The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994-2000.

BACKGROUND: This report describes data collected by the Czech Registry of Renal Biopsies (CRRB). METHODS: Twenty-eight centres provided data on all biopsies of native kidneys performed in the Czech Republic (population 10.3 million) over the period 1994-2000. Data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, serum albumin level, arterial hypertension, diabetes mellitus, histological diagnosis and complications after renal biopsy were collected. RESULTS: Altogether 4004 biopsies in 3874 patients were performed (males 57.9%, children < or = 15 years 17.7%, elderly >60 years 14.3%). Microhaematuria was present in 65.9%, macrohaematuria in 9.2%, nephrotic proteinuria (> or = 3.5 g/24 h) in 39.3%, and low-grade proteinuria (<3.5 g/24 h) in 41.4%. Among adults, hypertension was present in 45.2%, mild renal insufficiency in 23% (sCr 111-200 micromol/l) and advanced renal insufficiency in 13.7% (sCr 201-400), while 11.5% of patients had sCr >400 micromol/l. The most frequent renal diseases were primary (59.8%) and secondary (25.4%) glomerulonephritis (GN). Tubulointerstitial nephritis (TIN) was observed in 4.4% and hypertensive nephroangiosclerosis in 3.4%. The samples were non-diagnostic in 4.6%. Among primary GNs, the most frequent diagnoses were: IgA nephropathy (IgAN) 34.5%, minimal change disease (MCD) 12.4%, non-IgA mesangioproliferative GN (MesGN) 11.3%, focal segmental glomerulosclerosis (FSGS) 10.8% and membranous GN (MGN) 9.3%. Among secondary GNs, systemic lupus erythematosus (SLE) represented 23.0%, necrotizing vasculitis (NV) 15.5%, Henoch-Schonlein purpura 5.7%, thin basement membrane glomerulopathy (TBN) 19.3%, Alport syndrome 6.9%, renal amyloidosis 9.9% and myeloma kidney 2.9%. Among children, the most common were IgAN (19.2%), MCD (17.6%) and TBM glomerulopathy (12.3%), while among the elderly the most common were MGN (11.0%), NV (10.7%) and amyloidosis (9.6%). The most common in patients with nephrotic proteinuria were MCD (50.5%) among children, but IgAN (24.6%) in adults aged 16-60 years and MGN (16.8%) among the elderly. IgAN (21.3%) and FSGS (8.3%) were the most common diagnoses among patients with mild renal insufficiency, but TIN (11.6%) and NV (11.3%) were the most common in more advanced renal insufficiency. Since 1999, diabetic patients represented 12.2% of adults, with mean proteinuria 8.9 g/24 h; diabetic glomerulosclerosis was found in 42.4% (with microhaematuria present in 66%) and non-diabetic renal diseases in 47.5% (IgAN in 17.5%, MGN and NAS in 11.1% and NV in 9.5%). The mean annual incidence (per million population) was: primary GN 32.4, secondary GN 13.8, IgAN 11.2, MCD 4.0, MesGN 3.7, FSGS 3.5, SLE 3.2, MGN 3.0, TBM 2.7, TIN 2.4 and NV 2.1. Ultrasound needle guidance was used in 56%, preferably in children (79%). The frequency of serious complications (gross haematuria, symptomatic haematoma, blood transfusion) remained at 3%. CONCLUSION: The CRRB provides important data on the epidemiology of GN based on a whole country population.     

