Reduction In Urinary Albumin Excretion Research Articles

What can be learned from the experience with the fixed low-dose combination of perindopril/indapamide in the treatment of hypertension?

The association of low doses of perindopril and indapamide in a single pill has been developed to meet the criteria required for a fixed-dose combination to be used as first-line therapy. The experience accumulated so far has demonstrated a greater antihypertensive efficacy of this preparation compared with various monotherapies, but not at the expense of a worsening of tolerability. The perindopril/indapamide combination is particularly effective in lowering systolic and pulse blood pressure. Starting treatment with this fixed-dose combination improves arterial stiffness and allows a better regression of cardiac hypertrophy than angiotensin-converting enzyme-inhibition or β-adrenoceptor blockade alone. In hypertensive patients with Type 2 diabetes, a greater reduction of urinary albumin excretion can be obtained with the perindopril/indapamide association compared with an angiotensin-converting enzyme inhibitor administered as monotherapy. There is evidence that a first-line management of hypertension based on a low-dose perindopril/indapamide combination can provide a better efficacy/safety ratio than other well-established therapeutic strategies.

Antihypertensive treatment: should it be titrated to blood pressure reduction or to target organ damage regression?

The success of an antihypertensive treatment is difficult to estimate by the extent of blood pressure reduction alone. Above and beyond blood pressure values in an individual patient, it is necessary to monitor the impact of antihypertensive treatment on the development or regression of hypertension-induced early end-organ damage. The intermediate objectives or surrogate endpoints may provide additional valuable information about the level of success of a given therapy in a particular patient. Moreover, monitoring intermediate objectives may provide scientific evidence for delineating the best antihypertensive treatment. The importance of assessing left ventricular mass, microalbuminuria, carotid wall thickness and the development of new-onset diabetes during antihypertensive treatment has been stressed. Left ventricular hypertrophy during antihypertensive therapy is associated with a lower likelihood of cardiovascular morbidity and mortality, independent of blood pressure lowering and treatment modalities in people with essential hypertension. Likewise, a reduction in urinary albumin excretion seems to be followed by a reduction in cardiovascular morbidity and mortality. Risk implications of reducing carotid wall thickness or of developing new-onset diabetes have been more controversial, although it seems to be that both can have a desirable effect. The available findings support the necessity to monitor intermediate objectives, aside from blood pressure measurement, during the follow-up of hypertensives.

The Relationship Between Albuminuria and Hormone Therapy in Postmenopausal Women

Elevated urinary albumin excretion and hormone therapy (HT) are associated with increased risk for cardiovascular events. We assessed the relationship between albuminuria and the use of hormonal preparations in postmenopausal women. Data from the Insulin Resistance Atherosclerosis Study were obtained at baseline and 5-year follow-up for analysis. The generalized estimating equation procedure accounting for repeated measures was used for this analysis. HT was the main predictor variable, and log(e) urine albumin-creatinine ratio (ACR) was the main outcome variable. Four hundred ninety-one menopausal women were included in the analysis, 36% (n = 179) of whom received HT (either oral estrogen, progesterone, or combination therapy). At baseline, abnormal albuminuria (ACR > or = 25 mg/g) was present in 11% of women on HT and 17% not on HT (P = 0.02). After adjusting for demographics, the presence of diabetes and hypertension, and kidney function, HT was associated with a 19% reduction in ACR (P = 0.008) and an odds ratio of 0.67 (95% confidence interval, 0.43 to 1.01; P = 0.06) for the presence of abnormal albuminuria. Other predictors of abnormal albuminuria included diabetes, blood pressure, and triglyceride level. Results of this study suggest that HT is associated with a reduction in urinary albumin excretion in postmenopausal women.

Treatment of non-dipper essential hypertension with bedtime administration of valsartan

