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Chikungunya nephropathy is an uncommon etiology of acute kidney injury, associated with the mosquito-borne chikungunya arbovirus (CHIKV). The very limited number of pathologic reports to date have only involved postmortem analyses. We here report 5 cases of acute kidney injury for which kidney biopsies were performed in patients with confirmed acute CHIKV infection, during the recent outbreak of chikungunya disease in the French West Indies. The patients ranged from 42 to 76 years of age. All of the patients developed kidney injury, 3 of whom required short-term dialysis and underwent a kidney biopsy. Analysis of kidney biopsies revealed 2 main histopathologic patterns: acute interstitial nephritis with predominant lymphoid inflammation and acute tubular injury. Epithelioid granulomas were observed in 2 cases. There were no glomerular lesions, except in biopsies from 2 patients, including 1 with a previous known primary focal segmental glomerulosclerosis. CHIKV antigen immunofluorescence microscopy revealed staining in tubular cells. In all of the cases, the short-term outcome was favorable, with recovery of kidney function.

Primary focal segmental glomerulosclerosis (FSGS) is a podocytopathy with an irregular response to immunosuppressive therapies. FSGS relapse occurs in 30% to 80% of kidney grafts, and poor survival outcomes include large proteinuria and the nephrotic syndrome's cardinal clinical features. Thrombotic microangiopathy (TMA) is caused by endothelial injury due to complement dysregulation including acute kidney injury, proteinuria, and severe hypertension common renal presentations. Both pathologies have well-described genetic forms, but their relationship remains uncertain. FSGS lesions can be found in kidney biopsy specimens in patients with TMA, and TMA has been reported in patients with collapsing glomerulopathy. However, this combination has not been clearly described in renal transplant recipients. We present the case of a 22-year-old man who received his second kidney allograft and developed an early graft disfunction with nephrotic syndrome and clinical TMA. His background was remarkable for primary, biopsy-confirmed FSGS in childhood, and he started hemodialysis in 2006 and received a living donor kidney graft the same year. He presented with a FSGS relapse with malignant hypertension and seizures in the first posttransplant month and had an irregular response to plasma exchange and rituximab, and dialysis was reinitiated 10 years later. A total of 3 biopsies were performed after his second kidney transplant showing the evolution of a FSGS relapse with histologic and clinical TMA in the absence of identified genetic mutations. Partial responses to treatments with plasma exchange, eculizumab, and rituximab were obtained, but the allograft was lost after 26 months. This case is the first report of concomitant FSGS and TMA in a renal transplant recipient.

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia

Focal segmental glomerulosclerosis (FSGS) represents a glomerular scar formation downstream of various different mechanisms leading to podocytopathy and podocyte loss. Recently, significant advances were made in understanding genetic factors, podocyte intrinsic mechanisms, and adaptive mechanisms causing FSGS. However, while most cases of nephrotic FSGS are being treated with immunosuppressants, the underlying immune dysregulation, involved immune cells, and soluble factors are only incompletely understood. Thus, we here summarize the current knowledge of proposed immune effector cells, secreted soluble factors, and podocyte response in immune-mediated (primary) FSGS.

Mutations in the TTC21B gene have been identified in patients with nephronophthisis and were recently found in some patients with focal segmental glomerulosclerosis. We herein report a Japanese boy with end-stage renal disease due to medullary polycystic kidney disease and primary focal segmental glomerulosclerosis. Next-generation sequencing detected a new compound heterozygous missense mutation in the TTC21B gene. His renal pathological findings and gene mutations have not been previously reported in patients with ciliopathy. For children with severe renal dysfunction, mutations in the TTC21B gene cause both ciliopathy characterized by bilateral polycystic kidney disease and primary focal segmental glomerulosclerosis.

