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PubMed1996

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension.

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, combination therapy of verapamil SR 240 mg plus indapamide 2.5 mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg daily, those patients with diastolic blood pressures of <95 mm Hg were excluded from further study; 137 remaining patients with sitting diastolic blood pressure of 95--115 mm Hg, representing "incomplete" responders to verapamil SR 240 mg, were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. Efficacy was assessed after 16 weeks of double-blind therapy or at end point. All three treatments significantly reduced sitting diastolic and systolic blood pressure from baseline levels. Compared with Group I (verapamil SR 240 mg daily), there was a significant reduction (p < 0.05) in Group II combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction (p < 0.05) in Group II (verapamil SR 480 mg daily) of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Patients who had the least change in blood pressure (diastolic blood pressure decreases of <5 mm Hg) to lead-in verapamil SR 240 mg daily, prior to randomization, tended to have a greater response to combination therapy than to verapamil SR 480 mg. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving verapamil SR 480 mg daily (Group II). There was a significantly greater withdrawal from Group II than the other two treatment groups (8.5% from Group III and 4% from Group I). This trial demonstrated that adding indapamide 2.5 mg to the incomplete responders of verapamil SR 240 mg enhances efficacy and was well tolerated.

Journal Article↗
PubMed2006

Fracture risk and the use of a diuretic (indapamide SR) +/- perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET).

BACKGROUND: The Hypertension in the Very Elderly Trial (HYVET) is a placebo controlled double blind trial of treating hypertension with indapamide Slow Release (SR) +/- perindopril in subjects over the age of 80 years. The primary endpoints are stroke (fatal and non fatal). In view of the fact that thiazide diuretics and indapamide reduce urinary calcium and may increase bone mineral density, a fracture sub study was designed to investigate whether or not the trial anti-hypertensive treatment will reduce the fracture rate in very elderly hypertensive subjects. METHODS: In the trial considerable care is taken to ascertain any fractures and to identify risk factors for fracture, such as falls, co-morbidity, drug treatment, smoking and drinking habits, levels of activity, biochemical abnormalities, cardiac irregularities, impaired cognitive function and symptoms of orthostatic hypotension. POTENTIAL RESULTS: The trial is expected to provide 10,500 patient years of follow-up. Given a fracture rate of 40/1000 patient years and a 20% difference in fracture rate, the power of the sub study is 58% to detect this difference at the 5% level of significance. The corresponding power for a reduction of 25% is 78%. CONCLUSION: The trial is well under way, expected to complete in 2009, and on target to detect, if present, the above differences in fracture rate.

Journal Article↗
PubMed1979

Photolytic decomposition of indapamide.

Photolytic decomposition of indapamide (I) in nitrogen-flushed methanol yields 3-sulfamoyl-4-chlorobenzamide (II), 2-methylindoline (III), semicarbazide (IV), and 1-(N-formamido)-2-methylindoline (V); in oxygen-flushed methanol, II--V, 1-aminocarboxymethyl-2-methylindoline (VI), 3-sulfamoyl-4-chlorobenzoic acid (VII), methyl-3-sulfamoyl-4-chlorobenzoate (VIII), and 2-(N-acetamido)-benzoic acid (IX) are formed. A comparison is made with thermal decomposition of I.

Chemical Phenomena↗
PubMed1989

Comparison of indapamide and hydrochlorothiazide plus amiloride as a third drug in the treatment of arterial hypertension.

In a randomized, double-blind crossover trial, indapamide (IND) 2.5 mg and hydrochlorothiazide 25 mg + amiloride 2.5 mg (HCTZ + A) were found to be equally effective in reducing blood pressure (BP) in 13 patients with moderate to severe hypertension already receiving chronic treatment with a beta blocker and a vasodilatator (supine BP during run-in: 169/103 +/- 21/5 mmHg; on IND: 149/91 +/- 21/14 mmHg; on HCTZ + A 144/88 +/- 23/5 mmHg). Both drugs induced insignificant reductions in body weight, and no change in plasma volume was seen. Serum potassium was significantly reduced on both regimens--the values recorded on IND being significantly lower than those seen on HCTZ + A. Values below 3.0 mmol/l were found in two patients receiving IND, but no subjective side effects were reported. Hyperuricemia occurred with the same frequency on both regimens. It is concluded that IND, just like the thiazide diuretics, is useful as the third drug in patients needing triple drug therapy to control BP, but metabolic adverse effects are not avoided by the choice of this drug.

