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Biomedical subjects

M R Weir

Publications and source records attributed to M R Weir.

At least 37 records · Page 2Linked to original sources
PubMed2000

Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern?

BACKGROUND: Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy progression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal disease progression in patients with the greatest degree of renal insufficiency at study initiation. However, many physicians fail to use ACEIs or angiotensin receptor blockers in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise. OBJECTIVE: To determine if limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACEI or angiotensin receptor blocker use, results in long-term protection against decline in renal function in patients with renal insufficiency. METHODS: We reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double-blinded, and placebo controlled, with the remainder being smaller randomized studies with a minimum 2-year follow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACEI (N = 1,102). Sixty-four percent of these individuals (705/1,102) had renal function data at both less than 6 months and at the end of the study. RESULTS: Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACEI with a serum creatinine level of 124 pmol/L or greater (> or =1.4 mg/dL) demonstrated a 55% to 75% risk reduction in renal disease progression compared with those with normal renal function randomized to an ACEI. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACEI. CONCLUSIONS: A strong association exists between acute increases in serum creatinine of up to 30% that stabilize within the first 2 months of ACEI therapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 pmol/L (>1.4 mg/dL). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Implications of a health lifestyle and medication analysis for improving hypertension control.

BACKGROUND: National Health and Nutritional Examination surveys have documented poor rates of hypertension treatment and control, leading to preventable morbidity and mortality. OBJECTIVES: To examine covariation in the medication and health lifestyle beliefs and behaviors of persons with hypertension to identify and profile distinct subgroups of patients. METHODS: A sample of 727 patients with hypertension, weighted to match the 1992 National Health Interview Survey age and sex distribution of patients with hypertension, was interviewed by telephone about their beliefs and behaviors regarding hypertension and its management. Cluster analysis of key variables was used to identify 4 patient types. RESULTS: Subgroups differed significantly. Group A members use an effective mix of medication and health lifestyle regimens to control blood pressure. Group B members are most likely to depend on medication and have high adherence rates. Yet they also have high rates of smoking (29%) and alcohol use (average, 104 times per year) and are less likely to exercise regularly. Group C members are most likely to forget to take medication, are likely to be obese, and find it most difficult to comply with lifestyle changes (except for very low rates of smoking and alcohol use). Group D members are least likely to take medication, most likely to change or stop medication without consulting their physician (20%), most likely to smoke (40%), and least likely to control diet (29%). Group A and B members have better health outcomes than group C and D members. CONCLUSIONS: Optimal management strategies are likely to differ for the 4 patient types. Further research should be conducted to validate these findings on a separate sample and to devise and test tailored management algorithms for hypertension compliance and control.

Adult↗
PubMed2000

Diuretics and beta-blockers: is there a risk for dyslipidemia?

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease, particularly in combination with other risk factors such as obesity, smoking, diabetes, and dyslipidemia. Effective management of hypertension, even a modest reduction in blood pressure, results in reduced mortality and morbidity from cerebrovascular and cardiovascular disease. METHODS: Data from clinical trials were examined to assess the effect of low-dose diuretics or beta-blockers on lipoprotein profile. RESULTS: Results of numerous clinical trials demonstrate that low doses of thiazides or cardioselective beta-blockers alone or in combination result in minimal changes in lipid profile. CONCLUSIONS: Low doses of thiazide diuretics or beta-blockers are a safe and effective approach to the management of uncomplicated essential hypertension and have the advantage of an association with an evidence-based reduction in morbidity and mortality in long-term clinical trials. There is little or no evidence that the minimal changes in serum lipid profile associated with use of these drugs have resulted in a negation of the beneficial effects of these agents on blood pressure.

Adrenergic beta-Antagonists↗
PubMed2000

Effects of isradipine or enalapril on blood pressure in salt-sensitive hypertensives during low and high dietary salt intake. MIST II Trial Investigators.

