, P < 0.001) and healthy controls (598.4 ± 115.8 vs 67.44 ± 8.94 ng/g creatinine, P < 0.001). CD80 expression was observed in podocyte of MCD patient in relapse by immunofluorescence technique.ConclusionsThe cytokines GM-CSF and TRANCE are increased and the urinary CD80 levels are elevated in adult-onset MCD patients in relapse, indicating a disorder of Th1/Th2/Th17 balance and that the elevated excretion of CD80 may underlie the pathogenesis and development of adult-onset MCD.

Risk Factors of Acute Kidney Injury Complicating Adult Primary Nephrotic Syndrome

Objective To explore the risk factors of acute kidney injury(AKI)in adult primary nephrotic syndrome(PNS). Methods Totally 185 patients with PNS were divided into AKI group(n=51)and non-AKI group(n=134).The demographic data and clinical and histological features at admission were compared between the two groups.The independent risk factors for AKI were evaluated by Logistics regression analysis. Results In 51 PNS patients with AKI,the common pathological types of AKI included minor glomerular abnormalities(29.4%),IgA nephropathy(25.5%),and membranous nephropathy(17.6%).The incidences of renal tubular casts and epithelial vacuoles in the AKI group were significantly higher than those in the non-AKI group(P=0.004,P=0.030).Males were more likely to suffer from AKI than females(P=0.000).Patients in AKI group had significantly lower albumin level(P=0.015)and higher levels of random urine protein,serum creatinine,uric acid,urea nitrogen,and triglyceride than non-AKI group(P=0.030,P=0.000,P=0.000,P=0.000,and P=0.006),and polyserous and oliguria occurred more often in the AKI group(P=0.000,P=0.002).The AKI group had significantly higher incidences of high blood pressure and infections(P=0.035,P=0.000).Multivariate logistics regression analysis showed albumin(<25 g/L),serum creatinine(>96 μmol/L),urea nitrogen(≥6.8 mmol/L),uric acid(≥400 μmol/L),diabetes,infection,and renal tubular casts were the independent risk factors for AKI. Conclusions AKI complicating PNS is associated with a variety of factors.Its independent risk factors include the levles of albumin,serum creatinine,urea nitrogen,and uric acid,diabetes,infections,and renal tubular casts.

CircZNF609 is involved in the pathogenesis of focal segmental glomerulosclerosis by sponging miR-615-5p

As a set of distinct syndromes, focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome with diverse mechanisms. We recently found that expression of the circular RNA circZNF609 is increased in renal biopsies of lupus nephritis patients. In the present study, we aimed to determine whether circZNF609 participates in the pathogenesis of FSGS in mice given Adriamycin. In FSGS mice, circZNF609 was upregulated while miR-615-5p was downregulated in FSGS mice analyzed by qPCR and fluorescence in situ hybridization (FISH). Expression of podocyte proteins Wilms tumor 1 (WT1) and podocin were decreased, while expression of collagen 1 (COL1) and transforming growth factor-beta1 (TGF-β1) were increased on Western blotting. Renal circZNF609 levels were positively correlated and miR-615-5p levels were negatively correlated with the degree of podocyte injury and renal fibrosis. Importantly, circZNF609 and miR-615-5p co-localized to glomeruli and tubules on FISH. Perfect match seeds were found between circZNF609 and miR-615-5p and COL1 mRNA, leading us to explore mechanisms of circZNF609 in bovine serum albumin (BSA) stimulating HK-2 cells, which model the toxicity of proteinuria on tubular cells. In vitro studies, circZNF609 increased and miR-615-5p decreased after BSA treatment and were negatively correlated with each other. COL1 and TGF-β1 were both upregulated and negatively correlated with miR-615-5p. Lastly, circZNF609 expression increased in glomeruli and tubules of FSGS patient renal biopsies. We conclude that circZNF609 may play an important role in FSGS by sponging miR-615-5p.

