Rapidly progressive renal failure in type 2 diabetes in the tropical environment: a clinico-pathological study

BACKGROUND: Rapid decline of renal function in a diabetic suggests the presence of a nondiabetic kidney disease (NDKD). We designed a prospective study to evaluate the factors associated with a rapid decline in renal function in patients with type 2 diabetes. METHODS: Over a 2 and a half year period, all patients with type 2 diabetes who presented with documented doubling of serum creatinine in less than 4 weeks or recently diagnosed advanced renal failure were identified. Patients with prerenal causes, urinary tract obstruction, or systemic disease causing renal failure were not included. Renal histology was studied in all cases. RESULTS: A total of 26 patients satisfied the inclusion criteria. Over 75% had serum creatinine >4 mg/dL at presentation and 62% were dialysis dependent. Renal histology showed mixed lesions of diabetic nephropathy (DN) and NDKD in 11 cases, only DN in nine, and pure NDKD in six. Diffuse proliferative glomerulonephritis (DPGN) was the commonest NDKD (27% cases), all on a background of DN. History of preceding cutaneous or pharyngeal infection was available in five cases. The proportion of postinfectious glomerulonephritis in diabetics with rapidly progressive renal failure was over six times that of the nondiabetic adult RPRF population during the study period. Four patients had acute interstitial nephritis and three showed crescentic glomerulonephritis. Other lesions included amyloidosis, atheroembolic disease, and renal papillary necrosis (one each). The frequency of microscopic hematuria and retinopathy was similar in those with pure DN and NDKD. Four out of seven cases with DPGN showed partial recovery whereas the other three remained unchanged. CONCLUSIONS: About two-thirds of patients with type 2 diabetes presenting with rapid decline of renal function in a tropical environment show NDKD. The high incidence of postinfectious glomerulonephritis in this group is possibly related to the high prevalence of skin and soft tissue infections; and could contribute to progressive kidney disease.     

Acute Postinfectious Crescentic Glomerulonephritis: Clinicopathologic Presentation and Risk Factors

Background: Glomerular crescent formation is a feature of the most severe forms of human glomerulonephritis. The postinfectious form of rapidly progressive glomerulonephritis with crescents is a form of immune complex glomerulonephritis which seem to have a better prognosis. A relatively poorer prognosis for crescentic postinfectious glomerulonephritis in South Africa has been reported. In the present study, we have tried to determine the mode of presentation, and the prognostic factors for renal and patient outcome for cases with postinfectious crescentic glomerulonephritis (CGN). Methods:Between 1990 and 2000 a total number of 128 patients with CGN were managed at our center, among them 23 cases were diagnosed as postinfectious CGN. They were followed-up for a mean period of 40.1 ± 28.9 months. Among them 12 were males and 11 were females. The median age was 12.35 years (range 4–55 years). The median serum creatinine at presentation was 7.24 mg/dl (range 1.3–14.5 mg/dl). We studied the clinical, laboratory and histopathological data ^.of our cases and their impact on the renal and patient outcome. Results:By univariate study the risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors. The risk factors that significantly affected patient mortality were hypertension and serum creatinine at last follow-up. Conclusion: postinfectious CGN is a severe form of glomerulonephritis that usually presents with rapidly progressive renal failure. The persistence of hypertension and nephrotic range proteinuria during the follow-up are major bad prognostic predictors for renal dysfunction.     

Renal flares in 91 SLE patients with diffuse proliferative glomerulonephritis

BACKGROUND: Even when treated with current protocols, 25 to 30% of systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) evolve to end-stage renal disease (ESRD). The occurrence of renal flares is considered to be an important risk factor for the evolution to ESRD. The aim of this retrospective study was to evaluate the incidence and prognostic significance of renal flares in SLE patients with DPGN and to identify predictors for the occurrence of flares. METHODS: Ninety-one SLE patients were selected for study based on the following criteria: (a) evidence of renal involvement, (b) a follow-up of at least 6 months after the renal biopsy, and (c) a steady improvement in renal manifestations after the biopsy lasting for at least three months. RESULTS: Renal flares occurred in 54% of the patients after renal biopsy and appropriate treatment. A younger age at the time of renal biopsy correlated with the occurrence of renal flares. A high activity index (> or =10) and karyorrhexis on histology correlated with the occurrence of nephritic flares. Twenty-seven percent of the patients developed ESRD. The number of renal flares, nephritic flares, and "early" proteinuric flares (that is, those occurring in the first 18 months after renal biopsy) as well as serum creatinine levels, karyorrhexis, and chronicity index on renal histology were correlated with doubling serum creatinine. CONCLUSIONS: Our results suggest that (a) a distinct subgroup of SLE patients exists, made up of younger patients with extensive, active lesions on renal biopsy, who are at higher risk for renal flares, (b) renal flares represent important predictors of doubling serum creatinine.     