This large multicenter study, tested the antihypertensive effects of isradipine, a dihydropyridine calcium channel blocker and enalapril, an angiotensin-converting enzyme inhibitor, in salt-sensitive hypertensive patients under low and high salt intake diets. After a 3-week (weeks -9 to -6) of ad lib salt diet, those patients who had a sitting diastolic blood pressure (SDBP) of > or =95 but < or =115 mm Hg qualified to enter a 3-week (weeks -6 to -3) placebo run-in low salt diet (50 to 80 mmol Na+/day). Then high salt (200 to 250 mmol Na+/day) was added to the placebo treatment for 3 weeks (weeks -3 to 0). Those patients who demonstrated an increase in SDBP > or =5 mm Hg from the low to high salt diet were considered salt sensitive and were randomized into a 4-week (weeks 0 to 4) double-blind treatment period of either isradipine 2.5 to 10 mg twice a day, enalapril 2.5 to 20 mg twice a day, or placebo. Then they entered a 3-week (weeks 4 to 7) placebo washout phase of low salt diet (50 to 80 mmol Na+/day). After week 7 and while the low salt diet was continued the patients were restarted on their double-blind treatment for 4 more weeks (weeks 7 to 11) and the study was completed. Of 1,916 patients screened, 464 were randomized into the double-blind treatment phase and 397 completed the study. Both isradipine and enalapril decreased the sitting systolic blood pressure (SSBP) and SDBP during the high salt diet, to a similar degree, whereas enalapril caused a greater reduction in SSBP and SDBP than isradipine during the low salt diet (11.3 +/- 1.2/7.7 +/- 0.7 mm Hg v 7.7 +/- 0.9/4.8 +/- 0.6 mm Hg, mean +/- SEM, respectively, P < .02). Within drugs, the effect of isradipine on blood pressure (BP) was higher during the high than the low salt diet (14.9 +/- 1.5 v 7.6 +/- 1.3 mm Hg for SSBP and 10.1 +/- 0.6 v 4.8 +/- 0.9 mm Hg for SDBP, P < .001), but enalapril exerted a similar effect during both diets. Because salt restriction lowered both SSBP and SDBP, the lowest BP achieved with both drugs were during the salt restriction phase.

Age Factors↗
PubMed2000

Theoretical basis and clinical evidence for differential effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 blockers.

Drugs that block the renin-angiotensin system have multiple mechanisms of action that may be beneficial in stabilizing or delaying progression of renal disease. The most important of these actions is the simultaneous control of both systemic and glomerular capillary hypertension. Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs that have proven antihypertensive and antiproteinuric effects, with a demonstrated ability to delay progression of renal disease in conjunction with the ability to reduce systemic blood pressure. The mechanism of action for these drugs remains poorly described, but depends in part on an ability to reduce plasma angiotensin II levels and increase plasma bradykinin levels. Angiotensin II receptor subtype 1 (AT1) blockers differ in their mechanism of action from the ACE inhibitors. These drugs primarily block the binding of angiotensin II to its type 1 site. In so blocking the type 1 binding site, however, greater levels of circulating angiotensin II result, and the resultant biologic activity of angiotensin II or its metabolites such as angiotensin(1-7) and angiotensin(3-8) may be more directed to other angiotensin-binding sites. AT1 blockers have similar antihypertensive and antiproteinuric effects to those of ACE inhibitors and they may prove to be as useful as ACE inhibitors in delaying progression of renal disease. Because ACE inhibitors and AT1 blockers inhibit the renin-angiotensin system by different mechanisms, there is a possibility that combining them in clinical practice may prove efficacious for lowering blood pressure and for providing target organ protection.

Angiotensin II↗
PubMed2000

When antihypertensive monotherapy fails: fixed-dose combination therapy.

