The effect of enalapril on glomerular growth and glomerular lesions after subtotal nephrectomy in the rat: a stereological analysis

Amann, Kerstin; Irzyniec, Tomasz; Mall, Gerhard; Ritz, Eberhard

doi:10.1097/00004872-199309000-00011

Cited by 61 publications

(60 citation statements)

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“…Initially, an infarct of two branches of the renal artery of the left kidney was performed [22]. After 7 days, the animals underwent right nephrectomies [23]. Female Wistar rats are suitable for the study of renal fibrosis using a CKD model, as previously described by Fleck et al [24].…”

Section: Rat Remnant Kidney Modelmentioning

confidence: 99%

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

et al. 2009

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Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury, but their role in chronic kidney diseases is still unknown. More specifically, it is not known whether MSCs halt fibrosis. The purpose of this work was to investigate the role of MSCs in fibrogenesis using a model of chronic renal failure. MSCs were obtained from the tibias and femurs of male Wistar-EPM rats. Female Wistar rats were subjected to the remnant model, and 2|3|10 5 MSCs were intravenously administrated to each rat every other week for 8 weeks or only once and followed for 12 weeks. SRY gene expression was observed in female rats treated with male MSCs, and immune localization of CD73 1 CD90 1 cells at 8 weeks was also assessed. Serum and urine analyses showed an amelioration of functional parameters in MSC-treated animals at 8 weeks, but not at 12 weeks. Masson's trichrome and Sirius red staining demonstrated reduced levels of fibrosis in MSC-treated animals. These results were corroborated by reduced vimentin, type I collagen, transforming growth factor b, fibroblast specific protein 1 (FSP-1), monocyte chemoattractant protein 1, and Smad3 mRNA expression and a smooth muscle actin and FSP-1 protein expression. Renal interleukin (IL)-6 and tumor necrosis factor a mRNA expression levels were significantly decreased after MSC treatment, whereas IL-4 and IL-10 expression levels were increased. All serum cytokine expression levels were decreased in MSC-treated animals. Taken together, these results suggested that MSC therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal injury. The immunosuppressive and remodeling properties of MSCs may be involved in the decreased fibrosis in the kidney.

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Section: Rat Remnant Kidney Modelmentioning

confidence: 99%

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

et al. 2009

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“…The antiproteinuric and kidney-protecting effects of the ACE inhibitors originally were thought to be attributable purely to hemodynamic effects, relieving the glomerulus by opening the efferent arterioles (postglomerular), thereby reducing glomerular capillary pressure (31). However, it has become apparent that ACE inhibitors also affect glomerular function by their effects on glomerular size, glomerular permeability, and increasing negative electrical charge of the glomerular membrane (34,35). A meta-analysis of 12 trials in 698 patients who had type 1 diabetes with microalbuminuria and were followed for at least 1 yr revealed that ACE inhibitors reduced the risk for progression to macroalbuminuria by 62% compared with that of the placebo group (36).…”

Section: Role Of Ace Inhibitorsmentioning

confidence: 99%

Prevention and Treatment of Diabetic Renal Disease in Type 2 Diabetes

Remuzzi

Macía²,

Ruggenenti

2006

Journal of the American Society of Nephrology

188

121

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Diabetic nephropathy (DN) is the leading cause of end-stage renal failure in Western countries and carries an increased risk for cardiovascular mortality. Studies have identified a number of factors that play a part in the development of DN. Among them, hypertension and proteinuria are the most important. In the early stages of DN, when albumin is present in the urine in very low quantities (microalbuminuria) and an increase is seen in BP, there is no loss of filtrate and patients respond well to prophylactic measures. Microalbuminuria is considered an early marker of DN. Prevention of the onset of microalbuminuria, therefore, could be considered as the primary means of preventing DN. The Bergamo Nephrologic Diabetes Complication Trial (BENEDICT) was a prospective, randomized, double-blind, parallel-group study that was organized in two phases. Phase A included 1204 patients and was aimed at assessing the efficacy of the angiotensin-converting enzyme (ACE) inhibitor trandolapril, the non-dihydropyridine calcium channel blocker verapamil, and the trandolapril plus verapamil combination as compared with placebo in prevention of microalbuminuria in hypertensive patients with type 2 diabetes and normal urinary albumin excretion rate. Phase B was aimed at assessing the efficacy of the combination as compared with trandolapril alone in prevention of macroalbuminuria in patients with microalbuminuria. The BENEDICT Phase A study showed that DN can be prevented by ACE inhibitor therapy. The beneficial effect of ACE inhibition is not enhanced by combined nondihydropyridine calcium channel blocker therapy. The apparent advantage of ACE inhibitors over other agents includes a protective effect on the kidney against the development of microalbuminuria, which is a major risk factor for cardiovascular events and death in this population.