Introduction: The evolution of primary FSGS is often marked by the occurrence of relapse and corticosteroid resistance and the therapeutic options are numerous and have limited effectiveness. The objective of our study was to assess our practice in this lesion. Patients and Methods: We carried out a retrospective study of patients treated for primary FSGS the period January 1, 2010 to September 30, 2018. The clinical pathological, therapeutic and evolutive characteristics were studied. Results: Fifty-eight patients were included in the study. The average age was 30.74 ± 11.35 years and the sex ratio (M/F) was 2.41. Edema was found in 86.2% and hypertension in 37.9%. The average creatinine was 20.17 ± 16.06 mg/l and the average GFR according to MDRD was 82.43 ± 69.06 ml/min/1.73 m2. The average albumin level was 15.11 ± 5.78 g/l and the 24-hour proteinuria was 7.8 ± 3.79 g/24 h. Nephrotic syndrome was the main indication for renal biopsy in 84.48% and the classic form of FSGS was found in 90.9%. The average initial corticosteroid dose was 62.68 ± 10.04 mg/d and the average duration of regression was 11.78 ± 7.40 months. Forty-five patients (77.6%) were corticosensitive (27.6% complete remission and 50% partial remission). Corticosteroid resistance was observed in 19% and corticosteroid dependence in 11.1%. The proportion of relapse was 33.3% within an average of 15.4 ± 9.1 months. Cyclosporine was no longer prescribed as a second-line treatment in 8 patients. Infectious complications were more found in 19%. Two patients had progressed to ESRD and we noted 2 death cases. The male gender was correlated with the occurrence of a relapse. However, the impact of certain factors such as hypertension, proteinuria, hematuria and GFR level has not been demonstrated. Conclusion: The evolution of primary FSGS is unpredictable, often marked by relapses, hence the interest in identifying factors associated with therapeutic responses for better management.

Background: In children, focal segmental glomerulosclerosis (FSGS) is one of the most common primary glomerular diseases leading to end-stage renal disease. Exosomes facilitate communication between cells by transporting proteins and microRNAs. We aimed to investigate the utility of urine exosomal miR-193a for diagnosis and prognosis estimation among patients with primary FSGS, and preliminarily explore the regulation mechanism of exosome secretion from podocytes.Methods: Specimens of urine were obtained from patients with primary FSGS, minimal change nephropathy (MCN) and IgA nephropathy (IgAN), followed by exosome isolation. We quantified urine exosomal miR-193a based on quantitative reverse transcription-polymerase chain reaction, and evaluated its applicability using area-under-receiver-operating-characteristics curves (AUROCs). The semiquantitative glomerulosclerosis index (GSI) was used to evaluate the degree of glomerulosclerosis according to the method of Raij et al. We further used FAM-labeled miR-193a-5p to examine exosome shuttling using confocal microscopy for visualization, and explored the regulation mechanism of exosomes release from podocytes using Fluo-3AM dye.Results: Urine exosomal miR-193a levels were significantly higher in patients with primary FSGS than those with MCN and IgAN. The AUROCs for discriminating between primary FSGS and MCN or IgAN were 0.85 and 0.821, respectively. Urine exosomal miR-193a levels positively correlated with GSI in patients with primary FSGS. We further found that kidney tissues from these patients had increased CD63 expression involving podocytes in non-sclerotic tufts. Exosomes from cultured podocytes could transport miR-193a-5p to recipient cells, potentially through a calcium-dependent release mechanism.Conclusion: Urine exosomal miR-193a might be harnessed as a non-invasive marker for diagnosis and outcome assessment among patients with primary FSGS. Exosomes were potential vehicles for miRNAs shuttling between podocytes, and released from podocytes in a calcium-dependent manner.

Rationale: Lupus podocytopathy (LP) is an entity that is increasingly being reported in the literature on systemic lupus erythematosus (SLE). LP is characterized by nephrotic syndrome in SLE patients with diffuse glomerular podocyte foot process effacement and no immune complex deposits along the capillary loops. Histologically, LP typically mimics minimal change disease or primary focal segmental glomerulosclerosis (FSGS) on a background of ISN/RPS class I or II lupus nephritis. In situations where there are coexistent glomerular diseases, however, LP may be easily masked by background lesions and overlapping clinical symptoms. Patient concerns: We report the case of a 24-year-old woman with type I diabetes, hypertension, psoriasis/rash, and intermittent arthritis who presented with abrupt onset of severe nephrotic proteinuria and renal insufficiency. Renal biopsy revealed nodular glomerulosclerosis and FSGS. Immune deposits were not identified by immunofluorescence or electron microscopy. Ultrastructurally, there was diffuse glomerular basement membrane thickening and over 90% podocyte foot process effacement. With no prior established diagnosis of SLE, the patient was initially diagnosed with diabetic nephropathy with coexistent FSGS, and the patient was started on angiotensin-converting enzyme inhibitors (ACEI) and diuretics. However, nephrotic proteinuria persisted and renal function deteriorated. The patient concurrently developed hemolytic anemia with pancytopenia. Diagnoses: Subsequent to the biopsy, serologic results showed positive autoantibodies against double strand DNA (dsDNA), Smith antigen, ribonucleoprotein (RNP), and Histone. A renal biopsy was repeated, revealing essentially similar findings to those of the previous biopsy. Integrating serology and clinical presentation, SLE was favored. The pathology findings were re-evaluated and considered to be most consistent with LP and coexistent diabetic nephropathy, with superimposed FSGS either as a component of LP or as a lesion secondary to diabetes or hypertension. Interventions: The patient was started on high-dose prednisone at 60 mg/day, with subsequent addition of mycophenolate mofetil and ACEI, while prednisone was gradually tapered. Outcomes: The patient's proteinuria, serum creatinine, complete blood counts, skin rash, and arthritis were all significantly improved. Conclusion: The diagnosis of LP when confounded by other glomerular diseases that may cause nephrotic syndrome can be challenging. Sufficient awareness of this condition is necessary for the appropriate diagnosis and treatment.

