Susan J. Cheng

Influence of Age-Related Versus Non–Age-Related Renal Dysfunction on Survival in Patients With Left Ventricular Dysfunction

Normal aging results in a predictable decrease in glomerular filtration rate (GFR), and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age-related decreases in estimated GFR (eGFR) carry the same prognostic importance as disease-attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction limited data set (n = 6,337). The primary analysis focused on determining if the eGFR-mortality relation differed by the extent to which the eGFR was consistent with normal aging. Mean eGFR was 65.7 ml/min/1.73 m(2) (SD = 19.0). Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73 m(2)/year (95% confidence interval [CI] 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p for interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted hazard ratio 1.0 per 10 ml/min/1.73 m(2), 95% CI 0.97 to 1.1, p = 0.53), whereas a disease-attributable decrease in eGFR above the median carried significant risk (adjusted hazard ratio 2.8, 95% CI 1.6 to 4.7, p <0.001). In conclusion, in the setting of left ventricular dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis.

The Impact of Donor and Recipient Renal Dysfunction on Cardiac Allograft Survival: Insights Into Reno-Cardiac Interactions

BACKGROUND Renal dysfunction (RD) is a potent risk factor for death in patients with cardiovascular disease. This relationship may be causal; experimentally induced RD produces findings such as myocardial necrosis and apoptosis in animals. Cardiac transplantation provides an opportunity to investigate this hypothesis in humans. METHODS AND RESULTS Cardiac transplantations from the United Network for Organ Sharing registry were studied (n = 23,056). RD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). RD was present in 17.9% of donors and 39.4% of recipients. Unlike multiple donor characteristics, such as older age, hypertension, or diabetes, donor RD was not associated with recipient death or retransplantation (age-adjusted hazard ratio [HR] = 1.00, 95% confidence interval [CI] 0.94-1.07, P = .92). Moreover, in recipients with RD the highest risk for death or retransplantation occurred immediately posttransplant (0-30 day HR = 1.8, 95% CI 1.54-2.02, P < .001) with subsequent attenuation of the risk over time (30-365 day HR = 0.92, 95% CI 0.77-1.09, P = .33). CONCLUSIONS The risk for adverse recipient outcomes associated with RD does not appear to be transferrable from donor to recipient via the cardiac allograft, and the risk associated with recipient RD is greatest immediately following transplant. These observations suggest that the risk for adverse outcomes associated with RD is likely primarily driven by nonmyocardial factors.

Evidence of Mild Liver Dysfunction Identifies Stable Heart Failure Outpatients with Reversible Renal Dysfunction

Background: In decompensated heart failure (HF), reversible renal dysfunction (RD) is more frequently observed in patients with mild liver dysfunction likely due to the shared pathophysiologic factors involved. The objective of this study was to determine if these findings also apply to stable HF outpatients. Methods: Patients in the Beta-Blocker Evaluation of Survival Trial (BEST) were studied. Improvement in renal function (IRF) was defined as a 20% improvement in the estimated glomerular filtration rate from baseline to 3 months. Results: Elevated bilirubin (BIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly associated with signs of congestion or poor perfusion. IRF occurred in 12.0% of all patients and was more common in those with elevated BIL (OR = 1.5, p = 0.003), ALT (OR = 1.4, p = 0.01), and AST (OR = 1.4, p = 0.01). In a model containing all 3 liver parameters and baseline characteristics, including markers of congestion/poor perfusion, BIL (OR = 1.6, p = 0.001) and ALT (OR = 1.7, p < 0.001) were independently associated with IRF. Conclusions: Biochemical evidence of mild liver dysfunction is significantly associated with IRF in stable HF outpatients. Given the widespread availability and low cost of these markers, additional research is necessary to determine the utility of these parameters in identifying patients with reversible RD who may benefit from cardiorenal interventions.