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“…The hearts and the kidneys were processed and examined using morphometric and stereologic techniques as described below (23)(24)(25).…”

Section: Tissue Preparationmentioning

confidence: 99%

Beneficial Effects of Calcimimetics on Progression of Renal Failure and Cardiovascular Risk Factors

Ogata¹,

Ritz²,

Odoni³

et al. 2003

Journal of the American Society of Nephrology

Self Cite

139

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Abstract. In renal failure, parathyroid hormone (PTH) is not only involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa; it is also a permissive factor in the genesis of hypertension, cardiovascular damage, and dyslipidemia. The allosteric activator of the calcium sensing receptor NPSR-568 (R-568) has been shown to reduce the serum intact PTH (iPTH) concentration in uremic rats. It was the purpose of this study in subtotally nephrectomized (SNX) rats to compare pharmacologic abrogation of secondary hyperparathyroidism by R-568 with parathyroidectomy (PTX). The effects on progression of renal failure, BP, and lipid and structural parameters of kidney and heart were studied. Four groups of male SD-rats were studied: (1) sham-operated ϩ vehicletreated rats (controls); (2) SNX ϩ vehicle-treated rats (SNX); (3) parathyroidectomized SNX ϩ vehicle-treated rats (SNXϩPTX); and (4) SNX ϩ calcimimetic R-568 -treated rats (SNXϩR-568). R-568 (50 mol/kg per d) was administered by gavage. Eight weeks after SNX, serum creatinine concentration, urinary albumin excretion, BP, and serum LDL-cholesterol concentration were significantly lower in both R-568 -treated and parathyroidectomized SNX compared with vehicletreated SNX. In addition, structural abnormalities of the kidney (glomerulosclerosis, tubulointerstitial changes) and the heart (interstitial fibrosis, capillary length density, arteriolar wall thickness) were significantly less pronounced than in vehicletreated SNX. It is concluded that in experimental renal failure abrogation of hyperparathyroidism by administration of a calcimimetic or PTX similarly attenuates progression of renal failure. Furthermore, it interferes with the development of cardiovascular risk factors and cardiac remodeling.Secondary hyperparathyroidism (sHPT) is a known complication of chronic renal failure. Elevated concentrations of parathyroid hormone (PTH) play a role not only in the pathogenesis of renal bone disease (1,2), but also in the development of cardiovascular risk factors such as disturbed lipid metabolism (3,4), glucose intolerance (5), and hypertension (6 -8). Parathyroidectomy (PTX) attenuates progression of renal failure in subtotally nephrectomized rats (SNX) on a high protein (9) or high phosphate (10,11) diet. sHPT is also known to play an important role in the development of structural abnormalities of the heart in renal failure, including left ventricular hypertrophy, interstitial fibrosis, and arteriolar wall thickening of the heart (7,(12)(13)(14).Allosteric activators of the calcium sensing receptor, e.g., NPSR-568 (R-568), reduce PTH secretion in rats or patients with primary and secondary hyperparathyroidism (15-20).There is no information on whether calcimimetics also affect abnormalities of uremia other than calcemia, phosphatemia (21), PTH concentrations (22), and skeletal abnormalities (17).Therefore, it was the purpose of this study to compare the effects of the calcimimetic R-568 and of parathyroidectomy on progression of renal failure, ...

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The effect of enalapril on glomerular growth and glomerular lesions after subtotal nephrectomy in the rat: a stereological analysis

Cited by 61 publications

References 0 publications

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

Prevention and Treatment of Diabetic Renal Disease in Type 2 Diabetes

Beneficial Effects of Calcimimetics on Progression of Renal Failure and Cardiovascular Risk Factors

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