Spectrum of glomerulonephritides in adults with nephrotic syndrome in Pakistan

Background  There is currently little information in literature about the pattern of glomerulonephritides (GN) in adults with nephrotic syndrome in this part of the world, particularly that involving the use of immunofluorescence (IMF) and electron microscopy (EM). A few studies reported are based on light microscopic study alone and hence do not reflect the true pattern of GN underlying nephrotic syndrome. We carried out this study in the Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan to determine, for the first time, the true pattern of GN in adult nephrotic patients from Pakistan. SIUT is a tertiary care center for renal and urologic disease in Pakistan. The Histopathology Laboratory of SIUT is equipped with all the modalities, including EM, required for precise diagnosis of glomerular disease. Methods  This is a retrospective clinicopathologic study involving retrieval of clinical and pathological data from a review of original renal biopsy reports of adult patients with nephrotic syndrome who presented at the adult nephrology clinic of SIUT from July 1996 till July 2006. Two cores of renal tissue were routinely obtained. One core was fixed in 10% buffered formalin and processed for light microscopy; the other core was divided into two halves, for EM and the IMF study. Results  A total of 316 adult patients were included. Of these, 201 (63.6%) were male and 115 (36.4%) were female. Mean age was 28.4 ± 10.51 years with a range of 16–78 years. The spectrum of pathological lesions in the adult nephrotic population was wide and comprised focal segmental glomerulosclerosis (FSGS) (39.87%), followed by membranous GN (MGN) (26.58%), minimal change disease (MCD) (14.82%), mesangiocapillary GN (4.3%), mesangioproliferative GN (4.11%), post-infectious GN (2.84%), IgA nephropathy (2.53%), and other rare lesions. Conclusions  Results from this study indicate that FSGS is the single most common cause of nephrotic syndrome in adult nephrotic patients, followed by MGN, and MCD. Our data are similar to those reported in recent series from the US. The study defines the pattern of glomerular disease in adult nephrotic patients for the first time in this region, because it is based on light microscopy, serology, IMF, and EM findings. Disclosure: No financial interest of any of the authors is involved. The authors declare that the results of this paper have not been published previously in whole or in part, except in abstract form.     

Tumor necrosis factor-α production from mononuclear cells in nephrotic syndrome

Tumor necrosis factor-alpha (TNF-alpha) levels in supernatant fluid from cultured peripheral blood mononuclear cells (PBMC) were measured by ELISA in 54 children with active non-inherited forms of primary nephrotic syndrome (PNS), 10 nephrotics in remission, and 10 healthy controls. Children with active PNS included 21 patients with steroid-sensitive (SS) minimal change nephrotic syndrome (MCNS), 5 patients with steroid-resistant (SR) MCNS, 11 with SR focal segmental glomerulosclerosis (FSGS), 6 patients with SS diffuse mesangial proliferation (DMP), 5 patients with SR DMP, and 6 patients with mesangiocapillary glomerulonephritis (MCGN). Patients with active PNS had elevated TNF-alpha production compared with controls. Remission was associated with normalization of TNF-alpha production. There was a positive correlation between TNF-alpha production and the degree of proteinuria ( r=0.34, P=0.013), mesangial hypercellularity ( r=0.42, P=0.028), and glomerulosclerosis ( r=0.46, P=0.001). By using ROC curve, TNF-alpha production greater or equal to a cut-off point of 50 pg/ml could be used to predict resistance to steroid therapy (predictability 93.2%). By discriminate analysis, TNF-alpha production could be used to discriminate between patients with SR MCNS, SR FSGS, and SR DMP (predictability 100%). In conclusion, TNF-alpha from cultured PBMC might be involved in the pathogenesis of proteinuria as well as the pathological changes that occur in non-inherited forms of PNS. TNF-alpha levels in PBMC culture could be used to predict the pathological type of PNS and the response of these patients to steroid therapy.     