Previous results have indicated that valsartan administration at bedtime as opposed to upon wakening improves the day/night ratio of blood pressure (BP) (nocturnal decline of BP relative to the diurnal mean) towards a more dipper pattern without loss in 24-hour efficacy [Hypertension. 2003;42:283–290]. Some studies have found differential effects of antihypertensive drugs according to the dipping status of the patients. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients. We studied 190 non-dipper patients with grade 1–2 essential hypertension (72 men), 53.9±13.2 years of age, randomly assigned to receive single daily valsartan monotherapy (160 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 hours before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of BP on a per subject basis. The highly significant BP reduction after 3 months of treatment with valsartan (P<0.001) was slightly larger after bedtime dosing of valsartan (13.0 and 8.1 mm Hg reduction in the 24-hour mean of systolic and diastolic BP after valsartan on awakening; 15.2 and 10.6 mm Hg when valsartan was administered at bedtime). The day/night ratio was unchanged after valsartan on awakening (0.4 and 0.7 for systolic and diastolic BP; P>0.309). This ratio was significantly increased (7.2 and 7.1 for systolic and diastolic BP, P<0.001) when valsartan was administered at bedtime, which resulted in 75% of the patients reverted to dippers, a significant increase in the percentage of patients with controlled BP after treatment, and a significant reduction in urinary albumin excretion. Independently of dosing time, 160 mg/day valsartan monotherapy efficiently reduces BP for the entire 24 hours of the day. In hypertensive patients who are non-dippers at baseline, dosing time with valsartan should be chosen at bedtime, for increased efficacy during nocturnal resting hours, improved renal function, and the potential associated reduction in cardiovascular risk.

Transforming growth factor β1 and additional renoprotective effect of combination ACE inhibitor and angiotensin II receptor blocker in hypertensive subjects with minor renal abnormalities: a 24-week randomized controlled trial

To verify the benefit of renin-angiotensin system blockade in hypertension, the effects of 24 weeks' losartan and ramipril treatment, both alone and in combination, on urinary albumin excretion (UAE) and circulating transforming growth factor beta1 (TGF beta1) have been evaluated in hypertensive subjects with minor renal abnormalities. Fifty-one patients with stage 1 and 2 essential hypertension and with UAE > or = 20 mg/24 h but with maintained renal function have been included. After a 4-week run-in with placebo administration, a randomized double-blind, three-arm double-dummy trial was used. All the hypertensives (HT) were allocated randomly to three treatment arms (17 patients for each group) and they were single-matched for age, gender, body mass index (BMI), systolic and diastolic blood pressure. Active treatment consisted of losartan (50 mg/day), ramipril (5 mg/day) and combined (losartan 50 mg/day plus ramipril 5 mg/day) for 24 weeks. Hydrochlorothiazide 12.5 mg/day was added in HT patients with uncontrolled blood pressure (> or = 140/90 mmHg) during the active treatment period. In all patients UAE, by immunonephelometric assay; circulating TGF beta1 by a solid-phase specific sandwich enzyme-linked immunosorbent assay (ELISA); and blood urea nitrogen (BUN), creatinine and creatinine clearance and potassium, by routine laboratory methods, were determined after placebo treatment and 24 weeks follow-up. The three treatment groups were comparable for gender, age, BMI, blood pressure, UAE and renal function measurements. During the active treatment period it was necessary to add hydrochlorothiazide in five patients--two each of the losartan and ramipril groups and one of the combined group. At the end of treatment, significant (P < 0.05) reductions in systolic, diastolic and mean blood pressure, UAE and TGF beta1 levels were observed in all the groups. No change in renal function measurements were observed. The absolute and percentage reduction in UAE and TGF beta1 were significantly higher in the combined group than in the losartan or ramipril groups. No significant changes in absolute and percentage reduction of systolic, diastolic and mean blood pressure were found. All treatment regimens were well tolerated with few and transient side-effects. These data indicate an additional renoprotective effect of dual blockade of the renin-angiotensin system (RAS) in hypertensive patients with minor renal abnormalities. In addition, the contemporaneus and marked decrease in TGF beta1 and UAE levels in hypertensives treated with combined therapy might indicate the presence of a subset of subjects who may benefit from complete RAS blockade.

Inclusion of albumin as a target in therapy guidelines: Guidelines for chronic kidney disease

Slowing the rate of progression of chronic kidney disease (CKD) as a fundamental management goal has been greatly assisted by the development of clinical practice guidelines under the aegis of the National Kidney Foundation, through the K/DOQI process. Reductions in urinary protein and albumin excretion play important roles in these treatment strategies, with numerous studies describing short- and long-term successes in these endeavors. These approaches may also reduce the risks of cardiovascular and cerebrovascular morbidity and mortality, and of developing new onset diabetes mellitus. With enhanced sensitivity assays for urinary albumin, and the near-term availability of point-of-service testing, we will have the opportunity to address reduction of urinary albumin excretion as a defined goal and critical element in management of CKD. Carefully conducted clinical trials are needed to establish the utility of these assays, and to define optimal strategies for reducing urinary albumin excretion. With the successful outcomes of these studies, the reduction of urinary albumin excretion will receive its due emphasis in the management of patients with CKD.

