Focal and segmental glomerulosclerosis in children: a longitudinal assessment

Recent data suggest that the histologic finding of focal and segmental glomerulosclerosis (FSGS) is increasing among children. There are, however, limited longitudinal pediatric data on prevalence, demographics, and steroid responsiveness in FSGS. We identified 201 consecutive nephrotic children diagnosed between 1977 and 2002 with 2 years follow-up; 51% had undergone renal biopsy due to steroid sequelae or resistance; 48 children with FSGS were diagnosed. Compared with non-FSGS children, FSGS children were older at diagnosis (6.9 years vs 4.4 years, P < 0.02), more likely girls (54% vs 28%, P < 0.02), Black or Hispanic (42% vs 16%, P < 0.001), and the FSGS was more likely to be steroid resistant (73% vs 10%, P < 0.001). To assess for longitudinal differences, we grouped children by presentation: pre-1985, between 1985 and 1995, and post-1995. There was no difference in proportion of children biopsied or diagnosed with FSGS during each interval. Among FSGS children, there was no difference in racial or gender composition in each period, but there was a difference in age at diagnosis (2.6 vs 5.7 vs 8.5 years; P = 0.01), also observed in the non-FSGS children (2.2 vs 3.9 vs 4.9 years; P = 0.02). In contradistinction to non-FSGS children, there was a marked increase in steroid resistance with FSGS (43% vs 62% vs 86%; P = 0.03).     

Complete remission of nephrotic syndrome in an infant with focal segmental glomerulosclerosis: is it renin–angiotensin blockade?

Nephrotic syndrome presenting in the first year of life is often challenging, with substantial risk of progression to end-stage renal disease (ESRD). Focal segmental glomerulosclerosis (FSGS) comprises up to 20% of biopsy-proven glomerular disease in children and adults. We report on a 9-month-old infant who presented with nephrotic syndrome, hypertension and progressive deterioration of renal function due to FSGS. As immunosuppressive agents are often unsuccessful in treating this condition, we adopted renoprotection as the mainstay treatment for this patient, through rigorous control of blood pressure and proteinuria with a multi-drug regimen including renin-angiotensin axis blockade. Initially, there was partial improvement, with a gradual decline in proteinuria and a concomitant rise in the glomerular filtration rate, before the disease eventually passed into complete clinical and laboratory remission. We speculate that infants with steroid-resistant nephrotic syndrome due to FSGS may benefit from tight control of hypertension, mainly though early blockade of the renin-angiotensin axis. We believe that its renoprotecive mechanism counteracts the deleterious effects of both hypertension and proteinuria, thereby not only preventing progressive renal disease, but even paving the way for a remission, as in our patient. To the best of our knowledge, this is the first report of an infant with nephrotic syndrome (NS) due to FSGS that passed into complete remission while the patient was on renoprotective measures including the use of angiotensin-converting enzyme inhibitors (ACEis).     

Intensive and Prolonged Treatment of Focal and Segmental Glomerulosclerosis Recurrence in Adult Kidney Transplant Recipients: A Pilot Study

No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 ± 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05–0.3 g/day) and 0.19 g/day (range 0.05–1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients.     

Impact of Immunofluorescence on the Histological Pattern of Pediatric Kidney Biopsies from Northern Pakistan

Abstract

Kidney biopsy is an investigation for diagnosis and prognosis of a variety of nephritides. It also influences therapeutic options. Immunofluorescence (IMF) greatly adds in identifying the pathologies which may not be obvious on light microscopy (L/M), such as IgM, IgA nephropathy, pauci-immune glomerulonephritis, and anti-glomerular basement membrane disease. We present here data of 170 pediatric kidney biopsies from July 2005 to December 2009 from Department of Nephrology and Hypertension, Lady Reading Hospital, Peshawar, Pakistan. The study was undertaken to see whether IMF would alter the histological pattern of pediatric kidney biopsies and to compare these data with an earlier data from our department of 415 pediatric kidney biopsies done over 7-year period from 1998 to 2005, which were analyzed with L/M alone. Out of 170 kidney biopsies using L/M and IMF, IgM turns out to be most common pattern (20%), followed by minimal change disease (MCD) (17.05%), focal and segmental glomerulosclerosis (FSGS) (15.88%), chronic sclerosing glomerulonephritis (Chr. sclerosing GN) (12.35%), mesangio proliferative glomerulonephritis (MPGN) (7.65%), mesangio capillary glomerulonephritis (MCGN) (6.47%), membranous glomerulonephritis (Mem. GN) (5.29%), IgA nephropathy (5.29%), cresentic glomerulonephritis (Cres. GN) (3.53%), lupus nephritis (2.96%), and others (3.53%). Comparing these results of 170 cases with 415 renal biopsies without IMF, IgM dominated the histological pattern in IMF group whereas MCD followed by FSGS and MPGN were prominent in group without IMF. Therefore, variation in the overall histological pattern with IMF technique proved statistically significant (p < 0.0001). Addition of IMF has altered the frequency of MCD, a change from 24% (100/415) to 17% (29/170), FSGS from 18.3% (76/415) to 15.88% (27/170), and MPGN from 17.35% (72/415) to 7.65% (13/170).     

Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience

Abstract

Objectives: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. Methods: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤0.5?g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. Results: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9?g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. Conclusions: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.     

A case of crescentic glomerulonephritis in a patient with COVID-19 infection: A case report and literature review

Rationale:Kidney involvement with COVID-19 infection is a well-known complication, and the majority of kidney involvement is related to ischemic injury/acute tubular injury. However, there are some cases of glomerulonephritis, the etiology of which is not yet known, but an immune process is likely to be the trigger.Patient concerns:A 27-year-old man presented to our hospital with facial puffiness and lower-limb swelling.Diagnosis:Laboratory assessment revealed features of impaired kidney function with proteinuria and hematuria; COVID-19 polymerase chain reaction was positive, which was consistent with pauci-immune crescentic focal segmental glomerulonephritis.Intervention:After renal biopsy, the patient was started on methylprednisolone and rituximab. Due to worsening kidney parameters, he underwent intermittent hemodialysis as needed.Outcome:Kidney function tests partially improved; he was discharged on oral steroids with follow-up in the nephrology clinic to observe for the need for further hemodialysis.Lessons:We conducted a literature review of cases of glomerulonephritis associated with COVID-19 and described numerous types of glomerulonephritis. This report highlights the importance of recognizing emerging glomerulonephritis with COVID-19, the different pathological patterns of renal biopsies, and management interventions and responses.     

Focal and segmental glomerulosclerosis: multiple pathways are involved

Focal segmental glomerulosclerosis (FSGS) is not a disease but a clinicopathologic entity. The term FSGS itself is a misnomer because its lesions are not always focal, segmental, or sclerotic. Its clinical expression also widely varies and is nonspecific. Confronted with such diversity, one cannot but translate the title of this contribution into a unifying version focusing on the podocyte, initial culprit, or victim of multiple processes leading to FSGS. Some have been identified in human glomerulopathies and/or in animal or cell culture models, and are classified as secondary. Genetic forms, nonsyndromic or syndromic, have adduced a wealth of knowledge on the slit diaphragm architecture and explain the reason for their steroid resistance. Others, mostly expressed by a nephrotic syndrome, will be considered as idiopathic until the offending factor(s) that affect the molecular array of the slit diaphragm filtration barrier are identified and counteracted. Recent research has lead to suggesting that FSGS is not a T-cell–driven autoimmune glomerulopathy. Thus, treatments considered as etiologic, including glucocorticoids and calcineurin inhibitors, are in fact endowed with a mode of action on podocytes that suggests that drugs used such as immunosuppressors also might be considered as antiproteinuric agents.     

Reduced podocyte expression of alpha3beta1 integrins and podocyte depletion in patients with primary focal segmental glomerulosclerosis and chronic PAN-treated rats

Integrins attach cells to extracellular matrix (ECM) and mediate signals from ECM to cells or from cells to ECM. They regulate cell functions, including adhesion, migration, cell cycle regulation, and differentiation. Podocytes may detach from the glomerular basement membrane (GBM) and be excreted in the urine, and proteinuria is found in patients with primary focal segmental glomerulosclerosis (FSGS); both may be associated with loss of alpha3beta1integrins. In this study, we have examined the podocyte number in patients with primary FSGS and normal controls, and the alpha3- and beta1-integrin subunits expression of podocytes in patients with primary FSGS and chronic puromycin aminonucleoside (PAN)-treated rats by the morphometric, immunoperoxidase histochemical, and immunoelectron microscopic examination. We also measured their expression serially in rats that received repeated PAN injection. The results showed that the podocyte number was significantly decreased in patients with primary FSGS than in normal control (P < 0.05). The immunostaining score showed that both alpha3- and beta1-integrin subunits on podocytes in patients with primary FSGS were significantly lower than in normal controls (both P < 0.01). The number of immuno-gold particles of alpha3- and beta1-integrins at the effaced foot process area of patients with primary FSGS were also significantly decreased than that of normal controls (both P < 0.05). The immunostaining score of both alpha3- and beta1-integrin subunits was negatively correlated with the degree of glomerular sclerosing score and the amount of daily protein loss, and they were positively correlated with the number of podocytes. Chronic 12-week PAN-treated rats showed similar findings with decreased immunostaining expression and immuno-gold particles of alpha3-integrin on podocytes than in normal control (both P < 0.05). The chronic PAN-treated rats also showed a trend toward gradually decreased immunostaining expression of alpha3-integrin subunit on podocyte during the progress from normal to FSGS state. These studies indicate that podocyte expression of alpha3- and beta1-integrin subunits is significantly reduced in humans with primary FSGS and chronic PAN-treated rats, before the morphological changes of FSGS are observed. The decreased podocyte expression of alpha3beta1 integrins is closely related with podocyte depletion, glomerular sclerosis, and daily protein loss in patients with primary FSGS.