Primary glomerulonephritides with nephrotic syndrome. Limitations of therapy in adult patients

Thirty years of clinical studies have shown that a correct therapeutic approach to human glomerulonephritides with nephrotic syndrome requests the evaluation of three important parameters such as renal biopsy, long monitoring of daily proteinuria and renal function. In addition, age and clinical manifestations should be considered. Corticosteroids, alkylating agents (cyclophosphamide, chlorambucil) and purine analogues are currently used in the treatment of primary glomerulonephritis (minimal-change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous (MGN) and membranoproliferative glomerulonephritis (MPGN)), however results are different. Patients with nephrotic syndrome in MCD when treated with corticosteroids and/or cytotoxic drugs have complete or partial remission in a more than 90% of cases. On the contrary, nephrotic FSGS remits completely or partially only in 50% of treated cases when a more aggressive and prolonged immunosuppressive therapy is carried out. Data from clinical trials in MGN patients are controversial, however it is evident that a greater percentage of patients with stage 1 and stage 2 renal lesions benefit from corticosteroids in association with immunosuppressive drugs. Finally, no encouraging data have been obtained by clinically controlled trials in patients with MPGN. Future perspectives suggest the use of other drugs such as receptor blockade of cytokines and growth factors, administration of cytokine antagonists, intracellular signalling blockade and gene therapy with antisense oligonucleotides. Unfortunately, until specific therapies become available, we have to use unspecific or only symptomatic therapy.     

Increasing incidence of focal segmental glomerulosclerosis and an examination of demographic patterns

BACKGROUND: Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of the nephrotic syndrome in adults and an important cause of end-stage renal disease. Its incidence has dramatically increased in the last two decades and it is especially prevalent among black patients. The trend of FSGS incidence has not been reported beyond 1997. METHODS: We retrospectively reviewed all renal biopsies performed at our institution between 1986 and 2002 and identified patients with diagnoses consistent with primary glomerulopathy (PG), which included: minimal-change disease (MCD), idiopathic focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN), IgA nephropathy (IgA), membrano-proliferative glomerulonephritis (MPGN) and mesangioproliferative glomerulonephritis. Patients with possible secondary causes for their renal disease were excluded. Clinical data at the time of biopsy and follow-up data were collected and analyzed. RESULTS: During the period from January 1986-December 2002, 299 renal biopsies were performed and 132 patients were diagnosed with PG. FSGS was the most common form of PG representing 37.8% of all PG followed by IgA 27.3%, MGN 16.6% and MCD 9.1%. Among FSGS patients 59% were females, 64% had nephrotic range proteinuria and 54% had the nephrotic syndrome. Mean serum creatinine was 2.0 +/- 0.2 mg/dl and mean protein excretion was 6.1 +/- 1.0 g/day. The incidence of FSGS increased from 19.3% (1986-1991) and 16.6% (1992-1997) to 58.5% in the period from 2002. The increase occurred among black and Hispanic patients (33.3-79.2%) as well as white patients (12.5-51.5%). Black and Hispanic patients with PG presented for renal biopsy at a significantly younger age than white patients (p = 0.003), with mean age 37.5 +/- 2.0 years vs. 50.3 +/- 1.8 years. White FSGS patients were significantly older than white non-FSGS patients (mean age 56.4 +/- 3.2 years vs. 48.0 +/- 2.0 years, p = 0.03). Black and Hispanic FSGS patients were also older when compared to their non-FSGS counter-parts (mean age 40.6 +/- 2.8 years vs. 32.1 +/- 2.0 years, p = 0.04). When patients were stratified by age (< 45 years and > or = 45 years), FSGS was the most common diagnosis in both age groups among black and Hispanic patients (55.1% and 88.8%) but only among older white patients (36.2%). CONCLUSIONS: The incidence of FSGS as a proportion of PG in our population has increased markedly in the most recent time period analyzed (1998-2002). The increase has occurred among both white and black and Hispanic patients. We also found that FSGS was most prevalent in patients > or = 45 years.     

Do current recommendations for kidney biopsy in nephrotic syndrome need modifications?