Effects of Fosinopril and Pravastatin on Cardiovascular Events in Subjects With Microalbuminuria

Microalbuminuria is associated with increased risk of cardiovascular events. We assessed whether therapeutic intervention aimed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects (15 to 300 mg/24 hours). From the Prevention of Renal and Vascular Endstage Disease (PREVEND) cohort (n=8592), 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial (PREVEND IT). Of these subjects, 864 were randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo. The mean follow-up was 46 months, and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity. Mean age was 51+/-12 years; 65% of subjects were male, and 3.4% had a previous cardiovascular event. Mean cholesterol level was 5.8+/-1.0 mmol/L, mean systolic/diastolic blood pressure was 130+/-18/76+/-10 mm Hg, and median urinary albumin excretion was 22.8 (15.8 to 41.3) mg/24 hours. The primary end point occurred in 45 subjects (5.2%). Fosinopril reduced urinary albumin excretion by 26% (P<0.001). Subjects treated with fosinopril showed a 40% lower incidence of the primary end point (hazard ratio 0.60 [95% CI 0.33 to 1.10], P=0.098, log-rank). Pravastatin did not reduce urinary albumin excretion, and subjects treated with pravastatin showed a 13% lower incidence of the primary end point than subjects in the placebo group (0.87 [0.49 to 1.57], P=0.649, log-rank). In microalbuminuric subjects, treatment with fosinopril had a significant effect on urinary albumin excretion. In addition, fosinopril treatment was associated with a trend in reducing cardiovascular events. Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events.

C-peptide: new findings and therapeutic implications in diabetes.

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C-peptide is the ugly duckling that--nearly 40 years after its discovery--may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long-term complications.

Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in essential hypertension: a 3-year follow-up study

The objective of this study was to analyse the relationship of polymorphisms of the angiotensinogen (AGT) gene with the changes in microalbuminuria during 3 years of antihypertensive treatment in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=23), only beta-blockers (n=26), only angiotensin-converting enzyme inhibitors (ACEi) (n=57) or a combination of treatments (n=25). The office blood pressure, biochemical profile and urinary albumin excretion (UAE) were measured at the beginning and then yearly. The polymorphism A-6G of the AGT gene located in the promoter region was analysed. In total, 131 patients, 35 (27%) microalbuminurics, were included. Although no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose and UAE were observed among genotypes at the initial examination, during the 3 years of antihypertensive treatment the slope values for the DBP, fasting glucose and UAE differed significantly despite no differences in the distribution of treatments being present. The subjects carrying the AA-6 genotype had the largest DBP decrease, but the lowest UAE reduction and the highest slope of glucose. Out of 35 initially microalbuminuric patients, 24 became normoalbuminuric and the lowest reduction rates were observed in subjects who carried the allele A-6. No interaction between the type of treatment and genotype was observed on the changes in UAE, BP or glucose values. In the subset of 57 patients treated with ACEi, the changes in UAE, BP and glucose had the same trend as was observed in the total population. Subjects carrying the AA genotype of the A-6G AGT gene polymorphism are resistant to a reduction of microalbuminuria. Whether this can be attributed to a predisposition to glucose metabolic disturbance or not needs to be confirmed in further studies.

Regression of microalbuminuria in type 1 diabetes.

In the present study, we aimed to determine the frequency of a significant reduction in urinary albumin excretion and factors affecting such reduction in patients with type 1 diabetes and microalbuminuria. The study included 386 patients with persistent microalbuminuria, indicated by repeated measurements of urinary albumin excretion (estimated on the basis of albumin-to-creatinine ratios) in the range of 30 to 299 microg per minute during an initial two-year evaluation period. Subsequent measurements during the next six years were grouped into two-year periods, averaged, and analyzed for regression of microalbuminuria, which was defined as a 50 percent reduction in urinary albumin excretion from one two-year period to the next. Regression of microalbuminuria was frequent, with a six-year cumulative incidence of 58 percent (95 percent confidence interval, 52 to 64 percent). The use of angiotensin-converting-enzyme inhibitors was not associated with the regression of microalbuminuria. However, microalbuminuria of short duration, salutary levels of glycosylated hemoglobin (less than 8 percent), low systolic blood pressure (less than 115 mm Hg), and low levels of both cholesterol and triglycerides (less than 198 mg per deciliter [5.12 mmol per liter] and 145 mg per deciliter [1.64 mmol per liter], respectively) were independently associated with the regression of microalbuminuria. Patients with salutary levels of all modifiable factors had a hazard ratio for regression of 3.0 (95 percent confidence interval, 1.5 to 6.0), as compared with patients with no salutary levels of any modifiable factor. Frequent regression of microalbuminuria in patients with type 1 diabetes indicates that elevated urinary albumin excretion does not imply inexorably progressive nephropathy. Identification of the multiple determinants of the regression of microalbuminuria has implications for current theories about the mechanisms of early diabetic nephropathy.