New Aspects of Pathogenesis and Treatment of Membranous Glomerulopathy After the MENTOR Study

Membranous nephropathy (MN) is the major cause of nephrotic syndrome in adults, accounting for 20% of cases with an annual incidence of 1 per 100,000 population. In the past 10 years, the role of podocytes has been identified. Environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes, including PLA2R, THBS1, and NELL1, which become targets of specific autoantibodies with subsequent complement activation. The discovery of these mechanisms has opened a new horizon in the treatment of MN, and novel drugs are available with more specific mechanisms of action. Rituximab, a monoclonal antibody directed against CD20 expressed on B lymphocytes, has been used in several trials and appears to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial). The recently published results of the MENTOR trial documented the superior efficacy of rituximab in patients observed for up to 24 months. In MN, the concept of targeting disease control has introduced novel therapies with specific blocking mechanisms, such as belimumab; nonspecific blocking mechanisms, such as those against adrenocorticotropic hormone; and new therapeutic options, such as ofatumumab, bortezomib, and eculizumab, which have recognised the pathological processes involved in the glomerular diseases.

Modern view on treatment of membranous nephropathy

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Since the moment of animal model creation and the recognition of podocytes damage as a key mechanism of MN development, the identification of antigens, first of all the phospholipase A2 receptor (PLA2R), and the development of methods of PLA2R autoantibodies detection and its monitoring opened a new era in the idiopathic MN (iMN) diagnosis, treatment and prognosis evaluation. MN continues to be actively studied in the new millennium, since a number of aspects of its pathogenesis still need to be clarified, and there is still no clear opinion on the iMN treatment optimal approach. Comprehensive clinical and serological assessment of patients with iMN can be the key to individual choice of treatment protocols. In patients with aPLA2R-positive iMN, the predictor of disease remission is the aPLA2R titer decrease or aPLA2R disappearance in the blood serum, and disease relapse is associated with the aPLA2R appearance ore increase of aPLA2R titer in the circulation. Studies which were conducted by today (GEMRITUX, MENTOR, STARMEN, NICE, etc.) confirmed the acceptable safety profile and effectiveness of iMN therapy by anti-CD20 monoclonal antibodies (rituximab): more than half of of iMN patients had remission of nephrotic syndrome or proteinuria decrease, remissions in anti-CD20 monoclonal antibodies treated patients were longer compared to traditional therapy. The obtained data allows us to consider rituximab and anti-CD20 antibody therapy of a new generation not only as an alternative to the more toxic treatment with cyclophosphane and calcineurin inhibitors, but as an independent promising direction of therapy for patients with IMN, which completely changes the paradigm of treatment of this glomerulopathy.

The matrix of SDS integrated with linear hydrophilic polymer for resolution of high- and low-molecular weight hyaluronic acids in MEKC

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, when not effectively treated. The aim of this study was to discover new targets for the diagnosis and treatment of MN. A reliable mouse model of MN was used by the administration of cationic bovine serum albumin (cBSA). Mice with MN exhibited proteinuria, histopathological changes, and accumulation of immune complexes in the glomerular basement membrane. Label-free proteomics analysis was performed to identify changes in protein expression, and the overexpressed proteins were evaluated. There were 273 proteins that showed significantly different expression in mice with MN, as compared to the controls. String analysis showed that functions related to cellular catabolic processes were downregulated in MN. Among the differentially expressed proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2) were upregulated in the kidneys of mice with MN, as demonstrated by immunohistochemistry (IHC), and this upregulation was observed in both the tubular cells and glomeruli. Both shRNA-mediated knockdown of PHB1 or PHB2 inhibited tumor suppressor p53 expression and significantly promoted podocyte proliferation. In addition, both PHB1 and PHB2 were responsible for cBSA-induced cytotoxicity. Microarray analysis further revealed that the upregulation of PHB1 and PHB2 may be due to a blockage of proteasome activity. These data demonstrate that the upregulation of PHB2 is involved in cBSA-mediated podocyte cytotoxicity, which may lead to MN development. © 2019