Adult↗
PubMedDate not supplied

Preparation of indapamide slow-release pellets.

During the process of developing a slow-release formulation of indapamide, researchers created a drug-containing pellet coated with Eudragit RS100 (Rohm GMbH & Co. KG, Darmstadt, Germany) to control the rate at which the drug was released. The two main variables were the agglomerants used in the pellet preparation and the amount of Eudragit RS100 used to coat them. The optimal outcome was indicated by the greatest number of drug-containing pellets recovered through an 18- to 24-mesh sieve and a satisfactory 24-hour release curve. The kinetics of dissolution fit the Higuchi kinetics model. Stability tests of the drug pellets showed no notable changes in the rate of drug release, related substances (mean byproducts or impurities from interactions or decompositions), and drug content.

Biological Availability↗
PubMedDate not supplied

Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension.

This 12-week randomized, parallel-group, multicenter study compared fixed combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F) 20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to moderate essential hypertension. After a 2-week placebo run-in, sitting and standing systolic (SBP) and diastolic blood pressure (DBP) was measured by conventional sphygmomanometry. The primary efficacy endpoint was the percentage of normalized (sitting DBP < or =90 mm Hg) and responder (sitting DBP reduction of 10 mm Hg or DBP < or =90 mm Hg) patients. Treatment effects were analyzed in the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167) populations. The percentage of normalized and responder patients did not differ significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT groups. Similar results were seen in the PP population. In ITT and PP patients, sitting and standing SBP and DBP values were comparable at baseline in the two groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and 12. Neither treatment induced reflex tachycardia, and both regimens were well tolerated. Four patients in the F + H group dropped out because of adverse events. In this study, the efficacy and safety of D + I were comparable to those of F + H in patients with mild to moderate essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Efficacy of antihypertensive treatment with indapamide in patients with noninsulin-dependent diabetes and persistent microalbuminuria.

In patients with insulin-dependent diabetes, antihypertensive treatment has a beneficial effect on the rate of progression toward uremia of overt diabetic nephropathy (albumin excretion rate [AER] greater than 300 mg/24 hour). The influence of hypertension on the progression of "incipient" nephropathy (AER ranging between 30 and 300 mg/24 hours) is not well defined, particularly in patients with noninsulin-dependent diabetes. In this study, 21 patients with noninsulin-dependent diabetes and hypertension (11 with normoalbuminuria and 10 with microalbuminuria), who were comparable for age, duration of diabetes and hypertension, were treated with indapamide, 2.5 mg once daily, and followed up for 24 months. Blood pressure, glomerular filtration rate (GFR), albumin excretion rate and subclass 4 of urinary immunoglobulin G (IgG4) were indicated. In normoalbuminuric patients, blood pressure was significantly reduced, whereas AER, IgG4 and GFR did not show any variation throughout the study. In microalbuminuric patients, blood pressure, AER and IgG4 were significantly reduced, and GFR remained unchanged. In patients with noninsulin-dependent diabetes, antihypertensive treatment, which is begun during incipient diabetic nephropathy, may have a beneficial effect on the progression of the disease, although a long-term follow-up study is needed to confirm this.

Adult↗
PubMed1990

Long-term effects of indapamide: final results of a two-year Italian multicenter study in systemic hypertension.

