Circulating adipocytokines and chronic kidney disease.

BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors. RESULTS: Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval) of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels. CONCLUSIONS: These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.

A propensity-matched study of low serum potassium and mortality in older adults with chronic heart failure.

OBJECTIVE: Most HF patients are older adults, yet the associations of low serum potassium and outcomes in these patients are unknown. We studied the effect of low serum potassium in a propensity-matched population of elderly HF patients. METHODS: Of the 7788 patients in the Digitalis Investigation Group trial, 4036 were >or=65 years. Of these, 3598 had data on baseline serum potassium and 324 with potassium >or=5 mEq/L were excluded. Remaining patients were categorized into low (<4 mEq/L; n=590) and normal (4-4.9 mEq/L; n=2684) potassium groups. Propensity scores for low-potassium, calculated for each patient, were used to match 561 low-potassium and 1670 normal-potassium patients. Association of low potassium and outcomes were assessed using matched Cox regression analyses. RESULTS: Patients had a mean (+/-SD) age of 72 (+/-6) years, 29% were women and 12% were non-whites. Of the 561 low-potassium patients, 500 had low-normal (3.5-3.9 mEq/L) potassium. All-cause mortality occurred in 37% (rate, 1338/10,000 person-years) normal-potassium and 43% (rate, 1594/10,000 person-years) low-potassium patients (hazard ratio {HR} for low-potassium, 1.22; 95% confidence interval {CI}, 1.04-1.44; p=0.014). Low-normal (3.5-3.9 mEq/L) potassium levels had a similar association with mortality (HR, 1.19, 95% CI, 1.00-1.41, p=0.049). Low (HR, 1.10; 95% CI, 0.96-1.25; p=0.175) or low-normal (HR=1.09, 95% CI=0.95-1.25, p=0.229) serum potassium levels were not associated with all-cause hospitalization. CONCLUSIONS: In a propensity-matched population of elderly ambulatory chronic HF patients, well-balanced in all measured baseline covariates, low and low-normal serum potassium were associated with increased mortality but had no association with hospitalization.

Urinary angiotensinogen as a novel biomarker of the intrarenal renin-angiotensin system status in hypertensive patients.

We reported previously that urinary angiotensinogen (UAGT) levels provide a specific index of the intrarenal renin-angiotensin system (RAS) status in angiotensin II-dependent hypertensive rats. To study this system in humans, we recently developed a human angiotensinogen ELISA. To test the hypothesis that UAGT is increased in hypertensive patients, we recruited 110 adults. Four subjects with estimated glomerular filtration levels <30 mL/min per 1.73 m(2) were excluded because previous studies have already shown that UAGT is highly correlated with estimated glomerular filtration in this stage of chronic kidney disease. Consequently, 106 paired samples of urine and plasma were analyzed from 70 hypertensive patients (39 treated with RAS blockers [angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers; systolic blood pressure: 139+/-3 mm Hg] and 31 not treated with RAS blockers [systolic blood pressure: 151+/-4 mm Hg]) and 36 normotensive subjects (systolic blood pressure: 122+/-2 mm Hg). UAGT, normalized by urinary concentrations of creatinine, were not correlated with race, gender, age, height, body weight, body mass index, fractional excretion of sodium, plasma angiotensinogen levels, or estimated glomerular filtration. However, UAGT/urinary concentration of creatinine was significantly positively correlated with systolic blood pressure, diastolic blood pressure, urinary albumin:creatinine ratio (r=0.5994), and urinary protein:creatinine ratio (r=0.4597). UAGT/urinary concentration of creatinine was significantly greater in hypertensive patients not treated with RAS blockers (25.00+/-4.96 microg/g) compared with normotensive subjects (13.70+/-2.33 microg/g). Importantly, patients treated with RAS blockers exhibited a marked attenuation of this augmentation (13.26+/-2.60 microg/g). These data indicate that UAGT is increased in hypertensive patients, and treatment with RAS blockers suppresses UAGT, suggesting that the efficacy of RAS blockade to reduce the intrarenal RAS activity can be assessed by measurements of UAGT.