Estimated GFR Trajectories in Pediatric and Adult Nephrotic Syndrome: Results From the Nephrotic Syndrome Study Network (NEPTUNE)

Rationale & ObjectiveSurrogate outcomes for end-stage kidney disease often assume linear changes, which may not reflect true estimated glomerular filtration rate (eGFR) trajectories. This study’s objective was to characterize nonlinear eGFR trajectories in nephrotic syndrome.Study DesignObservational cohort study.Setting & ParticipantsNephrotic Syndrome Study Network (NEPTUNE) is a multicenter study of adult and pediatric patients with proteinuria enrolled at clinically indicated kidney biopsy or initial presentation of disease (pediatric only).PredictorsPatient demographic, clinical, and pathology variables at study enrollment and follow-up time.OutcomeeGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (patients ≥ 18 years old) or modified Chronic Kidney Disease in Children Study–Schwartz (patients < 18 years) formulas. The probability of nonlinearity (PNL) was calculated for individual eGFR trajectories.Analytical ApproachAssociations between predictors and PNL were assessed using multivariable linear regression.Results453 patients with ≥3 eGFR measurements and 1 or more year of follow-up were included (median follow-up, 3.6 years). Median PNL was 0.052; 56% and 16% had PNL < 10% and >50%, respectively. In both adults and pediatric patients, higher baseline eGFR was associated with higher PNL, whereas longer follow-up time was associated with lower PNL. Higher urine protein-creatinine ratio and steroid use were also associated with higher PNL in adults. Higher percentages of tubular atrophy and foot-process effacement were associated with lower and higher PNLs, respectively, in adults.LimitationsRelatively short follow-up time, inability to assess acute kidney injury events, and variable eGFR measurement frequency across patients.ConclusionsAlthough increasing follow-up time resulted in more linear trajectories, nonlinear eGFR trajectories were common in this cohort. Future studies in nephrotic syndrome should consider novel outcomes that do not rely on linearity assumptions.

P0417THE ABSENCE OF C3 DEPOSIT IN MEMBRANOUS NEPHROPATHY IS ASSOCIATED WITH SPONTANEOUS REMISSION

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes. Method We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD). Results A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)]. Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008). Conclusion Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive. These results would support the theory that complement activation in this entity can play an important role. It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.

P0452GLYCOSURIA IN MEMBRANOUS NEPHROPATHY: AN UNDERESTIMATED MARKER?

Abstract Background and Aims Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. Some studies have suggested that glycosuria is present in the most severe cases of MN and this finding may be associated with tubular injury caused by the overload of filtered proteins. The aim of this study was to evaluate the association between glycosuria in MN and severity and prognosis of the disease. Method We conducted a 36-month retrospective cohort study with all patients diagnosed in the last 10 years in our centre with primary MN confirmed by renal biopsy. Data collection was made from patients’ charts. Patients were divided in two groups according to their glycosuric status at the diagnosis. Exclusion criteria: patients with diabetes and glucose intolerance, use of SGLT2 inhibitors, transplant kidney patients and secondary MN. Results We studied 27 patients with primary MN. Four patients (14.8%) presented glycosuria at the time of diagnosis. Glycosuric and non-glycosuric groups had comparable demographic data. We found that glycosuric patients had higher baseline albuminuria (10.7±8.6 vs 4.6±4.1 g/g, p=0.029) and lower estimated glomerular filtration rate (eGFR) (39.2±24.6 vs 75.2±30.7 ml/min/1.73m2, p=0.037). We also found that patients with glycosuria had higher interstitial fibrosis and tubular atrophy (IFTA) (33.8%±21.4 vs 10.7%±17.1, p=0.035) but no differences in the percentage of glomerular sclerosis. There were no differences between groups in serum albumin, haemoglobin or therapy. At the end of the follow-up period there was no difference in eGFR decline rate (ml/min/year), 3-year eGFR, 3-year albuminuria and 3-year chronic kidney disease stage 5D incidence. Conclusion Prevalence of glycosuria in primary MN is approximately 15%. Its presence at the time of diagnosis was associated with more severe clinical and histological markers: lower eGFR, higher albuminuria and higher IFTA. However, we did not find association between glycosuric status at diagnosis and disease progression. Prospective, bigger and longer studies are needed to evaluate these questions.