To evaluate the antihypertensive efficacy and tolerability of a low-dose diuretic, indapamide, 2.5 mg once daily, was given to 248 patients with uncomplicated, mild to moderate hypertension for a period of 24 months. Blood pressure during sitting was 165 +/- 1/105 +/- 1 mmHg (mean +/- standard error of the mean) at the end of the placebo run-in period and 143 +/- 1/88 +/- 1 and 140 +/- 1/85 +/- 1 mmHg after 2 and 24 months, respectively; heart rate was clinically unmodified (from 77 +/- 1 to 75 +/- 1 beats/min). Total cholesterol, high-density cholesterol and serum triglycerides were unchanged, and uric acid increased significantly (from 292.0 +/- 6.5 to 377.7 +/- 56.5 mumols/liter). A mild reduction in serum potassium (-0.36 +/- 0.03 mmol/liter) was observed after 2 and 6 months of therapy; however, the degree of reduction appeared to be lower than that from reported studies with other thiazide diuretics. The incidence of hypokalemia (serum potassium less than 3.5 mmol/liter) was highest in northern Italy (17%), intermediate in the central region (14%) and lowest in southern Italy (2%), although the absolute reduction in serum potassium was similar in all the geographic areas. Blood glucose tolerance was unchanged despite the changes in serum potassium. The tolerability was good on the whole, with a tendency toward an improvement in the well-being of patients, most of whom were already asymptomatic before starting the study.

Adult↗
PubMed1984

A comparative study on possible calcium antagonistic properties of indapamide and other drugs potentially interfering with calcium transport in isolated vascular smooth muscle.

In the present study the effects of indapamide (IN) were compared with those of chlorthalidone (C) and of drugs potentially interfering with calcium transport, e.g. verapamil (V), papaverine (P), phentolamine (PH) and diazoxide (D) using isolated rabbit aorta in order to detect calcium antagonistic properties. IN and C failed to show any relaxation effect towards either noradrenaline (NA)- or high K+-precontracted aorta strips, whereas V and P reduced the K+ contraction dose dependently and PH, V, P and D induced a significant relaxation of the NA contraction. Preincubation with IN or C did not affect the dose-response curve of NA-induced contractions. PH antagonized the NA contraction strongly whereas V and P shifted the dose-response curve to the right only at the highest concentration. In a Ca2+-depleted and high K+-depolarized aorta preincubation with V was able to antagonize Ca2+-induced contraction effectively in a dose-dependent fashion whereas P only showed partial inhibition at the highest concentration. The effects of the drugs on responses to NA in a Ca2+-free medium were also investigated. This type of contraction is likely to be due to mobilization of internally located Ca2+. The results demonstrate that PH was able to counteract this type of contraction effectively whereas only a high concentration of V, P and D was effective in reducing the Na contraction in Ca2+-free medium. Both IN and C failed to affect this type of contraction. In conclusion, the present results indicate that neither IN nor C possess calcium entry and or intracellular calcium antagonistic properties under different conditions as measured in a conduit vessel of rabbits. Moreover, the results point to an additional site of calcium antagonistic action for V, P and D, especially at higher concentrations.

Animals↗
PubMed1996

Effect of indapamide on left ventricular hypertrophy in hypertension: a meta-analysis.

Left ventricular hypertrophy is a major risk factor for cardiovascular morbidity and mortality. Angiotensin-converting enzyme inhibitors, calcium antagonists, and beta-blockers prevent, and cause regression of, left ventricular hypertrophy after short-term therapy. The ability of diuretics to do the same is unclear. We have performed a meta-analysis of studies documenting the effect on left ventricular mass of 6 months' treatment with 2.5 mg indapamide daily. Six studies comprising 197 patients, aged 20-75 years, were included. There was an overall mean reduction in left ventricular mass index of 13.3%, which was principally due to a reduction in left ventricular wall thickness rather than internal diameter.

Adult↗
PubMed1996

Comparative effects of indapamide and captopril on blood pressure and albumin excretion rate in diabetic microalbuminuria.

