Glomerular lesions in the transplanted kidney in children

The glomerular pathology of 634 transplant specimens (526 biopsies and 108 transplantectomies) from 410 children was studied. Three types of glomerulopathies were observed: (1) recurrent glomerulonephritis (GN) (40 of 142 patients with glomerular nephropathy), (2) de novo GN (52 grafts), and (3) transplant glomerulopathy (29 grafts). The study of recurrent GN is considered of great interest because of the possible insight into the nature of the original disease and the opportunity to observe the evolution of the disease in sequential biopsies of the transplant. The two major forms of de novo GN were membranous GN and IgG linear deposits along glomerular and tubular basement membranes. Transplant glomerulopathy, although distinctive morphologically, may resemble membranoproliferative GN (MPGN) or thrombotic microangiopathy.     

Pattern of glomerular diseases among adults in Rajshahi, the Northern Region of Bangladesh

To obtain a recent and comprehensive insight into the pattern of glomerular diseases in the Bangladeshi population, we studied 95 adequate renal biopsies done during July 2008 to June 2009, by light and direct immunofluorescence microscopy in the Department of Pathology, Rajshahi Medical College, Northern Region of Bangladesh. Of these, 38 (40%) were males and 57 (60%) were females, with a male to female ratio of 1:1.5. The most frequent clinical presentation was nephrotic syndrome (67.37%). Primary glomerular disease accounted for 91.25% of all glomerular disease and, of them, focal and segmental mesangial proliferative glomerulonephritis was the most common histological lesion in 29.47%. Diffuse mesangial proliferative glomerulonephritis (GN) was the second most common lesion (15.79%), followed by focal segmental GN (11.58%), minimal change disease (10.53%), membranous GN (7.37%), IgA nephropathy (6.85%), chronic sclerosing GN (2.11%) and crescentic GN (2.11%). Lupus nephritis was the most prevalent among secondary GN.     

Paulista Registry of glomerulonephritis: 5-year data report.

BACKGROUND: The Paulista Registry of Glomerulopathies was created in May 1999 and comprises several centres of S?o Paulo, the most populous Brazilian State, that concentrates people from all regions of the country who look for health care. METHODS: This report includes data from 2086 patients from Brazil submitted to renal biopsy due to the presumed diagnosis of glomerular diseases, registered prospectively since May 1999 until January 2005. Data were collected by the integrants of the 11 centres involved, utilizing a standardized questionnaire. RESULTS: The mean age of the patients was 34.5+/-14.6 years. Primary glomerular diseases were more frequent in males (55.1%) than in females; on the other hand, secondary glomerular diseases were more frequent in females (71.8%). The most common clinical presentation was nephrotic syndrome and the frequency of hypertension, at this time, was 55.5%. There was a predominance of indication of biopsies in the third, fourth and fifth decades of life. The most common primary glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%). The most frequent secondary glomerular disease was lupus nephritis, corresponding to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%), diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%), hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary focal segmental glomerulosclerosis (0.6%) and others (0.9%). CONCLUSION: Focal segmental glomerulosclerosis was the most frequent primary glomerular disease, followed by membranous nephropathy and IgA nephropathy. Lupus nephritis predominated over all the other secondary glomerular diseases.     

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.     

Renal allograft glomerulopathy and the value of immunohistochemistry

Studies of late renal allograft biopsies focus on chronic damage investigated by light microscopy (LM). We evaluated the use of immunohistochemistry (IH) as applied in the routine study of transplant glomerulopathies. Among renal transplants in 1985 - 1997, 129 were identified where a graft biopsy had been obtained 6 months or more after transplantation, studied by LM and IH and the original renal disease was known. IH results were evaluated in relation to glomerular LM findings and the original diagnosis. The risk of graft loss in relation to recurrent and de novo glomerulopathy was evaluated. By LM, 69 biopsies (53%) showed glomerulopathy, mesangial sclerosis only in 26, proliferative changes in 15, membranous in 15 and combined membranous and proliferative in 13. By IH, 46 biopsies (36%) stained positive with IgM and/or complement only and 24 with immune complexes including IgA and/or IgG. Seven biopsies (5.4%) showed glomerular disease by IH in spite of normal LM. Recurrence was diagnosed in 22 grafts; 12 had IgA nephropathy, 3 had SLE, 6 other immune complex nephritides and 1 systemic vasculitis. Twenty-eight biopsies (22%) with proliferative and/or membranous glomerulopathy lacked clear connection to the original renal disorder. More than half of these had deposits of IgM and C3 only. The further graft survival was significantly reduced in the presence of de novo glomerulopathy by LM, relative risk 2.0 (confidence interval 1.1 - 3.8) in a Cox-proportional hazards analysis also including serum creatinine and Banff chronic allograft nephropathy (CAN) grade, p = 0.03. In conclusion, transplant glomerulopathy should be separated from recurrence. De novo glomerulopathy is frequent and ominous.     

