Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we examined the progression of chronic Adriamycin (ADR) nephropathy in mild leukopenic rats and tried to define the possible relationship between tubulointerstitial lesions and proteinuria in this model. Chronic ADR nephropathy was induced by 2 doses of ADR (2 mg/kg) in 32 Sprague-Dawley rats. Eight of these were randomly assigned to cyclophosphamide treatment (50 mg/kg), given intravenously every week, to keep the blood leukocyte count constantly lower than 5,000/mm3. Serial parameters were followed for 16 weeks including clearance studies with iothalamate and p-aminohippurate and the analysis of urinary protein composition by: (a) an enzymatic assay for beta-glucosidase; (b) specific ELISA using antibodies against rat albumin and RBP, and finally (c) two-dimensional electrophoresis. ADR-treated rats rapidly (within 2 weeks) developed massive proteinuria which was in constant increment throughout the disease evolution in each single component (i.e., high and low molecular weight proteinuria, enzymuria) and developed renal insufficiency. At week 8, in ADR rats, glomerulosclerosis was mild whereas tubulointerstitial infiltrates predominated, characterized mainly by CD4+ T lymphocytes while CD8+ T lymphocytes were inconspicuous, and macrophages were only occasionally present. All such alterations had worsened after 16 weeks when the tubulointerstitial infiltration was associated with marked interstitial fibrosis and tubular atrophy. Leukopenia induced by cyclophosphamide was in all cases associated with a net amelioration of renal histopathology reducing tubulointerstitial infiltrates (by 40%) and glomerulosclerosis (33 +/- 5 vs. 52.2 +/- 7.5% sclerotic glomeruli) and also ameliorated glomerular filtration indexes (Cl 780 +/- 40 vs. 447 +/- 66 microliters/min/kg-1). In spite of these differences, albuminuria and urinary-retinol-binding protein were comparable at weeks 4, 8 and 16 in this group, while urinary beta-glucosidase was decreased at week 16 (p < 0.001) in cyclophosphamide-treated rats. No other qualitative changes in urinary proteins were detectable by 2-dimensional electrophoresis during the disease development. We concluded that chronic leukopenia prevents interstitial cellular infiltration by lymphocytes, interstitial fibrosis and slows down the decline of renal function typical of chronic ADR nephropathy. Glomerulosclerosis is also reduced in leukopenic rats without any appreciable changes in the urinary excretion of high molecular weight proteins deriving from the glomerulus. Finally, the improvement in tubulointerstitial alteration is associated with the reduction in urinary lysosomal enzymes. Tubulointerstitial alterations are implicated with a prominent role in the progression towards renal failure in chronic ADR glomerulopathy.
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PMID:Progression of chronic adriamycin nephropathy in leukopenic rats. 844 56

The mechanisms of glomerular injury can be separated into nonimmunologically mediated glomerulonephritis (GN) such as diabetes, leading to glomerular hypertension and into immunologically mediated GN. The immunologically mediated GN may induce chronic glomerulopathy such as membranous GN or proliferative GN. The final pathway of these two types of GN is proteinuria and renal failure linked to glomerulosclerosis. In inflammatory GN, most of the mediators could be synthesized either by infiltrating cells or by resident glomerular cells. They include cytokines, lymphokines, complement activation, generation of superoxyde anions, arachidonic acid metabolites, and fibrin deposition. (a) We have investigated the interaction between isolated glomeruli and platelets and have demonstrated that lipidic and proteic extracts of glomeruli enhance thromboxane B2 platelet synthesis. This fact is related to the generation by isolated glomeruli of saturated fatty acids and tissue factor. (b) We investigated the interaction between rat isolated glomeruli and peritoneal macrophages. We have demonstrated that 12-HETE synthesized by isolated glomeruli induce macrophage prostaglandin synthesis which, in turn, inhibits the 12-HETE synthesis. (c) We have demonstrated, using human glomerular epithelial cells, that alpha-thrombin, the active form of thrombin, generated before fibrin formation, is able to induce cell proliferation and abolishes the profibrinolytic activity of these cells. In summary, the mechanisms of glomerular injury are complex, certainly acting by multiple pathways. So far, the mediators leading to proteinuria and renal failure after glomerular injury remain under investigation.
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PMID:Mechanisms of glomerular injury: overview and relation with hemostasis. 851 88

Nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS) is a common cause of renal failure leading to transplantation. Various immunosuppressive drugs, including cyclosporine, have been used in the treatment of FSGS with varying degrees of success. The patient described herein was afflicted with end stage renal disease secondary to steroid-resistant nephrotic syndrome due to FSGS with coexistent Kimura's disease. After kidney transplantation, the patient experienced a remission of both the Kimura's disease and the nephrotic syndrome in the native kidneys, leading to the resumption of renal function by the native kidneys in spite of severe transplant glomerulopathy. This case suggests that certain cases of FSGS without extensive interstitial disease may benefit from aggressive treatment with a combination of immunosuppressive drugs.
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PMID:Effects of cyclosporine, azathioprine and prednisone on Kimura's disease and focal segmental glomerulosclerosis in renal transplant patients. 861 52

An accurate assessment of which patient with glomerular disease will progress to end-stage renal failure would be an important addition to establishing prognosis and evaluating therapeutic strategies. We previously found the development of glomerular scarring in animal models was preceded by an increase in glomerular type IV collagen mRNAs and that the level of scarring predicted the rate of progression. The purpose of this study was to determine whether these findings apply to human glomerular diseases using microdissected glomeruli and assessment of mRNA by competitive PCR. After showing that the levels of type IV collagen mRNAs were elevated in sclerotic glomeruli isolated from nephrectomies, we undertook this preliminary cross-sectional study of type IV collagen subchain mRNAs in renal biopsies in two of the leading causes of glomerulosclerosis, diabetic nephropathy, and membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels were altered in disease-specific ways. The relative levels of the individual alpha-chains of type IV collagen depended on the anatomic site of the glomerular lesions. The alpha 2 type IV/alpha 3 type IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with those obtained from experimental animals, suggest that a dysregulation of basement collagen synthesis underlies progressive glomerular scarring. If these conclusions are verified in prospective studies it will be feasible to assess the risk of developing progressive glomerulosclerosis in the individual patient and to quantitatively assess therapeutic responses in a timely manner.
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PMID:Molecular analysis of glomerular diseases in renal biopsies: initial results of a collaborative international study. The International Study Group for Molecular Study of Kidney Biopsies. 877 54

Two forms of abnormal fibrillary protein deposition are considered: amyloidosis and fibrillary (immunotactoid) glomerulonephritis. Amyloid is characterised by an antiparallel, beta-pleated configuration which imparts to it a unique apple-green birefringence after Congo red staining. Inspite of its fairly constant physical properties, the chemical composition of amyloid fibrils is amazingly diverse, encomposing AA protein, light chain fragments, transthyretin, procalcitonin, islet amyloid polypeptide, atrial natriuretic peptides, beta-amyloid protein, beta-2-microglobulin, cystatin C, gelsolin, apolipoprotein A1, lyzozyme and their mutant variants. Amyloid P component and heparan sulphate proteoglycan are ubiquitous non-fibrillary amyloid components which have significant roles in the amyloidogenetic process, as do also precursor fibril proteins. Different amyloid fibril proteins relate to different amyloidosis syndromes and different histological patterns, and provide the basis for new diagnostic approaches to this disorder. Glomerular deposits in fibrillary glomerulonephritis (FGN), although often mistaken for amyloid, differ from it in its negative Congophilia, wider fibril width and highly organised, microtubular-tactoidal appearance ultrastructurally. FGN is essentially a primary glomerulopathy resulting in progressive renal failure. Despite certain differences, intriguing similarities between both entities of fibrillary deposition pose a challenge to researchers as to the mechanisms of abnormal protein crystallization and fibril formation in tissues.
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PMID:Fibrillary deposits: amyloids and tactoids. 890 98

