Nephrotic Syndrome In Adults Research Articles

Rituximab for Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome in Adults: A Retrospective, Multicenter Study in Spain.

Patients with difficult-to-treat idiopathic nephrotic syndrome (INS), steroid-dependent nephrotic syndrome (SDNS), or frequently relapsing nephrotic syndrome (FRNS) require long-term immunosuppressive therapy. Rituximab offers an alternative treatment for patients with disease that has not responded to multiple therapies. Our objective was to determine the efficacy and safety of rituximab in adult patients with difficult-to-treat (SDNS or FRNS) INS. We performed a retrospective multicenter study that included 50 adults with difficult-to-treat INS in six Spanish centers. All patients were treated with steroids in combination with another immunosuppressant: 28 patients received rituximab as the additional treatment (rituximab group), and the other 22 patients not treated with rituximab served as the control group. Of the patients treated with rituximab, 23 (82%) experienced complete remission, 20 (71%) had no relapses after receiving rituximab, and 13 (46%) did not receive any immunosuppressant. Of those in the control group, 14 (63%) experienced complete remission, including eight without immunosuppressants (29%). The rituximab group experienced highly significant reductions in total number of relapses per year (p < 0.001), proteinuria (p = 0.03), steroid doses (p = 0.002), and tacrolimus doses (p = 0.001). Mean follow-up after rituximab was 31±26 months (range 8-86). The need for steroids and other immunosuppressants to achieve sustained remission was lower in the rituximab group than in the control group. Rituximab treatment was safe and well tolerated. It effectively reduced the incidence of relapses and need for maintenance immunosuppressive therapy in adults with difficult-to-treat INS.

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.

Traitement de la glomérulonéphrite extramembraneuse

Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, evolving to 30 % end-stage renal disease after 10 years, in the absence of specific treatment. In 2009, the M-type phospholipase A2 receptor (PLA2R), a podocyte membrane glycoprotein, was identified as the first autoantigen involved in more than 70 % of primitive membranous nephropathy. Many studies have reported that high titers of PLA2R antibodies are correlated with a lower risk of spontaneous or immunosuppressant-induced remission, a higher risk of nephrotic syndrome and of progression to end-stage renal disease. Treatment is still challenging and controversial because of potential toxicity and lack of a reliable prognosis marker. In the past, the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines recommended immunosuppressive therapies as steroids and alkylating agents or cyclosporine in patients with persistent nephrotic syndrome or impaired renal function. Recent studies and one multicentric randomised controlled trial brought clear evidence to support the use of rituximab in these patients: rituximab regimen induces immunological and clinical remission in patients with membranous nephropathy, with a high safety profile. However, they have provided important data on the impact of PLA2R antibodies assessment as a prognostic biomarker in patients with membranous nephropathy. The next step will be the integration of this biomarker in KDIGO guidelines and the recommendation of rituximab as a first line immunosuppressive therapy in patient with persistent nephrotic syndrome due to membranous nephropathy.

Intravenous cyclophosphamide and oral prednisolone is a safe and effective treatment option for idiopathic membranous nephropathy.

BackgroundIdiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults. A proportion of patients will experience spontaneous remission and the decision to offer immunosuppression is guided by the presence of adverse prognostic features. Data relating to the efficacy of different immunosuppressive protocols is lacking, in particular there are little data available on the efficacy or benefits of an intravenous (IV) cyclophosphamide-based regimen. Since 2010, our unit has been using a treatment regimen based on IV cyclophosphamide and oral prednisolone for patients with IMN associated with adverse prognostic features. The outcomes of these patients were compared with a historic cohort of similar patients who did not receive immunosuppressive therapy.MethodsBetween January 2010 and 2014, a total of 41 patients were treated with pulse IV cyclophosphamide and oral prednisolone. The historical comparator group included 47 similar patients diagnosed between 2006 and 2010 who did not receive immunosuppression. Two-year follow-up data were collected. The primary outcome measure was time to remission of nephrotic syndrome (defined as normalization of serum albumin). Secondary outcomes included rate of progression of kidney disease as well as incidence of treatment-related adverse events.ResultsAs compared with supportive care alone, treatment with IV cyclophosphamide and oral prednisolone was associated with a significantly higher number of patients achieving remission. Within 18 months of therapy, 74% of treated patients had achieved a normal serum albumin level. Though there was a trend towards a more rapid decline in estimated glomerular filtration rate in the untreated cohort, this did not reach statistical significance. The IV cyclophosphamide-based regimen was well tolerated, with few significant treatment-associated side effects.ConclusionIV cyclophosphamide is a safe and effective treatment for IMN.

