spirapril and Diabetic-Nephropathies

The evidence from recent clinical outcome trials in arterial hypertension (AH) and the treatment guidelines from national and international authorities have placed a clear emphasis on "tight" blood pressure (BP) control. This has been particularly well illustrated in the treatment of patients with diabetes mellitus and AH where "tight" BP control clearly improves the outcome with reduced numbers of fatal and non-fatal cardiovascular events. Whilst the clinical trials in AH have identified benefits through BP reduction with a range of antihypertensive drugs there is a considerable volume of evidence to suggest that the optimal treatment for diabetic nephropathy and microalbuminuria should be based upon ACE inhibition. It is widely held that inhibition of intra-renal renin angiotensin systems leads to greater benefit than can be achieved by hemodynamic changes alone. Thus, management of AH and nephropathy in both DM and other forms of renal disease revolves around BP reduction through an ACE inhibitor-based treatment regimen. Where there is renal failure it may be prudent to administer a drug such as spirapril which has non-renal elimination mechanisms and which has been shown to have no accumulation problems or increased adverse effects.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetic Nephropathies; Enalapril; Humans; Hypertension; Kidney Failure, Chronic; Prognosis; Renal Circulation

The management of hypertension and nephropathy, in both diabetes and other forms of renal disease, is usually based on blood pressure reduction through an angiotensin-converting enzyme (ACE) inhibitor-based treatment regimen. With particular respect to the choice of ACE inhibitor drug, there are no definitive direct comparisons in the treatment of renal disease. In terms of blood pressure reduction, however, there is evidence that spirapril is at least as effective as the reference ACE inhibitor, enalapril. However, patients with diabetic nephropathy and/or chronic renal failure are at potential risk from drug accumulation if the preferred agent relies predominantly on glomerular filtration for its elimination. In this respect spirapril may have an advantage because it has been shown that there are no clinically relevant increases in the spirapril(at) concentrations (24 h post-dose) even in the setting of advanced renal failure (creatinine clearance <20 ml/min). Thus, there is no requirement to modify the dose and no concerns about drug accumulation or the potential for exaggerated therapeutic or adverse effects. In summary, an ACE inhibitor drug is seen as an integral component of the drug treatment regimen for patients with nephropathy. Where there is renal failure it may be prudent to administer a drug, such as spirapril, which also has alternative elimination mechanisms.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Clinical Trials as Topic; Diabetic Nephropathies; Enalapril; Humans; Kidney Failure, Chronic

To examine effectiveness and safety of quadropril.. Changes in blood pressure (BP), heart rate (HR), levels of glucose, potassium and creatinine, creatinine clearance were studied in 120 patients (48 males and 72 females, mean age 60.6 +/- 0.7 years) with mild to moderate arterial hypertension (AH) with average duration 13.8 +/- 0.7 years. The patients were divided into 3 groups: with AH (n = 40), AH + noninsulindependent diabetes mellitus (DM) (n = 43), AH and nephropathy (n = 37). 8-week treatment was performed with a standard dose of 6 mg/day (1 tablet of quadropril). Control examinations were made 2, 4 and 8 weeks after the treatment.. After 8 weeks of treatment a decrease in systolic blood pressure in AH group was 24.0 +/- 3.0 mm Hg and in diastolic blood pressure 16.3 +/- 1.3 mm Hg (P < 0.001). In the group with DM this decrease was 22.4 +/- 2.8 mm Hg and 15.7 +/- 1.4 mm Hg (p < 0.001), respectively. In the group with nephropathy this decrease was 26.4 +/- 2.4 and 16.5 +/- 1.3 mm Hg (p < 0.001), respectively. Heart rate changed significantly only in diabetics: from 75.1 +/- 1.7 to 72.9 +/- 1.3 beats/min. Biochemical parameters in the hypertensive and diabetic patients did not change significantly. In the nephropathy group there was a significant decrease in creatinine and increase in creatinine clearance. Their level of glucose and potassium changed insignificantly.. The treatment with quadropril results in a significant decrease in blood pressure, does not influence parameters of carbohydrate metabolism, improves nitrogen eliminating function of the kidneys.

Topics: Administration, Oral; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Creatinine; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Enalapril; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Safety; Treatment Outcome

The effects of spirapril and isradipine on blood pressure, urinary albumin excretion and sodium-volume homeostasis in hypertensive insulin-dependent diabetic patients with nephropathy were assessed. Fifteen Type 1 diabetic patients aged 28-53 years with a diabetes duration of 19-37 years were studied. All had hypertension and diabetic nephropathy with a urinary albumin excretion of more than 300 mg/24 h. After a single blind placebo treatment period of 4 weeks the patients were randomly assigned to treatment with the calcium antagonist isradipine SRO 5 mg once daily or the ACE inhibitor spirapril 6 mg once daily for 6 months in a double-blind design. Isradipine lowered ambulatory systolic blood pressure from 152 +/- 12 to 141 +/- 11 mmHg (p < 0.05) and ambulatory diastolic pressure from 91 +/- 9 to 86 +/- 8 mmHg (p < 0.05). The blood pressure lowering effect of spirapril was similar: 156 +/- 13 vs 143 +/- 11 mmHg (p < 0.01) and 90 +/- 4 vs 84 +/- 4 mmHg (p < 0.05). The fractional albumin clearance was unchanged on isradipine but decreased after 6 months treatment with spirapril with on average 20% (p < 0.05). Total body exchangeable sodium decreased on spirapril treatment: 2994 +/- 296 vs 2636 +/- 194 meq/1.73 m2 (p < 0.05) and extracellular volume tended to do so (p = 0.12). On isradipine treatment these parameters remained unchanged. In conclusion both isradipine and spirapril lowered blood pressure in patients with diabetic nephropathy. Only the ACE inhibitor had demonstrable beneficial effects on urinary albumin excretion rate and the sodium-volume expansion seen in these patients.

Topics: Adult; Albuminuria; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Enalapril; Endothelium, Vascular; Female; Humans; Hypertension; Isradipine; Lipoproteins; Male; Middle Aged; Potassium; Sodium

Glomerular hyperfiltration and renal hypertrophy are both considered important in the progression of diabetic nephropathy. The aim of this study was to compare the effects of an equivalent reduction in blood pressure produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPI) and an antihypertensive triple drug combination of hydralazine, reserpine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats.. Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hypertensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group received no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In each of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubular area and glomerular sclerosis were evaluated.. The blood pressure reduction was equal in rats receiving either SPI or HRH. The GFR, proteinuria, glomerular area and tubular area were significantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertrophy responses were prevented. In the HD-HRH group the GFR and proteinuria were slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of the development of glomerulosclerosis.. The results of this study suggest that the control of early adaptive hyperfiltration and renal hypertrophy by SPI may be relevant in the prevention of glomerulosclerosis.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Diabetic Angiopathies; Diabetic Nephropathies; Disease Progression; Diuretics; Drug Therapy, Combination; Enalapril; Glomerular Filtration Rate; Hydralazine; Hydrochlorothiazide; Hypertension; Hypertrophy; Kidney; Male; Proteinuria; Rats; Rats, Inbred SHR; Reserpine; Sodium Chloride Symporter Inhibitors