Primary biliary cirrhosis associated with membranous glomerulonephritis.
(1/397)
A 33-year-old woman was admitted to our department for evaluation of liver dysfunction and proteinuria. A liver biopsy specimen showed ductular proliferation and moderate portal fibrosis indicating stage II primary biliary cirrhosis. A renal biopsy specimen showed mild to moderate mesangial cell proliferation without crescent formation or interstitial nephritis. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG), third component of complement (C3), and Clq on glomerular basement membranes. The findings indicated stage I membranous glomerulonephritis. Administration of ursodesoxycholic acid together with prednisolone, azathioprine, and dipyridamole decreased proteinuria and improved cholestatic liver dysfunction. (+info)
Glomerular, tubular and interstitial nephritis associated with non-steroidal antiinflammatory drugs. Evidence of a common mechanism.
(2/397)
AIMS: To study the mechanisms behind NSAID-associated nephropathy. METHODS: Analysis of published case reports satisfying strict criteria for NSAID nephropathy. RESULTS: Ninety-seven cases with acute nephritis (AN; 19 patients), minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN; 19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis subgroups (8 patients) were identified. Hypersensitivity reactions were seen in all groups, most often in AN. Proteinuria was more severe in MC and FS than in MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely associated with hypersensitivity, interstitial damage and renal failure. Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had discontinued NSAID treatment had improved, 57 with normal renal function. CONCLUSIONS: NSAID nephropathy may be caused by hypersensitivity. The reaction is milder than in drug-induced acute tubulointerstitial nephritis, probably because the offending drug inhibits the inflammatory reaction it has started itself. Heavy proteinuria is probably due to lymphokines produced as a result of the immunological response. If the allergic reaction is strong, AN is produced rapidly with severe renal failure but little proteinuria; if it is less violent, immunocompetent cells may develop to produce lymphokines and proteinuria. Immune complexes may be formed eventually, secondary to the increased glomerular permeability, more easily in patients with a hyperactive immune system and with little consequence for renal function. (+info)
Gene expression of 5-lipoxygenase and LTA4 hydrolase in renal tissue of nephrotic syndrome patients.
(3/397)
Leukotrienes (LT) of the 5-lipoxygenase pathway constitute a class of potent biological lipid mediators of inflammation implicated in the pathogenesis of different models of experimental glomerulonephritis. The key enzyme, 5-lipoxygenase (5-LO), catalyses oxygenation of arachidonic acid to generate the primary leukotriene LTA4. This LT, in turn, serves as a substrate for either LTA4 hydrolase, to form the potent chemoattractant LTB4, or LTC4 synthase, to produce the powerful vasoconstrictor LTC4. To investigate the potential role of LT in the pathogenesis of human glomerulonephritis with nephrotic syndrome, we examined the gene expression of 5-LO and LTA4 hydrolase in renal tissue of 21 adult patients with nephrotic syndrome and 11 controls. The patients consisted of 11 cases of membranous nephropathy (MN), seven focal and segmental glomerulosclerosis (FSGS), two non-IgA mesangial glomerulonephritis and one minimal change disease. Total RNA purified from renal tissue was reverse transcribed into cDNA and amplified with specific primers in a polymerase chain reaction (RT-PCR). Eight patients' renal tissue, four MN and four FSGS, co-expressed 5-LO and LTA4 hydrolase. In situ hybridization analysis revealed 5-LO expression and distribution limited to the interstitial cells surrounding the peritubular capillaries. Comparative clinical and immunohistological data showed that these eight patients had impaired renal function and interstitial changes that significantly correlated with 5-LO expression. These findings suggest that leukotrienes may play an important role in the pathogenesis of MN and FSGS. These results are also relevant to elucidating the pathophysiologic mechanisms which underlie progression to renal failure in these diseases. (+info)
HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy.
