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Biomedical subjects

Donald G Vidt

Publications and source records attributed to Donald G Vidt.

At least 19 recordsLinked to original sources

Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate.

BACKGROUND: Most healthy people exhibit a decrease in systolic blood pressure (SBP) at night. A drop of less than 10% from mean daytime values (nondipping) is associated with chronic kidney disease, insulin resistance, and cardiovascular events. Whether nondipping precedes a decline in renal function remains unclear. We hypothesized that nondipping would predict a decline in the glomerular filtration rate (GFR) over time. METHODS: Consecutive patients referred for ambulatory blood pressure monitoring were included in our retrospective cohort if they had a serum creatinine level noted at the time of their ambulatory blood pressure recording and a follow-up creatinine level recorded at least 1 year later. Mean day and night SBPs were compared (nighttime SBP-daytime [corrected] SBP ratio). We defined nondipping as a nighttime [corrected] SBP-daytime [corrected] SBP ratio higher than 0.90. The GFR was calculated using the Modification of Diet in Renal Disease 4-variable equation. RESULTS: Of 322 patients included, 137 were dippers and 185 were nondippers; their mean baseline GFRs were 80.5 mL/min per 1.73 m(2) and 76.4 mL/min per 1.73 m(2), respectively. During a median follow-up of 3.2 years, the GFRs remained stable among dippers (mean change, 1.3%) but declined among nondippers (mean change, -15.9%) (P<.001). The creatinine levels increased by more than 50% in 2 dippers (1.5%) and in 32 nondippers (17.3%) (P<.001). These findings persisted after adjustment for other predictors of GFR decline. CONCLUSION: Blunted diurnal blood pressure variation is associated with a subsequent deterioration in renal function that is independent of SBP load and other risk factors for renal impairment.

Aged↗

Effect of short-term rosuvastatin treatment on estimated glomerular filtration rate.

To define the effect of short-term rosuvastatin treatment on the estimated glomerular filtration rate (eGFR), the database of controlled clinical trials in the Rosuvastatin Clinical Development Program was reviewed. Thirteen studies comprising 3,956 rosuvastatin-treated patients were selected based on a serum creatinine measurement at 6 or 8 weeks after initiation of rosuvastatin treatment, randomization to approved and marketed rosuvastatin doses (5 to 40 mg), and unchanged rosuvastatin dose from treatment initiation (baseline) through 6 to 8 weeks of treatment. eGFR was determined with the Modification of Diet in Renal Disease formula. eGFR significantly increased for each dose of rosuvastatin individually and for all doses combined compared with baseline (range +0.9 to +3.2 ml/min/1.73 m2). Further analysis of 5 blinded, placebo-controlled trials comprising 525 patients showed an increase in eGFR of +0.8 ml/min/1.73 m2 (95% confidence interval +0.1 to +1.5) for all rosuvastatin-treated patients, which was significantly different from baseline (p <0.04) and from a change of -1.5 ml/min/1.73 m2 in the placebo-treated patients (95% confidence interval -2.5 to -0.5, p <0.001). The increase in eGFR for rosuvastatin-treated patients was consistent across all major demographic and clinical subgroups of interest, including patients with baseline proteinuria, baseline eGFR <60 ml/min/1.73 m2, and in patients with hypertension and/or diabetes. In conclusion, these results are consistent with previous rosuvastatin studies that showed an upward trend in eGFR with long-term treatment (> or =96 weeks) and with the hypothesis that statins may have pleiotropic mechanisms of action that include beneficial renal effects.

Cholesterol, LDL↗

Inflammation in renal disease.

Inflammation is a component of the major modifiable risk factors in renal disease. Elevated high-sensitivity C-reactive protein (hs-CRP) levels have been shown to predict all-cause and cardiovascular mortality in patients dependent on dialysis and to predict worsening renal function in subjects without overt renal disease. Levels of hs-CRP are also predictive of hypertension, a major risk factor for renal disease, across all levels of blood pressure in subjects without initial hypertension. Many of the treatments used in patients with renal disease exert anti-inflammatory activities that constitute or contribute to their therapeutic effects. A number of studies have indicated that statin therapy exerts a renoprotective effect that is possibly mediated by anti-inflammatory activities.