243 Causes of Primary Nephrotic Syndrome in Adults According to Race: An Update

243 Causes of Primary Nephrotic Syndrome in Adults According to Race: An Update

Nephrotic Syndrome, Steroid Therapy andAssociated Cardiovascular Risk; is AnnexinA5 a Biomarker?

Aims: Thromboembolism is one of the major complications affecting nearly 25% of Nephrotic Syndrome patients. Annexin A5 is a calcium dependent positively charged glycoprotein with potent anti-coagulant activity. Previous studies have reported elevated Annexin A5 levels immediately after Myocardial Infarction and its plasma level reflected the severity of myocardial damage. Cardiovascular abnormalities during Nephrotic Syndrome and the role of Annexin A5 as a cardiac risk factor have been studied here. Methods: 72 adult Nephrotic Syndrome patients were studied for the blood levels of Annexin A5, lipid profile, Atherogenic Index and LDL/Annexin A5 ratio. The results were compared to age and sex matched healthy controls. The patients started on steroid therapy and they were followed up for a period of ten months. 27 patients attained remission during the time period and all the biochemical assays were repeated. Results: Nephrotic Syndrome patients exhibited dyslipidemia along with elevated Annexin A5, Atherogenic Index, Total Cholesterol/HDL ratio and LDL/Annexin A5 ratio. Annexin A5 was not correlated to cardiovascular risk but LDL/Annexin A5 ratio positively correlated with Atherogenic Index. Dyslipidemia and elevated atherogenic risk persisted in patients who attained remission. Conclusions: Cardiovascular risk persisted during remission even after effective steroid therapy. LDL/Annexin A5 can be considered as a cardiovascular risk factor in Nephrotic Syndrome patients.

The Landscape and Prognosis Potential of the T-Cell Repertoire in Membranous Nephropathy.

Membranous nephropathy (MN), a common pathological type of adult nephrotic syndrome, is an antibody-mediated kidney disease. It is widely accepted now that MN is an immune-related disease that involves the whole immune system. In this study, we analyzed the T-cell receptor beta chain (TCRβ) repertoire of the circulating T lymphocytes of MN patients and healthy controls using high-throughput sequencing. We compared multiple aspects of the TCRβ repertoire, including diversity and the Vβ and Jβ genes between MN patients and healthy controls, and we found that the diversities within the VJ cassette combination in the peripheral blood of MN patients were lower than in the healthy controls. We also found the TCRβ repertoire similarity between pre- and post-therapy could reflect the clinical outcome, and two Vβ genes in pre-therapy had the potential to predict the therapeutic effect. These findings indicated the potential of the TCRβ repertoire as non-invasive biomarkers for the prognosis prediction of MN. The characteristics of circulating T-lymphocyte repertoires shed light on MN detection, treatment, and surveillance.

Outcomes of renal transplantation in adult patients with primary focal segmental glomerulosclerosis: a single-centre experience over 5 decades

Primary focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome in adults and children and often leads to end-stage kidney disease.[1][1] The aetiology may be immune mediated or due to genetic mutations affecting glomerular proteins. Primary FSGS frequently recurs following

A Profile of Minimal Change Nephropathy in Adults at the Witwatersrand Academic Complex (2001–2010)