Nephropathy affects about one third of diabetic patients and its onset can be predicted almost a decade in advance by detecting small quantities of albumin in the urine (microalbuminuria). Thus, detection of proteinuria or microalbuminuria in diabetic patients carries important implications and merits intervention. Strategies for delaying the relentless progression of microalbuminuria to diabetic nephropathy and ultimately end-stage renal failure are focused on improving glycemic control and reducing blood pressure. Studies with beta-blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors in hypertensive diabetics with microalbuminuria have shown a significant reduction in urinary albumin excretion rates (AER), with effective lowering of blood pressure. In a crossover study, we compared the effects of captopril versus indapamide as monotherapy for 12 weeks on AER and blood pressure in 31 diabetic patients with established microalbuminuria. The 2 drugs were equally effective in reducing AER (average reduction 30-40%) and had comparable antihypertensive effects.

Albuminuria↗
PubMed1996

Indapamide (Natrilix): the agent of choice in the treatment of recurrent renal calculi associated with idiopathic hypercalciuria.

OBJECTIVE: To compare the hypocalciuric and potential side-effects of hydrochlorothiazide (HCT) to indapamide (IND; a thiazide-like drug) in patients with idiopathic hypercalciuria. PATIENTS, SUBJECTS AND METHODS: Twelve patients with recurrent renal calculi and renal hypercalciuria were studied using a randomized double-blind cross-over protocol. In addition, because the side-effects of HCT are attenuated using small doses, the hypocalciuric effect of 12.5, 25 and 50 mg daily was assessed in six normal subjects. RESULTS: There was a significant reduction in urinary calcium excretion using both agents, with a mean (SD) of 6.06 (2.68) and 3.37 (2.00) mmol/24 h using IND, and 5.58 (1.98) and 3.93 (2.35) mmol/24 h using HCT, before and after treatment (P < 0.05). The treatment was not sufficiently prolonged to assess adequately all the side-effects of either agent but both produced a similar decrease in serum potassium, whilst HCT significantly increased the mean (SD) serum urate levels, from 0.34 (0.09) to 0.43 (0.08) mmol/L (P < 0.01). There was also a significant decrease in mean (SD) urinary citrate excretion in those receiving HCT, from 1.41 (1.05) to 1.00 (0.71) mmol/24 h (P < 0.001), but not in those receiving IND, from 1.19 (0.71) to 1.18 (0.79) mmol/24 h. Although there was a hypocalciuric effect with doses of 12.5 and 25 mg HCT, it was sub-therapeutic when compared with the dose of 50 mg. CONCLUSION: At a daily dose of 2.5 mg, IND is at least as effective as 50 mg HCT in controlling hypercalciuria. Because of its safety profile and lack of effects on urinary citrate excretion, this agent should be the preferred therapy for patients with idiopathic hypercalciuria and recurrent renal calculi.

Calcium↗
PubMed1995

[Percutaneous extracorporeal circulation in cardiogenic shock caused by combined poisoning with methyldigoxin, nifedipine and indapamide].

HISTORY AND FINDINGS: A 38-year-old man with endogenous depression was found comatose and with gasping respiration. Empty packets of tablets pointed to poisoning with methyldigoxin, nifedipine and indapamide. Pupils reacted slowly to light and no peripheral blood pressure could be measured. TREATMENT AND COURSE: Routine resuscitation measures (intubation, mechanical ventilation, external cardiac massage and drugs) were undertaken during transport to hospital where, in addition to further symptomatic treatment, digoxin antibodies were administered, but without noticeable effect. Percutaneous cardiopulmonary bypass was therefore undertaken. It achieved a cardiac output of 3.2l and a systolic pressure of 80 mm Hg: a stable rhythm and circulation were obtained within 15 hours indicating that electromechanical uncoupling had for the time being been overcome. The EEG suggested a midbrain syndrome. After another 18 hours of mechanical ventilation and symptomatic treatment asystole suddenly occurred. Renewed resuscitation procedures were not undertaken because of the very poor neurological state and prognosis. CONCLUSION: Although haemodynamic stabilization was only temporarily achieved and the patient's death could not be prevented because of adverse pretreatment conditions, the application of percutaneously implantable, transportable heart-lung machine appears to be justified in cases of intoxication with cardio- and vasodepressive substances.

Adult↗
PubMed1991

Indapamide: a diuretic of choice for the treatment of hypertension?