IntroductionCircular RNAs (circRNAs), a novel class of non-coding RNAs, have been implicated in various diseases and are considered to play an important role in physiological and pathological processes. We aimed to profile renal circRNA in children with primary focal segmental glomerulosclerosis (FSGS) and predict the potential mechanism underlying the pathogenesis of FSGS.Material and methodsA global circRNA expression analysis was performed in renal tissues from patients with FSGS (n=3) and controls (n=3). Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression levels of three circRNAs in a cohort of 44 patients with FSGS, 44 age-matched healthy controls, and 15 patients with minimal change disease (MCD).ResultsA total of 152 circRNAs were differentially expressed in patients with FSGS compared with controls. Hsa_circ_0001461 and hsa_circ_0000605 were significantly increased in patients with FSGS compared with controls, as determined by qRT-PCR (p < 0.001). The receiver operating characteristic (ROC) curve areas of hsa_circ_0001461 and hsa_circ_0000605 were 0.948 and 0.934, respectively. Hsa_circ_0001461 was significantly elevated in patients with FSGS compared with those with MCD and was correlated with 24 h urinary protein in patients with FSGS (r = 0.732, p < 0.001). Bioinformatics analysis predicted mir-30a interaction with hsa_circ_0001461. Mir-30a was negatively correlated with the renal hsa_circ_0001461 level (r = -0.90, p < 0.001).ConclusionsHsa_circ_0001461 is identified as a novel biomarker in children with FSGS and might provide insights into the mechanism of FSGS pathogenesis.

Background and Aims After membranous nephropathy, focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in European population. According to Columbia classification, there are five histological variants of FSGS defined on light microscopy (tip, cellular, perihilar, collapsing and not otherwise specified - NOS) and this classification has a prognostic significance. The aim is to compare features and outcomes of tip and cellular variant of primary FSGS. Method All patients with FSGS were identified by a retrospective review of the Registry of kidney biopsies at the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, from 2003 until 2020. Each kidney specimen was analyzed by light, immunofluorescent and electron microscopy and Columbia classification was applied by experienced nephropathologist. Patients with primary FSGS met following criteria: full nephrotic syndrome and diffuse podocyte foot process effacement in absence of secondary causes of FSGS. Laboratory findings were obtained for every patient at the time of biopsy and following outpatient visits. Complete remission was defined as proteinuria < 0.3 g/day with normal kidney function and partial remission as proteinuria 0.3 - 3.5 g/day. Variables are expressed as median ± IQR (interquartile range) and frequencies. Statistical comparison between groups of patients with tip and cellular variant of primary FSGS and disease outcome analysis were done. Results Out of 200 patients with FSGS, 59 (29.5 %) had primary form of disease. Tip variant was the most common form of primary FSGS (22 patients, 37 %) followed by NOS (20, 34 %), cellular (13, 22 %), perihilar (2, 3.5 %) and collapsing (2, 3.5 %) variant. Demographic and clinical features with initial laboratory findings are shown in Table 1. There were no significant differences between two groups in all analyzed variables in Figure 1. All patients were treated by anti-RAAS agents and steroids. Median follow-up was 55 months (range 1 – 196 months), and followup data were unavailable for three patients. Figure 2 shows treatment regimens in both patient grouos with treatment outcomes. Remission rate was significantly higher in tip variant (90 % vs. 41 %, p = 0.002). There was no difference in relapse rate between the two groups (p = 0.717). Conclusion There were no significant differences in clinical features and laboratory findings at the time of clinical presentation between tip and cellular variant of primary FSGS. Patients with tip variant had significantly higher remission rate than patients with cellular variant.