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.     

Clinicopathological study of originally non-lupus “full-house” nephropathy

Background: Glomerular “full-house” immunofluorescence staining commonly indicates lupus nephritis. However, some non-lupus nephropathy also can present with a “full-house” immunofluorescence pattern mimicking lupus nephritis. The goal of this study is to define the clinicopathological spectrum of originally non-lupus “full-house” nephropathy. Methods: Records of 24 patients with “full-house” nephropathy in the absence of clinical or serological evidence of systemic lupus erythematosus (SLE) at the time of renal biopsy were abstracted for demographics, clinical presentation, laboratory data, renal biopsy findings, and clinical follow-up. Results: The clinicopathological diagnoses included membranous glomerulonephritis (GN) (46%), IgA nephropathy (21%), membranoproliferative GN (12.5%), postinfectious GN (12.5%), C1q nephropathy (4%), and unclassified mesangial GN (4%). No one had endothelial tubuloreticular inclusions. One patient originally diagnosed as IgA nephropathy developed anti-DNA antibody and another one patient with membranous GN developed hypocomplementemia 8 months and 10 months after renal biopsy, respectively. The two patients also developed clinical symptoms of lupus subsequently. Conclusions: There was a broad spectrum of glomerular histological findings in non-lupus “full-house” nephropathy. The possibility of “full-house” nephropathy preceding the emergence of overt systemic lupus erythematosus remained to be elucidated.     

Nephrotic syndrome in Namibian children.

BACKGROUND AND OBJECTIVES: Patterns of nephrotic syndrome vary between regions and countries, and influence approaches to management. In the mid-1970s the University of Stellenbosch became involved in providing tertiary care to Namibia, including a paediatric nephrology service. The aim of this study was to document the clinical, pathological and outcome features of nephrotic syndrome in Namibian children. SUBJECTS: Seventy black Namibian children with nephrotic syndrome were managed from 1975 to 1988. Sixty-eight renal specimens (67 biopsies and 1 autopsy specimen) were evaluated. RESULTS: Twenty-nine of the 70 children (41.4%) were hepatitis B virus (HBV) carriers, of whom 25 (86.2%) were male. Of the 29, 26 had predominantly membranous glomerulonephritis (MGN), 1 mesangiocapillary glomerulonephritis (MCGN), and 1 focal segmental glomerulosclerosis (FSGS); 1 child in advanced renal failure was not biopsied. Five children (7.4%) showed minimal change disease (MCD), 11 (16.2%) FSGS and 15 (22.1%) diffuse mesangial proliferative glomerulonephritis (DMP). The remaining 10 children showed diffuse glomerulosclerosis (6), MCGN (3) and endocapillary proliferative GN (1). Four of the 5 children with MCD went into remission on immunosuppressive treatment. Of the 15 with DMP, 4 improved spontaneously and only 1 of those treated did not improve. Only 2 of those with FSGS improved on treatment. The children with HBV-associated MGN and MCGN were offered symptomatic rather than specific treatment. Thirteen children presented with degrees of chronic renal failure. Eight are known to have died, 3 of relentless nephrotic syndrome and 4 (of whom 3 were HBV carriers) of end-stage renal failure. One child died of penicillin anaphylaxis. CONCLUSIONS: The pattern of nephrotic syndrome in black Namibian children differed greatly from the non-African pattern elsewhere in that MCD was uncommon and HBV-associated GN was the most common single group. The most frequent pattern of HBV-associated GN was MGN with some mesangiocapillary features showing marked male predominance. MCD and DMP were potentially treatable and could only be identified by biopsy. HBV carrier rates exert a major influence on the proportions of morphological subgroups of nephrotic syndrome in children. As these HBV carrier rates alter in future due to the influence of vaccination and urbanisation, the relative size of nephrotic subgroups seems likely to alter.     

Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?

AIMS: Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979-1999. METHODS: The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. RESULTS: We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979-1983), 23.7% (1984-1988), 35.7% (1989-1993), 33.9% (1994-1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994-1999. CONCLUSIONS: FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.     

De novo glomerulonephritis in renal allografts with hepatitis C virus infection

The purpose of this study was to examine the influence of hepatitis C virus (HCV) infection on the occurrence of posttransplant de novo glomerulonephritis (GN). Of 165 patients selected for the study, 44 were HCV positive and 121 HCV negative. Light and immunofluorescence microscopy were performed on all biopsies and clinical and laboratory findings reviewed. Fifteen (34%) of the 44 HCV positive patients showed de novo GN (4 membranous, 11 membranoproliferative) at a mean of 47 +/- 22 months. But only 8 (6.6%) of 121 HCV negative patients showed de novo GN (5 anti-glomerular basement membrane nephritis in recipients with Alport's disease, 2 membranous GN, 1 membranoproliferative GN) at a mean of 60 +/- 39 months. The risk of development of de novo GN was higher among patients with HCV infection (P < .001). The presence of de novo GN in HCV positive patients impaired graft survival compared with HCV positive patients without de novo GN (P < .01). The incidence of recurrence of primary disease, mainly focal segmental glomerulosclerosis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and IgA nephropathy, was higher in HCV negative patients (29%) compared with HCV positive patients (6.8%; P = .001), namely, 50%, 57.6%, 25%, and 69%, respectively. In conclusion, HCV infection showed a strong influence on the development of de novo GN. For this reason, it is important to follow HCV positive recipients with a renal biopsy even when there are no significant clinical or laboratory findings.     

Glomerular disease in cirrhosis of the liver: low frequency of IgA deposits

Twelve HBsAg-negative patients with histologically documented cirrhosis of the liver of either alcoholic (8 of 12) or cryptogenic (4 of 12) origin underwent renal biopsy to investigate proteinuria, hematuria and/or renal failure. Immunofluorescence was positive for IgA in 2 patients with mesangiocapillary glomerulonephritis (MCGN) and could not be performed in 2 additional patients with the same diagnosis. However, in the remaining 8 patients, immunofluorescence was negative for IgA and frequently positive for C3, IgG, IgM and/or fibrinogen. These 8 patients without IgA were classified as follows: MCGN with subendothelial electron-dense deposits (2 cases), IgM-IgG cryoglobulinemia with diffuse endocapillary glomerulonephritis (1 case), membranous nephropathy (1 case), diffuse endocapillary proliferative glomerulonephritis (1 case), vasculitis with focal segmental necrotizing glomerulitis and crescentic glomerulonephritis (2 cases). These results show that cirrhosis of the liver can be associated with a wide variety of glomerular disorders. Contrary to previous belief, IgA is absent in two thirds of patients with cirrhosis and glomerulopathy. Therefore, the pathogenetic importance of IgA in the development of glomerular disease in such patients is doubtful.     

Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA?

Over the past decade, focal segmental glomerulosclerosis (FSGS) has emerged as the most common primary glomerulopathy in adults in the USA. However in our practice, we became aware of increased numbers of patients with IgA nephropathy (IgAN). In order to further examine this, a retrospective analysis of renal biopsy diagnoses from adults was done from our biopsy database. Adult renal biopsies received from 3/1/2001 to 2/28/2005 were analyzed to determine the frequency of common primary glomerulopathies, which included FSGS, IgAN, membranous nephropathy (MN), minimal change disease, and membranoproliferative glomerulonephritis Type I (MPGN). The patients were grouped as all adults (>or=20 years) and young adults (20-39 years). The distribution of common primary glomerulopathies among the two age groups, expressed as a percentage of all non-transplant diagnoses (n = 4,504), was IgAN 6.9/3.4%, FSGS 9.6/3.2%, MN 6.8/1.6%, minimal change disease 2.5/0.9%, MPGN 1.2/0.2%. IgAN was as common as FSGS in young adults in our biopsy population (IgAN/FSGS 154/143 1.08:1). IgAN was the most common primary glomerulopathy in young adult Caucasians (IgAN/FSGS 2.1:1). IgAN was also the most common cause of end-stage renal disease (ESRD) in young adult Caucasians. In contrast, IgAN was rare in African Americans in whom FSGS remains more common (FSGS/IgAN 9.7:1). These findings from a large renal biopsy referral center serving 24 Midwestern and Southern states suggest that IgAN may be the most common primary glomerulopathy and the most common cause of ESRD in young adult Caucasians in the USA.     

