Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN).Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled.There were 74 cases of IgAN with ATIN,and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶ 1).The two groups were well matched with age,gender,follow-up time,mesangial hypercellularity(M),endocapillaryhypercellularity (E),segmental glomerulosclerosis(S),tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C).The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed.A composite end point,defined as 30％ or 50％ estimated glomerular filtration rate (eGFR)decline and end stage renal disease (ESRD) was used.Renal function and proteinuria during follow-up were observed.Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models.Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled.Serum creatinine [(185.6±83.2) μmol/L vs (146.3 ±69.2) μmol/L,P=0.010] and incidence of acute kidney disease (AKD) (31.1％ vs 5.4％,P ＜ 0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group.Patients in ATIN group received more immunosuppressive treatment (86.5％vs 58.1％,P＜ 0.001).During 1 year after biopsy,mean eGFR increased significantly in IgAN with ATIN group [(39.7+ 14.6) ml· min-1· (1.73 m2)-1 vs (47.2+ 19.9) ml· min-1· (1.73 m2)-1,P=0.017],but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml· min-1· (1.73 m2)-1 vs (59.0±31.7) ml· min-1· (1.73 m2)-1,P=0.567].Median follow-up was 23.0 months in IgAN with ATIN group,and Median follow-up was 30.0 months in IgAN without ATIN group.Incidence of composite end point had no significant differences between two groups.IgAN with ATIN was not the independent risk factor for end point.IgAN patients with ATIN were divided into two groups (with AKD and without AKD),then renal survival rate was higher (Log-rank test,x2=5.293,P=0.021) and the risk for composite end point decreased by 79.2％ (HR=0.208,95％CI 0.046-0.939,P=0.041) in the group with AKD.Conclusions In IgAN,there is a subgroup of patients with the specific pathological phenotype combined with ATIN.Compared with those without AKD,the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2％ decrease.

Objective To analyze the renal IgG subclasses in special patients whose renal HBsAg and HBcAg are positive, but plasma HBsAg, HBeAg, and HBcAg are negative.Methods Renal IgG subclasses were compared between 14 cases hepatitis-related nephropathy patients(diagnosed by renal biopsy pathology,whose blood hepatitis B antigens were negative) and 18 cases idiopathic membranous nephropathy patients.HBcAg and HBsAg were detected by indirect immunofluorescence assay, IgG, IgG1, 2, 3, 4 were stained by immunofluorescence.Results Renal IgG1-4 deposits were 100％ (14/14), 78.6％ (11/14), 78.6％ (11/14), 100％(14/14) separately in hepatitis B-related nephropathy group, and renal IgG1-4 deposits were 88.9％ (16/18), 5.6％ (1/18), 5.6％ (1/18), and 83.3％ (15/18) in idiopathic membranous nephropathy group.Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group (78.6％ vs 5.6％ ,78.6％ vs 5.6％;P =0.000) , but no significant difference in IgG1 and IgG4 deposit.Conclusion Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group, and may help some in diagnosis.

China ; Humans ; Kidney ; pathology

OBJECTIVETo study the clinicopathologic features of collagen III glomerulopathy and its cause, pathogenesis and prognosis.

METHODSFive cases of collagen III glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy. The morphologic characteristics were studied by light microscopy, immunofluorescence, immunohistochemical and electron microscopy.

RESULTSThe glomerular mesangium became expansion but no hypercellularity, basement membrane appeared thickened. The glomeruli showed collagen type III deposit by immunohistochemistry method, and collagen fibers increased by electron microscopy. The patients often show serious proteinuria, nephrotic syndrome and renal function damage.

CONCLUSIONSCollagen III glomerulopathy is an idiopathic glomerular disease, characterized by massive accumulation of collagen type III within the glomerular mesangial areas and basement membrane. Collagen III glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the abnormality of collagen III gene. There is no specific treatment for it and its prognosis is poor.

