Comparative Effect of Captopril and Nifedipine in Normotensive Patients With Incipient Diabetic Nephropathy

Mimran, A; Insua, A.; Ribstein, Jean; Bringer, J.; Monnier, L.

doi:10.2337/diacare.11.10.850

Cited by 66 publications

(14 citation statements)

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“…The importance of this early effect is bolstered further by the findings in the RENAAL, IDNT, and AASK trials. Thus, it is clear that the projection made more than a decade ago that reductions in proteinuria correlated with a slowed progression of kidney disease now are supported by several clinical trials (48,49).…”

Section: Resultsmentioning

confidence: 97%

Lessons Learned from Recent Hypertension Trials about Kidney Disease

Khosla¹,

Bakris²

2006

Clinical Journal of the American Society of Nephrology

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Section: Resultsmentioning

confidence: 97%

Lessons Learned from Recent Hypertension Trials about Kidney Disease

Khosla¹,

Bakris²

2006

Clinical Journal of the American Society of Nephrology

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“…This disparate effect on proteinuria of CEI and calcium antagonist has been previously reported in rats 27 -28 and patients. 39 As discussed above, the renal hemodynamic profiles of these two classes of antihypertensive agents are distinctly different. In particular, although it is clear that CEIs reduce glomerular capillary pressure in addition to systemic blood pressures, 1314 equivalent reduction in systemic pressure with a CCB may not lower glomerular capillary pressure 2021 because of a concomitant reduction in preglomerular resist-ances 19 and impairment of renal autoregulatory responses.…”

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confidence: 99%

Comparison of converting enzyme inhibitor and calcium channel blocker in hypertensive glomerular injury.

Tolins

Raij

1990

Hypertension

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The protective effect of converting enzyme inhibitors in experimental hypertensive glomerular injury is associated with decreased systemic arterial and glomerular capillary pressure. Although calcium channel Mockers effectively lower systemic blood pressure, their effect on glomerular capillary pressure and on hypertensive glomerular injury is uncertain. We compared equihypotensive treatment with the calcium antagonist TA 3090 or the converting enzyme inhibitor captopril in post-salt hypertensive Dahl salt-sensitive (DS) rats for up to 5 weeks after five sixths nephrectomy. Before the nephrectomy, all rats demonstrated hypertension (mean 177 mm Hg), proteinuria (mean 175 mg/day), and mild glomerulosclerosis (mean injury score 35). Rats treated with captopril or TA 3090 demonstrated a significant and equivalent decrease in systolic blood pressure compared with untreated rats at 2,3, and 5 weeks after five sixths nephrectomy; however, only captopril reduced proteinuria. Final proteinuria was actually increased in rats treated with TA 3090 compared with untreated rats. Glomerular injury score was significantly decreased in captopril-treated compared with untreated rats at 2 weeks (33±9 versus 117±10, p<0.05) and 5 weeks (46±9 versus 94±24, p<0.05), whereas treatment with TA 3090 delayed but did not prevent progressive glomerular injury (2-week score 35±7,p<0.05 versus untreated; 5-week score 109±19,p=NS versus untreated). Thus, in hypertensive DS rats after subtotal nephrectomy, treatment with a converting enzyme inhibitor reduced systemic blood pressure, proteinuria, and glomerulosclerosis. However, equihypotensive treatment with a calcium channel blocker did not reduce proteinuria and delayed but did not prevent glomerulosclerosis. Thus, in the rat similar reductions in systemic blood pressure with these two classes of agents have disparate effects on the progression of chronic renal failure. {Hypertension 1990;16:452-461) S ystemic hypertension complicates the course of most patients with chronic renal failure. 1 It has been recognized for some time that uncontrolled hypertension may accelerate deterioration of renal function in these patients. 2 On the other hand, adequate blood pressure control has clearly been shown to slow the rate of disease progression. now suggests that hypertensive glomerular injury results from free transmission of elevated systemic pressures to the glomerulus and that it is elevated glomerular capillary hydraulic pressure, rather than systemic hypertension itself, that induces progressive injury. 89 Effective autoregulation of the preglomerular resistance vessels, preventing transmission of elevated systemic pressures to the glomerular capillaries, underlies the observation that glomerular injury does not invariably develop in the face of systemic hypertension. 710Early workers 1112 demonstrated that after the removal of about three quarters of the renal mass in the rat, the initially normal remaining nephrons developed progressive glomerulosclerosis and the rats developed proteinuria...

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“…tive) on proteinuria in streptozotocin diabetic rats. Mimran et al 36 reported an increase in urinary albumin excretion with nifedipine (a dihydropyridine derivative) treatment in insulin-dependent diabetic patients with incipient diabetic nephropathy (urinary albumin excretion >15 jig/min). This is in contrast to the results reported by the Melbourne Diabetic Nephropathy Study Group, 37 in which nifedipine treatment significantly reduced albuminuria in hypertensive diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Effect of diltiazem on glomerular heparan sulfate and albuminuria in diabetic rats.

Jyothirmayi

Reddi

1993

Hypertension

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Calcium entry blockers, particularly diltiazem, have been shown to lower not only systemic blood pressure but also improve proteinuria in non-insulin-dependent diabetic patients. The presence of proteinuria is attributed to the loss of glomerular heparan sulfate, which confers a negative charge on the basement membrane. In the present study, we evaluated the efficacy of diltiazem in lowering blood pressure and proteinuria in diabetic rats and also examined the possibility that diltiazem prevents proteinuria through glomerular preservation of heparan sulfate. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg). One group of diabetic rats was treated with diltiazem (25 mg/L) in drinking water for 20 weeks. Another group of diabetic rats and a group of nondiabetic rats were given tap water only. Systolic blood pressure was measured at 4, 8,12, and 20 weeks. Urinary excretion of albumin was done at 4, 8,12, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of [-"S] sulfate. Diltiazem lowered blood pressure significantly in diabetic rats at 8,12, and 20 weeks. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from normal rats. Characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCI was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. Diltiazem therapy returned not only glomerular synthesis but also various fractions of heparan sulfate to normal. Urinary albumin excretion was significantly higher in diabetic than in normal rats; diltiazem therapy significantly lowered albuminuria in diabetic rats. The data suggest that diltiazem therapy prevents albuminuria through preservation of glomerular heparan sulfate in diabetic rats. 1 The onset of these changes is believed to be signaled by the appearance of microalbuminuria (urinary albumin excretion of 30-300 mg per day).2 -4 If untreated, this microalbuminuria may progress to macroalbuminuria and then to nephrotic syndrome. It appears likely that albuminuria of either degree indicates the escape of albumin across the glomerular basement membrane (GBM). This escape appears to be due to the loss of negative electrostatic properties of the GBM. One constituent of the membrane, heparan sulfatecontaining proteoglycan, can confer a negative charge on the lamina rara interna and externa of this structural element. It therefore seems probable that a decrease in heparan sulfate content would result in altered electrostatic properties and thus produce proteinuria.5 Indeed, it has been shown, for example, that removal of heparan sulfate from the GBM of rats by means of heparinase

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Comparative Effect of Captopril and Nifedipine in Normotensive Patients With Incipient Diabetic Nephropathy

Cited by 66 publications

References 0 publications

Lessons Learned from Recent Hypertension Trials about Kidney Disease

Lessons Learned from Recent Hypertension Trials about Kidney Disease

Comparison of converting enzyme inhibitor and calcium channel blocker in hypertensive glomerular injury.

Effect of diltiazem on glomerular heparan sulfate and albuminuria in diabetic rats.

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