OBJECTIVE -The objective of this study was to evaluate the safety and short-term effect of adding spironolactone to conventional antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor or an angiotensin II receptor blocker (ARB) on albuminuria and blood pressure in type 2 diabetic patients with nephropathy.RESEARCH DESIGN AND METHODS -Twenty-one type 2 diabetic patients with nephropathy were enrolled in a randomized, double-masked, cross-over study. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for 8 weeks, respectively, in addition to ongoing antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor and/or an ARB. At the end of each treatment period, albuminuria, 24-h ambulatory blood pressure (ABP), and glomerular filtration rate (GFR) were determined.RESULTS -During the addition of placebo, values were as follows: albuminuria (geometric mean [range]) 1,566 762] mg/24 h, ABP (mean Ϯ SE) 138 Ϯ 3/71 Ϯ 1 mmHg, and GFR (mean Ϯ SE) 74 Ϯ 6 ml/min per 1.73 m 2 . During the addition of spironolactone, albuminuria was reduced by 33% (95% CI 25-41) (P Ͻ 0.001), fractional clearance of albumin by 40% (24 -53) (P Ͻ 0.001), and 24-h ABP by 6 mmHg (2-10) for systolic and 4 mmHg (2-6) for diastolic (P Ͻ 0.001 for both). The change in albuminuria did not correlate with the change in systolic 24-h ABP (r ϭ 0.19, P ϭ 0.42) or diastolic 24-h ABP (r ϭ 0.01, P ϭ 0.96). Spironolactone treatment induced an insignificant reversible reduction in GFR of 3 ml/min per 1.73 m 2 (Ϫ0.3 to 6) (P ϭ 0.08). One patient was excluded from the study due to hyperkalemia. Otherwise treatment was well tolerated.CONCLUSIONS -Our study suggests that spironolactone safely adds to the reno-and cardiovascular protective benefits of treatment with maximally recommended doses of ACE inhibitor and ARB by reducing albuminuria and blood pressure in type 2 diabetic patients with nephropathy. Diabetes Care 28:2106 -2112, 2005A ldosterone, the end product of the renin-angiotensin-aldosterone system (RAAS), has attracted renewed attention as an important mediator of both cardiovascular and renal disease (1,2). Accumulating experimental evidence suggests that circulating aldosterone per se contributes directly to renal and cardiovascular disease by inducing inflammation, fibrosis, and necrosis in end-organ tissues such as the heart, brain, and kidney (3). Moreover, aldosterone blockade has been shown to greatly improve survival in patients with chronic heart failure (4,5).Angiotensin II has long been considered the main mediator of the pathophysiological effects of the RAAS, and in diabetic nephropathy the renoprotective effects of treatment with an ACE inhibitor or an angiotensin receptor blocker (ARB) are well established (6 -9). Both ACE inhibitor and ARB treatments initially suppress plasma aldosterone. Eventually, however, plasma aldosterone may return to pretreatment levels, i.e., the aldosterone escape phenomenon. Aldosterone e...

The prognosis of diabetic nephropathy has improved during the past decades, predominantly because of effective antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mmHg to 129/84 mm Hg and albuminuria decreased from 1038 [tg/min to 504 [tg/min. The rate of decline in the glomerular filtration rate decreased from 0-89 (range 0.44-1.46) ml/min/month before treatment to 0-22 (range 0-01-0.40) mllmin/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (-6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/ 1-74 m2).Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