(4/397)
BACKGROUND: Hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) is an important cause of childhood nephrotic syndrome in regions endemic for the virus, but little is understood of the biosocial context in which the disease develops. We evaluated HBV status and proteinuria in family members and household contacts of index children with HBVMN to test the hypothesis that HBV carriage and asymptomatic proteinuria are closely linked and may be causally associated. METHODS: Thirty-one black children with biopsy-proven HBVMN were the index cases. One hundred and fifty-two family members and 43 black household contacts were the subjects of the study. We assessed HBV carrier status by testing for HBV antigens and antibodies using enzyme-linked immunosorbent assays (ELISA) and for HBV DNA by using slot-blot hybridization and the polymerase chain reaction. Sequencing of the precore region of HBV was done in a subset of both index cases and subjects. Proteinuria was assessed by measuring the urinary protein/creatinine ratio. RESULTS: Seventy-two (37%) of the 195 family members and household contacts were HBV carriers, and 53 (27%) had a protein/creatinine ratio greater than the physiological limit. The frequency of abnormal proteinuria was not significantly different in those with [22 out of 72 (30.5%)] or without [33 out of 104 (32%)] HBV carriage. This lack of association remained when carriers were classified into those who were HBsAg positive only and those with active viral replication (HBsAg and/or HBeAg and/or HBV DNA; P = 0.01). Family members were more predisposed to HBV carriage than household contacts, but abnormal proteinuria was present with equal frequency (P = 0.48). Age had a significant impact on proteinuria, with children less than five years being more likely to have abnormal proteinuria (P = 0.008). The prevalence of abnormal proteinuria in family members and household contacts of the index cases was more than that in community-based controls. The 10 index HBVMN cases and the 14 family members and household contacts who were tested all had HBV of genotype A. CONCLUSION: These results suggest that the family members and household contacts of children with HBVMN are at very high risk of HBV carriage; they also have asymptomatic proteinuria at a significantly higher rate than community-based controls. The HBV carrier status was not associated with proteinuria, a finding supported by peak prevalences of proteinuria in those under five years but no corresponding peak for HBV carriage. Proteinuria may indicate glomerular basement membrane dysfunction. Environmental and social factors may underpin development of these two covert disorders, but are insufficient to account for the index cases of HBVMN. The emergence of children with HBVMN from such households additionally depends on unidentified and possibly genetic factors. (+info)
Hepatitis C virus-associated glomerular disease in patients with human immunodeficiency virus coinfection.
(5/397)
Chronic infection with hepatitis C virus (HCV) has been linked to the development of glomerular disease. HCV infection is highly prevalent among intravenous drug users, a population that is also at risk for HIV coinfection. This study reports the clinical-pathologic features and outcome of HCV-associated glomerular disease (HCV-GD) in 14 patients with HIV coinfection. All were intravenous drug users and all but one were African-Americans. Renal presentations included renal insufficiency, microscopic hematuria with active urine sediment, hypertension, and nephrotic syndrome or nephrotic-range proteinuria without hypercholesterolemia. Hypocomplementemia and cryoglobulinemia were present in 46 and 33% of patients, respectively. The predominant renal biopsy findings were membranoproliferative glomerulonephritis type 1 or type 3 (Burkholder subtype) in 79% of patients and membranous glomerulopathy with atypical features in 21% (including overlap with collapsing glomerulopathy in one patient). The clinical course was characterized by rapid progression to renal failure requiring dialysis. The overall morbidity and mortality were high with median time of 5.8 mo to dialysis or death. Although most patients died in renal failure, cause of death was primarily attributable to long-term immunosuppression and advanced AIDS. Patients with AIDS had shorter survival than those without (median survival time of 6.1 mo versus 45.9 mo, log-rank test P = 0.02). Only two patients were alive with stable renal function at follow-up of 28.5 mo. In patients with HCV-GD, coinfection with HIV leads to an aggressive form of renal disease that can be easily confused with HIV-associated nephropathy. Although hypocomplementemia, cryoglobulinemia, and more prominent hypertension and microscopic hematuria may provide clues to the presence of HCV-GD, renal biopsy is essential to differentiate HCV-GD from HIV-associated nephropathy. (+info)
Effect of protein A immunoadsorption in nephrotic syndrome of various etiologies.
