Renoprotection by nitric oxide donor and lisinopril in the remnant kidney model.

Previous studies showed a renoprotective effect of l-arginine in experimental uremia. Whether this was caused by an increased nitric oxide (NO) release or depended on l-arginine per se is not clear. Here, we evaluated whether chronic administration of an NO donor, molsidomine, controlled systemic blood pressure and renal disease progression and prolonged survival in rats with renal mass reduction (RMR).

Nature and mediators of renal lesions in kidney transplant patients given cyclosporine for more than one year.

Background: Cyclosporine (CSA) has improved patients and organ-graft survival rates, but its chronic nephrotoxicity is still an issue. Although prolonged vasoconstriction could contribute to chronic CsA tubulointerstitial changes by producing chronic ischemia, this relationship has been difficult to demonstrate thus far, and cellular origin and mediators of these structural alterations remain ill-defined.

Methods: As a part of a clinical trial in kidney transplant recipients on triple immunosuppressive therapy (CsA, azathioprine and steroid), which includes renal biopsy as "per protocol," 22 patients enrolled between 12 and 24 months posttransplantation underwent renal hemodynamic evaluation by measuring glomerular filtration rate and renal plasma flow by the plasma clearance of unlabeled iohexol and the renal clearance of para-aminohippuric acid, respectively.

Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes.

Chronic nephropathies are associated with enhanced renal synthesis of endothelin (ET)-1. A recent study demonstrated that an ET(A) receptor antagonist given to diabetic rats at the moment of disease induction prevented the development of renal injury. Here we investigated whether an unselective ET(A)/ET(B) receptor antagonist, PD 142,893, was renoprotective when given to streptozotocin diabetic rats when animals were already proteinuric.

Pharmacologic control of angiotensin II ameliorates renal disease while reducing renal TGF-beta in experimental mesangioproliferative glomerulonephritis.

We evaluated the effect of blocking angiotensin II (AngII) on the development of proteinuria and glomerular injury in antithymocyte serum (ATS) glomerulonephritis. Disease was induced in Sprague-Dawley rats by a single intravenous injection of rabbit ATS. Three groups of rats were considered: group 1 (n = 13), ATS rats with no therapy; group 2 (n = 13), ATS rats treated with angiotensin-converting enzyme inhibitor (40 mg/L lisinopril in the drinking water); and group 3 (n = 13), ATS rats treated with AngII receptor antagonist (50 mg/L L-158,809 in the drinking water).

Time course and localization of endothelin-1 gene expression in a model of renal disease progression.

Experimental and human proteinuric glomerulopathies are associated with tubulo-interstitial injury that correlates with the decline of renal function even better than glomerular lesions do. Mechanism(s) leading to tubulo-interstitial damage are unknown. It has been proposed that excessive reabsorption of filtered proteins activates renal cells to produce vasoactive and inflammatory molecules including endothelin-1.

Role of increased glomerular protein traffic in the progression of renal failure.

Clinical and experimental data have indicated that heavy proteinuria in renal glomerular diseases is associated with the formation of tubulointerstitial fibrosis and contributes to the progression of renal failure. In recent years studies have focused on the possibility that albumin and other proteins that accumulate in the lumen of proximal tubular cells as a consequence of glomerular permeability dysfunction, are a direct cause of tubular cell injury. Specific proteins that have been shown to be cytotoxic are transferrin/iron, lipoproteins and complement components, all of which appear in the urine in proteinuric states.

Endothelin: a mediator of renal disease progression.

Glomerulosclerosis and tubulointerstitial damage are characteristics of progressive renal diseases associated with chronic proteinuria. Since numerous studies have demonstrated a correlation between proteinuria and the degree of renal damage, a causal role for proteinuria in the development of progressive renal failure has been postulated. Some in vitro data suggest that endothelins (ET), a family of endogenous peptides, could be involved in the genesis and progression of glomerular damage.

Passive Heymann nephritis: evidence that angiotensin-converting enzyme inhibition reduces proteinuria and retards renal structural injury.

In nonimmunological models of renal damage, abnormal traffic of proteins through the glomerular capillary is one of the possible causes of renal disease progression. Here we investigated whether in a model of immune-mediated glomerulonephritis long-lasting proteinuria resulted in renal structural damage and whether chronic treatment with perindopril, an angiotensin-converting enzyme (ACE) inhibitor, lowered proteinuria and retarded disease progression. Passive Heymann nephritis (PHN), a model of human membranous nephropathy, was induced with 0.

Endothelin is a key modulator of progressive renal injury: experimental data and novel therapeutic strategies.

1. Glomerulosclerosis and tubulointerstitial damage are common histological abnormalities of many renal diseases that progress to end-stage renal failure. 2.

Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins.

Abnormal traffic of proteins through the glomerular capillary has an intrinsic renal toxicity possibly linked to the subsequent process of over-reabsorption by proximal tubular cells. We investigated in vitro the effect of different protein concentrations on proximal tubular cell endothelin-1 (ET-1) synthesis. Rabbit proximal tubular RC.

ACE inhibition prevents renal failure and death in uninephrectomized MWF/Ztm rats.

Many studies have consistently documented that angiotensin converting enzyme (ACE) inhibitors prevent proteinuria and glomerulosclerosis in progressive renal disease, but very few data are available on whether they also prevent renal failure and death. The mechanisms of the beneficial effect of ACE inhibition are only partially understood. Recent data suggest that angiotensin II modulates renal synthesis of endothelin-1, a vasoactive peptide implicated in the process of renal injury.

Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion.

Renal toxicity, possibly due to vasoconstriction and vascular injury, is the most relevant side-effect of chronic cyclosporine (CsA) therapy given to prevent graft rejection. In kidney transplant recipients each oral dose of CsA is invariably followed by a transient reduction in renal plasma flow (RPF) and glomerular filtration rate (GFR) that results from a form of acute reversible hypoperfusion. We sought to determine whether the Ca2+ channel blocker, lacidipine, prevented CsA-associated renal hypoperfusion in these patients.

Renal endothelin gene expression is increased in remnant kidney and correlates with disease progression.

We previously demonstrated that urinary endothelin excretion is increased in rats with extensive renal mass reduction, a model of progressive renal disease. Here we explored whether the increased urinary endothelin in this model were due to induction of renal pre-pro-endothelin-1 gene and whether changes in endothelin synthetic pathway correlated with the development of glomerulosclerosis. Four groups of rats with renal mass reduction and four groups of sham-operated control rats were studied 7, 30, 60 and 120 days after the surgical procedure.