2型糖尿病肾脏病与2型糖尿病合并非糖尿病肾损害的临床及病理比较

目的分析比较2型糖尿病。肾脏病与2型糖尿病合并非糖尿病肾损害的临床及病理特征异同点。方法回顾性分析2008年1月至2011年4月在我科住院的患者,临床诊断2型糖尿病、并有蛋白尿,行经皮肾活检穿刺术病理检查共105例患者的临床病理资料。结果（1）非糖尿病肾损害组5I例,占48．57％,一般情况如糖尿病病程、高血压病程、代谢紊乱及肾脏损害均较2型糖尿病肾脏病轻。病理类型以原发性肾小球疾病为主,病理改变包括。肾小球损伤及小管-间质改变较2型糖尿病肾脏病组轻微。（2）2型糖尿病肾脏病患者54例,占51．43％。病理损伤的严重程度与体质量指数、血肌酐、胱抑素C、视黄醇结合蛋白、尿素氮呈正相关,而与血红蛋白、白蛋白和肌酐清除率呈负相关。结论在f临床上,对于病程长、代谢紊乱及临床肾损害指标严重的患者,考虑2型糖尿病肾脏病可能性大。     

Immunohistochemical staining of renal biopsy samples in patients with diabetic nephropathy in non-insulin dependent diabetes mellitus using monoclonal antibody to advanced glycation end products

Summary: Immunohistochemical staining of glomeruli in patients with diabetic nephropathy (DN) in non-insulin dependent diabetes mellitus (NIDDM) using the monoclonal anti-advanced glycation end products (AGE) antibody is described. In order to detect the localization of AGE in human renal tissues, we performed immunohistochemical staining using the monoclonal anti-AGE antibody in the glomeruli of 11 patients with DN and 11 age-matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls.
Emergence of AGE in the mesangial area was more marked in the glomeruli of patients with severe mesangial expansion than in those with mild expansion. AGE in the extraglomerular arteriolar walls was also observed. In contrast, there was no positive staining using the same antibody in renal tissue obtained from DPGN.
These data support the concept that deposition and/or formation of AGE in the mesangial area might be associated with the progression of diabetic nephropathy.     

The Spectrum of Adult Postinfectious Glomerulonephritis in the New Millennium

Background. Postinfectious glomerulonephritis is rare in adults. The characteristics of the disease now differ from what were described decades ago. The goal of this study is to illustrate the clinicopathological spectrum of the disease in the modern era. Methods. Between July 2000 and June 2008, 20 adult cases of postinfectious glomerulonephritis were identified at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. Results. There were 14 males and 6 females. The mean age was 61 years. All patients developed acute renal failure, and the majority (65%) required dialysis support during the disease course. Hypocomplementemia was present in 60% of patients. The most frequently identified infectious agent was Staphylococcus (60%). Histological characteristics showed two distinct patterns of glomerulonephritis: diffuse endocapillary proliferative glomerulonephritis (65%) and focal mesangial proliferative glomerulonephritis (35%). There were no significant differences in the clinical presentation and outcome between the two groups. However, glomerular neutrophil infiltration was more commonly present in diffuse endocapillary proliferative pattern (p = 0.017). The percentage of patients with focal mesangial proliferative pattern significantly increased over time (p < 0.001). At the last follow-up, 6 patients (30%) had died, 6 (30%) were in complete remission, 4 (20%) had partial remission with renal insufficiency, and 4 (20%) were on chronic dialysis. Conclusions. Our data suggested that Staphylococcus had become the leading pathogen in adult postinfectious glomerulonephritis over the past 10 years. Furthermore, atypical histological feature with focal mesangial proliferative pattern was increasingly identified over time. The prognosis was still guarded, carrying a considerable mortality rate and risk for developing chronic renal failure.     