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.

Role of Immunofluorescence in Adult Onset Nephrotic Syndrome-A Study in a Tertiary Care Centre of Western India.

Study of renal Immunofluorescence (IF) is an ancillary but essential technique in evaluation of renal biopsies in glomerulopathies and also it enlightens on the pathogenesis of nephrotic syndrome. To determine the role of IF in evaluating definite subtyping and diagnosis of adult onset nephrotic syndrome and attempting clinicopathological correlation. A total of 52 patients of adult onset nephrotic syndrome were evaluated clinically and with pertinent investigations; and subjected to USG guided percutaneous renal biopsy which was processed and stained for light microscopy and for immunofluorescence by direct method (DIF) using antibodies against IgG, IgM, IgA and C3. The predominant age group affected was 18-47 years (78.85%). Male:female ratio was 1:0.63. The most frequent glomerular lesion encountered was Focal Segmental Glomerulosclerosis (FSGS, 36.54%) followed by lupus nephritis (26.92%) and IgA nephropathy (9.62%). The most common glomerular lesion in males was FSGS and that in females was lupus nephritis. DIF was mainly coarsely granular whenever present. One case of lupus nephritis and diabetic nephropathy, showed non specific IF. It was negative in all cases of FSGS, Minimal Change Disease (MCD) and renal amyloidosis. The IF helped in differentiating eight cases that were normal on light microscopy as IgA nephropathy (n=5) and authentic MCD (n=3). It helped in endorsing 19 cases of FSGS to be a progression of MCD. It was also of help in sub-typing all cases of Membranoproliferative Glomerulonephritis (MPGN) (n=3) as MPGN-Type I. IF was of great help in diagnosing exact type of glomerulopathy in adult onset nephrotic syndrome and provided insight in its pathogenesis.

EVOLUTION IN THE UNDERSTANDING OF IDIOPATHIC MEMBRANOUS NEPHROPATHY PATHOGENESIS: FROM EXPERIMENTAL MODELS TO THE CLINIC

Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. This review describes a 60-year history of MN study and represents an evolution in the understanding of its pathogenesis from experimental models to the clinic. Due to the development in 1959 of an MN animal model (active and passive Heymann's nephritis) the renal autoantigen podocyte-related protein megalin was identified. Experimental studies confirmed that the immune deposits consisting of megalin with circulating antimegalin antibodies are formed in situ. That leads to the complement activation providing with the membrane attack complex formation in the subepithelial space which causes a sub-lethal podocyte injury with a reorganization of their actin cytoskeleton and a dissociation of slit diaphragm proteins. As the result, the permeability of the filtration barrier increases leading to the proteinuria. Thus, the understanding of an idiopathic MN pathogenesis evolved from an immune complex-mediated damage into a podocytopathy so the pathway for the other podocyte-related antigens search was opened. Mechanisms of podocytes damage were considered to be the leading ones in the human idiopathic MN development. Nevertheless, the searching for antigenic targets different from the megalin was continued for many years, as human podocytes do not express this protein. In the first decade of the 21st century such autoantigens as neutral endopeptidase, M-type phospholipase A2 receptor, and thrombospondin type-1 domain-containing 7A were identified. Furthermore, the leading role of autoantibodies directed against these podocyte targets was confirmed. New knowledge formed the basis for modern diagnostics and treatment methods of MN.