In recent years, the therapeutic approach to mild hypertension has evolved from a stepped care approach to one including varied, initial monotherapies, with the selection of drug based on factors present in an individual patient, followed by combination therapy. The greatest cumulative experience of the value of antihypertensive therapy has been obtained with diuretics. The reduction in risk of cardiovascular disease with successful antihypertensive therapy using conventional agents, including diuretics, is not as great as might have been anticipated by the magnitude of change in blood pressure. This could be due to antecedent cardiovascular injury prior to therapy or to risk factors induced by therapy. The recent introduction of a new generation of drugs with combined diuretic and hypotensive effects that reduce blood pressure without inducing the biochemical changes associated with thiazides, offers an opportunity to evaluate this question. Indapamide is the first of this new generation to be released. Its pharmacologic characteristics show that it has the prerequisites to be considered a first-line drug for use in hypertension. It meets the requirements of a Phase II or second generation drug in that it has similar efficacy, but less short term toxicity than first generation drugs. It has been introduced at a cost that is competitive with thiazides and potassium-sparing combination drugs and is cheaper than many other classes of antihypertensive drugs. The major caution in promoting its use is that its long term effect on morbidity and mortality in hypertensive disease has not yet been evaluated. In summary, this is a promising new drug that has the potential to replace first generation thiazides in the routine management of hypertension.

Blood Glucose↗
PubMed2002

Gender influence on the dose-ranging of a low-dose perindopril-indapamide combination in hypertension: effect on systolic and pulse pressure.

BACKGROUND: Dose-ranging of antihypertensive agents have been done to optimize diastolic blood pressure (DBP) reduction, but with little information on systolic (SBP), mean (MBP), or pulse (PP) pressures. A low-dose combination of perindopril (Per) and indapamide (Ind) has been shown to reduce more SBP than atenolol for the same DBP reduction. However, the possible influence of gender on this finding has never been tested. PURPOSE: A database of five randomized, double-blind, dose-ranging studies was established to determine the optimal dose of the Per/Ind combination in hypertensive men and women. A total of 2907 patients were treated by either placebo or various combinations associating Per (2, 4, 8 mg) and Ind (0.625, 1.25, 2.5 mg). RESULTS: In the overall population, there was a significant dose-response relationship (P < 0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in SBP, DBP, MBP. When men and women were analyzed by dose, SBP, DBP and MBP (but not PP) decreased significantly more in women than in men until the Per 4/Ind 1.25 dosage was reached. Thereafter, with higher dosages, generating a slight but significant hypokalemia, the finding was reversed, resulting in a gender interaction in the overall population. CONCLUSION: In hypertensive subjects, the low-dose combinations Per 2/Ind 0.625 and Per 4/Ind 1.25 are the most effective in reducing blood pressure and avoiding hypokalemia. This effect is more pronounced in women, in which increased SBP and PP are predominant hemodynamic features.

Adult↗
PubMedDate not supplied

Comparative trial of indapamide and hydrochlorothiazide in essential hypertension, with forearm plethysmography.

Seventeen patients (11 males) 34-66 years in age with uncomplicated essential hypertension completed a randomized, placebo-controlled, double-blind cross-over study comparing indapamide (IND) 2.5 mg q am with hydrochlorothiazide (HCT) 50 mg q am. The lead-in placebo period of 2 months was followed by two active drug phases of 3 months' duration separated by a 2-month placebo-washout period. The mean standing systolic/diastolic pressures (+/- SD) during placebo were 150 +/- 18/98 +/- 6 mm Hg. The pressures were 137 +/- 16/90 +/- 7 IND and 137 +/- 17/91 +/- 7 mm Hg on HCT. Thus the drugs produced similar systolic, diastolic, and mean arterial pressures. Orthostatic changes in mean pressure and heart rate were similar with the two drugs. Both drugs decreased serum potassium (-14.3% with IND and -13.7% with HCT), and increased serum uric acid (+26.7% with IND and +25.7% with HCT), and cholesterol (+11.7% with IND and +11.1% with HCT) equally. Forearm blood flow (FBF) and venous compliance (FVC) were measured by a plethysmographic technique in six of the patients. FBF during placebo of 3.53 +/- 0.58 ml/min/100 ml forearm volume was increased to 4.01 +/- 0.74 ml/min during IND and decreased to 3.40 +/- 1.16 ml/min on HCT, but our sample size did not permit detection of significant differences. FVC was not altered from baseline by the drugs. No side effects attributable to either of the two drugs were elicited. We conclude that IND did not differ from HCT in its effect on blood pressure, heart rate, venous compliance, or biochemistry. A possible peripheral arteriolar vasodilator effect on IND should be investigated further.

