Margaret Kiser

Serum Potassium and Outcomes in CKD: Insights from the RRI-CKD Cohort Study

BACKGROUND AND OBJECTIVES The relationship between serum potassium (S(K)) and mortality in chronic kidney disease (CKD) has not been systematically investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the predictors and mortality association of S(K) in the Renal Research Institute CKD Study cohort, wherein 820 patients with CKD were prospectively followed at four US centers for an average of 2.6 years. Predictors of S(K) were investigated using linear and repeated measures regression models. Associations between S(K) and mortality, the outcomes of ESRD, and cardiovascular events in time-dependent Cox models were examined. RESULTS The mean age was 60.5 years, 80% were white, 90% had hypertension, 36% had diabetes, the average estimated GFR was 25.4 ml/min per 1.73 m(2), and mean baseline S(K) was 4.6 mmol/L. Higher S(K) was associated with male gender, lower estimated GFR and serum bicarbonate, absence of diuretic and calcium channel blocker use, diabetes, and use of angiotensin-converting enzyme inhibitors and/or statins. A U-shaped relationship between S(K) and mortality was observed, with mortality risk significantly greater at S(K) < or = 4.0 mmol/L compared with 4.0 to 5.5 mmol/L. Risk for ESRD was elevated at S(K) < or = 4 mmol/L in S(K) categorical models. Only the composite of cardiovascular events or death as an outcome was associated with higher S(K) (> or = 5.5). CONCLUSIONS Although clinical practice usually emphasizes greater attention to elevated S(K) in the setting of CKD, our results suggest that patients who have CKD and low or even low-normal S(K) are at higher risk for dying than those with mild to moderate hyperkalemia.

Predictors of heart rate variability and its prognostic significance in chronic kidney disease

BACKGROUND Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney disease (CKD). METHODS HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3-5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD). RESULTS A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker. CONCLUSIONS This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study.

The Longitudinal Chronic Kidney Disease Study: A Prospective Cohort Study of Predialysis Renal Failure

Chronic kidney disease (CKD) is a significant public health problem: every year the number of Americans living with CKD and requiring renal replacement therapy increases. In addition, individuals with CKD have substantially increased morbidity and mortality compared to the general population. The Longitudinal Chronic Kidney Dialysis (LCKD) Study is a multicenter, prospective, observational study of patients with moderate to severe CKD that was designed to better describe the course of the disease and the determinants of patient outcomes. Patients with moderate to severe CKD (glomerular filtration rate [GFR] < 60 ml/min/m2) from four academic nephrology clinics were enrolled between 2000 and 2002. Special cardiac and vascular testing has recently commenced as phase II of this study. Areas that have been or are currently being studied include anemia management, health‐related quality of life (HRQOL), medication use, and markers of cardiovascular disease. This article describes the LCKD Study in the context of current knowledge of CKD.

Association between markers of collagen turnover, arterial stiffness and left ventricular hypertrophy in chronic kidney disease (CKD): the Renal Research Institute (RRI)-CKD Study

BACKGROUND Markers of collagen turnover have not been well studied in the context of cardiovascular disease in patients with chronic kidney disease (CKD). We investigated the associations between serum markers of collagen turnover [N-terminal procollagen type 3 propeptide (PIIINP) and carboxy-terminal telopeptide (C1TP)] and both pulse wave velocity (PWV) and left ventricular mass index (LVMI) in a CKD cohort. METHODS The study included 242 patients (mean age 60 ± 15 years, 53% males, 80% Caucasian, CKD Stages 3-5) from the Renal Research Institute (RRI)-CKD Study. Serum PIIINP and C1TP levels were analyzed by radioimmunoassay. PWV was obtained by applanation tonometry from carotid and femoral pressure wave contours. LVMI was measured by echocardiography. Statistical analyses included Pearsons correlations and multiple linear regression. RESULTS Both PIIINP and C1TP values were significantly higher in more advanced stages of CKD (P < 0.05). A positive correlation was demonstrated between PWV and LVMI (r = 0.25, P = 0.0018), persisting after adjustment for potential confounders (partial r = 0.27, P = 0.0009). PIIINP correlated with PWV (r = 0.16, p = 0.029) and LVMI (r = 0.16, P = 0.0018), while C1TP correlated with LVMI (r = 0.18, P = 0.013) but not with PWV (r = 0.12, P = 0.09). In multivariable analysis adjusting for race, diabetes, estimated glomerular filtration rate (eGFR) and renin-angiotensin-aldosterone system inhibitors, only PWV (β = 0.45, P = 0.0017) but not LVMI (P = 0.09) remained significantly associated with serum PIIINP. CONCLUSIONS Our results demonstrate the association of PIIINP (but not C1TP), a circulating biomarker of collagen synthesis with arterial stiffness (but not with LVMI) in a CKD cohort, independent of eGFR. This suggests that altered collagen turnover may play a role in the pathogenesis of arterial stiffness in CKD.