We have previously shown that idiopathic focal segmental glomerulosclerosis (FSGS) is the most common non-proliferative primary glomerulopathy in adult African Americans. In this report we present our experience with treated FSGS in 15 such patients followed over five years. They were all treated with prednisone 60 mg daily for three months, followed by a slow tapering. In addition, two patients later had cyclophosphamide, and five had enalapril. At entry hypertension was present in 73% of the patients, nephrotic syndrome in 87%, and elevated serum creatinine (> or = 1.4 mg/dl) in 40%. Five of the 15 patients (33%) developed end-stage renal failure (ESRF), one of them having a "malignant" course after the advent of pregnancy. Two patients (13%) have chronic renal insufficiency (CRI; serum creatinine > 2.5 mg/dl); three (20%) have mild renal insufficiency (serum creatinine 1.4-2.5 mg/dl), and five patients (33%) have normal renal function. The cumulative renal survival was 93% at five years, but only 26% at eight years. At last follow-up all the ten patients who did not develop ESRF were in partial remission (urinary protein of 1.3 g/day +/- 1.21), but 4 of the 5 patients who did not develop ESRF had no prolonged partial remission of nephrotic syndrome. Neither the initial clinical parameters not the use of enalapril correlated with the renal outcome (univariate analysis). However, 4 of the 5 patients who developed ESRF had elevated serum creatinine at entry, versus only 2 of the 10 not developing ESRF (p = 0.09 by two-sided, and 0.045 by one-sided Fisher's exact test). We conclude that the short-term renal outcome in nephrotic adult African Americans with treated FSGS is comparable to that of the non-African Americans, but their long-term prognosis may be poorer. Patients developing ESRF were more likely to present with elevated serum creatinine. Enalapril did not seem to modify the course of renal disease, but its utility and that of other ACE inhibitors in the treatment of FSGS must await prospective randomized studies.
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PMID:Focal segmental glomerulosclerosis in adult African Americans. 895 19

We describe a patient with idiopathic membranous glomerulopathy who developed acute deterioration in renal function; this was associated with hemoptysis, severe hypertension, and anti-glomerular basement membrane (anti-GBM) antibody in the serum. Despite aggressive therapy with plasmapheresis, cyclophosphamide and prednisone, the patient progressed to end-stage renal failure and is on maintenance hemodialysis.
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PMID:Goodpasture's syndrome superimposed on membranous nephropathy. A case report. 896 42

HIV-infected patients may present with a variety of patterns of renal involvement. Acute renal failure is common and most often a result of sepsis, hypotension, and nephrotoxic agents. It is potentially avoidable, and support through the period of renal failure may lead to resolution of the renal dysfunction. HIV-associated nephropathy is a unique pattern of sclerosing glomerulopathy that ranges in prevalence from 1 to 10% of the HIV-infected population in different geographic locales. This complication of HIV infection will likely present a growing challenge to the medical community as HIV infection continues to spread worldwide. Deciphering the pathogenetic mechanisms of this most rapidly progressive form of focal segmental sclerosis is not only clinically relevant, but will hopefully provide valuable insights into the mediation of the more common idiopathic form of the disease. The potential for improved renal survival of patients with HIV-associated nephropathy has become more realistic with the development and use of antiretroviral agents, as well as studies on the role of immunosuppression and ACE inhibition in this population. An awareness of other glomerular lesion and tubulointerstitial lesions has broadened our understanding of populations with renal disease who have been infected by HIV. Moreover, as prolonged survival of HIV-infected individuals is being achieved with modern antiviral therapy, the percentage of patients surviving with nephropathy will likely grow in coming years. Awareness of the growth of this population and those requiring short- and long-term hemodialysis and peritoneal dialysis will allow appropriate planning for ESRD in the HIV-infected population.
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PMID:HIV infection and the kidney. 901 59

Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, "collapsing" glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and "collapsing" glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group.
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PMID:Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus. 910 39

Mesangiocapillary glomerulonephritis (MCGN) accounting for 15 percent of adult glomerulopathy has not received proper attention in the Hungarian medical literature. The present study offers a detailed description of the procedures to be used for distinguishing its three types, which is only possible by histological, mainly electron microscopic examination of kidney biopsy samples. Type I represents subendothelial deposits; Type II is the "sausage-like" dense deposits localised on the lamina densa of the glomerular basal basement membrane; Type III is the mixed type. There is no significant difference in their clinical appearance. They occur most frequently as "coloured nephrosis" (the syndrome of nephrosis is associated with haematuria and/or hypertension). The course of the disease is characterised by periodicity, and in 50 percent of the cases kidney failure may develop. The therapy for MCGN has not been established. The administration of steroid, cyclophosphamide and anticoagulant can have a favourable effect.
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PMID:[Mesangiocapillary glomerulonephritis]. 918 65


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