Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.

Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs' Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.

Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥ 30 ml per minute per 1.73 m(2) if the initial estimated GFR was ≥ 60 ml per minute per 1.73 m(2) or a decline of ≥ 50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217.).

ISK STRATIFICATION FOR HEART failure (HF) in older adults involves unique clinical challenges. Elderly individuals comprise the largest subgroup of patients hospitalized for HF, accounting for 80% of the more than 1.1 million US admissions per year. 1,2 Once diagnosed with HF, older patients respond less well to guideline-based therapy than their younger counterparts, are more likely to require readmission, and are at higher risk for death. 2-4 Furthermore, prediction models based on traditional cardiovascular risk factors are less adept at identifying cardiovascular risk in older adults compared with younger populations. 5 Blood-based biomarkers, including C-reactive protein (CRP), natriuretic peptides, and troponins, have been advocated as adjuncts to clinical risk factors to identify community-dwelling older patients at high risk for adverse cardiovascular outcomes, but studies examining the additive prognostic value of these markers have reported inconsistent results.

Background Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of hyperkalemia in CKD and whether it is associated with excess mortality. Methods This retrospective analysis of a national cohort comprised of 2,103,422 records from 245,808 veterans with at least one hospitalization and at least one inpatient or outpatient serum potassium record during fiscal year 2005. CKD and treatment with ACE-I and/or ARBs (RAAS blockers) were the key predictors of hyperkalemia. Death within one day of a hyperkalemic event was the principal outcome. Results Of the 66,529 hyperkalemic events (3.2% of records), more occurred inpatient (34937 (52.7%)) versus outpatient (31322 (47.3%)). The adjusted rate of hyperkalemia was higher in patients with CKD than without CKD among individuals treated with RAAS blockers (7.67 vs. 2.30 per 100 patient months, p<0.0001) and those without RAAS blocker treatment (8.22 vs. 1.77 per 100 patient months, p<0.0001). The adjusted odds (OR) of death with a moderate (K+≥ 5.5 and < 6.0mg/dl) and severe (K+≥ 6.0 mg/dl) hyperkalemic event was highest with no CKD (OR: 10.32, 31.64, respectively), versus Stage 3 (5.35, 19.52), Stage 4 (OR: 5.73, 11.56), or Stage 5 CKD (OR: 2.31, 8.02) with all p<0.0001 versus normokalemia and no CKD. Conclusion The risk of hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within one day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.

Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.

In older adults, measurements of physical performance assess physical function and associate with mortality and disability. Muscle wasting and diminished physical performance often accompany CKD, resembling physiologic aging, but whether physical performance associates with clinical outcome in CKD is unknown. We evaluated 385 ambulatory, stroke-free participants with stage 2-4 CKD enrolled in clinicbased cohorts at the University of Washington and University of Maryland and Veterans Affairs Maryland Healthcare systems. We compared handgrip strength, usual gait speed, timed up and go (TUAG), and 6-minute walking distance with normative values and constructed Cox proportional hazards models and receiver operating characteristic curves to test associations with all-cause mortality. Mean age was 61 years and the mean estimated GFR was 41 ml/min per 1.73 m 2 . Measures of lower extremity performance were at least 30% lower than predicted, but handgrip strength was relatively preserved. Fifty deaths occurred during the median 3-year follow-up period. After adjustment, each 0.1-m/s decrement in gait speed associated with a 26% higher risk for death, and each 1-second longer TUAG associated with an 8% higher risk for death. On the basis of the receiver operating characteristic analysis, gait speed and TUAG more strongly predicted 3-year mortality than kidney function or commonly measured serum biomarkers. Adding gait speed to a model that included estimated GFR significantly improved the prediction of 3-year mortality. In summary, impaired physical performance of the lower extremities is common in CKD and strongly associates with all-cause mortality. CKD is a growing global health problem that affects .25 million US adults. 1 CKD leads to the retention of metabolic waste products and hormonal disturbances that adversely affect multiple target organ systems, including skeletal muscle. A major consequence of loss of skeletal muscle (sarcopenia) is skeletal muscle dysfunction, which is associated with impaired mobility and reduced physical performance. Among general older adult populations, decreased physical performance is independently associated with subsequent disability, fracture, falls, hospitalization, and mortality. [2][3][4] In particular, usual gait speed has been used as an adjunct for risk stratification by quantifying the burden of recognized and unrecognized multisystem comorbidity,

Background and objectives: This study set out to determine the incidence of hypoglycemia in patients with chronic kidney disease (CKD), with and without diabetes, and the association of hypoglycemia with mortality.Design, setting, participants, & measurements: This was a retrospective cohort analysis of 243,222 patients who had 2,040,206 glucose measurements and were cared for at the Veterans Health Administration. CKD was defined as an estimated GFR of <60 ml/min per 1.73 m 2 . Hypoglycemia was set at <70 mg/dl. Mortality was measured 1 day after glucose measurement. Results: The incidence of hypoglycemia was higher in patients with CKD versus without CKD. Among patients with diabetes, the rate was 10.72 versus 5.33 per 100 patient-months and among patients without diabetes was 3.46 versus 2.23 per 100 patient-months, for CKD versus no CKD, respectively. The odds of 1-d mortality were increased at all levels of hypoglycemia but attenuated in CKD versus no CKD. Adjusted odds ratios for 1-d mortality that were associated with glucose values of <50, 50 to 59, and 60 to 69 mg/dl, respectively, versus glucose of >70 mg/dl were 6.09, 4.10, and 1.85 for inpatient records from patients with CKD; 9.95, 3.79, and 2.54 for inpatients records from patients without CKD; 6.84, 3.28, and 3.98 for outpatient records from patients with CKD; and 13.28, 7.36, and 4.34 for outpatient records from patients without CKD.Conclusions: CKD is a risk for hypoglycemia, with or without diabetes. The excessive mortality associated with hypoglycemia makes this complication a significant threat to patient safety in CKD.