Romulo E. Colindres

Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: A systematic overview of randomized placebo-controlled trials

Clinical trials have shown the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in delaying the progression of diabetic renal disease. There is less evidence from primary clinical trials of nondiabetic renal disease. We performed an updated meta-analysis to determine the efficacy of ACE inhibitors in slowing the progression of renal disease over a broad range of functional renal impairment. We included published and unpublished randomized, placebo-controlled, parallel trials with at least 1 year of follow-up available from January 1970 to June 1999. In nine trials of subjects with diabetic nephropathy and microalbuminuria, the relative risk for developing macroalbuminuria was 0.35 (95% confidence interval [CI], 0.24 to 0.53) for individuals treated with an ACE inhibitor compared with placebo. In seven trials of subjects with overt proteinuria and renal insufficiency from a variety of causes (30% diabetes, 70% nondiabetes), the relative risk for doubling of serum creatinine concentration or developing end-stage renal disease was 0.60 (95% CI, 0.49 to 0.73) for individuals treated with an ACE inhibitor compared with placebo. Treatment of individuals with chronic renal insufficiency with ACE inhibitors delays the progression of disease compared with placebo across a spectrum of disease causes and renal dysfunction.

Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua

Background and objectives: Endemic renal insufficiency (RI) of unknown etiology is a major public health issue with high mortality in the Pacific coastal regions of Central America. We studied RI in León and Chinandega, Nicaragua, evaluating associations with known risk factors and hypothesized exposures. Methods: A cross-sectional survey was conducted with assessment of medical, social, and occupational history and exposures in conjunction with measurement of serum creatinine. Cases were defined by an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 using the modified four-variable Modification of Diet in Renal Disease (MDRD) study equation for non-African Americans. Logistic regression models controlling for known risk factors of kidney disease were used to evaluate associations between exposures and RI. Results: A total of 124 RI cases were compared to 873 persons without RI. Cases had no significant differences in the odds of having a systolic blood pressure (SBP) > 140 or diastolic blood pressure (DBP) > 90 mmHg, or in reporting diabetes. Agricultural labor was associated with RI (OR = 2.48, 95%CI: 1.59, 3.89, p < 0.0001). There was no association with agricultural non-field work (OR = 0.91, 95%CI: 0.60, 1.38, p = 0.65). Consumption of unregulated alcohol (“lija”) was associated with RI (OR = 2.10, 95%CI: 1.31, 3.39, p = 0.0023), as was drinking 5 L or more of water per day (OR = 3.59 vs. 1 L 95%CI: 1.52, 4.46, p = 0.0035). Conclusions: Agricultural field labor and lija consumption were associated with RI in this region. Water intake may also be important. Identifying specific risk factors for RI within these exposures, such as individual pesticides or lija ingredients, may facilitate prevention in a setting where dialysis and transplantation are limited.

Clinical pharmacology of carvedilol in normal volunteers

The mechanism of the vasodilatory action of carvedilol (BM 14190), a new antihypertensive agent, was investigated in normal volunteers. Intra‐arterial blood pressure and ECG were monitored continuously. Carvedilol (1 mg/min for 15 minutes) produced a rapid reduction in blood pressure and a transient increase in heart rate. At the end of infusion, systolic and diastolic blood pressure were reduced by 23% (−32.3 mm Hg) and 18% (−13.6 mm Hg), respectively, whereas heart rate was not different from baseline. At the doses used, the hypotensive effect of carvedilol was greater than that of labetalol (36 and 72 mg in 15 minutes). Carvedilol and labetalol antagonized isoproterenol‐induced hypotension and tachycardia, at serum levels ≥8 and 20 mg/ml, respectively. Both drugs antagonized phenylephrine pressor effects. A similar degree of inhibition (25% of control) of pressor effects was observed for carvedilol and labetalol when their respective serum concentrations were 23 ng/ml and 80 ng/ml. Neither carvedilol nor labetalol had any effect on AII pressor responses. Carvedilol serum levels as high as 150 ng/ml failed to inhibit AII‐induced pressor responses. Our results suggest that at the doses used in this study, carvedilol has both α1‐ and nonselective β‐receptor blocking properties. Moreover, carvedilol is approximately three to five times more potent than labetalol in blocking α1‐ and β‐receptors and in reducing blood pressure.