Renal thrombotic microangiopathy in systemic lupus erythematosus: clinical correlations and long-term renal survival

Background. Renal thrombotic microangiopathy (TMA) is an uncommon vascular complication of systemic lupus erythematosus (SLE). Its clinical symptoms and impact on renal survival remain unclear. Methods. Eight patients aged 25±6 years with biopsy-proven renal TMA and at least four ARA criteria for the diagnosis of SLE were retrospectively studied over a 7-year period. Results. All patients presented with renal failure (creatinine 3.3±2.1 mg/dl), six had proteinuria (2.5±1.3 g/day) with microscopic haematuria in four cases. Six patients had hypertension, which was severe in five cases. Renal histology disclosed arterial and/or arteriolar thrombosis with parietal thickening without angeitis (8 patients), glomerular microthrombi (3 patients), and vascular fibrin deposits (5/6 patients). In two cases, vascular lesions were associated with a mesangial or a proliferative glomerulonephritis. Thrombocytopenia was present in four patients with haemolytic microangiopathic anaemia in one case. Lupus anticoagulant (LA) was detected in five of eight patients, who also had anticardiolipin antibodies (3/7 patients) and/or were positive for VDRL (3/6 patients). Four patients with LA experienced arterial thrombosis and/or repeated spontaneous abortions. Treatment consisted of corticosteroids (8 patients), cytotoxic drugs (4 patients), plasma exchanges and/or intravenous immunoglobulins (4 patients) and antiplatelet and/or anticoagulant therapy (3 patients). Two patients recovered normal renal function and five had persistent renal insufficiency. One patient started haemodialysis on admission and died of sepsis 2 months later. Conclusions. TMA may also be the sole renal complication in SLE and is not usually associated with haemolytic microangiopathic anaemia. In our series renal survival was influenced by the extent and severity of vascular lesions. Despite a frequent association with antiphospholipid antibodies, pathophysiological mechanisms of renal TMA in SLE remain unknown. Renal histology is mandatory for the diagnosis and the prognostic evaluation of renal vasculopathy in SLE.     

507例2型糖尿病合并慢性肾脏病患者肾活检的临床病理特点

目的 总结和分析糖尿病肾病(diabetic kidney disease,DKD)与非糖尿病肾病(non-diabetic kidney disease,NDKD)患者临床病理特点,为临床2型糖尿病合并慢性肾脏病患者肾活检指征提供循证医学证据.方法 通过南方医科大学南方医院大数据库收集2002年2月至2018年6月在该院接受肾活检的2型糖尿病合并慢性肾脏病患者,并根据肾活检结果将其分为DKD组和NDKD组(包括DKD合并NDKD),比较两组间临床表现及病理类型特点,并采用Logistic回归模型分析DKD和NDKD患者的相关因素.结果 共纳入507例患者,DKD患者114例(22.5%),NDKD患者393例(77.5%).病理表现:NDKD的最常见病理类型为膜性肾病(30.0%)和IgA肾病(19.1%),其中有5.6%患者为DKD合并NDKD.临床表现:与NDKD组患者相比,DKD组患者有更长的糖尿病史(>1年,76.3%比36.1%,P<0.001),更易发生糖尿病视网膜病变(42.1%比4.8%,P< 0.001),24h尿蛋白量更高[3.69(1.70,6.74)g比2.21 (0.91,4.97)g,P<0.001],血肌酐更高[117.5 (85.8,194.5) μmol/L比89.0 (68.0,143.8) μmol/L,P<0.001],血红蛋白更低[(105.07±20.85) g/L比(124.41±25.02) g/L,P=0.002],胆固醇更低[(5.69±1.87) mmol/L比(6.43±2.75) mmol/L,P=0.001].Logistic回归分析显示,糖尿病史(OR=4.162,95%CI 1.717~10.098,P=0.002)、较高收缩压(每增加1 mmHg,OR=1.028,95%CI 1.011~1.045,p=0.001)、降压药服用史(OR=3.141,95%CI 1.496~6.591,P=0.002)、糖尿病视网膜病变(OR=5.561,95%CI2.361~13.100,P<0.001)、较高糖化血红蛋白(每增加1%,OR=1.680,95%CI1.333~2.118,P<0.001)是DKD的相关因素,而血尿(OR=2.781,95%CI 1.334~5.798,P=0.006)和较高血红蛋白(每增加1g/L,OR=1.022,95%CI1.008~1.037,P=0.002)则为NDKD的相关因素.结论 DKD与NDKD之间的临床表现及病理类型存在差异,糖尿病病史、眼底检查、大量蛋白尿、降压药服用史、较高的糖化血红蛋白水平对DKD的诊断有较好的预测作用,而血尿和较高的血红蛋白水平对NDKD的诊断有一定指导意义.糖尿病合并慢性肾脏病患者行肾活检的指征需根据各临床表现综合分析.     