Basement Membrane ; metabolism ; Biopsy ; Collagen Type III ; genetics ; metabolism ; Female ; Fluorescent Antibody Technique ; Glomerular Mesangium ; metabolism ; Humans ; Immunohistochemistry ; Kidney Diseases ; etiology ; pathology ; Kidney Glomerulus ; pathology ; Microscopy, Electron ; Prognosis ; Proteinuria ; diagnosis

Objective To study the clinicopathologic features of collagen Ⅲglomerulopathy and its cause, pathogenesis and prognosis.Methods Five cases of collagen Ⅲglomerulopathy that collected from 2005 to 2014 were observed by renal biopsy.The morphologic characteristics were studied by light microscopy , immunofluorescence , immunohistochemical and electron microscopy.Results The glomerular mesangium became expansion but no hypercellularity , basement membrane appeared thickened.The glomeruli showed collagen type Ⅲdeposit by immunohistochemistry method , and collagen fibers increased by electron microscopy.The patients often show serious proteinuria , nephrotic syndrome and renal function damage.Conclusions Collagen Ⅲ glomerulopathy is an idiopathic glomerular disease , characterized by massive accumulation of collagen type Ⅲ within the glomerular mesangial areas and basement membrane.Collagen Ⅲglomerulopathy is extremely rare.The etiology and pathogenesis may relate to the abnormality of collagen Ⅲgene.There is no specific treatment for it and its prognosis is poor.

Objective To identify the prevalence of different amyloid types in renal biopsies.Methods The renal biopsies of 205 patients diagnosed as renal amyloidosis from January 1990 to December 2011 were reassessed.Immunohistochemistry was performed with a penal of antibodies directed against λ-light chain,κ-light chain,amyloid A,fibrinogen,transthyretin,apolipoprotein A1,and lysozyme.Immune electron microscopy and gene analysis were performed when the results of immunohistochemistry were indeterminate.Results Among 205 patients,190 cases (92.7％) were classified as immunoglobulin light chain amyloidosis (AL),1 (0.5％) case as amyloid A amyloidosis and 1 (0.5％) case as fibrinogen A α-chain amyloidosis.The amyloid types of remaining 13 (6.3％) cases were undetermined.In the AL patients,the distribution of λ and κ was 6.6∶1.Conclusion AL is the most common form of renal amyloidosis in China,with a predominant light chain type of λ.

Objective To elucidate the clinicopathological and hereditary characteristics in Fabry nephropathy.Methods The clinical and pathological features of 14 patients with Fabry nephropathy were collected.The activities of α-Gal A were measured in 4 probands.Screenings of GLA mutations were done in 12 patients.Results The ratio of Fabry nephropathy in the patients with renal biopsy was 0.074 ％ (14/19 005),the average diagnostic age was (30.57±9.32) years,male to female ratio was 2.5∶ 1.All the patients had proteinuria,and the median of urine total protein (UTP)was 1.71 g/24 h (0.32-4.71 g/24 h).Two of them got nephrotic proteinuria,5 of them got microscopic hematuria,4 of them got renal function insufficiency.Angiokeratomas was the most common manifestation (10/14),followed by cardiac involvement (6/14).Hypohidrosis and diseases of central neural system could also be seen in these patients.There were 9 classic phenotype,the remaining 5 were variants/renal variants.The family information was collected in 10 pedigrees,6 of them had family histories of kidney disease.Renal pathology showed vacuolization of glomerular visceral epithelial cells was the prominent feature,global and segmental glomerulosclerosis were seen in some patients by light microscopy.The myelin bodies or zebra bodies were identified in podocytes by electron microscopy,but only were found in some podocytes of 2 females.The activity of α-Gal A was decreased compared with the normal range in 4 probands.The mutations of GLA were demonstrated in 11 patients.Three novel mutations of GLA gene were identified,which were all deletion/insertion mutations with classic phenotypes.Most variants carried the mutations located in the buried/partial buried areas of α-Gal A (3/11).The classical phenotype carried GLA mutations as W162X,F169S,S201F,N272K,L310R,while variant phenotype carried GLA mutations as I91T,R112H,Q312H.Conclusions The ratio of Fabry nephropathy in patients with renal biopsy is 0.074％.Angiokeratomas and cardiac involvement are often accompanied with Fabry nephropathy.The genotypes of GLA may have close relationships with the phenotypes of Fabry nephopathy.