Effect of combination therapy with a calcium channel blocker and an angiotensin-converting enzyme inhibitor on renal hypertrophy and urinary albumin excretion in diabetic rats.

The objective of this study was to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker on the development of renal changes in diabetic rats. Diabetes was induced by an intravenous injection of streptozotocin in normotensive Wistar rats. Treatment was commenced immediately in 1 set of rats with 4 treatment arms: nitrendipine (250 mg/kg fodder), enalapril (35 mg/L drinking water), both treatments in combination, or placebo. Treatment was continued for 9 weeks. Another set of rats was left with untreated diabetes for 3 months followed by 7 weeks treatment as above. When starting treatment right after induction of diabetes, nitrendipine significantly reduced urinary albumin excretion (UAE) to the nondiabetic level (P < .05) without reducing blood pressure (BP), whereas enalapril failed to significantly reduce UAE despite a reduction in BP. Combining the two treatments showed no further reduction in UAE compared to monotherapy with nitrendipine, despite a lower BP. When leaving diabetic rats untreated for 3 months, only the coadministration of nitrendipine and enalapril showed a significant reduction in UAE compared to monotherapy and placebo treatment, but showed no significant effect on BP.

Combination of Pentoxifylline with Angiotensin Converting Enzyme Inhibitors Produces an Additional Reduction in Microalbuminuria in Hypertensive Type 2 Diabetic Patients

Objective. To investigate the anti proteinuric effect of pentoxifylline in diabetic patients, we prospectively studied in 25 hypertensive type 2 diabetic patients with persistent microalbuminuria and normal renal function the impact of combining pentoxifylline with an angiotensin converting enzyme inhibitor, lisinopril, on urinary albumin excretion and compared the results with those obtained in a control group of 25 type 2 diabetic patients treated with lisinopril only. Material and Methods. Fifty hypertensive type 2 diabetic patients with persistent microalbuminuria (31 males and 19 females, aged between 47–73 years) were randomly assigned to two groups. Group A received lisinopril 10 mg/day, while group B was given lisinopril 10 mg/day and pentoxifylline 600 mg/day for nine months. There were no significant differences between serum creatinine, HbA1c, blood pressure and urinary albumin excretion in both groups (p>0.05). Results. Serum creatinine, creatinine clearance, blood pressure, HbA1c levels did not change significantly during the study. Urinary albumin excretion decreased from 228 ± 28 to 148 ± 15 mg/day in group A (p<0.05). In group B urinary albumin excretion decreased from 219 ± 26 to 128 ± 12 mg/day (p<0.05). Pentoxifylline and lisinopril combination caused a significant additional reduction in urinary albumin excretion when compared to lisinopril regimen (p<0.05).Conclusions. Our findings suggest that the combination of pentoxifylline with an angiotensin converting enzyme inhibitor in hypertensive type 2 diabetic patients with persistent microalbuminuria causes a significant reduction in urinary albumin excretion and this effect seems independent from blood pressure and glycemic control.

Microalbuminuria in essential hypertension.