Discrimination between postinfectious IgA-dominant glomerulonephritis and idiopathic IgA nephropathy

Background: A unique form of postinfectious glomerulonephritis (PIGN) with IgA-dominant deposition mimicking IgA nephropathy has been increasingly reported. Methods: We compared the clinical and histological features of 12 patients with postinfectious IgA-dominant glomerulonephritis to 134 patients with idiopathic IgA nephropathy. Results: In addition to hypocomplementemia and subepithelial hump-shaped deposits characteristic of PIGN, patients with postinfectious IgA-dominant glomerulonephritis had older age (62.3 ± 16.9 vs. 37.9 ± 16.3 years; p < 0.001) and more frequently presented with acute renal failure (83.3% vs. 10.4%; p < 0.001) than patients with idiopathic IgA nephropathy. Moreover, glomerular changes including endocapillary proliferation, neutrophil infiltration, and capillary loops deposits by immunofluorescence were more commonly present in postinfectious IgA-dominant glomerulonephritis group (p < 0.001). Conclusions: PIGN could be characterized by glomerular IgA-dominant deposition resembling idiopathic IgA nephropathy. It is essential to differentiate postinfectious IgA-dominant glomerulonephritis from idiopathic IgA nephropathy because of the different treatments and prognosis of the two diseases.     

2型糖尿病合并非糖尿病肾病的临床及病理分析

目的：回顾性分析2型糖尿病合并非糖尿病肾病的临床表现及病理特征。方法：回顾性分析2004年1月～2009年12月临床疑为合并非糖尿病肾病的110例2型糖尿病患者的肾活检资料。根据肾活检结果分为单纯糖尿病肾病（DN）组和糖尿病肾病合并非糖尿病肾病（NDRD）组,并对临床和病理资料进行分析。结果：110例2型糖尿病肾病患者中,50例（45.5%）合并非糖尿病肾病。糖尿病肾病合并非糖尿病肾病组蛋白尿、血尿发生率高于单纯糖尿病肾病组,但糖尿病视网膜病变发生率低于单纯糖尿病肾病组。两组年龄、糖尿病病程、高血压、血肌酐和肾小球滤过率差异无统计学意义。所有合并的非糖尿病肾病中,IgA肾病的比率最高为34%,其他依次为膜性肾病22.0%,系膜增殖性肾小球肾炎14%,HBV相关性肾小球肾炎8.0%,微小病变型肾小球肾炎10%,高血压肾小球硬化4.0%,FSGS4.0%,新月体肾小球肾炎2.0%,狼疮性肾炎2.0%。结论：2型糖尿病肾病合并非糖尿病肾病发生率45.5%,IgA肾病最常见。血尿、蛋白尿同时缺乏糖尿病视网膜病变强烈提示合并非糖尿病肾病。对于临床表现不典型的患者,肾活检是一项排除糖尿病肾脏病变的重要手段。     

Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus

Background: Several studies had suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. Methods: We prospectively studied the prevalence of NDRD among a Chinese NIDDM population. Renal biopsy specimens were evaluated with light-, immunohistological and electron-microscopy. The cohort consisted of 51 patients who had NIDDM and proteinuria >1 g/24 h. Results: Patients with both isolated diabetic nephropathy (DN, n=34) and NDRD (n=17) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and glycosylated haemoglobin levels, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had microscopic haematuria (P=0.043) or non-nephrotic proteinuria (P=0.004). IgA nephropathy accounted for 59% of the NDRD identified. Conclusions: In this study, microscopic haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients presenting with renal disease.     

Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome

Prerandomization renal biopsy specimens were examined in 102 patients upon entry into prospective therapeutic trials of lupus nephritis in an attempt to identify early predictors of renal failure outcome. All 11 renal failures occurred among the 72 individuals with diffuse proliferative or membranoproliferative glomerulonephritis (DPGN/MPGN); thus, these patients were at modestly, but significantly, increased risk of endstage renal disease compared to those with focal proliferative, membranous, or mesangial glomerulonephritis. Considering the low incidence of endstage renal disease among patients with DPGN/MPGN, we sought to refine the prognostic information obtained from renal morphology by semiquantitative scoring of individual histologic features and by derivation of composite histologic scores specified by Activity (AI) and Chronicity (CI) Indices. Among the 72 patients with DPGN/MPGN, the composite AI was more strongly predictive of renal failure than were the individual active histologic features; cellular crescents and extensive fibrinoid necrosis yielded positive associations, while endocapillary proliferation, leucocytic exudation, and hyaline thrombi in glomeruli and interstitial inflammation by themselves did not emerge as useful prognostic indicators. However, chronicity items (glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis) considered individually, as well as in the composite CI, were highly predictive of renal failure outcome. Particularly striking was the prognostic value of tubular atrophy; all 11 renal failures were among the 43 patients with tubular atrophy on prerandomization renal biopsy. While no single pathologic variable improved outcome predictions among those with tubular atrophy, examination for interactions among variables revealed that glomerular sclerosis and cellular crescents had a synergistic effect which augmented the prognostic information derived from analysis of tubular atrophy alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome

Abstract

Background: Renal involvement in type 2 diabetes is mostly due to diabetic nephropathy (DN), but a subset of diabetic patients could present with pure non-diabetic renal disease (NDRD) or NDRD superimposed on DN. We conducted a prospective cohort study to identify the underline renal pathology in type 2 diabetic patients with defined clinical criteria for renal biopsy. Methods: A total of 46 patients (27 female, mean age of 48.9?±?11.9 years) with type 2 diabetes mellitus (DM) and atypical features of DN with unexpected proteinuria, hematuria, and/or renal impairment were enrolled in this study. Results: Of 46 patients with type 2 diabetes, 16 (34.8%) had DN, 20 (43.5%) had NDRD, and 10 (21.7%) had NDRD superimposed on DN. Membranous nephropathy (34%) was the most common NDRD. Patients with NDRD had a lower frequency of diabetic retinopathy (5%), shorter duration of diabetes, higher range of proteinuria, and better kidney survival. In multiple logistic regression analysis, only lack of diabetic retinopathy was independent predictor of NDRD. Positive and negative predictive value of diabetic retinopathy (DR) for diabetic nephropathy was 94 and 68%, respectively. Conclusion: Kidney biopsy is strongly recommended for patients with type 2 diabetes and atypical renal presentation for DN, particularly in the absence of DR. This approach could lead to diagnosis of NDRD with better renal survival.     

The prognosis of segmental glomerulonephritis in systemic lupus erythematosus

Severe segmental glomerulonephritis (Seg GN) (greater than or equal to 50% involvement) in systemic lupus erythematosus (SLE) is classified as diffuse GN (DPGN) in the WHO classification. We tested the validity of the assumption that severe Seg GN and DPGN have the same prognosis by determining the proportion of glomeruli involved by active segmental inflammation in a series of 127 patients and by comparing the prognosis in various categories of Seg GN with patients with DPGN. In Seg GN we found mild involvement (1 to 19%) in 19 patients, moderate involvement (20 to 49%) in 9 patients and severe involvement (greater than or equal to 50%) in 17 patients. There were 28 cases of DPGN. The actuarial five-year survival of patients with mild and moderate Seg GN was 82%. The survival of patients with severe Seg GN and DPGN were 59 and 53%, respectively. The incidence of adverse outcomes, including death, end-stage kidney disease, and deterioration of renal function was similar in patients with severe Seg GN and DPGN, and greater than in patients with mild and moderate Seg GN. Although there was a trend associating increasing glomerular involvement with elevated urinary protein excretion and serum creatinine and decreased serum C3 and C4, the differences were not significant. Cumulative prednisone dose and prednisone given in the first and second years following biopsy were not different in the various categories of Seg GN and DPGN, suggesting that differences in outcome were not related to the amount of prednisone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stopping smoking slows accelerated progression of renal failure in primary renal disease