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Summmr/ Diabetic nephropathy is the main cause of increased mortality and morbidity in IDDM patients. The effect of antihypertensive treatment on the progression of the nephropathy is highly variable. The aim of this study was to evaluate putative predictors of the progression in diabetic nephropathy during long-term antihypertensive treatment. Eighteen hypertensive IDDM patients with diabetic nephropathy, who had not been treated previously, were followed during 3 years of treatment with captopril and frusemide or bendrofluazide. Glomerular filtration rate, arterial blood pressure, albuminuria and adjusted albuminuria were used as putative predictors of rate of decline in glomerular filtration. Fall rate in glomerular filtration rate was 4.6 (4.0) ml. min-1 .year 1 (mean (SD)) during treatment. Relative change in albuminuria (ratio of first year of treatment/baseline) and albuminuria during first year of treatment were significantly correlated to fall rate in glomerular filtration rate during 3 years of treatment (r --0.73, p < 0.001) and (r = 0.60, p < 0.01), respectively. Arterial blood pressure and glomerular filtration rate measured at baseline, during first year of treatment or relative changes in these variables did not correlate with fall rate in glomerular filtration rate during 3 years of treatment. Haemoglobin AI:, serum-cholesterol, protein intake and sodium excretion remained unchanged during treatment, and were not correlated with loss of kidney function. Reduction in albuminuria during captopril treatment predicts an attenuated rate of decline in glomerular filtration rate in early diabetic nephropathy (glomerular filtration rate > 70 ml. rain -1-1.73 m-Z). The finding suggests a clinical application in monitoring the efficacy of antihypertensive treatment in early diabetic nephropathy. [Diabetologia (1994) 37: 511-516] Key words Diabetic nephropathy, albuminuria, antihypertensive treatment, glomerular filtration rate.Diabetic nephropathy develops in 30-40 % of IDDM patients [1,2], and nephropathy is the main cause of increased morbidity and mortality in these patients [1]. Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in glomerular filtration rate, and raised arterial blood pressure [3]. Human and animal studies have demonstrated a correlation between elevation in arterial Received: 21 September 1993 and in revised form: 3 December 1993Corresponding author: Dr. R Rossing~ Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, DenmarkAbbreviations: IDDM, Insulin-dependent diabetes mellitus blood pressure and development and progression of diabetic glomerulopathy [4][5][6][7][8][9][10]. Several studies [11][12][13][14][15][16][17] have demonstrated that the rate of decline in glomerular filtration rate can be reduced by antihypertensive treatment. However the beneficial effect of antihypertensive treatment on the progression of the diabetic nephropathy is highly variable. From a clinical point of view, identification of predic...

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Type 2 diabetes patients with non-dipping of night blood pressure were at higher risk of death as compared to dippers, independent of known cardiovascular risk factors. Since non-dipping has a high prevalence in patients with diabetic nephropathy, 24-h ambulatory blood pressure should be used to assess a full risk profile and blood pressure-lowering therapy in these patients.

We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 (non-insulin-dependent) diabetic patients with biopsy-proven diabetic glomerulosclerosis. Twenty-six patients (1 female) with a mean age of 52 (standard error 2) years and a known mean duration of diabetes of 9 (1) years were followed-up prospectively for a mean of 5.2 (range 1.0-7.0) years. Twenty-one patients received antihypertensive treatment. During the observation period the glomerular filtration rate decreased from 83 (24-146) to 58 (2-145) ml.min-1 x 1.73 m-2 (mean (range)) (p < 0.001). The mean rate of decline in glomerular filtration rate was 5.7 (-3.5 to 22.0) ml/min per year. Albuminuria increased from 1.2 (0.3-7.2) to 2.3 (0.4-8.0) g/24 h (geometric mean (range)) (p < 0.001). Arterial blood pressure remained unchanged: 162/93 (SE 4/3) and 161/89 (4/2) mm Hg. Univariate analysis showed the rate of decline in glomerular filtration rate to correlate with systolic blood pressure (r = 0.71, p < 0.001), mean blood pressure (r = 0.56, p < 0.005), albuminuria (r = 0.58, p < 0.005) and the initial glomerular filtration rate (r = -0.49, p < 0.02). The rate of decline in glomerular filtration rate did not correlate significantly with dietary protein intake, total cholesterol, high-density lipoprotein cholesterol or HbA1c. Three patients died from uraemia and four patients died from cardiovascular disease. Two patients required renal replacement therapy at the end of the observation period. Our prospective observational study revealed that one-fifth of the patients developed end-stage renal failure during the 5-year observation period.(ABSTRACT TRUNCATED AT 250 WORDS)