Microalbuminuria (urinary albumin excretion equal to 30-300 mg/24 h) is a reliable indicator of premature cardiovascular mortality in diabetic patients and in the general population. In insulin-dependent and non-insulin-dependent diabetes mellitus microalbuminuria is a marker of initial diabetic nephropathy and predicts the evolution toward renal insufficiency. In essential hypertension the clinical and prognostic role of microalbuminuria is more controversial. While it is a recognised marker of cardiovascular complications and a reliable predictor of ischaemic heart disease, its prognostic value on the risk of progressive renal alterations is still uncertain because no prospective studies, taking microalbuminuria as a selection criterion and renal insufficiency as an end point, are available. Blood pressure control with antihypertensive drugs is accompanied by a reduction in urinary albumin excretion. The favourable effects of antihypertensive agents on microalbuminuria appear to be proportional to blood pressure reduction, but angiotensin-converting enzyme inhibitors and angiotensin-II-receptor antagonists show an additional beneficial effect on urinary albumin excretion. Whether the reduction of microalbuminuria obtained through pharmacological intervention has favourable prognostic implications remain to be demonstrated. However, screening for microalbuminuria is a relatively easy and inexpensive procedure and reveals a potentially treatable abnormality. Thus, considering that microalbuminuria identifies hypertensive subjects at higher risk than standard, urinary albumin excretion should be routinely measured in hypertensive patients and, in the presence of microalbuminuria, antihypertensive treatment should be intensified in order to obtain an optimal blood pressure control.

Changes in Renal Resistive Index and Urinary Albumin Excretion in Hypertensive Patients under Long-Term Treatment with Lisinopril or Nifedipine GITS

Introduction: Increased renal vascular resistance and microalbuminuria are associated with hypertensive target organ damage and may be predictors of hypertensive nephrosclerosis. Aim: We investigated changes in renal resistive index (RI) and urinary albumin excretion (UAE) in a group of patients with primary hypertension before and during long-term antihypertensive treatment. Methods: Thirty-two patients were randomized to receive antihypertensive treatment with either a calcium channel blocker (nifedipine GITS, up to 90 mg/day, n = 16) or an ACE inhibitor (lisinopril, up to 20 mg/day, n = 16), alone or in association with a diuretic (chlortalidone, 25 mg/day). Blood pressure, renal resistive index (by US Doppler) and UAE (mean of three nonconsecutive timed urinary collections, µg/min) were evaluated at baseline and over the course of 24 months of treatment. Results: Both regimens effectively lowered blood pressure (mean blood pressure from 123 ± 1.8 at baseline to 103 ± 1.5 mm Hg at 24 months in the lisinopril group and from 122 ± 1.9 at baseline to 104 ± 0.8 at 24 months in the nifedipine group, p < 0.001 for both groups). Overall, blood pressure decrease was associated with a reduction in UAE and no change in RI throughout the study. However, despite similar blood pressure reduction, the two regimens showed different specific effects. Lisinopril was associated with a significant decrease in both UAE (33.8 ± 16.2 at baseline and 9.1 ± 2.1 at 24 months, p < 0.01) and renal RI (0.61 ± 0.02 at baseline and 0.56 ± 0.04 at 24 months, p < 0.05) while nifedipine GITS did not significantly influence UAE (35.7 ± 12.2 at baseline and 31.2 ± 12.1 at 24 months, n.s.) or RI (0.61 ± 0.01 at baseline and 0.59 ± 0.02 at 24 months, n.s.). Conclusion: Effective blood pressure control over a long period of time reduces the severity of organ damage, namely UAE while maintaining renovascular resistance in patients with essential hypertension. Different classes of antihypertensive agents might convey additional specific renal protection beyond blood pressure control. These data could be useful in devising individualized therapeutic strategies in hypertensive patients at increased renal risk.

Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.

C-peptide: a new potential in the treatment of diabetic nephropathy.

C-peptide is formed in the biosynthesis of insulin and the two peptides are subsequently released in equimolar amounts to the circulation. C-peptide has long been considered to be without physiologic effects. Recent data now demonstrate that C-peptide in the nanomolar concentration range binds specifically to cell surfaces, probably to G protein-coupled receptors, with subsequent activation of Ca(2+)-dependent intracellular signaling pathways and stimulation of Na+, K(+)-ATPase activities. C-peptide replacement in animal models of type 1 diabetes results in diminished hyperfiltration, improved functional reserve, reduction of urinary albumin excretion, and prevention of glomerular and renal hypertrophy. Administration of C-peptide to physiologic concentrations in patients with type 1 diabetes and incipient nephropathy for periods of 3 hours to 3 months is accompanied by reduced glomerular hyperfiltration and filtration fraction, and diminished urinary albumin excretion. C-peptide replacement together with insulin therapy may be beneficial in type 1 diabetes patients with nephropathy.