The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study their usefulness in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis (MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or more clinical (hematuria and hypertension) or biochemical (renal insufficiency) parameters were present in all children with MPGN. Low C3 was present only in children with MPGN. All the steroid responders were found to have MCD, FSGS, or MesPGN on biopsy. Cyclophosphamide response correlated better with steroid responsiveness (P=0.02) than with histo- pathology (P=0.80) in MCD, FSGS, and MesPGN. Based on these observations, we suggest some modifications in current recommendations for kidney biopsy to minimize biopsying children with MCD. These are (1) biopsies in children (age 1–16 years) should be restricted (a) to a subgroup with two or more clinical and biochemical parameters and (b) in steroid non-responders, (2) the decision to administer cyclophosphamide should be based on steroid response pattern without requiring a prior routine biopsy. Received: 16 July 1999 / Revised: 20 November 2001 / Accepted: 24 November 2001     

Virus-related glomerular diseases: histological and clinical aspects

Viral infections can be the causative agent in many glomerular diseases, and diagnostic criteria include clinical and laboratory data and tissue molecular analysis. Hepatitis B virus (HBV) is a well known cause of membranous glomerulonephritis (MGN), membranoproliferative GN (MPGN) and IgA nephropathy (IgAN), frequently in Asian populations. Hepatitis C virus (HCV), besides cryoglobulinemia-mediated glomerulonephritis (GN), is reported to cause other forms of GN. Human immunodeficiency virus (HIV) infection is closely related to a collapsing focal segmental glomerulosclerosis (FSGS), a distinct disease that affects mainly Africans and African-Americans. In the course of HIV infection other immune complex (IC) GN can occur, most frequently in whites. Nephrotic syndrome and progression to renal insufficiency are the main clinical manifestations. HIV-HCV co-infection is related to an IC glomerular disease, sometimes with immunotactoid deposits. Recent reports emphasize the role of parvovirus B19 (PV B19) for "idiopathic" collapsing FSGS and ICGN, and of Coxsackie B virus for IgAN. Renal biopsy is useful for defining virus-related glomerular lesions and a guide for prognostic and therapeutic evaluation.     

Impact of immunofluorescence on the histological pattern of pediatric kidney biopsies from northern Pakistan

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).     

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).     

Remission of hepatitis B virus-associated membranoproliferative glomerulonephritis in a cirrhotic patient after lamivudine therapy

We describe a 39-year-old man with hepatitis B virus-(HBV) related chronic hepatitis who presented with nephrotic syndrome and decompensated cirrhosis. A kidney biopsy revealed membranoproliferative glomerulonephritis (MPGN) which was thought to be related to the HBV infection. Because interferon-alpha therapy was generally not recommended in patients with advanced liver disease, we chose lamivudine as an alternate treatment for the HBV-associated glomerulonephritis (GN). After 3-month treatment with oral lamivudine, resolution of the renal disease dramatically occurred together with improvement in liver function. To our knowledge, this is the first case of HBV-associated MPGN successfully treated with oral lamivudine therapy. The possible role of lamivudine in the treatment of HBV-associated GN is discussed.     

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children

Hepatitis B virus (HBV)-associated glomerulonephritides have been increasingly reported, and the association between HBV and glomerulopathy is striking, especially in children. In this study, we investigated clinical and immunohistological features of HBV-associated glomerulonephritis in 14 children aged from 2.5 to 16 years (mean 10 years). The nephrotic syndrome was present in 9 (64%) and the nephritic syndrome in 8 children (57%). Five children had both nephrotic and nephritic syndrome together (35%). Renal insufficiency was determined in 4 of 14 patients (28%). Surface antigen (HBsAg) was present in all, with no history of clinically apparent hepatitis. Investigation of all renal tissue samples with light and immunofluorescence microscopy confirmed the diagnosis of membranous glomerulonephritis (MGN) in 6, membranoproliferative glomerulonephritis (MPGN) in 7, and IgA nephropathy (IgAN) in 1 child. Renal tissue samples were studied by the immunoperoxidase method for HBsAg in all cases; only in 4 children was HBsAg detected in the glomeruli. Examination of liver tissue samples was available in 4 cases, revealing chronic hepatitis in all, with additional development of cirrhosis in 1 and the presence of HBsAg in hepatocytes in all. Of the patients, 8 received corticosteroid treatment; 1 of them achieved a complete remission, while 4 had a partial remission with persistent proteinuria and hematuria. Four patients who received no treatment had a spontaneous remission within 5 months to 10 years following the onset of the renal disease. Two patients died of renal failure, while 1 died of intercurrent sepsis. The patient with IgAN received interferon-alpha 2a and lamuvidine, which resulted in a remission and a marked decrease in HBV DNA titer. The remaining 2 were lost to follow-up. Although MGN has been reported as the nephropathy most commonly associated with HBsAg antigenemia in adults, our study revealed that MPGN could occur in children as well as MGN, without any clinical or historical evidence of hepatitis. The present study provides further evidence for a causal relationship between HBV hepatitis and HBs antigenemia-related glomerulonephritides in the pediatric age group. It also indicates the prognosis (71%) of the associated nephropathies with or without treatment is quite favorable in childhood.     