Clinicopathological features of paediatric renal biopsies in Shanghai over a 31 year period

Aim: To identify the variations in paediatric renal biopsy pathology and clinicopathological features during the past 31 years. Methods: A retrospective analysis of paediatric renal biopsies performed at a single institution in Shanghai from January 1979 to December 2009 was conducted. Results: The major pathologies included minor glomerular abnormalities (MGA, 26.1%), IgA nephropathy (IgAN, 17%) and mesangial proliferative glomerulonephritis (MsPGN) without IgA deposition (11.3%). The major clinical presentations included nephrotic syndrome (NS, 39.4%), haematuria with proteinuria (24.4%) and persistent microscopic haematuria (15.1%). MGA accounted for 46.9% of the cases in NS. IgAN and HSN accounted for 24% and 28.9% of patients with concomitant haematuria and proteinuria, and thin basement membrane nephropathy accounted for 51.2% of cases with persistent microscopic haematuria. The frequency of IgAN (78.6%) was much higher than that of TBMN (29.0%) in patients with persistent microscopic haematuria with abnormal urinary albumin. Conclusion: Minor glomerular abnormalities and IgAN were the major renal diseases in our study population, and the focus of our paediatric nephrologists. The high proportion of TBMN suggested that there should be limited use of renal biopsy for patients with persistent microscopic haematuria and renal biopsy should be performed in the presence of proteinuria or abnormal levels of urinary albumin.     

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.     

Immunohistochemical study of epidermal growth factor receptor (EGFR) in various types of renal injury

Epidermal growth factor (EGF), a polypeptide with a potent mitogenactivity, and its receptor [EGFR] have been previously identifiedin the kidney, but their expression in normal and diseased kidneyshas not been fully elucidated. In order to evaluate EGFR invarious histological types of renal injury, EGFR expressionwas studied by the immunohisto-chemical avidin–biotincomplex (ABC) method with a monoclonal antibody EGFR on paraffinsections from 10 normal kidneys, 56 renal biopsies with varioustypes of glomerulonephritis (GN), and 20 renal grafts with rejection. EGFR expression was observed in (a) 3 of 10 (30%) normal kidneys,(b) 17 of 39 (43.6%) renal biopsies with various types of GNmainly in membranous GN (57%) and in focal segmental glomerulosclerosis(FSG) (62.5%), (c) 6 of 17 (35.3%) biopsies with various typesof systemic lupus erythematosus GN, and (d) 12 of 20 (60%) renalgrafts with acute (42.9%) and chronic (69.2%) rejection. EGFRwas mainly localized to the epithelial cells of the distal andcollecting tubules and extraglomelar vessels, while it was observedless fre quently in parietal epithelial cells and along glomerularbasement membranes. Notably EGFR was detected in the epithelialcells adjacent to adhesions with Bowman's capsule and in theconnective tissue of fibrocellular crescents. In conclusion, EGFR expression was observed more frequentlyin diseased than in normal kidneys. The increased incidenceof EGFR expression in FSG, in chronic rejection, in small adhesionswith Bowman's capsule and fibrocellular crescents suggest thatEGF/EGFR may be correlated with a disturbed extra-cellular matrixproduction resulting in formation of early sclerotic lesions.     