Serum sodium levels and patient outcomes in an ambulatory clinic-based chronic kidney disease cohort.

Background: Chronic kidney disease (CKD) patients are prone to both hypo- and hypernatremia. Little has been published on the epidemiology of hypo- and hypernatremia in ambulatory patients with non-dialysis CKD. Methods: Data collected in two contemporaneous CKD cohort studies, the Renal Research Institute (RRI)-CKD study (n = 834) and the Study of Treatment of Renal Insufficiency: Data and Evaluation (STRIDE) (n = 1,348) were combined and analyzed to study the association between serum sodium (Na+) and clinical outcomes. Results: Baseline estimated glomerular filtration rate (eGFR) and Na+ were 26 ± 11 ml/min/1.73 m2 and 140.2 ± 3.4 mEq/l, respectively. The prevalence of Na+ ≤135 mEq/l and ≥144 mEq/l was 6 and 16%, respectively. Higher baseline Na+ was significantly associated with male sex, older age, systolic blood pressure, BMI, serum albumin, presence of heart failure, and lower eGFR. The risk of end-stage renal disease (ESRD) was marginally significantly higher among patients with Na+ ≤135 mEq/l, compared with 140< Na+ <144 mEq/l (referent), in time-dependent models (adjusted hazard ratio, HR = 1.52, p = 0.06). Mortality risk was significantly greater at 135< Na+ ≤140 mEq/l (adjusted HR = 1.68, p = 0.02) and Na+ ≥144 mEq/l (adjusted HR = 2.01, p = 0.01). Conclusion: CKD patients with Na+ ≤135 mEq/l were at a higher risk for progression to ESRD, whereas both lower and higher Na+ levels were associated with a higher risk of mortality. While caring for CKD patients, greater attention to serum sodium levels by clinicians is warranted and could potentially help improve patient outcomes.

Association of carotid intima-media thickness with cardiovascular risk factors and patient outcomes in advanced chronic kidney disease: the RRI-CKD study.

Background: Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and an increased risk of adverse cardiovascular disease (CVD) outcomes. The relationships of intima-media thickness (IMT), a measure of subclinical atherosclerosis, with traditional and nontraditional risk factors and with adverse outcomes in CKD patients are not well-established. Methods: IMT, clinical characteristics, cardiovascular risk factors, and clinical outcomes were measured in 198 subjects from the Renal Research Institute (RRI) CKD study, a four-center prospective cohort of patients with estimated glomerular filtration rate (eGFR) ≤ 50 mL/min/1.73 m2 not requiring renal replacement therapy. Results: The patients averaged 61 ± 14 years of age; the mean eGFR was 29 ± 12 mL/min/1.73 m2. Maximum IMT was more closely associated with traditional cardiovascular risk factors, including age, diabetes, dyslipidemia, and systolic blood pressure, than with nontraditional risk factors or with eGFR. Higher values of maximum IMT were also independently associated with clinical CVD and with other markers of subclinical CVD. Maximum IMT ≥ 2.6 mm was predictive of the composite endpoint of CVD events and death (hazard ratio (HR): 5.47 (95% confidence interval (CI): 2.97 – 10.07, p < 0.0001)) but was not related to progression to end-stage renal disease (HR: 1.67 (95% CI: 0.74 – 3.76, p = 0.21)). Conclusion: In patients with advanced pre-dialysis CKD, higher maximum IMT was associated with traditional cardiovascular risk factors, CVD, and other markers of subclinical CVD and was an independent predictor of cardiovascular events and death. Additional research is needed to examine the clinical utility of IMT in the risk stratification and clinical management of patients with CKD.