Glomerular volume and renal function in children with different types of the nephrotic syndrome

Glomerular hypertrophy has been suggested to be an important factor in the pathogenesis of focal glomerular sclerosis. The aim of the present study was to analyse retrospectively the renal biopsies of 58 children (0.2–16.1 years of age) with different types of the nephrotic syndrome, minimal change nephrotic syndrome (MCNS), diffuse mesangial proliferation (DMP) and focal segmental glomerulosclerosis (FSGS). Glomerular surface area was measured and glomerular volume was calculated and related to steroid responsiveness and to renal function, measured by clearances of inulin and para-aminohippuric acid. Glomerular volume correlated with body surface area (BSA) and age. Because of this, patients with FSGS and DMP were matched according to BSA and age, with corresponding MCNS patients. Glomerular volumes of FSGS and DMP patients were significantly larger than those of MCNS patients. In the MCNS patients, significant correlations were found between glomerular volumes and glomerular filtration rate and effective renal plasma flow. Steroid-dependent and steroid-resistant patients showed larger glomeruli than the steroid-responsive children. We suggest that hyperfiltration and hyperperfusion, among other factors, may contribute to glomerular hypertrophy, mesangial proliferation and glomerulosclerosis.     

Remission of hepatitis B-associated membranous glomerulonephritis in human immunodeficiency virus infection

Hepatitis B virus (HBV) infection has been associated with several renal diseases, the most common being membranous glomerulonephritis (MGN). The role of concurrent human immunodeficiency virus (HIV) infection in affecting the course of the renal involvement is largely unknown. We report the case of a HIV-infected adult male with chronic HBV-associated MGN who had complete remission of the nephrotic syndrome associated with spontaneous seroconversion from hepatitis B e antigen (HBeAg)-positive to HBeAg-negative. The present case illustrates that HIV infection does not preclude improvement of chronic HBV infection or an associated membranous nephropathy. Such improvement may be dependent on the ability of the host immune system to clear HBeAg.     

