Changes in the spectrum of kidney diseases: a survey of 2803 patients from 2010 to 2018 at a single center in southeastern China

Primary glomerular disease was the leading cause of chronic kidney disease (CKD) in China; however, changes in the economy and environment introduce variations in the spectrum of kidney diseases. This study aimed to analyze renal biopsy data to inform disease prevention and public health interventions. In this retrospective cohort study, data from 2,803 consecutive renal biopsies conducted at our center between January 2010 and December 2018 were analyzed. The sample was disaggregated by age and the date of biopsy to facilitate analysis. Primary glomerulonephritis (PGN) is the most frequent (81.84%) finding, followed by secondary glomerulonephritis (SGN; 15.38%), tubulointerstitial nephritis (15.38%), and others (1.57%). IgA nephropathy (IgAN), idiopathic membranous nephropathy (iMN), and minimal change disease were the primary causes of PGN. Among PGN cases, the incidence of iMN arose, especially among those aged ≥ 60 years old, during the observation period. Contrary to the case of iMN, the proportion of IgAN in PGN trended downward, continuously, and at length. Moreover, IgAN mainly affected those aged 25–44 years old and less so those aged ≥ 60 years old. Lupus nephritis, Henoch–Schönlein purpura nephritis, and diabetic nephropathy (DN) were key causes of SGN. A ratio reversal between infectious disease and chronic disease dramatically changed SGN patterns. In the past year, the incidence of hepatitis B–related nephritis has constantly declined; however, the proportion of DN among SGN had steadily increased. The incidence of iMN significantly increased during these years. Among SGN cases, the proportion of DN has increased.     

Abnormal expression of glomerular basement membrane laminins in membranous glomerulonephritis.

BACKGROUND: Proteinuria associated with glomerular diseases is secondary to alterations of the charge-selective and/or size-selective properties of the glomerular basement membrane (GBM), but molecular alterations that are responsible for these functional changes are still poorly understood. Analysis of mice harbouring a null mutation in the gene encoding the beta 2 chain of laminin has suggested that the presence of abnormal laminin chains within the GBM can be responsible for proteinuria. METHODS: We have investigated whether abnormal laminin ss chains could be detected by immunohistochemistry within the GBM of patients with proteinuria and minimal change disease (five patients), focal and segmental glomerulosclerosis (five patients), or primary membranous glomerulonephritis (10 patients). Three patients with mesangiocapillary glomerulonephritis and three patients with IgA nephropathy were also studied as controls. RESULTS: We showed that the GBM of all 10 patients with membranous glomerulonephritis, but not of patients with other glomerulopathies, contained laminin beta 1, which is normally expressed only during metanephros development. The re-expression of the beta 1 chain of laminin was not associated with that of the embryonic alpha 1 chain of type IV collagen, or with the loss of expression of vimentin and synaptopodin, two markers of differentiated podocytes. CONCLUSIONS: The presence of new laminin isoforms within the GBM of patients with membranous glomerulonephritis could play a role in the occurrence of proteinuria, by modifying either the sieving properties of the GBM or the interactions between podocytes and the GBM.     

Molecular analysis of glomerular diseases in renal biopsies

Summary: The purpose of this study was to determine the pattern of gene expression of type IV collagen alpha chains in several chronic human glomerular diseases using micro dissected glomeruli and assessment of mRNA by competitive polymerase chain reaction (PCR). After showing that the level of a2 type IV collagen mRNA was elevated in sclerotic glomeruli isolated from nephrectomies, we undertook a preliminary cross-sectional study of type IV collagen alpha chain mRNA in renal biopsies in two of the leading causes of glomerulosclerosis: (i) diabetic nephropathy; and (ii) membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels alterations were disease-specific. the relative levels of the individual α-chains of type IV collagen depended on the anatomic site of the glomerular lesions. the α-2IV/α-3IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with that obtained in experimental animals, suggest that a defective basement collagen synthesis is associated with progressive glomerular scarring. If these conclusions are verified in studies of repeat biopsies, the risk of progressive glomerulosclerosis in individual patients could be estimated, leading to the means to assess therapeutic responses.     