BACKGROUND: Antihypertensive monotherapy fails to control blood pressure in many patients. METHODS: Data on the efficacy and tolerance of fixed dose angiotensin-converting enzyme (ACE) inhibitor/calcium antagonist combinations were reviewed, since they are the most widely prescribed medications for hypertension. RESULTS: A fixed-dose combination of two drug classes is an option for hypertension treatment. Four fixed-dose ACE inhibitor/calcium antagonist combinations are available. They achieve superior blood pressure control with no increase in adverse events compared with their monotherapy components. In addition, they antagonize some class-specific adverse effects and may exhibit beneficial effects on target organ disease, such as renal dysfunction and left ventricular hypertrophy. CONCLUSIONS: Fixed-dose combination therapy is an attractive option when reasonable doses of initial antihypertensive monotherapy fail. Use of such combinations could increase patient compliance, by virtue of better tolerance compared with increased-dose monotherapy and simplicity of administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Indicators and treatment of hypertensive heart disease.

The relation of systolic and diastolic pressure to hypertrophic cardiomyopathy and congestive heart failure must be understood if we are to recognize the earliest manifestations of hypertensive heart disease and prevent its progression. Many such issues have to be resolved before the most effective combination of medical and nonmedical therapies can be determined.

Aged↗
PubMed1999

Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation.

BACKGROUND: The introduction of the potent immunosuppressive drugs tacrolimus (FK) and cyclosporine (CSA) has markedly improved the outcome of solid organ transplantation. However, these drugs can cause posttransplantation diabetes mellitus. Abnormalities in the glucose metabolism are of particular significance in pancreas transplantation. METHODS: We studied 26 pancreas allograft biopsies, performed 1-8 months posttransplantation, from 20 simultaneous kidney-pancreas transplant recipients, randomized to receive either FK or CSA. The biopsies were studied by light microscopy, immunoperoxidase stains for insulin and glucagon, in situ DNA-end labeling for detection of apoptosis, and electron microscopy. The islet morphology was correlated with the mean and peak levels of CSA and FK in serum, with corticosteroid administration and with glycemia. RESULTS: On light microscopy cytoplasmic swelling, vacuolization, apoptosis, and abnormal immunostaining for insulin were seen in biopsies from patients receiving either FK or CSA. The islet cell damage was more frequent and severe in the group receiving FK than in the group receiving CSA (10/13 and 5/13, respectively) but the differences were not statistically significant. Significant correlation was seen between the presence of islet cell damage and serum levels of CSA or FK during the 15 days previous to the biopsy, as well as with the peak level of FK. Toxic levels of CSA or FK and administration of pulse steroids were associated with hyperglycemia when these occurred concurrently (P=0.005). Toxic levels of CSA or FK by themselves were associated with hyperglycemia in a minority of cases (8 and 26%, respectively). Electron microscopy showed cytoplasmic swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells; the changes were more pronounced in patients on FK. Serial biopsies from two hyperglycemic patients receiving FK and evidence of islet cell damage demonstrated reversibility of the damage when FK was discontinued. CONCLUSIONS: The structural damage to beta cells demonstrated in this study is similar to morphological and functional abnormalities previously described in experimental animal models and can at least partially account for the glucose metabolism abnormalities seen in patients receiving these drugs. Toxic levels of CSA or FK and higher steroid doses potentiate each others' diabetogenic effects.

Adult↗
PubMed1999

Regulation of the epithelial cell-specific integrin, CD103, by human CD8+ cytolytic T lymphocytes.