Biomarkers↗

Relation of diurnal blood pressure variation and triglyceride-to-high-density lipoprotein cholesterol ratio in patients without diabetes mellitus.

A night-time decrease in systolic blood pressure that differs <10% from mean daytime values ("nondipping") is associated with increased rates of cardiovascular morbidity and mortality. We hypothesized that insulin resistance would be associated with nondipping in patients who did not have frank diabetes mellitus or hypertension. We included 106 consecutive outpatients who had been referred for 24-hour ambulatory monitoring of blood pressure. Our data suggest that insulin resistance, defined as a high ratio of triglyceride to high-density lipoprotein, is associated with blunted diurnal blood pressure variation (odds ratio 6.3, 95% confidence interval 2.6 to 16.4, p <0.0001) before the development of abnormal levels of fasting blood glucose.

Aged↗

Statins and proteinuria.

The proteinuria associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors is composed of primarily low-molecular weight proteins that disappear rapidly following discontinuation of the statin agent. More importantly, no evidence exists of nephrotoxicity or reduced renal function observed with the approved clinical dosages of any available statins. Recent clinical studies have suggested actual improvement in renal function demonstrated by decreases in creatinine concentrations and improvement in estimated glomerular filtration rates with both short-term and long-term administration of these agents. The progressive fibrosis and renal scarring of chronic kidney disease appears to be the end result of increased protein traffic in the proximal renal tubule. Early animal and recent clinical studies have suggested that treatment with statin agents in established chronic kidney disease can, in fact, provide renoprotection over and above that observed with aggressive blood pressure control and the use of angiotensin II antagonists.

Animals↗

Rosuvastatin-induced arrest in progression of renal disease.

Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants were initially included in controlled clinical trials that evaluated the lipid-lowering efficacy and safety of rosuvastatin when compared with placebo or other lipid-lowering agents (i.e., atorvastatin, simvastatin, pravastatin, cholestyramine, fenofibrate or extended-release niacin). The median duration of treatment with the various doses of statins in these trials was approximately 8 weeks. Following completion of a controlled clinical trial, patients were permitted to enter an open-label extension trial and received rosuvastatin treatment. These data permitted assessment of renal function in a diverse group of over 10,000 patients who received rosuvastatin in its recommended dose range (5-40 mg) for up to 3.8 years. Mean serum creatinine concentrations were lower when compared with baseline both early and later in the course of rosuvastatin treatment. In contrast, no change in mean serum creatinine was observed with placebo. Mean glomerular filtration rates (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) equation were higher when compared with baseline both early and later in the course of rosuvastatin treatment. No change in GFR was observed in the placebo group. Among patients who received long-term rosuvastatin treatment (> or =96 weeks), GFR was unchanged or tended to increase, rather than decrease, when compared with baseline irrespective of age, gender, hypertensive or diabetic status, level of renal function (GFR > or =60 vs. <60 ml/min/1.73 m(2)) at entry or urine dipstick protein status prior to or during the period of treatment. These findings suggest that rosuvastatin may arrest the progression of renal disease.

Aged↗

ALLHAT says diuretics are better; ANBP2 says ACEs are better--can we resolve the differences?

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the second Australian National Blood Pressure Study (ANBP2) came to different conclusions about which class of drug to try first for treating high blood pressure: a diuretic or an angiotensin-converting enzyme (ACE) inhibitor. But when examined closely, the results may not be all that different after all.

Angiotensin-Converting Enzyme Inhibitors↗

Microalbuminuria: is it a valid predictor of cardiovascular risk?

Microalbuminuria strongly predicts cardiovascular morbidity and mortality, clinical nephropathy, and progression of renal disease in high-risk populations. We recommend screening patients with type 2 diabetes, older patients with type 1 diabetes, and older patients with stage 2 hypertension or higher (ie, > or = 160/100 mm Hg).

Adult↗

The ALLHAT Trial. Diuretics are still the preferred initial drugs for high blood pressure.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared four antihypertensive agents in patients 55 years and older: chlorthalidone, doxazosin, amlodipine, and lisinopril. The doxazosin arm was terminated early because of an excess of congestive heart failure. Chlorthalidone was at least equivalent to amlodipine and lisinopril in all of the outcomes measured, and was better in some, notably heart failure.

Aged↗