Histopathological spectrum of childhood nephrotic syndrome in Indian children

Nephrotic syndrome in children is a clinical manifestation of different histopathological subtypes. There is a paucity of recent large studies dealing with the histopathological spectrum from developing countries. A prospective study was performed from January 1990 to December 2000 at our center, involving 600 children (with age of onset up to 16 years) with idiopathic nephrotic syndrome (INS). The objectives were: (1) to study the histopathological distribution of different subtypes of INS and (2) to compare the clinical and biochemical parameters at the time of diagnosis of minimal change disease (MCD) with non-MCD subtypes. For the purpose of this study we analyzed only those children with INS who underwent biopsies. The study group included 290 children in which adequate biopsy reports were available. There were 213 males and 77 females. Mean age at onset of INS was 7.9+5.1 years. Facial edema was found in 286 (98.6%), microhematuria in 120 (41.3%), gross hematuria in 7 (2.5%), and hypertension in 77(26.8%) patients. All patients of the study group were seronegative for HBsAg and HIV. Focal and segmental glomerulosclerosis (FSGS) was the most common histopathological subtype, occurring in 110 of 290 children (38%). Other subtypes included MCD in 95 children (32%), membranoproliferative glomerulonephritis (MPGN) in 44 children (15%), mesangioproliferative glomerulonephritis in 33 children (11%), membranous glomerulonephritis in 5 children (2%), and diffuse mesangial sclerosis in 3 children (1%). In children under 8 years of age, MCD was the most common entity, whereas FSGS predominated in children with age at onset greater than 8 years. The age at onset of nephrotic syndrome was significantly higher in the non-MCD group than the MCD group. The incidence of hypertension, microhematuria, and gross hematuria was significantly lower in the MCD group. MCD remains the most common histopathological subtype in Indian children with INS and onset under 8 years of age. The incidence of MPGN continues to be high. MCD can be differentiated from non-MCD subtype by younger age at onset, absence of hypertension, and absence of microscopic hematuria.     

Posttransplantation glomerulonephritis: risk factors associated with kidney allograft loss

AIM OF THE STUDY: Chronic glomerulonephritis (GN) is reported as a common cause of late kidney allograft loss. The aim of this study was to identify risk factors associated with kidney allograft loss in the course of posttransplantation GN. PATIENTS AND METHODS: The study analyzed 75 kidney allograft recipients with biopsy-confirmed posttransplantation GN, including 27 cases of immunoglobulin (Ig)A nephropathy (IgAN), 30 of membranous GN (MGN), 6 of mesangiocapillary GN (MCGN); and 12 of focal segmental GN (FSGS). The risk factors for kidney allograft loss, defined as dialysis reintroduction after GN onset, were identified through are historical cohort study. CLINICAL FINDINGS: After the onset of posttransplantation GN, the median time to dialysis introduction was 46 months. The risk factors for kidney allograft loss were as follows: male gender (hazard ratio [HR] = 1.92; 95% confidence intervall [CI] 1.0-3.70; P = .052), initial unsatisfactory kidney function (HR = 1.86 per 1 mg/dL serum creatinine increment; 95% CI 1.0-3.46; P < .05), graft dysfunction at diagnosis (HR = 1.65 per 1 mg/dL serum creatinine increment; 95% CI 1.32-2.07; P < .001), nephrotic syndrome (HR = 2.3; 95% CI 1.13-4.99; P < .05) late-onset GN (HR = 1.1 per each additional year of observation, 95% CI 1.0-1.21; P < .05), and MPGN as a type of GN. Enhanced immunosuppression increased and ACEI and/or statin treatment decreased the risk of return to dialysis, respectively: HR = 1.56, 95% CI 0.76-3.18, P = .22; HR = 0.39, 95% CI 0.16-0.98, P = .0037; and HR = 0.367, 95% CI 0.15-0.88, P = .025. CONCLUSIONS: Identification of risk factors can help discover patients who will have a faster progression to kidney allograft loss due to GN. In posttransplantation GN, statins and/or ACEI should be prescribed, if there are no contraindications.     

Recurrent and de novo renal disease after kidney transplantation with or without cyclosporine A