BACKGROUND: The destruction of the graft epithelium by CD8+ cytolytic T lymphocytes (CTL) is an important aspect of organ allograft rejection. Our recent finding in a mouse model that the epithelial cell-specific integrin, CD103, defines a subset of CD8+ CTL potentially sheds new light onto such interactions. The goal of the present study was to assess the relevance of these data to the human system. METHODS: CD103 expression by human T-cell populations generated in mixed lymphocyte cultures or isolated from transplant nephrectomy specimens was quantitated using multiparameter FACS analyses. RESULTS: CD103 defined a major subset (26-76%) of CD8+ CTL generated in human mixed lymphocyte cultures; cell sorting experiments confirmed that the CD103+ and CD103- subsets both possess allospecific lytic activity. Anti-transforming growth factor (TGF)-beta blocked the appearance of the CD103+ CTL subset, and persistent expression of CD103 by CD8+ CTL was dependent on bioactive TGF-beta. Isolated CD103+ and CD103- CD8 subsets maintained their phenotypic integrity during in vitro expansion, although optimal CD103 expression on the former was TGF-beta dependent. Although CD103+ cells were rare among activated CD8 cells in peripheral lymphoid compartments (< 10%), analyses of transplant nephrectomy specimens revealed that a major subset (21-61%) of CD8 memory/effector cells that infiltrate rejecting renal allografts express high levels of CD103. CONCLUSIONS: We conclude that CD103 defines a discrete and stable subset of human CD8+ CTL and that CD103 expression by such cells is initiated and maintained by bioactive TGF-beta. These data point to the existence of a human effector subset that is uniquely specialized for the destruction of the graft epithelium.

Animals↗
PubMed1999

A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. METHODS: We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. RESULTS: Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.8+/-0.3 and 1.8+/-0.2 mg/dl, respectively; P=0.005) and at 1 month (2.0+/-0.1 and 1.6+/-0.1 mg/dl, P=0.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.7+/-0.1 versus 1.5+/-0.05 mg/dl, and 1.7+/-0.1 versus 1.7+/-0.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.4+/-0.1 and 1.7+/-0.1 mg/dl, P=0.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. CONCLUSION: Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function.

Adult↗
PubMed1999

Hypertensive cardiovascular disease in African Americans.

Hypertension is the most common public health challenge in the United States because of its prevalence and associated increase in comorbid cardiovascular diseases. Yearly expenses related directly or indirectly to the treatment and detection of hypertension in the United States are approximately $10 billion, excluding the enormous yearly financial burden of $259 billion and the social burden from heart disease and stroke, which remain the first and third leading causes of death, respectively, in the United States. Despite the importance of these observations, blood pressure is poorly controlled in the United States.

Black or African American↗
PubMed1999

Human polyoma virus in renal allograft biopsies: morphological findings and correlation with urine cytology.

Human polyoma virus (PV) interstitial nephritis occurs in immunosuppressed patients after reactivation of latent virus in renal epithelium. Currently, there is neither general consensus about the incidence of clinically significant PV infection in renal transplants nor conclusive evidence determining its significance in the long-term graft outcome. We evaluated 601 renal transplant biopsy specimens (from 365 patients) by routine light microscopy and immunoperoxidase stains with antibody against SV40 (which cross reacts with PV). We also examined urine samples from 200 patients (100 obtained concurrently with a renal biopsy in patients presenting with acute graft dysfunction and 100 from patients with stable graft function). Electron microscopic evaluation was performed in 50 renal biopsy specimens and in 23% of all urine samples. PV was identified in 1.8% biopsy specimens (1.9% of patients). PV interstitial nephritis showed the typical viral cytopathic changes in tubular epithelial cells associated with marked tubular damage and a disproportionately mild degree of tubulitis. There was no difference in the incidence of PV in the urine of patients with acutely deteriorating versus stable renal function (18% and 19%, respectively); however, urines with large numbers of infected cells (> 10/cytospin) and inflammatory changes in the sediments corresponded invariably to patients with acute allograft dysfunction (8 of 8), and in most cases to biopsy specimens showing PV interstitial nephritis (7 of 8). Based on these findings, urine samples seem to be the most sensitive and cost-effective screening method for PV infection; only urine samples with inflamed sediments and abundant infected cells correlate with clinically significant disease. In these cases, examination of a renal biopsy is indicated. Immunohistochemical stains are useful to confirm the presence of PV but do not increase the sensitivity of diagnosis of PV if this is not already suspected on routine light microscopy. In our material, immunostains were helpful ruling out the presence of PV in a small number of biopsy specimens (2%) that showed markedly reactive tubular cells resembling PV infection. Most patients with PV interstitial nephritis responded to decreased immunosuppression; however, the decay in graft function (based on creatinine slopes) was significantly more rapid in these patients than in matched controls. Evidence of PV infection should be systematically sought in renal biopsy specimens and urine samples from renal allograft recipients.