Adult↗
PubMed1995

Effects of indapamide on atherosclerosis development in cholesterol-fed rabbits.

We examined the effect of indapamide (IND) on the development of atherosclerosis lesions in rabbits maintained on a 1% (wt/wt) cholesterol-enriched diet for a 16-week period. IND was supplemented to the diet at three different levels to correspond to doses of 0.1, 0.3, and 1 mg/kg/day. Throughout the treatment, dietary consumption and body weight gains were comparable among the experimental and control groups. IND had no significant effect on plasma cholesterol, triglycerides, or phospholipids concentrations. Despite the lack of effect of the drug on these parameters, its administration produced a tendency toward a reduction in the aortic content of cholesterol and a dose-dependent and significant decrease in aortic damage. In the aortic arch, the extent of intimal aortic surface covered by grossly discernible atherosclerotic lesions was decreased by IND 1 mg/kg/day from 11.02 +/- 1.10 to 6.00 +/- 1.00% (p < 0.05) and from 9.72 +/- 1.39 to 5.37 +/- 1.20% (p < 0.05) in the remaining thoracic sections. In addition, the former dose also reduced the number of lesions per square centimeter from 3.69 +/- 0.68 to 1.72 +/- 0.53% (p < 0.05), and from 3.37 +/- 0.85 to 1.55 +/- 0.46% (p < 0.05) in aortic arch and in thoracic sections, respectively. The possibility that IND reduces the development of atherosclerotic lesions produced by diet-induced hypercholesterolemia through a mechanism involving its calcium antagonist and/or its antioxidant activity is discussed.

Administration, Oral↗
PubMed2006

Renal protection in diabetic patients: benefits of a first-line combination of perindopril-indapamide (Preterax).

Type 2 diabetes mellitus (T2DM) is often accompanied by high blood pressure (BP) and the clustering of several cardiovascular risk factors, and is the most frequent cause of end-stage renal disease. The stages of development of overt nephropathy in T2DM patients range from an initial alteration in renal function with an increased GFR, followed by the development of microalbuminuria and macroalbuminuria or proteinuria, featuring an established diabetic nephropathy, which eventually progresses to end-stage renal disease. Early intervention is needed to prevent the development of diabetic nephropathy and requires effective control of the different risk factors, and in particular high BP. In the initial stages of the disease, strict BP control is crucial to prevent the development of initial renal and vascular damage. Adequate BP control is particularly difficult in T2DM patients and in most cases requires the use of combination therapy. Preterax, a fixed-dose combination of perindopril 2 mg and indapamide 0.625 mg, allows BP to be significantly reduced compared with conventional strategies; this combination can be uptitrated to BiPreterax when further BP control is needed. In the PREMIER study performed in T2DM over 12 months, the perindopril/indapamide combination brought about, in addition to excellent BP control, a significant reduction in urinary albumin excretion, compared with monotherapy with enalapril. In more advanced degrees of renal damage, higher doses of the fixed combination have to be considered. The pharmacological basis of the renoprotective effect of perindopril/indapamide is the demonstration that this combination prevented nephropathy as well as proteinuria in obese Zucker rats, independently of BP control. Strict BP control from the initial stages of nephropathy together with inhibition of the renin-angiotensin system is mandatory to prevent albuminuria. The fixed combination of perindopril/indapamide can greatly help clinicians in achieving the above goals, using Preterax in the early and BiPreterax in the late stages of nephropathy.

Albuminuria↗