The Pisa experience of renal biopsies, 1977-2005

INTRODUCTION: Although several registries collecting data of patients with kidney diseases exist, only a few specifically collect data relating to renal biopsy. Kidney biopsy has been performed routinely in Pisa since 1977; the aim of this study was to report the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on histological diagnoses during the years 1977 through 2005. During this time, 3,810 kidney biopsies were performed, of which 89.3% were from native (n=3,446) and 10.7% from transplant kidneys. Throughout this period, 5% of renal biopsies were not diagnostic, so in this paper we report data regarding 3,269 native kidney nephropathies. METHODS: During the years 1977 through 2005, data for renal biopsies were collected on specific registers filled out by clinicians. Information collected in the database included a variety of indicators, such as clinical anamnesis, creatinine clearance, daily proteinuria, hemoglobin levels, blood pressure, height and weight, clinical presentation, and current medications. Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS) and acute nephritic syndrome (ANS). Renal diseases were divided into 4 major categories: primary glomerulonephritis (GN), secondary GN, tubulointerstitial nephropathies (TIN) and vascular nephropathies (VN). RESULTS: From 1977 up to 1987, a mean of 95 +/- 18 renal biopsies/year were performed; this number significantly increased to 185 +/- 22 renal biopsies/year (range 138-200) (p<0.001) in the following period (1988-2005). Renal biopsy was more frequently performed in males (59%) compared with females (41%). Of all diseases of the native kidney, primary GN was the most frequent (66%), followed by secondary GN (25.6%), TIN (4.2%) and VN (4.2%). The type of primary GN with the highest frequency was mesangial GN (both IgA and non-IgA) (45.7%), followed by membranous GN (23%), focal segmental glomerulosclerosis (19.8%), minimal change disease (5.3%), crescentic GN (4.2%) and postinfectious GN (2%). In terms of age, renal biopsy was more frequently performed in patients aged 20 to 60 years, and nearly 60% of patients presented a glomerular filtration rate (GFR) >60 ml/min at the time of biopsy. The main clinical reason for performing renal biopsy was UA, in all the types of nephropathies.CONCLUSIONS: We confirm data that renal diseases are more frequent in men, with the exception of secondary GN. The mean age at diagnosis was 42 years resulting from the tendency not to perform renal biopsies in children and in elderly patients. Renal biopsy was mainly performed in patients with GFR >60 ml/min and asymptomatic urinary abnormalities suggesting concern on the part of clinicians regarding glomerular diseases. The tendency to perform renal biopsies has been significantly increasing throughout our follow-up period.     

Tissue-specific expression of renin-angiotensin system components in IgA nephropathy

BACKGROUND: The renin-angiotensin II system (RAS) has been implicated in the development of glomerulonephritis. The aims of this study were to determine (1) the expression of RAS components, angiotensin (Ang II)-forming enzymes [angiotensin-I-converting enzyme (ACE) and chymase], and Ang II receptors, and (2) the correlation between RAS expression and severity of tissue injury in IgA nephropathy (IgAN). METHODS: The expression levels of ACE, chymase, and Ang II type 1 and type 2 receptor (AT1R and AT2R) mRNAs were determined by in situ hybridization in renal specimens from 18 patients with IgAN, 5 patients with non-IgA mesangial proliferative glomerulonephritis (non-IgAN) and 10 patients with nonmesangial proliferative glomerulonephritis (minimal change nephrotic syndrome, n = 5, and membranous nephropathy, n = 5). Normal portions of surgically resected kidney served as control. RESULTS: In normal kidney, a few mesangial cells and glomerular and tubular epithelial cells weakly expressed ACE, chymase and AT1R mRNAs. In IgAN and non-IgAN samples, ACE, chymase, AT1R and AT2R mRNAs were expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells and cells of Bowman's capsule. The glomerular expressions in IgAN were stronger than in minimal change nephrotic syndrome and membranous nephropathy. In IgAN, the expressions in glomeruli correlated with the degree of mesangial hypercellularity, whereas the expression levels were weaker at the area of mesangial expansion. IgAN with severe tubulointerstitial injury showed expression of ACE, chymase, AT1R and AT2R mRNAs in atrophic tubules and infiltrating cells and such expression correlated with the degree of tubulointerstitial damage. CONCLUSION: Our results suggest that renal cells can produce RAS components and that locally synthesized Ang II may be involved in tissue injury in IgAN through Ang II receptors in the kidney.     