A major complication of primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of these relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in the urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in the urine of native primary FSGS patients, this feature has been associated with prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study, we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (non-FSGS). In recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells, while in the non-FSGS patients, ApoA-I was found along the cytoplasm of the tubular cells. The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution.

A new type of glycine bridged Cu(II)-containing Schiff base coordination polymer {[Cu2(HL)2](H2O)4}n (1, H3L = (2,2′-(((1E,1′E)-(2-hydroxy-5-methyl-1,3-phenylene)bis(methaneylylidene))bis(azaneylylidene))diacetic acid) was composed by the condensation of glycine, Cu(NO3)2·6H2O as well as 2,6-diformyl-4-methylphenol in the water surrounding. To make the size of complex 1 in nanoscale, a green grinding treatment approach was utilized to generate the nano sheets of complex 1 which has excellent water dispersibility. We firstly constructed the primary focal segmental glomerulosclerosis mice model and evaluate the reduction effect of nano 1 on the level of 24-h urine protein contents. Then, the nf-κb and tlr4 gene expression level was measured by RT-PCR to reveal the mechanism of nano 1. Further, motivated by the drug-like potential that observed from experimental results, the binding interaction has been probed by using molecular docking simulation.

In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.

Objectives Primary idiopathic focal segmental glomerulo-sclerosis is a serious disease, frequently progressing to end-stage kidney failure. Management of recurrence after kidney transplant is challenging despite multiple proposed therapeutic approaches. Available treatment for focal segmental glomeru-losclerosis recurrence is plasma exchange, intravenous cyclosporine, and rituximab. In this study, we investigated kidney transplant recipients with focal segmental glomerulosclerosis who were at high risk for recurrence. Patients were given preemptive rituximab at day 0 posttransplant. Materials and methods Between January 2013 and June 2017, our center had 8 patients with primary focal segmental glomerulosclerosis at high risk for recurrence who were scheduled for kidney transplant. These patients received a single rituximab infusion of 375 mg/m2 on day 0 posttransplant. Recurrence of focal segmental glomerulosclerosis posttransplant was defined as repeated proteinuria > 2 g/day, without evidence of clinical or biopsy-proven rejection. Results Follow-up showed that none of our patients had immediate posttransplant proteinuria. Only 1 patient developed proteinuria at almost 4 months posttransplant. Mean follow-up duration was 8 months. With regard to complications, 2 patients had serious bacterial infections and 1 patient had cytomegalovirus infection. Conclusions Rituximab at day 0 posttransplant may be used safely to prevent focal segmental glomeru-losclerosis recurrence in the graft in the early posttransplant period. However, longer follow-up studies with larger series are needed.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5‐year‐old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52‐year‐old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs., Successful management of recurrent primary focal segmental glomerulosclerosis after kidney transplantation includes retransplantation of an allograft that failed in the first recipient due to disease recurrence into a second recipient and ofatumumab pretreatment before kidney retransplantation in the patient with fulminant recurrence of focal segmental glomerulosclerosis in the first graft.

Background Introduction In patients under 16 presenting with nephrotic syndrome, primary focal segmental glomerulosclerosis (FSGS) is an important differential. High recurrence rates following transplantation, and a considerable risk of progression to end-stage renal disease, are well-recognised in cases with presumed circulating permeability factors rather than a genetic cause. To limit the risk of graft loss, it is therefore crucial to monitor for relapsing disease. The main marker of recurrence is proteinuria, however this can be challenging to interpret in a patient with high proteinuria pre-transplantation. Objectives This is a case of a 14-year-old with FSGS, who developed early recurrence post-transplantation. Methods Case Presentation Pre-emptive renal transplantation was discussed with the family of a 14-year-old male with steroid-resistant FSGS, who had also not responded to tacrolimus, mycophenolate and rituximab. Proteinuria would be difficult to interpret post-transplantation, as he continued to produce high levels of proteinuria with a significant urine output. A number of options were explored including; (1) bilateral nephrectomies or embolization pre-transplantation to shut down native function altogether; (2) a tube into the transplant renal pelvis passing through the bladder, serving as a catheter to monitor urine exclusively from the transplant kidney; (3) delay of transplantation until native kidney function completely ceased. Given the challenging practicality of (2), and uncertain timescale of (3), bilateral nephrectomies were arranged a few weeks prior to transplantation. Results Outcome After day five following a live donor kidney transplant, proteinuria developed progressively. Daily therapeutic plasma exchange was commenced for two weeks. Renal function continued to deteriorate, and lipoprotein apheresis was trialled. A transplant renal biopsy, nine days following lipoprotein apheresis, reported early recurrence of FSGS. Conclusions Discussion The leading cause of renal graft failure in primary FSGS, within the paediatric cohort, is disease recurrence. Removal of circulating permeability factors using extracorporeal systems, such as therapeutic plasma exchange and lipoprotein apheresis, could theoretically improve graft survival. Despite a number of possibilities considered, this case highlights the difficulties of monitoring and treating disease recurrence post-transplantation.

Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. To date, few studies have investigated predictive factors for treatment responses in recurrent FSGS. We retrospectively analyzed 16 patients who were < 16 years at the age of onset and had post-transplant recurrence of FSGS from 1993 to 2018. Patients who achieved complete remission or partial remission after initiating therapy for recurrent FSGS were defined as responders. We compared several clinical characteristics between responders and non-responders. Time to remission was also analyzed. Ten patients were responders, and six patients were non-responders. Univariate analysis showed that responders had a significantly lower amount of maximum proteinuria at the time of recurrence (P = 0.015) and more highly selective proteinuria (P = 0.013) than non-responders. The time to remission from initiation of therapy was 2 months (interquartile range 0.2–4.4). In all responders, except for one patient, remission was achieved within 6 months. Therapeutic responses may be predicted by examining the amount and selectivity of proteinuria at the time of recurrence. Further studies with larger numbers of patients are clearly required to validate these findings.

Objectives: To find out frequency, clinicopathological features, response of treatment and outcome among children with primary focal segmental glomerulosclerosis (FSGS). Methods: This retrospective, non-interventional medical charts review study was conducted from a period of January 2011 to January 2020 at Pediatric Department of Nishtar Medical University Hospital, Multan, Pakistan. During the nine years study period, children of both genders, aged less than 16 years, with renal biopsies proven FSGS were included. Patient’s demographic along with clinical and laboratory data, urine dipstick for proteinuria, renal functions, 24 hours urinary protein and ultrasonography findings of kidneys, ureters and bladder (KUB) were noted from case records. Response rates of various treatment options and their outcome like remission, partial remission, no remission with stable kidney disease & no remission with progression of kidney disease were noted. Results: During the study duration, out of 307 renal biopsies performed in glomerulonephritis cases, 124 (40.4%) had primary FSGS. In 124 primary FSGS cases, mean age was 8.83±3.05 years while most of the children, 70 (56.5%) were above 10 years of age. Majority of the cases, 64 (51.6%) were male. Mean follow up duration was noted to be 28.35+18.47 months. Most of the cases, 68 (54.8%) were found to have complete remission, 22 (17.7%) partial remission while 11 (8.9%) progressed to ESKD. Conclusions: Among children, frequency of primary FSGS was high at our setting. Most of the cases achieved sustained remission rates with the help of immunosuppressive drugs. Cyclosporine and tacrolimus were found to be the most effective drugs. doi: https://doi.org/10.12669/pjms.37.2.3535 How to cite this:Safdar RS, Mehar MF, Khan AA, Buzdar N. Focal Segmental Glomerulosclerosis in Paediatric Population of South Punjab Pakistan: A Tertiary Care Hospital Experience. Pak J Med Sci. 2021;37(2):510-514. doi: https://doi.org/10.12669/pjms.37.2.3535 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions.

Background: Evidence suggesting a role for including calcineurin inhibitors(CNIs) in early therapy remains limited for low quality and mainly based on small observation cohort study. We will conduct a systematic reviews to explore the effect and adverse effect of calcineurin inhibitors compared with other interventions in the treatment of primary focal segmental glomerulosclerosis (FSGS). Methods: A comprehensive literature search of MEDLINE (through PubMed), EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) will be conducted. Two investigators will independently select studies, extract data and assess the quality of the included study. Extracted information will include study characteristics, the contents of included randomized controlled trials, outcomes, the quality of randomized controlled trials and etc. A risk of bias tool will be used to assess the methodological quality. Any disagreement will be resolved by the third investigator. There is no requirement of ethical approval and informed consent. Results: This study will provide high-quality evidence for treatment of FSGS in terms of effectiveness and safety. Conclusion: This systematic review aims to provide evidence for treatment of FSGS in different CNIs. Registration: The systematic review and meta-analysis is registered in the OSF REGISTERS (10.17605/OSF.IO/3B7DE) international prospective register of systematic review.