(6/397)
Protein A immunoadsorption (IA) has proved effective in reducing proteinuria in patients with nephrotic syndrome after recurrence of focal and segmental glomerulosclerosis (FSGS) in kidney transplants. The effect of IA in nephrotic syndrome of other etiologies remains unknown. Nine patients with nephrotic syndrome secondary to membranous nephropathy (four cases), diabetes mellitus (one case), IgA nephropathy (two cases), and amyloidosis (two cases) had three to five IA of 2.5 plasma volumes over 4 to 8 d. Patients received no concomitant immunosuppressive treatment, and antihypertensive drugs were left unchanged. Proteinuria decreased from 12.64 +/- 5.49 to 3.35 +/- 2.2 g/24 h (mean +/- SD) in all patients after three to five IA. Hematocrit decreased from 37.32 to 32.64% (12.5% hemodilution) and serum albumin from 25.43 to 18.6 g/L (26.4% decrease). Proteinuria returned to baseline levels within 1 mo, as described in recurrent FSGS following transplantation. When serum albumin balance was controlled by albumin infusion after IA in two patients, comparable decreases in proteinuria were observed. Therefore, IA is effective in producing short-term reduction of proteinuria in nephrotic syndromes related not only to FSGS but also to membranous and IgA nephropathies, diabetes mellitus, and amyloidosis, which suggests that IA removes a nonspecific circulating hemodynamic-altering or permeability-increasing factor. (+info)
Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy.
(7/397)
BACKGROUND: Previous studies have shown that short-term treatment with adrenocorticotrophic hormone (ACTH) has a strong and rapid lipid-lowering effect. In this long-term study of nephrotic patients with idiopathic membranous nephropathy, the influence of ACTH on the serum lipoprotein profile and glomerular function as well as the dose-effect relationship was investigated. METHODS: Fourteen patients received ACTH intramuscularly at increasing doses during 56 days. Serum concentrations of lipids, lipoproteins, and apolipoproteins as well as variables of glomerular function were analyzed, and the side-effects were recorded. ACTH treatment, in the estimated optimal dosage, was then continued in five patients with severe steroid-resistant nephrotic syndrome. In these five patients, the total treatment period was 12 months, and the follow-up time after discontinuing treatment was 18 months. RESULTS: Taking both the statistically significant therapeutic effects and the modest side-effects into consideration, the optimal dosage of ACTH was estimated to be 1 mg twice per week. At that dose, reductions by 30 to 60% in the serum concentrations of cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a) were observed, whereas the serum concentrations of high-density lipoprotein cholesterol and apolipoprotein AI rose by 30 to 40%. In addition, the urinary albumin excretion decreased by 90%, and the glomerular filtration rate increased by 25%. Deterioration was observed in all cases when ACTH was discontinued after a treatment duration of 56 days. However, the five patients in whom ACTH therapy was resumed were still in remission 18 months after discontinuance of treatment. CONCLUSIONS: In nephrotic patients with idiopathic membranous nephropathy, treatment with ACTH 1 mg twice per week was associated with significant long-term improvements in serum lipoprotein pattern and glomerular function. (+info)
Membranous glomerulonephritis induced in the pig by antibody to angiotensin-converting enzyme: considerations on its relevance to the pathogenesis of human idiopathic membranous glomerulonephritis.
(8/397)
In the course of studies on the humoral consequences of swine to primate xenotransplantation, the investigators induced formation of glomerular subepithelial immune deposits and tubular lesions in pigs injected with heterologous antibody to angiotensin-converting enzyme. This study describes the morphology of the lesions, discusses their mechanism, explains their relevance for understanding the pathogenesis of human idiopathic membranous glomerulonephritis, and proposes future directions for investigations. (+info)