Mutant mice provide new insight into the role of (mis-)glycation in IgA nephropathy and other glomerular diseases.

In the 24 October 2006 issue of PNAS, Alexander and colleagues[1] describe the results of a systematic search for thrombocytopenicmice generated by large-scale mutagenesis. Amongst 3523 mice,one pedigree indeed exhibited 50% reduction in platelet counts.Apart from thrombocytopenia, the only other notable featureof these mice was prominent renal disease (albuminuria/proteinuria,glomerulosclerosis and tubulointerstitial inflammatory infiltration)leading to uraemia and death at around 200 days after birth.This renal disease was not immune mediated, since it persistedin mutant mice crossed to     

Clinical features, pathogenesis and treatment of hepatitis B virus-associated membranous nephropathy in children

Summary: Membranous nephropathy (MN) is the commonest named lesion associated with hepatitis B virus (HBV) infection in Taiwanese children. This review focuses on the clinical features, the pathogenesis and immune abnormality and possible treatment of HBV-MN.     

Expression of Ras GTPases in normal kidney and in glomerulonephritis.

BACKGROUND: Small monomeric Ras GTPases play critical and specific roles in the control of cellular proliferation and apoptosis but the expression of the three Ras isoforms (Ha-Ras, Ki-Ras and N-Ras) in human renal tissue is unknown. This work is an immunohistochemical study of Ras expression in normal renal tissue and in membranous glomerulonephritis (MGN), IgA nephropathy (IgAN) and IgA-negative mesangioproliferative glomerulonephritis (MPGN). METHODS: Formalin-fixed, paraffin-embedded tissue was stained using pan-Ras monoclonal antibody (mAb) and Ras isoform-specific mAb. Detection employed a (DAKO Envision) modified polymer system. RESULTS: The expression of Ras isoforms in normal human kidney was cell-specific. For example, N-Ras was detected in tubule epithelial cells but not in glomerular or interstitial cells. Ki-Ras was expressed in mesangial cells, interstitial cells and in proximal convoluted tubule cells (PCT) (particularly localized at brush borders) and in collecting duct cells (CD) (localized to cell membranes) but not in podocytes. Cytoplasmic Ha-Ras was detected in all the above cell types except podocytes. MGN was associated with podocyte expression of all three Ras isoforms and with reduced mesangial cell expression of Ha-Ras and Ki-Ras. IgAN was characterized by podocyte expression of Ha-Ras (but not Ki-Ras) and reduced mesangial cell expression of Ki-Ras without alterations in mesangial Ha-Ras expression. MPGN was associated with reduced mesangial cell Ha-Ras and Ki-Ras expression without significant podocyte Ras expression. CONCLUSION: These disease-specific and isoform-specific alterations in Ras expression may be of significance in pathogenesis and warrant further functional investigation.     

Pathology of glomerular deposition diseases and fibrillary glomerulopathies associated with paraproteinemia and haematopoietic disorder

SUMMARY:   The primary glomerulopathies with a deposit of ultrastructural fibrillary structure, which are negative for Congo-red stain but positive for immunoglobulins, include fibrillary glomerulonephritis and immunotactoid glomerulopathy. Several paraproteinemias, including cryoglobulinemia, monoclonal gammopathy and light chain deposition disease as well as haematopoietic disorders including plasmacytoma, plasma cell dyscrasia and B cell lymphoproliferative disorders involve glomerulopathy with an ultrastructural fibrillary structure. A rare glomerulopathy with fibrillary structure showing negative stain for Congo-red and for immunoglobulins has been also reported. The pathological diagnoses of these glomerulopathies with ultrastructural fibrillary deposits can include either glomerular diseases, or paraproteinemic diseases, or haematopoietic diseases. The terminology is still confusing when glomerular diseases can be combined with paraproteinemic diseases and/or haematopoietic diseases. Therefore, the generic term, 'glomerular deposition disease', has been proposed by pathologists with a requirement for clinicians to detect autoantibodies, paraproteins and to carry out a bone marrow check. An attempt has been made to elucidate the correlation among the glomerular deposition disease, paraproteinemia and haematopoietic disorder.     