BACKGROUND: Cigarette smoking accelerates the progression of renal failure in primary kidney diseases. It is not known, however, whether stopping smoking slows this accelerated loss of renal function. METHODS: 45 patients with progressive primary nephropathies (glomerulonephritis or tubulointerstitial nephritis) and moderate renal failure were encouraged to stop heavy cigarette smoking (1-2 packs per day); 26 patients refused to change their smoking habits (current smokers), and 16 successfully stopped (ex-smokers) during the 24 month study period. Carboxyhemoglobin and creatinine clearance were measured every six months. The primary end-point of the study was end-stage renal disease requiring renal replacement therapy. RESULTS: There were no significant differences between the two patient groups in demographic, renal and treatment characteristics at the start of the study. Current and ex-smokers had similar rates of decline of creatinine clearance during the 24 months before the investigations. Compared to ex-smokers or matched non-smoking renal patients, permanent smokers had a significantly faster decline in creatinine clearance during the two-year study period. Renal replacement therapy had to be started in six smokers, but only in one ex-smoker and none of the non-smokers during the study period. CONCLUSIONS: Giving up smoking slowed the rapid progression of renal failure, but did not reverse the loss of renal function induced by smoking. We recommend that increased efforts should be made to encourage renal patients to give up smoking in order to prolong dialysis-free kidney survival.     

Apoptosis and proliferation in childhood acute proliferative glomerulonephritis

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p <0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03±2% versus 0.32±0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4±1.9 versus 1.52±0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89±0.8 versus 0.73±0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.     

IgA-Dominant Postinfectious Glomerulonephritis: Not Peculiar to Staphylococcal Infection and Diabetic Patients

Background: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. Methods: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. Results: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1?mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group (p?=?0.007). There were no significant differences in other clinical parameters and outcome between the two groups. Conclusions: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.     

Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features

BACKGROUND: Controversy surrounds the relatedness of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulonephritis (IT). METHODS: To better define their clinicopathologic features and outcome, we report the largest single center series of 67 cases biopsied from 1980 to 2001, including 61 FGN and 6 IT. FGN was defined by glomerular immune deposition of Congo red-negative randomly oriented fibrils of < 30 nm (mean, 20.1 +/- 0.4 nm). IT was defined by glomerular deposition of hollow, stacked microtubules of > or = 30 nm (mean, 38.2 +/- 5.7 nm). RESULTS: FGN comprised 0.6% of total native kidney biopsies and IT was tenfold more rare (0.06%). Deposits in FGN were immunoglobulin G (IgG) dominant and polyclonal in 96%. IgG subtype analysis in 19 FGN cases showed monotypic deposits in four (two IgG1 and two IgG4) and oligotypic deposits in 15 (all combined IgG1 and IgG4). In IT, deposits were IgG dominant in 83% and monoclonal in 67% (three IgG1 kappa and one IgG1 lambda). FGN patients were a mean age of 57 years, 92% were Caucasian, and 39% were male. At biopsy, FGN patients had the following clinical characteristics (mean, range): creatinine 3.1 mg/dL (0.5 to 14), proteinuria 6.5 g/day (0.8 to 25), 60% microhematuria, and 59% hypertension. Histologic patterns of FGN were diverse, including diffuse proliferative glomerulonephritis (DPGN) (nine cases), membranoproliferative glomerulonephritis (MPGN) (27 cases), mesangial proliferative/sclerosing (MES) (13), membranous glomerulonephritis (MGN) (four), and diffuse sclerosing (DS) (eight). The more proliferative (MPGN and DPGN) and sclerosing (DS) forms presented with a higher creatinine and greater proteinuria compared to MES and MGN. Median time to end-stage renal disease (ESRD) was 24.4 months for FGN and mean time to ESRD varied by histologic subtype: DS 7 months, DPGN 20 months, MPGN 44 months, compared to MES 80 months and MGN 87 months. There was no statistically significant effect of immunosuppressive therapy (given to 36% of FGN patients). By Cox regression (hazard ratio, confidence interval, P value), independent predictors of progression to ESRD were creatinine at biopsy [2.05 (1.55 to 2.72) P < 0.001] and severity of interstitial fibrosis [2.01 (1.05 to 3.85) P = 0.034]. Although IT had similar presentation, histologic patterns, and outcome compared to FGN, it had a greater association with monoclonal gammopathy (P = 0.014), underlying lymphoproliferative disease (P = 0.020), and hypocomplementemia (P = 0.032). CONCLUSION: FGN is an idiopathic condition characterized by polyclonal immune deposits with restricted gamma isotypes. Most patients present with significant renal insufficiency and have a poor outcome despite immunosuppressive therapy, and outcome correlates with histologic subtype. By contrast, IT often contains monoclonal IgG deposits and has a significant association with underlying dysproteinemia and hypocomplementemia. Differentiation of FGN from the much more rare entity IT appears justified on immunopathologic, ultrastructural, and clinical grounds.     

Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction

Seven patients with acute renal failure due to gross haematuriacaused by glomerulonephritis are described. Gross haematurialasting 4–40 days led to acute impairment of renal functionof variable severity (peak plasma creatinine 1.3–12 mg/dl)and duration. While partial recovery of renal function occurredin all patients within few days, complete remission was observedonly some months later. Three patients had IgA nephropathy (2the primary form and 1 nephritis secondary to Schönlein-Henochpurpura), two patients had acute postinfectious glomerulonephritis,andtwo others had focal necrotizing (pauci-immune) glomerulonephritis.The glomerular changes seen in renal biopsy were not enoughto explain per se the renal function impairment. Tubular changes,however, were severe and consisted of tubular necrosis, erythrocytecasts, erythrocyte phagocytosis by tubular cells, accompaniedby interstitial damage (oedema, red-cell extravasation, andinflammatory infiltrates). Study of the renal biopsies by immunofluorescencerevealed retrodiffusion of Tamm-Horsfall protein into the glomerularBowman’s space, a sign of obstructed tubular flow in anycase. It is concluded that acute renal failure due to grosshaematuria in glomerulonephritic patients may not occur onlyin IgA nephropathy, as reported so far, and is not associatedwith intratubular obstruction.     

Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

Background. Recently we showed that antinuclear autoantibodies Complexed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GBM) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In addition, a decreased HS staining in the GBM was found, most probably due to masking by deposition of antibodies complexed to nucleosomes. Methods. In this study we first investigated whether histones or nucleosomes could be identified in glomerular deposits in human lupus nephritis, and secondly whether the presence of these nuclear components was correlated with absence of HS staining. Kidney biopsies of SLE patients (11 with diffuse proliferative glomerulonephritis (DPGN) and six with membranous glomerulonephritis (MGN)) and of non-SLE glomerular diseases were stained for histones, DNA, nucleosomes, IgG and HS. Results. Using a polyclonal anti-H3 1-21 antiserum, histones were detected in all patients with DPGN and in two of six patients with SLE-MGN (P <0.01(. Using a monoclonal antihistone antibody, histones were stained in three patients with DPGN, but in none of the biopsies with MGN. Using nucleosome specific monoclonal antibodies, nucleosomes were detected in five patients with DPGN, in two patients with MGN, but in none of the biopsies with non-SLE glomerulonephritis. HS staining was nearly absent in DPGN, whereas staining was only moderately reduced in patients with MGN and controls (P=0.001). Conclusion. Using polyclonal and monoclonal antihistone antisera, histones were identified in all patients with DPGN and their presence was associated with a decrease of HS staining. Nucleosomes were identified in five of 11 patients with DPGN and in two of six patients with MGN. This is the first demonstration of nucleosomes in glomerular deposits in SLE nephritis.