Focal segmental glomerulosclerosis (FSGS) is a histological term that describes a pathologic renal entity affecting both adults and children, with a wide array of possible underlying etiologies. Podocyte damage with scarring, the hallmark of this condition, leads to altered permeability of the glomerular barrier, which may result in massive proteinuria and relentless renal function deterioration. A definite cause of focal segmental glomerulosclerosis can be confirmed in a minority of cases, while most forms have been traditionally labeled as primary or idiopathic. Despite this definition, increasing evidence indicates that primary forms are a heterogenous group rather than a single disease entity: several circulating factors that may affect glomerular permeability have been proposed as potential culprits, and both humoral and cellular immunity have been implicated in the pathogenesis of the disease. Consistently, immunosuppressive drugs are considered as the cornerstone of treatment for primary focal segmental glomerulosclerosis, but response to these agents and long-term outcomes are highly variable. In this review we provide a summary of historical and recent advances on the pathogenesis of primary focal segmental glomerulosclerosis, focusing on implications for its differential diagnosis and treatment.

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KT) appears in 30 % of the recipients. Sometimes it can cause the loss of the allograft. Although many treatments for this condition have been reported, 20 %-40 % of the affected patients are refractory or presents frequents relapses. In this paper we describe the evolution of three recipients treated with long-term plasmapheresis therapy after a recurrence of FSGS with a bad or incomplete response to other treatments. Although our findings require confirmation, long-term plasmapheresis could be a therapeutic option for this condition.

SARS-CoV-2 is characterized by a multiorgan tropism including the kidneys. Recent autopsy series indicated that SARS-CoV-2 can infect both tubular and glomerular cells. Whereas tubular cell infiltration may contribute to acute kidney injury, data on a potential clinical correlative to glomerular affection is rare. We describe the first case of nephrotic syndrome in the context of COVID-19 in a renal transplant recipient. A 35 year old male patient received a kidney allograft for primary focal segmental glomerulosclerosis (FSGS). Three months posttransplant a recurrence of podocytopathy was successfully managed by plasma exchange, ivIG, and a conversion from tacrolimus to belatacept (initial proteinuria > 6 g/l decreased to 169 mg/l). Six weeks later he was tested positive for SARS-CoV-2 and developed a second increase of proteinuria (5.6 g/l). Renal allograft biopsy revealed diffuse podocyte effacement and was positive for SARS-CoV-2 in RNA in-situ hybridation indicating a SARS-CoV-2 associated recurrence of podocytopathy. Noteworthy, nephrotic proteinuria resolved spontaneously after recovering from COVID-19. The present case expands the spectrum of renal involvement in COVID-19 from acute tubular injury to podocytopathy in renal transplant recipients. Thus, it may be wise to test for SARS-CoV-2 prior to initiation of immunosuppression in new onset glomerulopathy during the pandemic. Electronic supplementary material The online version of this article (10.1007/s40620-020-00855-5) contains supplementary material, which is available to authorized users.

Background and Aims The indication of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation (KT) remains controversial. The objective of our study was to evaluate the benefit and tolerability of adding RTX to the standard of care (SOC) comprising plasmapheresis (PP), corticosteroids, and high-dose anticalcineurins for the treatment of FSGS recurrence after KT. Method This retrospective, multicenter study reports on 148 patients, transplanted between 31 December 2004 and 31 December 2018, aged 39.9 + 13.4 years, who developed FSGS recurrence at 7 [3–23] days. In all 109 patients received a SOC (Group 1). RTX was introduced in this group after more than 28 days of SOC for failure or for therapeutic intensification (n = 19, Group 1a), or for early discontinuation of PP (n = 12, Group 1b); 39 patients received RTX associated at the outset with SOC (Group 2). Results We observed 46.6% complete remission (CR) and 33.1% partial remission (PR). Ten-year graft survival was 65.6% [51.4–76.6] and 13.4% [3.4–30.0] in responders and non-responders respectively. There was no difference in CR + PR rate between G1 (82.5%) and G2 (71.8%), p = 0.08, confirmed by propensity score +4.3% (95% CI [−9.0%-17.5%], p = 0.53). Following addition of RTX (Group 1a), we observed a CR rate of 26.3% and a PR rate of 31.6%. Patients with and without RTX experienced similar rejection rates (18.6% and 28.2%, p = 0.17) and infection rates (71.4% and 79.5%, p = 0.40). In multivariate analysis, the infections were associted with hypogammaglobulinemia Conclusion Rituximab could be used in cases of SOC failure or in remission patients for early weaning of plasmapheresis, without increasing infectious risk.