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy

The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjects with early nephropathy. The tolerability of these agents and their effect on the metabolic profile were also evaluated. The study was a one-year prospective, double-blind trial with losartan and enalapril administered alone or in combination with hydrochlorothiazide and other antihypertensive agents. ABP and renal and biochemical parameters were measured at baseline and after 12, 28, and 52 weeks of active treatment. Ninety-two hypertensive type 2 diabetics with early nephropathy completed the study. Both losartan and enalapril administered alone or in combination with other agents induced significant reductions in sitting clinic (P < 0.05) and ABP (P < 0.002) without a statistical difference between groups. Geometric means for urinary albumin excretion (UAE) decreased significantly (P < 0.001) in patients treated with losartan from 64. 1 to 41.5 microg/min and in those treated with enalapril from 73.9 to 33.5 microg/min after 52 weeks of therapy. A significant relationship (P < 0.05) between changes in systolic and diastolic ABP and the decrease in UAE at 52 weeks was seen in both groups. The decline in glomerular filtration rate (GFR) was stabilized at the end of therapy and was identical in both treatment groups. Treatment with enalapril was associated with a significantly higher incidence of cough (P = 0.006) and a rise in serum uric acid (P = 0.002) compared with losartan. Our results indicate that a one-year course of antihypertensive therapy with either losartan or enalapril significantly reduces UAE in hypertensive type 2 diabetic patients with early nephropathy. The reduction in UAE with each treatment is similarly related to decrements in ABP. In addition, the rate of decline in GFR is similar in both treatment groups.

Estudio de los factores relacionados con los cambios en la microalbuminuria durante el tratamiento antihipertensivo

The objective of the present study was to analyze the factors related with changes of microalbuminuria during antihypertensive treatment in patients with essential hypertension. One hundred and six patients (57 men, mean age 40.8 [SD 6.6] years) never treated with antihypertensive treatment were included. At the beginning and after one year, blood pressure biochemical profile and urinary albumin excretion (UAE) were measured. After the initial evaluation, 53 patients received angiotensin converting enzyme inhibitors (ACEi) and 53 beta-blockers (BB). Hydrochlorothiazide was added to achieve the blood pressure target < 140/90 mmHg. The average of UAE was 32.1 (43.1) mg/24 h, and 41 (39%) patients had microalbuminuretics. After 12 months of treatment, a significative fall of systolic BP (-20.6 [8.03] mmHg, p < 0.001), and diastolic BP (-14.18 [10.34] mmHg, p < 0.001) were observed, whereas baseline glucose increases (3.08 [11.07] mg/dl, p = 0.006). The changes of UAE were only related with the baseline UAE values. Neither, age, sex, baseline diastolic BP and changes in diastolic BP were significantly related with the changes in UAE. In spite of similar mean BP reduction (medial BP 17.4 [10.9] vs 14.8 [10.4] mmHg), UAE only was reduced in patients treated with ACEi (LogUAE: 0.203 [0.872] mg/24 h; p < 0.04). In addition, in patients treated with BB a significative increase in baseline glucose (4.4 [12.3] mg/dl; p = 0.013) and uric acid (1.18 [4.18]; p = 0.031) were observed. In patients with essential hypertension, changes in microalbuminuria depends of the initial UAE values and the kind of antihypertensive treatment. ACEi produced higher UAE reduction and lower derangement of the glucose metabolism than BB.

The Calcium Channel Blocker Nitrendipine Attenuates Renal and Glomerular Hypertrophy in Diabetic Rats

The efficacy of the calcium channel blocker nitrendipine in preventing early renal and glomerular hypertrophy and increased urinary albumin excretion (UAE) was studied in experimental diabetes in rats, starting treatment at the onset of diabetes. Female Wistar rats were randomised into four groups: diabetic and non-diabetic rats were given either placebo or nitrendipine (250 mg/kg) in the diet for 8 weeks. After 8 weeks the kidneys in the diabetic animals had increased significantly compared to the non-diabetic controls. In the diabetic nitrendipine-treated animals renal and glomerular hypertrophy was significantly smaller than in the diabetic placebo-treated group (p < 0.05). After an initial increment within the first week, the UAE remained constant throughout the study period in the diabetic nitrendipine-treated animals, while a steady increase was seen in the diabetic placebo-treated group (p < 0.05). No differences were seen in systemic blood pressure between calcium- channel-blocker-treated groups and placebo-treated groups. In conclusion, administration of nitrendipine to diabetic rats for 8 weeks had a significant inhibitory effect on renal and glomerular hypertrophy, and showed a tendency towards a reduction in UAE (p = 0.06) without affecting metabolic control or systemic blood pressure.