Calcineurin Inhibitors in the Treatment of Primary Focal Segmental Glomerulosclerosis

Purpose of review:Primary focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in adults. Glucocorticoids have been evaluated in the treatment of primary FSGS in numerous retrospective studies. Evidence suggesting a role for including calcineurin inhibitors (CNIs) in early therapy remains limited. The aim of this study was to systematically review the literature examining the efficacy of CNIs in the treatment of primary FSGS both as first-line therapy and as an adjunctive agent in steroid-resistant patients, with respect to remission in proteinuria and renal survival.Sources of information:PubMed and EMBASE were searched from inception to August 2014 for prospective controlled trials, and case-control and cohort studies.Findings:After systematically applying our inclusion criteria, a total of 152 titles and abstracts were identified. Six randomized controlled trials and 2 cohort studies were reviewed. Three randomized controlled trials compared CNIs with placebo or supportive therapy. The pooled relative “risk” of proteinuria remission associated with cyclosporine was 7.0 (95% confidence interval, 2.9-16.8) compared with placebo/supportive therapy. There was very low heterogeneity among these studies with an I-squared of 0%. Three studies compared CNIs with another immunosuppressive agent. All prospective trials were conducted in patients with primary FSGS deemed steroid-resistant.Limitations:The relatively small number of included studies and their heterogeneity with respect to treatment protocols, and possible publication bias, limit conclusions drawn from this systematic review.Implications:The efficacy of CNIs has been evaluated in steroid-resistant primary FSGS patients. There is no evidence supporting their role as first-line therapy. Further studies are needed to determine this role.

Recent Progress in Deciphering the Etiopathogenesis of Primary Membranous Nephropathy.

Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50–100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up. Immunologic remission precedes reduction of proteinuria by months. Pretransplant evaluation of PLA2R antibodies is warranted to predict recurrence of disease following renal transplantation. Several risk alleles related to the PLA2R1 gene and within the HLA loci have been identified, whereas epitope spreading of PLA2R may predict treatment response. More recently, thrombospondin type 1 domain-containing 7A (THSD7A) antibodies have been discovered in primary MN. Several other rare antigens have been described, including antibodies against neutral endopeptidase as a cause of antenatal MN and circulating cationic bovine serum albumin as an antigen with implications in childhood MN. This review focuses on the progress with a special focus on diagnostic accuracy, predictive value, and treatment implications of the established and proposed antigens.

Membranous nephropathy: thinking through the therapeutic options.

Idiopathic membranous nephropathy (IMN) remains the most common cause of the nephrotic syndrome in adults and one of the leading identifiable causes of end-stage kidney disease. Prior to considering the best approach to treatment, three important components need to be considered. First, the natural history of the typical membranous patient today; second, the importance of identifying the causative factors; and third, the integration of the current data on the known autoantibody/antigen systems involved in IMN into the diagnosis and management of the patient. Combining this with information on the known indicators associated with a poor prognosis plus new data on surrogate markers that provide important clues that the treatment plan is correct has provided us with a more secure platform for choosing the right treatment for each patient. This already provides a more rational and precise approach to the use of our current therapeutic options. Even today, we can slow disease progression and in the future new approaches and new therapies are likely to lead to prevention of progression or even reversal of the injury in IMN, thereby leading to improved quality of life of our patients.

Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome.

The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS)) since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs) in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications.

Influence of acute kidney injury on the time to complete remission in adult minimal change nephrotic syndrome: a single-centre study.

