Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Feb 2007
Downregulation of renal sodium transporters and tonicity-responsive enhancer binding protein by long-term treatment with cyclosporin A.
Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. ⋯ This was associated with reduced expression of active sodium transporters-sodium/potassium/chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal medullary interstitium.
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J. Am. Soc. Nephrol. · Jan 2007
N-terminal pro-brain natriuretic peptide: an independent risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic peritoneal dialysis patients.
This study was performed to determine whether the N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is a useful biomarker in predicting cardiovascular congestion, mortality, and cardiovascular death and event in chronic peritoneal dialysis (PD) patients. A prospective cohort study was conducted in 230 chronic PD patients in a dialysis unit of a university teaching hospital. Serum NT-pro-BNP was measured at baseline together with echocardiography and dialysis indices. ⋯ In the univariate Cox regression model, NT-pro-BNP was a significant predictor of cardiovascular congestion, mortality, and cardiovascular death and event. In the fully adjusted multivariable Cox regression analysis that included residual GFR, left ventricular ejection fraction, and left ventricular mass index, the hazard ratios for cardiovascular congestion, mortality, composite end point of mortality and cardiovascular congestion, and cardiovascular death and event for patients of the fourth quartile were 4.25 (95% confidence interval [CI] 1.56 to 11.62; P = 0.005), 4.97 (95% CI 1.35 to 18.28; P = 0.016), 5.03 (95% CI 2.07 to 12.26; P < 0.001), 7.50 (95% CI 1.36 to 41.39; P = 0.021), and 9.10 (95% CI 2.46 to 33.67; P = 0.001), respectively, compared with the first quartile. These data showed that NT-pro-BNP is an important risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic PD patients and adds important prognostic information beyond that contributed by left ventricular hypertrophy, systolic dysfunction, and other conventional risk factors.
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J. Am. Soc. Nephrol. · Jan 2007
Automated external defibrillators and survival from cardiac arrest in the outpatient hemodialysis clinic.
Automated external defibrillators (AED) have been recommended for use in outpatient dialysis clinics to improve outcomes from cardiac arrest, the most common cause of death in patients with ESRD. The effectiveness of this policy is unknown. The study cohort consisted of 43,200 hemodialysis patients in the US Gambro Healthcare System from 2002 to 2005. ⋯ Medications including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, calcium channel blockers, other BP medications, aspirin, antibiotics, and antiarrhythmics were associated with survival and considered confounders. After controlling for case mix and confounders, AED presence was not associated with outcome (HR 0.98; 95% CI 0.82 to 1.18; P = 0.83). Presence of AED in the dialysis clinic is not sufficient by itself to improve the abysmal outcome from in-clinic cardiac arrest in hemodialysis patients in the United States.
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J. Am. Soc. Nephrol. · Dec 2006
Randomized Controlled TrialImpact of blood pressure control and angiotensin-converting enzyme inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: a post hoc analysis of the BENEDICT trial.
For assessment of the independent renoprotective effect of BP control and angiotensin-converting enzyme inhibitor (ACEi) therapy, the relationships of baseline BP, BP reduction, and follow-up BP with the incidence of persistent microalbuminuria were evaluated in 1204 hypertensive patients who had type 2 diabetes and normoalbuminuria and were included in the BErgamo Nephrologic Diabetic Complications Trial (BENEDICT) study and were randomly assigned to 3.6 yr of treatment with the ACEi trandolapril (2 mg/d), the nondihydropyridine calcium channel blocker (ndCCB) verapamil SR (240 mg/d), their fixed combination Veratran (trandolapril 2 mg/d plus verapamil SR 180 mg/d), or placebo, plus other antihypertensive medications targeted at systolic/diastolic BP <130/80 mmHg. Follow-up (from month 3 to study end) systolic, diastolic, mean, and pulse BP and their reductions versus baseline--but not baseline BP--independently predicted (P < 0.001) the risk for microalbuminuria. In patients with follow-up BP above medians, ACEi significantly reduced the risk for microalbuminuria to levels that were observed among patients with BP below medians, regardless of ACEi treatment. ⋯ In hypertensive, normoalbuminuric patients with type 2 diabetes, BP reduction and ACEi therapy both independently may prevent microalbuminuria. ACEi therapy is particularly effective when BP is poorly controlled, whereas ndCCB therapy is ineffective at any level of achieved BP. As compared with trandolapril, Veratran may help with achievement of target BP with less need for concomitant antihypertensive medications.