Objective To elucidate the features of clinicopathology and mutation in Fabry disease complicated with thin basement membrane nephropathy (TBMN), and to investigate the kindred. Methods Data of clinicopathology and gene mutation of a female patient of Fabry disease complicated with TBMN admitted to the Department of Nephro]ogy in our hospital were analyzed. Members of her kindred were investigated simultaneously. Results Proband was a 41-year-old Chinese woman who presented syndrome of Fabry disease and TBMN including angiokeratomas, chronic pain, tinnitus, vertigo, left ventricular hypertrophy and nephropathy as proteinuria, microscopic hematuria and hypertension. A percutaneous renal biopsy was performed on the proband, which was consistent with FSGS and vaculization of podocytes by light microscopy.Electron microscopy showed concentric lamellated inclusions in some podocytes. Diffuse thinning of glomerular basement membrane (GBM) with a mean thickness of (216±31) nm was found. The diagnosis of TBMN with suspected Fabry disease was identified. Family screening showed that her daughter had microscopic hematuria, tinnitus and neuropathic pain. One of her sisters only had microscopic hematuria. The activity of α-galacsidase A (α-Gal A )enzyme in the proband and her daughter was 33 units and 75 units respectively (the normal range is 100 to 500 units). They all carried the novel GLA mutation 1208 ins 21 bp and COL4A3 SNP c: 3627G＞A(p:M1209I). While her sister who only had microscopic hematuria just carried the variant of COL4A3 gene-c:3627G ＞A (p:M1209I), and had the normal activity of α-Gal A with no mutation of GLA.Conclusion TBMN should be considered in the patients of Fabry disease with the condition of benign familial hematuria.

ObjectiveTo investigate the clinicopathological characteristics of non-diabetic renal diseases (NDRD) in the patients with diabetes mellitus.MethodsClinicopatholigical data of 202 patients with diabetes mellitus and NDRD identified by renal biopsy from January 1st,2003 to December 31st,2010 were analyzed retrospectively.All the patients were divided into three groups:the young (≤35 years old),the middle-aged (36-59 years old) and the elder (≥60 years old).Clinicopathological characteristics were compared among 3 groups.ResultsIn the young group (n=33),42.4％ of patients presented as chronic glomerulonephritic syndrome,while 36.4％ as IgA nephropathy for pathology.In the middle-aged group(n=136),35.3％ of patients presented as chronic glomerulonephritic syndrome,27.2％ as nephritic syndrome,17.6％ as chronic renal failure,14.7％ as latent glomerulonephritis,and 5.1％ as acute renal failure,while42.6％ as IgA nephropathy for pathology.In the elder group(n=33),30.3％ of patients presented as nephritic syndrome,30.3％ as chronic renal failure,while 27.3％ as membranous nephropathy for pathology.ConclusionsIn clinical manifestation,young patients are mainly chronic glomerulonephritic syndrome,middle-aged patients are diversified,and elder patients are mainly nephritic syndrome andchronicrenalfailure. Inpathology, youngandmiddle-agedpatientsaremainlyIgA nephropathy,and elder patients are mainly membranous nephropathy.

ObjectiveTo investigate the clinical and pathological features of patients with anti-glomerular basement membrane(GBM) disease lacking linear IgG deposition along GBM on renal biopsy.Method Ninety-three patients with anti-GBM disease were collected in our hospital from 1991 to 2008,with 40 patients presenting negative linear IgG deposition along GBM on renal biopsy by direct immunofluorescence(group A) and 53 patients presenting classical linear IgG deposition along GBM(group B).The clinical manifestation,pathological presentation and prognosis were compared between two groups.Results Between two groups,there were no significant differences in gender,age,hemoptysis,oliguria or anuria,gross hematuria,proteinuria,anemia,ANCA positivity,level of circulating anti-GBM antibodies,the percentage of crescent formation in glomeruli and patient outcomes(P＞0.05).Patients in group A were diagnosed significantly later than patients in group B(68 d vs 36 d,P=0.013) and serum creatinine was significantly lower at diagnosis(716.0 μmol/L vs 896.8 μmol/L,P=0.027).Direct immunofluorescence was performed on the paraffin-embedded renal sections from four patients in group A,and all of them revealed positive linear IgG deposition along GBM.Conclusions Patients with circulating anti-GBM antibodies but withont IgG deposition along GBM present slower progress of renal injury,but same clinical,pathological and prognostic features as those with classical anti-GBM disease.Serum anti-GBM antibodies should be prescribed earlier to the suspected patients,and the diagnosed patients should be treated with plasmapheresis and extensive immunosuppression to improve prognosis.