Acute kidney injury (AKI) is a common complication of minimal change nephrotic syndrome (MCNS), particularly in adults. We evaluated the prevalence of AKI at the onset of adult MCNS and analyzed the influence of AKI on the duration of achieving complete remission (CR). A retrospective, single-centre, dynamic cohort study was conducted with biopsy-proven, first-onset, adult MCNS patients treated with corticosteroids. Fifty-three consecutive patients diagnosed with MCNS from January 2000 to April 2014 were enrolled. Age, gender, daily urinary protein excretion, and serum creatinine levels were measured. To evaluate AKI during induction, we used the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI and judged AKI stage according to the fluctuations in serum creatinine levels during the first 4 weeks of starting corticosteroid therapy. Twenty patients (37.7%) met the AKI criteria and all 53 patients achieved CR within 1 year. Kaplan-Meier analysis showed that the median time to CR was significantly longer in patients with AKI than in patients without AKI. Cox proportional hazard analysis showed that the hazard ratio (HR) associated with the presence of AKI for achieving CR within 4 weeks was 0.36 after adjustment for age, gender, serum albumin, daily urinary protein excretion, hypertension, administration of 25% albumin, and methylprednisolone pulse therapy. A graded association was also observed between AKI stage and HR for achieving CR. The prevalence of AKI is high in adult patients with MCNS during induction therapy. AKI is an independent factor that delays the time to CR.

Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis.

BackgroundVariability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis.MethodsParticipating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy.ResultsWe studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients.ConclusionsWe found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.

Treatment of membranous nephropathy with mizoribine: A control trial

AimMembranous nephropathy remains the most common form of the nephrotic syndrome in adults. The combination therapy of steroid and cyclophosphamide has routinely been used. Although satisfactory therapeutic efficacy can be achieved, its side effect on reproductive system has been a concern. Mizoribine is an imidazole nucleoside and a novel immunosuppressant that has been used to treat other immune-related diseases. In this study we examine if the combined regimen of mizoribine and steroid would be advantageous over the use of cyclophosphamide and steroid in treating adult membranous nephropathy. MethodsThere were total of fifty-five patients completed the study. These patients had membranous nephropathy with presentation of proteinuria. They were treated with combined regimen of mizoribine and steroid or cyclophosphamide and steroid, and were followed up for one year to monitor safety and efficacy. ResultsWe found the condition of proteinuria was significantly improved in the mizoribine group and the improvement was comparable to the patients treated with cyclophosphamide. These patients also exhibited an increase of serum albumin. There was no significant increase of adverse events with the use of mizoribine-based therapy, suggesting the tolerability of mizoribine in adult patients with membranous nephropathy. ConclusionIn conclusion, the results indicated the satisfactory safety and efficacy of the combination regiment of mizoribine and steroid in treating adult patients with membranous nephropathy.

Urinary sediment mRNA level of extracellular matrix molecules in adult nephrotic syndrome

BackgroundGlomerular and tubulointerstitial fibrosis play important roles in the progression of chronic kidney disease. We determine whether urinary mRNA levels of extracellular matrix proteins reflect the degree of kidney fibrosis and predict renal function decline in adult nephrotic patients. MethodsWe studied 56 adult nephrotic patients and 20 controls. Urinary mRNA levels of collagen I A1 chain (COL1A1), collagen IV A3 chain (COL4A3), and fibronectin were measured. ResultsUrinary sediment mRNA levels of COL1A1 and fibronectin were significantly higher in nephrotic patients as compared to the control, irrespective to the pathological diagnosis. Urinary COL1A1 mRNA level correlates with proteinuria, glomerular and interstitial fibrosis, and inversely with estimated glomerular filtration rate (GFR); urinary fibronectin mRNA level significantly correlates with glomerular and interstitial fibrosis, and inversely with estimated GFR. After 42.4±12.6months follow-up, the rate of GFR decline inversely correlates with urinary mRNA level of COL1A1 (r=−0.273, p=0.044). Multivariate analysis confirmed that urinary COL1A1 mRNA level is an independent predictor of serum creatinine doubling or progressing to end stage renal disease; for each 10-fold increase in urinary COL1A1 mRNA level, there is 15.1% excess in risk (95% confidence interval, 1.9% to 30.4%, p=0.022). ConclusionsUrinary COL1A1 mRNA level is elevated in nephrotic patients irrespective to the pathological diagnosis, and it correlates with proteinuria, histological scarring, and inversely with renal function. Furthermore, urinary COL1A1 mRNA level predicts renal function loss during follow-up. Our results suggest that urinary COL1A1 mRNA level may be used for risk stratification of adult nephrotic syndrome.