Adolescent↗
PubMed1999

Double-masked comparison of the quality of life of hypercholesterolemic men treated with simvastatin or pravastatin. International Quality of Life Multicenter Group.

The efficacy, safety, and impact on quality of life of once-daily treatment with simvastatin 20 mg and pravastatin 40 mg were compared in a multinational, randomized, double-masked trial involving 387 men 21 to 72 years of age with primary mild-to-moderate hypercholesterolemia. The trial consisted of a 12-week baseline period, which included 6 weeks of single-masked placebo administration, and a 12-week double-masked active treatment period. Throughout the trial, patients were maintained on a standard lipid-lowering diet. Efficacy variables were plasma lipid levels and a measurement of health-related quality of life evaluated by means of a self-administered questionnaire (the Nottingham Health Profile [NHP]) and other questionnaires related to general health, sexual function, and stress/life events. Clinic visits were scheduled at study entry (week -12), at initiation and week 5 of placebo (weeks -6 and -1, respectively); at randomization (week 1, day 1); and after 4, 8, and 12 weeks of active treatment. At each visit, blood samples were collected for determination of lipid levels and the NHP, the principal measure of health-related quality of life, was administered. Primary safety measures were adverse events and laboratory test results. All statistical comparisons were two-sided, and significance was defined as P< or =0.05 except for the NHP questionnaire, which was P< or =0.01. Treatment with simvastatin 20 mg/d for 12 weeks (n = 194) resulted in significantly greater reductions in plasma total cholesterol and low-density lipoprotein cholesterol levels (25.7% and 33.6%, respectively) compared with pravastatin 40 mg/d for 12 weeks (n = 193) (19.0% and 26.3%, respectively) (P<0.001). No detrimental effects on health-related quality-of-life measurements were reported with either drug. A small but statistically significant improvement in emotional reaction from baseline (P<0.001) was observed after 12 weeks of treatment with simvastatin. At least 75% of simvastatin-treated patients indicated no change in response from baseline on NHP domain scores; these findings were similar to those for pravastatin-treated patients. The differences in the changes in lipid profiles between the 2 treatment groups were not associated with any observed differences in tolerability or health-related quality-of-life measures.

Adult↗
PubMed1999

Risk for posttransplant Diabetes mellitus with current immunosuppressive medications.

With improvements in the practice of transplantation and the introduction of new immunosuppressive medications, there has been a substantial increase in 1-year allograft survival rates. Consequently, the pool of potential candidates for organ transplants continues to grow and a greater preponderance of older patients with more comorbidities are undergoing transplantation. As a result, there is interest in such medical complications as posttransplantation diabetes mellitus (PTDM) that develop after the transplantation of a successful allograft. PTDM is an undesirable consequence of transplantation because of its associated morbidity and impairment of both patient and graft survival. Although some controversy exists, it is likely that glucose intolerance after transplantation results in both macrovascular and microvascular disease, and there is an increasing risk for infectious and cardiovascular diseases, to which transplant recipients are already at increased susceptibility. Both experimental and clinical observations have shown that immunosuppressive agents currently used in transplantation account for a large degree of the increased risk for PTDM. Consequently, improved understanding of the effects of currently used immunosuppressive medicines on glycemic tolerance is of interest in clinical transplantation.

Blood Glucose↗
PubMed1999

The renin-angiotensin-aldosterone system: a specific target for hypertension management.