Background: Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the risk factors of progression of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors.Methods: 201 patients with primary FSGS (59% male, mean age: 38±15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated.Results: During 55±27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR:1.39, 95%CI: 1.15-1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR: 1.03, 95% CI: 1.02-1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR: 1.03, 95% CI: 1.01-1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95%CI: 0.77-0.90). Median renal survival was 3.1 years (95% CI: 2.2-4.1 years) in patients with highest risks score (baseline eGFR2+ IF/TA/SGS> 50%), and 8.1 years (95% CI: 7.7-8.6 years).in those with lowest score (baseline eGFR>75 ml/min/1.73 m2+ IF/TA/SGS Conclusion: In primary FSGS, higher baseline SCr, increased SGS and IF/TA, but not baseline proteinuria and collapsing pathology, were the predictors for CKD/ESKD. These findings indicated the importance of timely detection and referral in prognosis of primary FSGS.

Biomarcadors; Algoritme de diagnosi; Glomerulosclerosi segmentària focal Biomarcadores; Algoritmo de diagnóstico; Glomeruloesclerosis segmentaria focal Biomarkers; Diagnosis algorithm; Focal segmental glomerulosclerosis Primary or idiopathic focal segmental glomerulosclerosis (FSGS) is a kidney entity that involves the podocytes, leading to heavy proteinuria and in many cases progresses to end-stage renal disease. Idiopathic FSGS has a bad prognosis, as it involves young individuals who, in a considerably high proportion (∼15%), are resistant to corticosteroids and other immunosuppressive treatments as well. Moreover, the disease recurs in 30–50% of patients after kidney transplantation, leading to graft function impairment. It is suspected that this relapsing disease is caused by a circulating factor(s) that would permeabilize the glomerular filtration barrier. However, the exact pathologic mechanism is an unsettled issue. Besides its poor outcome, a major concern of primary FSGS is the complexity to confirm the diagnosis, as it can be confused with other variants or secondary forms of FSGS and also with other glomerular diseases, such as minimal change disease. New efforts to optimize the diagnostic approach are arising to improve knowledge in well-defined primary FSGS cohorts of patients. Follow-up of properly classified primary FSGS patients will allow risk stratification for predicting the response to different treatments. In this review we will focus on the diagnostic algorithm used in idiopathic FSGS both in native kidneys and in disease recurrence after kidney transplantation. We will emphasize those potential confusing factors as well as their detection and prevention. In addition, we will also provide an overview of ongoing studies that recruit large cohorts of glomerulopathy patients (Nephrotic Syndrome Study Network and Cure Glomerulonephropathy, among others) and the experimental studies performed to find novel reliable biomarkers to detect primary FSGS. The authors are current recipients of research grants from the Fondo de Investigación Sanitaria-Feder, Instituto de Salud Carlos III (PI17/00257, PI18/01704 and PI18/01832) and REDinREN (RD16/0009/0030).

Background: Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence. Objectives: To examine the safety and probable benefit at 1, 3, 6, 12, and 24-months following completion of apheresis treatment using Liposorber® LA-15 system in patients with nephrotic syndrome (NS), due to refractory primary FSGS or primary FSGS associated NS, in post renal transplant children. Material and Methods: Prospective, multicenter, single-arm intervention study using Liposorber® LA-15 system. Patients ≤21 years old with drug resistant or drug intolerant NS secondary to primary FSGS with glomerular filtration rate (GFR) ≥60 ml/min/1.73 m2 or post renal transplant patients ≤21 years old with primary FSGS associated NS were included in the study. Each patient had 12 dextran-sulfate plasma adsorption lipoprotein apheresis sessions over a period of 9 weeks. All patients were followed up at 1, 3, 6, 12, and 24-months following completion of treatment. Results: Of 17 patients enrolled, six were excluded from the outcome analysis (protocol deviations). Of the remaining 11 patients, all but one have completed apheresis treatments. Three patients were lost to follow-up immediately after completion of apheresis and excluded from outcome analysis. At one-month follow-up, 1 of 7 patients (14.3%) attained partial remission of NS while 2 of 4 subjects (50%) and 2 of 3 subjects (66.7%) had partial/complete remission at 3- and 6-months follow-up, respectively. One of two patients followed up for 12 months had complete remission and one patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all patients over the follow-up period. Conclusion: The results of our multicenter study showed improvement in the response rates to steroid or immunosuppressive therapy and induced complete or partial remission of proteinuria in some of the patients with drug resistant primary FSGS. The main limitation of our study is the small number of subjects and high dropout rate.

