Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case history of a patient having multiple myeloma with a remarkably high level of Bence Jones proteinuria (more than 20 g/day) is presented. The patient has responded well to therapy, and at no stage has he shown impairment of renal function as determined by creatinine clearance studies. A review of published reports has shown that such marked Bence Jones proteinuria at presentation is rare and is usually accompanied by renal impairment and a short survival. Additional presentation data from selected patients in the MRC First Myelomatosis Trial is presented. This suggests a higher incidence of marked Bence Jones proteinuria, and underlines the lack of correlation between the quantity excreted and the degree of renal impairment. The mechanisms by which Bence Jones protein may cause renal damage are discussed.
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PMID:Multiple myeloma with massive Bence Jones proteinuria and preservation of renal function. 26 96

Heymann's nephritis (HN), a rat model of the membranous glomerulonephritis in man, is thought to be mediated by auto-Ig with subsequent activation of C. Whether T cell mechanisms are involved in the mediation of HN, apart from CD4+ cells providing help for auto-Ig production, was examined by treatment with mAb specific for T cell subsets for 6 weeks after immunization to induce HN. Anti-CD4 mAb therapy totally prevented proteinuria, in that at 6, 8, and 12 week treated rats had less than 15 mg/day of protein compared to controls that all had greater than 260 mg/day. Ig and C deposition in the glomerulus was significantly less and auto-Ig titers in serum were partially suppressed by anti-CD4 therapy. Anti-CD8 mAb therapy markedly reduced proteinuria at all time points, for example at 6 weeks there was 51 +/- 40 mg/day compared to 183 +/- 120 mg/day (P = 0.0003), but had no effect on auto-Ig titers or on Ig and C deposition in the glomerulus. A non-specific effect of high dose mouse mAb therapy was excluded by the findings that a mAb that did not bind to rat cells had no effect on the induction of HN and that serum C was not depleted in any of the mAb treated animals. A role for T effector mechanisms was further supported by the finding that therapy with mAb to T cell receptor alpha/beta chain or with cyclosporine also markedly delayed the onset of proteinuria. Examination of renal biopsies showed a T cell infiltrate in glomeruli and the interstitium of the untreated HN controls that was not present in MRC Ox35 or MRC Ox8 treated groups. This infiltrate included CD4+ and CD8+ T cells and macrophages. These results suggest induction of proteinuria in HN was totally dependent upon CD4+ T cells, and that CD4+ and CD8+ cells may have a direct role in the mediation of glomerular dysfunction in HN.
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PMID:The role of T cells in the mediation of glomerular injury in Heymann's nephritis in the rat. 159 Dec 15

The effects of mAb therapy to CD4 or CD8 on induction of unresponsiveness to Heymann's nephritis by preimmunization with renal tubular antigen in IFA. Anti-CD4 mAbs (MRC Ox35) given for 2 weeks after RTA/IFA completely prevented the induction of resistance to HN, all rats developing proteinuria as well as high titers of autoantibody and Ig and C deposits in glomeruli. Anti-CD8 mAbs (MRC Ox8) did not prevent induction of unresponsiveness, even though it totally depleted CD8+ cells. In control rats not preimmunized with RTA/IFA, mAb therapy did not suppress disease induction, but in the case of anti-CD4 therapy enhanced the severity of disease. Persistent depletion of T cell subsets or complement components did not explain the effects of mAb therapy. These studies suggest that CD4+ cells are critical for the induction of unresponsiveness to HN and that therapy with mAb to CD4 can prevent induction of tolerance to an antigen, which has implications for its use in the induction of tolerance.
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PMID:Induction of unresponsiveness to Heymann's nephritis: inhibited by monoclonal antibody to CD4 but not to CD8. 190 70

Puromycin aminonucleoside nephropathy with heavy proteinuria and oedema was induced in rats by 10 consecutive daily subcutaneous injections of aminonucleoside (1.67 mg/100 g of body weight). The main ultrastructural lesions were vacuolation of podocytes and total fusion of foot processes with loss of colloidal iron-reactive polyanion layer on the epithelial surface adjacent to the basement membrane. On the other hand the outer surface of podocytes and intravacuolar granular substance stained with colloidal iron. In scanning electron microscopy of freeze-fractured tissue the swollen podocytes and the urinary spaces displayed granular and filamentous precipitates. Seven cell surface antigens were examined by indirect enzyme immunohistochemistry with a series of MRC OX monoclonal antibodies. Glomeruli of control rats exhibited rare isolated Ia- positive endocapillary cells, possibly monocytes; these elements were significantly reduced in puromycin aminonucleoside nephropathy but there was an increase in Ia- positive cells in the cortical interstitium. Control kidneys harboured scanty interstitial T lymphocytes. These latter, especially the T8- positive cytotoxic/suppressor subpopulation, were markedly augmented in puromycin aminonucleoside nephropathy. The expression of class I histocompatibility antigens and of differentiation antigens (Thy 1) was not altered by aminonucleoside.
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PMID:Puromycin aminonucleoside nephropathy: ultrastructure, glomerular polyanion, and cell surface markers. 351 67