Hepatitis C Virus Infection and de Novo Glomerular Lesions in Renal Allografts

In the present study we examine whether hepatitis C virus (HCV) infection status influences glomerular pathologic findings in renal allografts and its effect on graft outcome. Renal allograft biopsies performed between January 1991 and June 1999 were considered. Exclusion criteria were insufficient sample, unknown HCV serological status at time of biopsy and final diagnosis of acute rejection. Light microscopy and immunofluorescence studies were performed on all biopsies. According to a predefined protocol, electron microscopy was carried out. Of 138 eligible renal allograft biopsies, 42 fulfilled at least one exclusion criterion. Of 96 biopsies selected for the study, 44 (45.8%) were from HCV-positive and 52 from HCV-negative recipients. Renal biopsy was performed 74 +/- 55 and 60 +/- 39 months after transplantation in HCV-positive and HCV-negative groups, respectively (p = 0.12). Of 44 HCV-positive biopsies, 20 (45.4%) showed membranoproliferative glomerulonephritis (MPGN) (16 type I and 4 type III). Conversely, in HCV-negative biopsies there were only three cases of MPGN (2 type I and 1 type III). De novo membranous GN (MGN) was diagnosed in 8/44 (18.2%) HCV-positive and in 4/52 (7.7%) HCV-negative cases. The prevalence of chronic transplant glomerulopathy was similar in HCV-positive and HCV-negative groups (11.4% and 11.5%, respectively). The prognosis of de novo GN (either MPGN or MGN) was worse in HCV-positive than in HCV-negative recipients (relative risk 4.89; 95% confidence interval, 1.15-20.69; p = 0.03). By multivariate analysis, HCV-positive serology infection was the only independent predictor of graft loss (relative risk 2.64; 95% confidence interval, 1.35-5.17; p = 0.005). In diagnostic renal allograft biopsies the presence of de novo immune-mediated glomerulonephritis, especially type I MPGN, is strongly associated with HCV infection and results in accelerated loss of the graft.     

Live donor renal allograft in end-stage renal failure patients from immunoglobulin A nephropathy

BACKGROUND: The purpose of this study was to attempt to resolve two important issues, i.e. to determine (1) whether the course of recurrent immunoglobulin A nephropathy (IgAN) is benign, and (2) whether it is advisable to use a related donor. METHODS: We evaluated the long-term outcome, in terms of recurrence and graft survival, after live related or unrelated donor renal transplantation, and assessed the validity of the use of related donors in 90 grafts in 89 IgAN patients. RESULTS: Ten-year graft survival for IgAN patients was 66%, compared with 84% for 107 reference recipients who had other kinds of glomerulonephritis (GN), and with 69% in 90 other recipients who had non-GN renal failure (P=0.27). In 43 grafts, 54 event graft biopsies were performed, documenting the presence of mesangial IgA deposits in 19 of those grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. Ten grafts were lost: by CR (n=3) or acute rejection (n=1) in 24 recurrence-free recipients, by CR (n=2) or recurrence (n=2) in 19 recurrent patients, and by patient death (n=2) in 46 patients devoid of graft biopsy. We found no difference in 10-year graft survival between the recurrent and recurrence-free patients (63% vs. 74%, P=0.98), or the proportion of related donors (68% vs. 83%, P=0.25). The presence or matching of HLA B12, B35, or DR4 did not affect the recurrence. CONCLUSIONS: Recurrence increased to 44% with longer follow-up, but this did not limit the graft outcome. Recurrence was not affected by the kind of live donor. We conclude that live related or unrelated kidneys should be offered to IgAN patients.     

Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies

Renal biopsy specimens of 13,519 cases were collected during the period of January 1979 to December 2002 from the Research Institute of Nephrology, Nanjing University School of Medicine, Nanjing, China. Analysis of the data of this group of patients showed that primary glomerulonephritis (GN) remained the most important and prevalent renal disease in China. The ratio of primary to secondary GN was 2.75:1. However, it is declining progressively in the past two decades with an increment in the incidence of diabetic nephropathy and nephrosclerosis. IgA nephropathy (IgAN) constituted 45.26% of the primary GN, while non-IgA mesangial proliferative lesions were 25.62%. Membranous nephropathy was 9.89% and minimal change disease was 0.93%, remarkably less. The most prevalent etiology of secondary GN was systemic lupus erythrematosus (SLE) (54.3%) followed by Henoch-Sch?nlein purpura (20.3%), diabetic nephropathy (6.6%), systemic vasculitides (4.0%), and amyloidosis (2.2%). Based on the study of biopsy materials obtained from 607 cases manifesting chronic renal failure, IgAN was identified as the most frequent cause (26.69%) of chronic renal failure.