Effects of different antihypertensive drugs on human diabetic proteinuria (original) (raw)
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Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria
Kidney International, 1993
Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxaninduced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA; TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P <0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (P0w). Treatment with lisinopril lowered the P0c to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090.
Effect of antihypertensive treatment on kidney function in diabetic nephropathy
BMJ, 1987
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.
American Journal of Nephrology, 2008
In late diabetic nephropathy (DN) the initial lowering of albumin excretion rate (AER) with antihypertensive therapy is proportional to the degree of subsequent preservation of glomerular filtration rate (GFR). Whether a similar relationship exists between AER and GFR in early diabetes is not known. The present analysis has compared AER and GFR responses to antihypertensive therapy in 33 published studies (77 treatment groups) of early and late DN in type 1 (T1) and type 2 (T2) diabetes, analyzed on an intention-to-treat basis. Prospective trials were included if the initial change in AER during the first year of therapy and the change in GFR during at least 2 years of follow-up could be estimated from group mean data. The initial % decreases in AER were 5.9 ± 4.3 (T1), 10.5 ± 5.4 (T2, normotensive) and 18.4 ± 6.2 (T2, hypertensive) in early DN and 7.6 ± 11.1 (T1) and 20.8 ± 5.5 (T2) in late DN. The corresponding annual % rates of decline of GFR were 2.0 ± 0.5 (T1), 1.6 ± 0.5 (T2, n...
The Tohoku Journal of Experimental Medicine, 1990
The relationship between blood pressure and progression of nephropathy was studied (the mean follow-up period of 32.6+ 17.9 (s.D.) months in 20 Type 2 (non-insulin-dependent) diabetic patients with clinical nephropathy (proteinuria >0.5 g/day) and preserved renal function (serum creatinine level <150 ,a mol/liter). Fifteen hypertensive patients under antihypertensive treatment were divided into 2 groups : those with the mean diastolic blood pressure >_ 90 mmHg and/or the mean systolic blood pressure >150 mmHg during the follow-up period were designated as Group A (n = 6) and the remainders as Group B (n = 9). Five normotensive patients without any antihypertensive treatment throughout the follow-up period served as a control group (Grgoup C). The decline rate in GFR was significantly greater (p <0.05) in Group A (1.15+0.39 (s.E.) ml/min/month) than those in Groups B (0.33+0.08 ml/min/ month) and C (0.40+0.09 ml/min/month), respectively. The decline rate in GFR showed significant positive correlations both with systolic (r8 = 0.553, p <0.05) and diastolic (rs=0.493, p <0.05) blood pressures in the 15 hypertensive patients. The age, initial glomerular filtration rate, duration of diabetes and mean HbA1C level during the observation period were comparable in Groups A, B and C, respectively. The results indicate that an uncontrolled hypertension is associated with a rapid progression of kidney impairment in Type 2 diabetic patients with overt nephropathy, as has been suggested in Type 1 (insulin-dependent) diabetic patients. Type 2 diabetes ; hypertension ; nephropathy ; anti-hypertensive treatment Hypertension contributes to the leading causes of morbidity and mortality in
Effects of long-term antihypertensive treatment on kidney function in diabetic nephropathy
Hypertension, 1985
The purpose of our prospective study was to evaluate the long-term effect of aggressive antihypertensive treatment on glomerular filtration rate and albuminuria in young female and male patients with insulin-dependent diabetes mellitus with diabetic nephropathy and blood pressure greater than 90 mm Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients). All patients except one had diabetic retinopathy. Glomerular filtration rate was measured after a single intravenous injection of 51Cr-labeled ethylenediaminetetraacetic acid. Urinary albumin concentration was determined with a radial immunodiffusion method. The investigations were performed two to four times per year in each patient. The mean observation period was 59 and 27 months in the tr...
Update in Diabetic Nephropathy
International Journal of Diabetes and Metabolism
Diabetic nephropathy has become the leading cause of end-stage kidney disease worldwide and is associated with an increased cardiovascular risk. The earliest clinical manifestation is microalbuminuria. Tight blood glucose and blood pressure control reduce the risk of microalbuminuria. Once microalbuminuria is present, the rate of progression to end stage kidney disease and cardiovascular disease can be delayed by aggressive management of blood pressure, glucose, and lipids. Inhibition of the reninangiotensin system is important in reducing intraglomerular pressure but other classes of antihypertensive agents may also be needed to obtain adequate control of systemic blood pressure. Such measures can at least reduce by half the rate of progression of nephropathy and cardiovascular disease.