Membranous nephropathy was diagnosed in 54 patients between January 1975 and June 1983 in the Royal Infirmary, Glasgow. It was the commonest cause of the nephrotic syndrome and, with IgA nephropathy, the commonest primary glomerular disease. A cause was found in 10 patients. The last seven patients diagnosed were enrolled in the MRC trial. The natural history of the remaining 37 patients with idiopathic membranous nephropathy was studied. After an average observation period of 64 months, 50 per cent had stable renal function with or without proteinuria and 50 per cent had progressive renal failure or had died of other causes (five patients). Of the factors examined only heavy proteinuria and hypertension were significantly more common in patients who developed progressive renal failure. No patient who entered remission relapsed. Vascular complications were an important cause of morbidity and mortality. Incidence of events of arterial occlusion was significantly higher in these patients compared with patients with IgA nephropathy. Treatment of patients with membranous nephropathy should, therefore, be judged not only by its efficacy in preventing progressive renal failure, but also by its effect on vascular disease and by its toxicity.
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PMID:The natural history of membranous nephropathy in the West of Scotland. 377 62

During March 1980 to February 1982, 73 out of 80 patients in renal failure admitted to the fourth MRC myelomatosis trial were managed by a planned policy of high fluid intake (greater than or equal to 3 1/24 h) in addition to receiving one of the two chemotherapeutic regimens being tested in the main trial. Patients were also randomised to receive either sodium bicarbonate to render their urine neutral or no supplement. Follow up continued till death or to April 1983. Of 49 patients who survived more than 100 days, 39 achieved reversal of their renal failure (18 complete, 21 partial). Recovery of renal function, as assessed by a fall in the serum creatinine concentration, was achieved even when light chain proteinuria persisted. Partial recovery of renal function was associated with prolonged useful life in several patients. In only 14 of the 80 patients studied was death directly attributable to renal failure. Survival of patients in the study was appreciably better than in equivalent groups of patients in other MRC trials in which less stringent policies of fluid intake were used. Patients randomised to receive alkali fared marginally better than the others, but the difference was not significant. These results show that in many cases patients with myelomatosis who develop renal failure may have this complication reversed by taking a high fluid intake. Furthermore, though light chain is an essential component of renal disease in these patients, other factors are also important and are accessible to treatment.
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PMID:Analysis and management of renal failure in fourth MRC myelomatosis trial. MRC working party on leukaemia in adults. 632 27

Although hypertension accounts for approximately 15-20% of end-stage renal disease and renal impairment occurs in 15% of patients with essential hypertension, there are few data available on the clinical features of patients with benign hypertensive nephrosclerosis, the histological consequence of hypertension on the kidney. To determine its prevalence on renal biopsy and its clinical features (including proteinuria and renal function), we used the U.K. MRC Glomerulonephritis Registry of 7339 biopsies from 20 centres to define all patients with benign hypertensive nephrosclerosis. In patients with no co-existing disease, 185 biopsies were classified solely as benign hypertensive nephrosclerosis (2.5%). Sixty-nine percent of patients were male and 72% aged over 50 years. Sixty-four percent had diastolic blood pressure above 90 mmHg and severe hypertension (diastolic > 120 mmHg) was present in 9%. Protein excretion of > 1.5 g/day was noted in 40%, with 22% excreting > 3 g/day. Eighteen percent had serum albumin values under 30 g/l. Eighty-one percent had serum creatinine > 120 mumol/l; in 51% this was > 250 mumol/l. There was significant correlation between serum creatinine and systolic blood pressure at time of biopsy (p = 0.01) and between serum creatinine and serum albumin (p = 0.001). Benign hypertensive nephrosclerosis accounts for 2.5% of all registered biopsies. Significant proteinuria is a common finding and proteinuria within the nephrotic range does occur. Systolic blood pressure appears to influence serum creatinine levels. Hypertensive nephropathy should be considered in all patients with heavy proteinuria and renal impairment.
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PMID:Clinical features of benign hypertensive nephrosclerosis at time of renal biopsy. 832 42

Angiotensin-converting enzyme (ACE-I) inhibitors and ARBs have shown real efficacy in reducing blood pressure, proteinuria, in slowing the progression of chronic kidney disease (MRC) and in clinical improvement. in patients with heart failure, diabetes mellitus and ischemic heart disease. However, their use is limited by some side effects such as the increase in serum potassium (K), which can be particularly severe in patients with renal insufficiency. In the 23,000 patients followed by the PIRP project of the Emilia-Romagna Region, hyperkalaemia at the first visit (K> 5.5 mEq / L) was present in about 7% of all patients. The prevalence of K values> 5.5 mEq / L increased in relation to the CKD stage, reaching 11% in patients in stage 4 and 5. Among patients with values of K> 5.5 at baseline, 44.8% were in therapy with ACE-I / ARB inhibitors, 3.8% with anti-mineralcortoid and a further 3.9% concurrently taking SRAA-blocking agents and K-sparing diuretics. Counter-measures to avoid the onset of hyperkalemia during treatment with drugs that block the RAAS range from the low-K diet, to diuretics and finally to drugs that promote fecal elimination of K. Among these, polystyrene sulfonates, which have more than 50 years of life, exchange K with sodium or calcium. These drugs, however, in chronic use, can lead to sodium or calcium overload and cause dangerous intestinal necrosis. Recently two new highly promising drugs have been introduced on the market for the treatment of hyperkalemia, the patiromer and sodium zirconium cyclosilicate. The patiromer, which is a potassium-calcium exchanger, acts at the level of the colon where there is a higher concentration of K and where the drug is most ionized. Sodium zirconium cyclosilicate (ZS-9) is a resin with micropores of well-defined dimensions, placed in the crystalline structure of the zirconium silicate. The trapped K is exchanged with other protons and sodium. However, even these drugs will have to demonstrate their long-term efficacy and safety to be considered true partners of RAAS blockers in some categories of patients.
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PMID:[Hyperkalemia as a limiting factor in the use of drugs that block the Renin Angiotensin Aldosterone System (RAAS)]. 2978 83