Abstract Background: Minimal change nephropathy (MCN) is amongst the commonest causes of nephrotic syndrome worldwide, accounting for up to 15% of cases of primary nephrotic syndrome in adults. Limited data is available in African subjects. Methods: We retrospectively reviewed the demographic, clinical profile and treatment outcomes of adult patients presenting with primary MCN at the Witwatersrand Academic Complex between 2001 and 2010. Results: Forty-seven cases of MCN (2.9%) were diagnosed in 1618 patients undergoing native kidney biopsy. The patients with MCN were predominantly of Black race (83%), the male-to-female ratio was 1.04:1 and the mean age was 31.8 ± 12.1 years. Records of treatment and outcomes were available for 28 patients, all of whom received initial corticosteroid therapy (average dose of prednisone 0.8 mg/kg/day). The mean duration of steroid therapy was 24.8 ± 19.0 months. About 57.1% of patients achieved remission with no further relapse and 39.2% had probable steroid resistance. The mean time to relapse was 27.8 ± 19.4 months with 83% of patients relapsing within 48 months. The mean time to relapse was significantly longer in males (39.3 ± 17.5 months) compared to females (18 ± 16.9 months) (P = 0.09). Conclusion: MCN is rare amongst adult Black Africans but should be considered in the differential diagnosis of nephrotic syndrome. The disorder in these patients may be less responsive to corticosteroids and a longer course of therapy may be required to induce remission. Males may be more likely to remain in remission for a longer period.

SAT-387 B LYMPHOCYTE SUBSET CHANGES IN PRIMARY MEMBRANOUS NEPHROPATHY

Primary membranous nephropathy (PMN) is the most common cause of nephrotic syndrome in adults. Rituximab a chimeric monoclonal anti-CD20 antibody has been supposed to eliminate autoantibody-producing B cells via direct signaling, complement-mediated cytotoxicity (CMC), and antibody-dependent cellular cytotoxicity. According to the fact that a wide range of B lymphocytes may carry this marker, we aimed to identify which subset is more(or less) frequent in PMN patients and which one is more affected by rituximab administration. Three groups were enrolled, included a healthy control group and two patient groups having the clinical, laboratory, and pathological diagnostic criteria of PMN, comprising either patients on standard treatment or patients on standard treatment plus rituximab. The latter group was studied just before receiving rituximab (pre-rituximab) and two months later (post rituximab). Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-hypaque (inno-train, Germany) gradient. Afterward, cells stained with mouse antihuman CD19-Cy5-conjugated antibody (Cytognos, Spain), mouse antihuman CD24-PE-conjugated antibody (Cytognos, Spain), and mouse antihuman CD38-FITC-conjugated antibody (Cytognos, Spain). In post-rituximab analysis, CD19+ cell count showed notable reduction (P value = 0.003) B CD19+CD24+CD38- cells, representing the memory B cell population, did not show any significant difference between healthy controls and patients. Furthermore, the count of these cells did not decrease significantly two months after rituximab administration. The subset of CD19+CD24-CD38+ B lymphocytes, a class of naïve/mature lymphocytes with normal function, was significantly higher in the control group than in standard treatment patients (P value = 0.01). However, no statistically significant difference was found in CD19+CD24-CD38+B lymphocytes neither between the rituximab and control groups nor between pre-rituximab and post-rituximab patients. Left Panel:CD19+CD24highCD38high cells frequency (percentage in CD19+ cells) in four groups of standard treatment (steroid + immunosuppressive), pre-rituximab (steroid + immunosuppressive + rituximab), post-rituximab (two months after RTX administration), and healthy controls; *P < 0.05 **P < 0.001 ***P < 0.0001 The number of regulatory B cells decreased in both standard treatment and rituximab-receiving PMN patients and the proportion of naïve/mature B-lymphocytes was lower in the former group. Moreover, the memory B cells count did not reduce significantly two months after rituximab administration. Hence, it might be the best choice to target the memory B cell subset in immunosuppressive therapy while avoiding the Breg or naïve/mature B lymphocyte depletion to obtain more favorable sustained outcomes.