To compare the efficacy of glucocorticoids in primary focal segmental glomerulosclerosis (pFSGS) patients with moderate proteinuria. Registered at http://www.chictr.org.cn/ , study No. ChiCTR-OPN-17012789. pFSGS patients with urine protein between 1.0 and 3.5 g/24 h were recruited from 2006 to 2016. No decline in urine protein > 50% was observed after 2 months of run-in angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB) treatment. Patients were assigned to study group (glucocorticoids with ACEI/ARB) or control group (ACEI/ARB without glucocorticoids). Variables including 24-h urinary protein, serum albumin and serum creatinine during the trial were recorded. Remission was defined as proteinuria 50%, and our composite end point as > 30% decrease of eGFR or eGFR

Background Focal segmental glomerulosclerosis (FSGS) is often accompanied with tubulointerstitial lesion. This study aimed to assess the role of urinary biomarkers in predicting tubulointerstitial lesion and treatment response in FSGS patients. Methods Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β- d -glucosaminidase (NAG) and retinol-binding protein (RBP) were measured in 32 FSGS patients and 22 patients with minimal change nephrotic syndrome. Patients with FSGS were followed up to investigate the value of these markers in predicting treatment response. Results FSGS patients had higher urinary NGAL, NAG and RBP than patients with minimal change nephrotic syndrome with comparable proteinuria. A cutoff value of 15.87 ng/mL NGAL demonstrated 87.1% sensitivity and 59.1% specificity for the diagnosis of FSGS, with an area under the receiver operator characteristic curve of 0.801. In FSGS, these markers correlated significantly with the degree of acute tubulointerstitial damage but not with chronic tubulointerstitial lesion. Response to immunosuppressive therapy was significantly different in patients with KIM-1, NAG and RBP levels below and above the cutoff values. Conclusions Urinary NGAL, KIM-1, NAG and RBP are reliable biomarkers of tubulointerstitial lesion in FSGS patients. The measurements of these markers may be useful in diagnosing FSGS, detecting acute tubulointerstitial lesion and predicting treatment response.

Primary focal segmental glomerulosclerosis recurrence occurs in 10% to 50% of recipients after kidney transplant and may affect both children and adults. Treatment after recurrence with plasma exchange and immunosuppression is quite variable and challenging, and those who do not respond usually progress to allograft failure. Podocyte injury and B7-1 expression and subsequently its blockade (abatacept) have been reported to be associated with complete remission of proteinuria in 4 patients with focal segmental glomerulosclerosis recurrence after kidney transplantation and in 1 patient with focal segmental glomerulosclerosis in native kidney. Here, we report our experience of successfully treating 3 consecutive patients with focal segmental glomerulosclerosis recurrence after kidney transplant with abatacept, which induced proteinuria remission.

Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binucleation. Variable amounts of intraglomerular lipid were present in all dogs. All dogs were proteinuric, with measured values for the urine protein-to-creatinine ratio ranging from 1.2 to 6.5. Azotemia was mild to absent and dogs were euthanatized at 5.1 to 14 years of age, in all cases due to nonrenal diseases. The underlying cause of FSGS in these Miniature Schnauzer dogs has yet to be determined, but contributors likely include genetic podocytopathy, lipid abnormalities, and glomerular hypertension.

BACKGROUND Focal segmental glomerulosclerosis (FSGS) is a kidney-specific autoimmune disease, but its pathogenesis is not fully known. The present study detected the frequencies of circulating memory B cells and plasmablasts and other clinical parameters in FSGS. METHODS We monitored 16 primary FSGS patients and 23 healthy controls (HC). Flow cytometry was used to analyze circulating memory B cell and plasmablastspercentages. Serum IgG levels were detected using a cytometric bead array (CBA). RESULTS The proportions of CD27 + IgD- class-switched memory B cells (P = 0.0002), CD27 + IgD-IgG + class-switched memory B cells (P