Serum ferritin levels are increased in patients with glomerular diseases and proteinuria.

BACKGROUND: Ferritin is a high molecular weight protein which reflects body iron stores, but may also rise in the case of an acute phase response. Recently, ferritin has been identified as a predictive factor in the development and progression of atherosclerosis. This is the first report on serum ferritin levels in patients with proteinuria. METHODS: We have analysed the data of 142 male patients with a glomerular disease, and proteinuria exceeding 1 g/day. In all patients, we measured various parameters related to proteinuria, serum ferritin and serum iron. Serum beta2-microglobulin and the Modification of Diet in Renal Disease (MDRD) equation were used as measures of the glomerular filtration rate (GFR). RESULTS: Mean age (+/-SD) was 46+/-15 years, MDRD-GFR 57+/-25 ml/min/1.73 m2 and median proteinuria 8.0 g/day [interquartile range (IQR) 3.6-13]. Serum albumin (29+/-9 g/l) and transferrin levels (1.7+/-0.5 g/l) were low, and cholesterol levels were elevated (median 7.3, IQR 5.9-9.5 mmol/l). Median serum ferritin was 148 microg/l (IQR 89-282), and exceeded 280 microg/l, the upper limit of normal, in 36 patients (25%). Elevated serum ferritin levels could not be explained by an acute phase response as determined by C-reactive protein, or haemochromatosis (DNA analysis). Regression analysis showed an independent relationship between ferritin levels and serum cholesterol, GFR and serum transferrin. CONCLUSIONS: Serum ferritin levels are elevated in patients with overt proteinuria. The independent negative relationship between serum ferritin and transferrin points to a specific process and suggests that increased production of ferritin may compensate for the loss of the iron-binding protein transferrin, thus reducing the amount of free iron. Further studies are needed to elucidate the role of ferritin in patients with proteinuria, especially because of the suggested association between ferritin and atherosclerosis.     

Concomitant presence of three different glomerular diseases in the same patient. Report of a case and review of the literature

A 51-year-old man with diabetes mellitus and the nephrotic syndrome on renal biopsy was found to have diabetic glomerulosclerosis, amyloidosis and membranous glomerulopathy. The presence of three distinct glomerular diseases in the same patient is unique. Possible factors involved in their pathogenesis are discussed and the literature on concomitant glomerular diseases is reviewed.     

Nontraumatic hemobilia: disparate episodes 7 years apart in the same patient.

A case is reported of nontraumatic hemobilia, which occurred twice in the same patient. Initially it was due to carcinoma of the gallbladder and 7 years later it was due to a ruptured intrahepatic aneurysm. The management of these two conditions is reviewed. The clinical marker of nontraumatic hemobilia originating in the gallbladder is the hemocholecyst and the treatment is cholecystectomy. Ruptured intrahepatic aneurysm can be diagnosed only by angiography. Cholangiography is indicated to rule out pathologic conditions of the ducts. In the absence of hepatobiliary sepsis selective hepatic artery ligation is the preferred treatment, otherwise hepatic resection is required.     

The fate of glomerular mesangial IgA deposition in the donated kidney after allograft transplantation

OBJECTIVE: To investigate the fate of the mesangial IgA deposits in the donor kidney after allograft transplantation. METHODOLOGY: Routine pre-transplant cadaveric donor kidney biopsy and repeated renal biopsies were performed at months 1, 3, and 6 after renal transplantation. The patients, 342 in number, were divided into IgA positive deposition kidney group (group A, n = 83) and non-IgA deposition kidney group (group B, n = 259). There were no significant differences between the two groups' sex, age, time of hemodialysis, warm ischemia time, cold ischemia time, complement-dependent cytotoxicity, level of panel-reactive assay, and the distribution of original disease. RESULTS: Recipients in group A received donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition. All of them showed edema, nephrotic range protienuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. Borderline change was higher in group A than in group B, 37.3 and 16.2% (p < 0.001), respectively. Acute allograft rejection was higher in group A than in group B, 31.3 and 19.3% (p < 0.001), respectively. The glomerular mesangial IgA deposits gradually disappeared from the mesangial regions in grafts of acute rejection. Graft survival in both groups was not significant, being 93.8 and 95.6% in 1 yr, and 86.7 and 88.3% in 3 yr. CONCLUSION: Clinical features of the recipients which received from donor kidney with glomerular mesangial proliferation and marked diffuse granular IgA deposition: edema, proteinuria, microhematuria, hypoalbuminemia, hypertension, and delayed graft function. The presence of IgA deposits on donated kidney, by a possible increase of the immunogenicity of these kidneys, might be a cause of increased rejection. There were no significant differences between the two groups on long-term allograft survival.     