Genetic risk variants for membranous nephropathy: extension of and association with other chronic kidney disease aetiologies.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Previous genome-wide association studies (GWAS) of 300 000 genotyped variants identified MN-associated loci at HLA-DQA1 and PLA2R1. We used a combined approach of genotype imputation, GWAS, human leucocyte antigen (HLA) imputation and extension to other aetiologies of chronic kidney disease (CKD) to investigate genetic MN risk variants more comprehensively. GWAS using 9 million high-quality imputed genotypes and classical HLA alleles were conducted for 323 MN European-ancestry cases and 345 controls. Additionally, 4960 patients with different CKD aetiologies in the German Chronic Kidney Disease (GCKD) study were genotyped for risk variants at HLA-DQA1 and PLA2R1. In GWAS, lead variants in known loci [rs9272729, HLA-DQA1, odds ratio (OR) = 7.3 per risk allele, P = 5.9 × 10-27 and rs17830558, PLA2R1, OR = 2.2, P = 1.9 × 10-8] were significantly associated with MN. No novel signals emerged in GWAS of X-chromosomal variants or in sex-specific analyses. Classical HLA alleles (DRB1*0301-DQA1*0501-DQB1*0201 haplotype) were associated with MN but provided little additional information beyond rs9272729. Associations were replicated in 137 GCKD patients with MN (HLA-DQA1: P = 6.4 × 10-24; PLA2R1: P = 5.0 × 10-4). MN risk increased steeply for patients with high-risk genotype combinations (OR > 79). While genetic variation in PLA2R1 exclusively associated with MN across 19 CKD aetiologies, the HLA-DQA1 risk allele was also associated with lupus nephritis (P = 2.8 × 10-6), type 1 diabetic nephropathy (P = 6.9 × 10-5) and focal segmental glomerulosclerosis (P = 5.1 × 10-5), but not with immunoglobulin A nephropathy. PLA2R1 and HLA-DQA1 are the predominant risk loci for MN detected by GWAS. While HLA-DQA1 risk variants show an association with other CKD aetiologies, PLA2R1 variants are specific to MN.

Treatment pattern in patients with idiopathic membranous nephropathy-practices in Sweden at the start of the millennium.

BackgroundIdiopathic membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults and may result in end-stage renal disease (ESRD). In this retrospective study, we describe the outcomes and treatment patterns of patients with idiopathic MN in six nephrology clinics in the western part of Sweden.MethodsSeventy-three consecutive patients with biopsy-proven MN in the years 2000–12 were classified as idiopathic, i.e. secondary forms were excluded. The patients were followed retrospectively for a mean period of 83 months and clinical data were collected through the medical files.ResultsA high proportion (88%) of the patients received supportive treatment with angiotensin-converting enzyme inhibition, angiotensin receptor blockade and/or statins. At the end of follow-up, 43 patients were in complete remission, 12 in partial remission, 10 patients had developed ESRD and 8 patients had on-going proteinuria. Fifty-one per cent of the patients received immunosuppressive therapy and the choice of therapy varied between and within the clinics. There was a tendency to initiate specific treatment at an early point instead of awaiting a possible spontaneous remission (21% of the patients), and non-recommended therapy such as corticosteroids only was used in a high proportion of these cases (47%).ConclusionsEven though the treatment recommendations in idiopathic MN have not changed the last decade, the question of whom and when to treat seems to lead to uncertainty. Recent studies have presented promising results supporting the PLA2R antibody the predictive marker needed for this patient group. The diverse treatment approach presented in this study might have resulted in a worse outcome than expected. Hopefully, unnecessary exposure to immunosuppressive therapy or delayed treatment can be avoided through better support, education and treatment forums, and thus result in an improved outcome.

Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms.

Membranous nephropathy is a frequent cause of nephrotic syndrome in adults. In most patients, it appears as a primary renal disease but in about 20% of cases membranous nephropathy is associated with systemic conditions such as systemic lupus erythematosus, infections or cancer, or with drug exposure. Reliable differentiation between primary and secondary membranous nephropathy has important implications for the patient, because of different therapeutic approaches between the different forms. The recent in vivo definition of glomerular targets of autoimmunity in idiopathic membranous nephropathy represented a real breakthrough and nowadays more than one podocyte antigen is considered in some way implicated in the pathogenesis of human membranous nephropathy. Specific antibodies against all these components have been detected in serum of patients and could become biomarkers of membranous nephropathy and/or of disease activity. In this brief review, we discuss the usefulness of newly described autoantibodies in the differential diagnosis of secondary membranous nephropathy. Histological clues for recognizing the two pathological entities are also analysed with regard to the available scientific evidence on this issue. Our evaluation shows that more research is needed to identify the best approach to reach a correct diagnosis of primary or secondary membranous nephropathy.

Trend of Changing Morphological Pattern of Adult Nephrotic Syndrome, Global and Bangladesh Perspective

Nephrotic Syndrome (NS) is a clinical condition characterized by massive proteinuria, hypoalbuminemia, hypercholesterolemia, and generalized oedema. It occurs more commonly in children than in adults, and usually manifests as one of two usually idiopathic diseases: Minimal change NS (MCNS) or focal segmental glomerulosclerosis (FSGS). It has also an incidence of three new cases per 100000 each year in adults. During 70s and 80s membranous nephropathy was considered to be the prime cause of adult NS worldwide. In USA, Brazil, Singapore and South East Asian countries specially in India and Pakistan FSGS has exceeded all other causes of adult NS during last three decades. While in most of the countries of Europe, Australia, Japan, Iran IgA nephropathy has become the main cause of adult NS. Membranoproliferative glomerulonephritis (MPGN) is the predominant cause in certain countries like Russia, South Africa, Singapore etc. In some countries like UAE and Nepal MN is still found to be the main cause of adult NS. In Bangladesh only a few studies are documented which show variable predominant causes of adult NS. It is possibly due to inconsistent renal pathology facilities available in the countries and lack of dedicated renal pathologists.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.12(1) 2016: 100-108

Subclinical pulmonary congestion is prevalent in nephrotic syndrome.

In patients with nephrotic syndrome (NS), the lung is considered an organ protected from the risk of edema. However, data on objectively measured lung water in NS patients is lacking. Here we measured lung water by an ultrasound (US) technique as well as by transthoracic impedance in 42 asymptomatic patients with active NS, in 14 stage G5D CKD patients on chronic hemodialysis, and in 21 healthy individuals. In patients with active NS, the median number of US-B lines (a metric of lung water) after 5 min in a supine position was significantly higher (12; interquartile range: 7-25) compared with that in healthy individuals (4; 2-9) but similar to that in hemodialysis patients (23; 10-39). The difference between NS patients and healthy individuals was significantly amplified (16; 10-35 vs. 4; 2-9) after 60 min of supine resting and significantly attenuated after 5 min of standing (10; 7-25 vs. 3; 1-6). Posture-dependent changes in lung water in patients with active NS were significantly accentuated compared with both hemodialysis patients and healthy individuals. After NS remission, the number of US-B lines was significantly reduced to 5 (4-18) at 5 min and to 6 (5-22) at 60 min approaching the normal range. Lung congestion in patients with active NS was confirmed by transthoracic impedance. Thus, asymptomatic pulmonary congestion is pervasive in patients with NS. A clinical trial is needed to assess the utility of lung US for the management of patients with NS.