Association of Cigarette Smoking with Albuminuria in the United States: The Third National Health and Nutrition Examination Survey

Background. The association of cigarette smoking with albuminuria has been reported but not examined in a representative U.S. population. No study has evaluated the association between serum cotinine (a biological marker for tobacco exposure) and kidney damage. Methods. A cross-sectional analysis was conducted among 15,719 adult participants of the third National Health and Nutrition Examination Survey to assess the association between smoking exposure and kidney damage. Smoking was assessed by self-reported lifetime cigarette use and serum cotinine. Kidney damage was assessed by urine albumin-to-creatinine ratio (ACR), with albuminuria defined as ACR of ≥17 μg/mg in males and ≥25 μg/mg in females. Results. The analysis included 13,121 with normal albumin (mean ACR 6.3 μg/mg) and 2,414 with albuminuria (mean ACR 143 μg/mg); hypertension was prevalent in 27% and 59%, respectively. Former smoking was similar between groups (21%), while current smoking was more common in persons with albuminuria (26%) compared to normal ACR (21%). Adjusted for other risk factors, among hypertensives, current smokers were 1.85 (95% CI: 1.29, 2.64) times more likely to have albuminuria than never smokers. Current smokers with a ≥40 pack-year history were at highest risk for albuminuria. Among non-smoking hypertensives, those exposed to passive smoke (highest versus lowest quartile of serum cotinine) were 1.41 (95% CI: 1.04, 1.90) times more likely to have albuminuria. Former smoking with cessation of ≥1 year among hypertensives was not associated with albuminuria. Among non-hypertensives, smoking and albuminuria were not consistently associated. Conclusion. Current and passive smoking, but not former smoking, were associated with the presence of albuminuria in the general U.S. population with hypertension, indicating a benefit to the kidney from smoking cessation.

Mechanism of the vasodilatory effect of carvedilol in normal volunteers: a comparison with labetalol.

Summary: In a single blind parallel design, saline (n = 9), labetalol i.v. (40 mg n = 4, 80 mg n = 3), and carvedilol i.v. (15 mg n = 8) were given to volunteers with blood pressure (BP) recorded intraarterially. The effect of these treatments on the response to challenge doses of angiotensin II (to give a rise in mean BP of 20–25 mm Hg), isoproterenol (to give an increase in heart rate of 30–35 beats/min), and phenylephrine (to give a rise in mean BP of 20–25 mm Hg) were studied. The dose of i.v. carvedilol employed gave a greater fall in BP than the dose of labetalol used. Carvedilol appeared to be about four times more potent than labetalol in inhibiting the tachycardia to isoprenaline. Likewise, from inhibition of the pressor response to phenylephrine, it is concluded that carvedilol is four times more effective at the alpha receptor than labetalol. Neither drug was found to antagonize the pressor effects of angiotensin. Calculation of the half‐life of carvedilol gave values of 2.2 to 9 h. The volume of distribution was found to be 1.54 1/kg and the total body clearance was 0.521 1/h/kg.

A Hypertension Risk Score for Middle-Aged and Older Adults

J Clin Hypertens (Greenwich).

A Multi-Institutional Trial of an Objective Structured Clinical Examination

This study investigated the feasibility of implementing the same 10 cases in an objective structural clinical examination (OSCE) to evaluate medical students’ clinical skills following the medicine clerkship at four geographically dispersed medical schools. Results indicated that a clinically equivalent, standardized test of clinical performance could be developed at multiple schools. Generalizability of student scores ranged from .26 to .50. Overall performance averaged 63%, with case scores ranging from 74% for a history of recurrent urinary tract infections to 52% for a fever and cough. Significant differences were found among schools for individual cases, but performance from any one school was not consistently highest. Clinical skills scores ranged from 72% for physical examination technique to 58% for initial management, with varying significant differences among schools, suggesting inconsistent clinical training within and among schools. Performance was not higher for students examined later in the...