We evaluated the clinical course of 700 renal transplantations, including 1,305 transplant histologies performed in 611 patients between 1970 and 1988, to estimate the influence of cyclosporine A (CsA) after kidney transplantation on the incidence of recurrent or de novo renal disease. Primary renal disease recurred in 11 of 583 functioning transplants (1.9%) with transplant loss in seven patients (1.2%): focal segmental glomerulosclerosis (FSGS, three patients); membranous glomerulonephritis (GN, one patient); mesangiocapillary GN (one patient); rapidly progressive IgA nephropathy (one patient); hemolytic-uremic syndrome (HUS, three patients); and oxalosis in two transplants (one patient). De novo renal disease occurred in six patients (1.0%), including mesangiocapillary GN type I (three patients); nonpurulent focal GN in septicemia (one patient); HUS (one patient); and nodular glomerulosclerosis in steroid diabetes (one patient). De novo membranous GN was seen in 14 additional cases (2.4%). No statistically significant difference could be established between the treatment groups without (n = 225) and with (n = 358) CsA in recurrent and de novo renal disease (n = 7/225 v 10/358, NS); in recurrent and de novo GN (n = 4/225 v 6/358, NS); in recurrent FSGS (n = 1/7 v 2/8, NS); in recurrent and de novo HUS (n - 1/1 v 2/7, NS); and in de novo membranous GN (n = 7/225 v 7/358, NS). Transplant loss by recurrent and de novo GN was higher without than with CsA (n = 4/4 v 1/6, P = 0.004). On the basis of our investigation, we conclude that recurrent and de novo renal disease in the transplant occur rarely and are not prevented by CsA. However, even if the incidence of transplant GN is unchanged by CsA treatment, its clinical course seems to be mitigated. CsA treatment also does not increase the incidence of HUS.     

C1Q nephropathy in children

C1q nephropathy (C1qNP) is a peculiar form of glomerulonephritis characterized by mesangial immunoglobulin and complement deposits, predominantly C1q, with no evidence of systemic lupus erythematosus. We describe the incidence, manifestation, histopathologic findings, follow-up, treatment and outcome of C1qNP. Twelve C1qNP patients were identified among 131 children who had undergone renal biopsy, accounting for a 9.16% incidence of C1qNP. Light microscopy examination showed focal segmental glomerulosclerosis (FSGS) with or without diffuse mesangial proliferation (n=6), minimal change disease (MCD) (n=4) or focal glomerulonephritis (n=2). C1q deposits were found in all, while electron microscopy revealed visible deposits in nine cases. Eight children presented with nephrotic syndrome, while one had nephrotic proteinuria and renal insufficiency that progressed to end-stage renal failure. The remaining three patients presented with nonnephrotic proteinuria associated with microhematuria, hypertension or renal insufficiency. Only one nephrotic syndrome patient responded excellently to corticosteroids, while four became corticosteroid dependent, and three were corticosteroid resistant, showing a very poor response to other immunosuppressive therapy as well. Patients with non-nephrotic proteinuria demonstrated fixed laboratory findings. Most C1qNP patients had FSGS or MCD, the majority of them presenting with corticosteroid-dependent or corticosteroid-resistant nephrotic syndrome. The latter showed a very poor response to any immunosuppressive therapy and high risk for progressive renal insufficiency.     

Membranous glomerulonephritis associated with hepatitis B antigen in children: a comparison with idiopathic membranous glomerulonephritis

The laboratory and pathological findings are reported for 16 children with membranous glomerulonephritis (MGN) associated with hepatitis B virus (HBV) infection and compared with those of 12 children with idiopathic MGN. Serum hepatitis B surface antigen (HBsAg) was found in all children with HBV associated MGN and serum hepatitis B e antigen (HBeAg) in 11 of the 15 examined. Five patients with HBV associated MGN, but none with idiopathic MGN, showed reduced serum C3 values. Otherwise there was no difference in laboratory findings. HBeAg was detected in the glomeruli of all 7 patients with HBV-associated MGN examined but HBsAg was not detected. Of the 14 children with HBV-associated MGN examined by electron microscopy, all but one showed small mesangial deposits and 4 subendothelial deposits, whereas of 9 with idiopathic MGN only 2 showed mesangial deposits and none subendothelial deposits. Thus most of the children with HBV-associated MGN are characterized by some laboratory and pathological features of membrano proliferative glomerulonephritis in addition to those of idiopathic MGN. These observations are consistent with HBV inducing a spectrum of glomerulopathy from typical MGN to typical membranoproliferative glomerulonephritis.