The Kidney and Hypertension in Diabetes Mellitus, 1996
Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression to ward end-stage renal failure. However, some au thors reported disparate renal protective effects of different antihypertensive drugs in diabetic ani mals and humans. In an attempt to resolve the controversy surrounding this possibility, previ ously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca 2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clin ical proteinuria (UProt), treated during >4 weeks with ACE inhibitors, Ca 2+ antagonists, or conven tional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on av erage-45%) than on conventional therapy (on av erage-23%) or Ca 2+ antagonists other than nifed ipine (on average-35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, Ρ < .05). On the basis of multiple regression anal ysis, ACE inhibitor-induced UProt changes corre lated with BP changes (r = 0.77, Ρ < .00001), aver aged-28% at zero BP change, and varied 1.5% for each percent BP change. On conventional therapy, UProt and BP changes also correlated (r = 0.62, Ρ < .005), but UProt began to decrease only after a BP reduction of >5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca 2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, Ρ < .05) was in an intermediate position between ACE inhibi tors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r =-0.55, Ρ < .0001). On conventional therapy or Ca 2+ .antagonists, vari ations in GFR were unrelated to changes in BP. As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbu minuria or overt proteinuria in initially normoten sive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca 2+ antagonists all have a distinct an tiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal ef fects may antagonize a BP-dependent antiproteinu ric action and even counteract the effect of lower ing systemic pressure. It is of note that ACE inhib itors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR.
American Journal of Kidney Diseases, 2005
Background: Little is known of the effects of blood pressure reduction by specific classes of antihypertensive drugs on the association between proteinuria reduction and progression of kidney insufficiency and development of end-stage kidney disease in patients with overt diabetic nephropathy in type 2 diabetes mellitus. Methods: Associations between baseline proteinuria and proteinuria reduction by either irbesartan, amlodipine, or control for similar decrements in blood pressure and the cumulative incidence of renal end points were examined using the Kaplan-Meier method in patients enrolled in the Irbesartan Diabetic Nephropathy Trial. Results: Risk for kidney failure doubled for each doubling of baseline proteinuria level (hazard ratio, 2.04; 95% confidence interval, 1.87 to 2.22; P < 0.001). For each halving of proteinuria level between baseline and 12 months with treatment, risk for kidney failure was reduced by more than half (hazard ratio, 0.44; 95% confidence interval, 0.40 to 0.49; P < 0.001). For the same proportional change in proteinuria, the reduction in risk for kidney failure was significantly greater for irbesartan compared with amlodipine (P ؍ 0.048), but not control (P ؍ 0.245). Proteinuria reduction in the first 12 months of therapy with irbesartan is associated with 36% of the total renoprotective effect observed. Conclusion: Baseline proteinuria is an important risk factor for kidney failure and provides a means to identify patients at greatest risk. Halving proteinuria halves the kidney risk. Proteinuria reduction using an angiotensin receptorblocking agent, such as irbesartan, should be regarded as an important therapeutic goal in renoprotective strategies. Am J Kidney Dis 45:281-287.
Antihypertensive Therapy in the Presence of Proteinuria
American Journal of Kidney Diseases, 2007
The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events. Increased blood pressure has a major role in the development of proteinuria in patients with either diabetic or nondiabetic kidney disease, and all recent guidelines recommend a blood pressure goal less than 130/80 mm Hg in patients with proteinuria to achieve maximal renal and cardiovascular protection. Drugs interfering with the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, should be used as first-line antihypertensive therapy in patients with proteinuria because they seem to have a blood pressure-independent antiproteinuric effect, and if blood pressure levels are still out of goal, a diuretic should be added to this regimen. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease proteinuria further. This review provides an extended summary of current evidence regarding the associations of blood pressure with proteinuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients. Am J Kidney Dis 49:12-26.