A population-based study of prevalence and risk factors of chronic kidney disease in León, Nicaragua

BackgroundRecent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations.ObjectivesWe conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD.MethodsEstimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census.ResultsCKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males.ConclusionsOur findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy.AbrégéContexteSelon de récentes études, il existerait une prévalence d’insuffisance rénale chronique (IRC) excessive chez les jeunes adultes de sexe masculin de la côte du Pacifique du Nicaragua. Ces études, qui ont été conduites sur des échantillons non représentatifs de la population, suggèrent une étiologie non classique de l’IRC dans cette région.Objectifs de l’étudeNous avons effectué une étude transversale portant sur un vaste échantillon de population, afin de pouvoir estimer la prévalence d’IRC dans la ville nicaraguéenne de León, d’une part, et évaluer la présence de liens entre l’IRC et certains facteurs de risque ayant été étudiés, d’autre part.MéthodePour déterminer le statut d’IRC de 2275 résidents de la ville de León, nous avons utilisé le débit de filtration glomérulaire estimé, selon l’équation du MDRD. Une régression logistique multivariée a été utilisée pour estimer les ratios de probabilité corrigés de prévalence. La prévalence d’IRC de León a également été normalisée sur la base de la distribution démographique du Health and Demographic Surveillance System de León et avec son recensement de 2005.RésultatsLa prévalence d’IRC était de 9,1%; elle était deux fois plus élevée chez les hommes (13,8%) que chez les femmes (5,8%). D’autres facteurs ont été liés de façon significative à l’IRC: la vieillesse, la vie rurale, un niveau d’éducation faible, une hypertension autodéclarée, plusieurs années de travail en agriculture, et la consommation de lija (alcool non contrôlé) et de grandes quantités d’eau. Le diabète autodéclaré était également lié à l’IRC dans les modèles ajustés chez les femmes, mais non chez les homm es.ConclusionsNos résultats sont comparables à ceux des études locales et supportent l’hypothèse de l’existence d’une néphropathie méso-américaine.

Ankle brachial index independently predicts early kidney disease

Introduction. Chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (CVD) are often both present in selected populations. The independent association of early renal disease and atherosclerosis has not been studied in the general population. We hypothesized that the presence of low ankle brachial index (ABI), a surrogate measure of atherosclerotic cardiovascular disease, is associated with a low estimated glomerular filtration rate (GFR). Methods. The study population consisted of 14,917 middle‐aged black and white men and women from the Atherosclerosis Risk in Communities (ARIC) Study. An ABI < 0.90 was defined as the exposure, and an estimated GFR < 90 mL/min/1.73 m2 was defined as the outcome. Logistic regression analysis was performed cross‐sectionally using an ABI of 1.00–1.19 as the reference, and was adjusted for the usual cardiovascular risk factors. Results. The presence of an ABI < 0.90 was associated with an increased odds of having an estimated GFR < 90 (OR: 1.80; 95% C.I.: 1.40–2.32) compared to the reference group. After adjustment, an ABI < 0.90 remained significant, and increased the odds of having an estimated GFR < 90 (OR: 1.54; 95% C.I.: 1.17–2.04) compared to the reference group. The odds ratio for GFR < 90 was higher among African Americans than Whites, 1.88 versus 1.36 respectively. Discussion. This study gives support to the independent association of early CKD and atherosclerotic CVD. The relationship appears to be stronger among African Americans than among Whites. It will be necessary to investigate this observation more fully with prospective studies given the rising incidence of CKD.

Phosphate Reabsorption in the Distal Convoluted Tubule

Phosphate excretion by the mammalian kidney is subject to regulation by a number of factors including, but not limited to, dietary phosphorus intake, parathyroid hormone (PTH), and extracellular volume expansion. The primary quantitative importance of the proximal tubule in this regulation is well known, but the role of more distal nephron segments has been less clearly defined. It has long been recognized that the fraction of filtered phosphate delivered to distal convolutions accessible to micropuncture on the surface of the rat kidney may exceed fractional excretion, especially in phosphate retaining states, suggesting that further phosphate reabsorption occurs in the distal tubule and/or collecting duct (1). Early microinjection studies, however, failed to reveal significant distal phosphate reabsorption (2,3). Since the composition of the final urine reflects the pooled contributions of both superficial and deep nephrons, nephron heterogeneity, with more avid reabsorption in proximal tubules of juxtamedullary nephrons, was suggested as an alternative to distal reabsorption to explain the low urinary phosphate excretion (4). These two postulated mechanisms, distal reabsorption and nephron heterogeneity, need not of course be mutually exclusive.