Angiotensin II plays a central role in the regulation of systemic arterial pressure through its systemic synthesis via the renin-angiotensin-aldosterone cascade. It acts directly on vascular smooth muscle as a potent vasoconstrictor. In addition, it affects cardiac contractility and heart rate through its action on the sympathetic nervous system. Angiotensin II also alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone. Furthermore, it enhances thirst and stimulates the secretion of the antidiuretic hormone. Consequently, angiotensin II plays a critical role in both the acute and chronic regulation of blood pressure through its systemic endocrine regulation. A potent neurohormone that regulates systemic arterial pressure, angiotensin II also affects vascular structure and function via paracrine and autocrine effects of local tissue-based synthesis. This alternate pathway of angiotensin II production is catalyzed in tissues via enzymes such as cathepsin G, chymostatin-sensitive angiotensin II-generating enzyme, and chymase. Intratissue formation of angiotensin II plays a critical role in cardiovascular remodeling. Upregulation of these alternate pathways may occur through stretch, stress, and turbulence within the blood vessel. Similar processes within the myocardium and glomeruli of the kidney may also lead to restructuring in these target organs, with consequent organ dysfunction. Additionally, angiotensin II may increase receptor density and sensitivity for other factors that modulate growth of vascular smooth muscle, such as fibroblast growth factor, transforming growth factor beta-1, platelet-derived growth factor, and insulin-like growth factors. Atherosclerosis may also be related, in part, to excessive angiotensin II effect on the vessel wall, which causes smooth muscle cell growth and migration. It also activates macrophages and increases platelet aggregation. Angiotensin II stimulates plasminogen activator inhibitor 1 and directly causes endothelial dysfunction. Other postulated effects of angiotensin II on vascular structure that could promote atherogenesis include inhibition of apoptosis, increase in oxidative stress, promotion of leukocyte adhesion and migration, and stimulation of thrombosis. Inhibition of angiotensin II synthesis with an angiotensin-converting enzyme inhibitor has been demonstrated to be beneficial in modifying human disease progression. This is clearly apparent in clinical trials involving patients with diabetic nephropathy, postmyocardial infarction, or advanced degrees of systolic heart failure. Thus, angiotensin II is an excellent target for pharmacologic blockade. Not only does it play a pivotal role in both the acute and chronic regulation of systemic arterial pressure, but it also is an important modulator of cardiovascular structure and function and may be specifically involved in disease progression. Modification of angiotensin II effect may therefore serve a dual purpose. Not only will blood pressure reduction occur with less stretch, stress, and turbulence of the vascular wall, but there will also be less stimulation, either directly or indirectly, for restructuring and remodeling of the cardiovascular tree.

Angiotensin II↗
PubMed1999

Are drugs that block the renin-angiotensin system effective and safe in patients with renal insufficiency?

Extensive clinical experience with angiotensin-converting enzyme (ACE) inhibitors in patients with renal disease has demonstrated efficacy in reducing blood pressure, proteinuria, and the rate of progression of renal disease. This is evident in both diabetic and nondiabetic nephropathy, particularly that associated with proteinuria. The ability of ACE inhibitors to stabilize renal function is not attenuated by more severe renal insufficiency, but greater caution with these drugs is necessary, as there may be drug accumulation and a greater propensity for an increase in serum potassium and creatinine levels. Both of these effects are self-limited and rarely require discontinuation of the drug. Increases in creatinine up to 20% are expected; greater increases are indicative of volume depletion or anatomic renal artery disease. Angiotensin II receptor blockers reduce blood pressure to a degree comparable to that achieved with ACE inhibitors, and like ACE inhibitors, they reduce proteinuria to an extent greater than what would be expected by blood pressure reduction alone. Angiotensin II receptor blockers are currently being evaluated in comparison with other therapies in two large clinical trials of non-insulin-dependent diabetic nephropathy with proteinuria to assess impact on the rate of progression of renal disease. Because of their antihypertensive/ antiproteinuric properties, it is likely they will provide some advantages over conventional drugs in protecting renal function. Early clinical experience with these drugs in patients with renal disease suggests that there might be a lesser incidence of functional renal insufficiency and hyperkalemia compared with ACE inhibitors.

Angiotensin Receptor Antagonists↗