Decreasing incidence of membranoproliferative glomerulonephritis in Spanish children

Thirteen paediatric nephrology units contributed to a retrospective review of 1447 kidney biopsies which were performed on children under 15 years of age from 1972 to 1986 and were examined by immunofluorescence and light microscopy. The histological studies were grouped into three 5-year periods: (1) 1972–1976 (248 biopsies), (2) 1977–1981 (607 biopsies), and (3) 1982–1986 (592 biopsies). The incidence of membranoproliferative glomerulonephritis (MPGN) was significantly lower during periods 2 (6.6%) and 3 (5.4%) than in period 1 (10.9%,P<0.05 and <0.01 respectively). The reasons for the significant decrease in the incidence of MPGN in Spanish children cannot be determined, but the observation agrees with those from French, Italian and Spanish studies involving adult patients.San Juan de Dios (Barcelona); Vall d'Hebron (Barcelona); Enrique Sotomayor (Bilbao); La Paz (Madrid); Niño Jesus (Madrid); Gregorio Marañon (Madrid); Ramon y Cajal (Madrid); General de Asturias (Oviedo); Virgen de Covadonga (Oviedo); Valdecilla (Santander); Virgen del Rocio (Sevilla); La Fe (Valencia); Miguel Servet (Saragossa). Offprint requests to: N. Gallego, Servicio de Nefrologia, Hospital Ramon y Cajal, Carretera de Colmenar Km 9.100, E-28034 Madrid, Spain     

A comprehensive study of the association between hepatitis C virus and glomerulopathy.

BACKGROUND: Hepatitis C virus (HCV)-related infection is commonly associated with a wide range of glomerulonephritides (GN) including membranoproliferative glomerulonephritis (MPGN). The causal link between HCV infection and renal disease has been postulated through the induction of cryoglobulinaemia and secondary GN. However, the detection of viral particles or genomes within the kidneys of HCV-infected patients has proved to be difficult. With that in mind, we have studied a population of Egyptian HCV-positive patients with associated GN in an attempt to detect viral particles, antigens or RNA within their kidneys. METHODS: Fifty patients were found to be HCV positive out of 303 who presented with a glomerulopathy between 1998 and 1999 at the Mansoura Urology and Nephrology Center, Egypt. Comprehensive investigations of these 50 patients were undertaken including an evaluation of their clinical, biochemical, histological, virological and immunological parameters. In addition, their kidney biopsy material was analysed by electron microscopy (EM) to detect viral particles, by immunohistochemistry to detect a viral core antigen and by RT-PCR to detect RNA. This was compared with 50 HCV-negative controls. RESULTS: Positivity for HCV antibodies was higher among patients with GN (38%) compared with healthy blood donors (16%). Genotype 4 was sequenced in 70% of the HCV-positive samples examined. MPGN was the most common type of GN accounting for 54% of patients. Extrarenal manifestations were absent in the majority (80%) of patients even though 54% had cryoglobulinaemia. EM revealed virus-like particles in 50% of biopsies. Immunohistochemistry failed to reveal HCV-related antigens in kidney sections. HCV RNA was detected in the cryoprecipitates in 66% of patients and 22% of frozen renal sections. Control sections were negative. CONCLUSION: Our findings suggest a causal link between HCV and GN based on the observation of virus-like particles as well as viral RNA within the kidney sections of patients with HCV-associated glomerulopathies.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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