Background

Prior small studies have suggested an association between low serum albumin and increased risk of venous thromboembolic (VTE) events in patients with nephrotic syndrome (NS).

Methods

From a nationally representative prospective cohort of over 3 million US veterans with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 , we identified 7037 patients with NS based on ICD-9 codes. Association between serum albumin and risk of incident VTE was assessed using Cox regression analysis with adjustments for age, gender, race, comorbidities, eGFR, body mass index and anticoagulant treatment.

Results

Mean age was 57 ± 11 years, patients were 96% male, 32% African-American and 60% diabetic. There were a total of 158 VTE events over a median follow-up of 8.1 years; 16 events [absolute event rate (AER) 4.1%, event rate 8.5/1000 patient-years (PY)] in patients with albumin <2.5 g/dL, 18 events (AER 3.4%, event rate 5.7/1000 patient-years) in patients with albumin 2.5-2.99 g/dL, 89 events (AER 2.5%, event rate 3.4/1000 patient-years) in patients with albumin 3-3.99 g/dL and 35 events (AER 1.4%, event rate 1.9/1000 patient-years) in patients with albumin ≥4 g/dL. Compared with patients with albumin ≥4 g/dL, those with albumin levels of 3-3.99 g/dL [adjusted hazard ratio (HR): 1.51, 95% confidence interval (CI): 1.01-2.26], 2.5-2.99 g/dL (HR: 2.24, 95% CI: 1.24-4.05) and <2.5 g/dL (HR: 2.79, 95% CI: 1.45-5.37) experienced a linearly higher risk of VTE events.

Conclusions

Lower serum albumin is a strong independent predictor for VTE events in NS. The risk increases proportionately with declining albumin levels. Clinical trials are needed to determine benefit of prophylactic anticoagulation in NS patients with moderately lower serum albumin levels.

Background/aims

Abnormal serum potassium is associated with higher mortality in dialysis patients, but its impact on outcomes in predialysis chronic kidney disease (CKD) is less clear. Furthermore, blacks with normal kidney function have lower urinary potassium excretion, but it is unclear if such differences have a bearing on race-associated outcomes in CKD.

Methods

We studied predialysis mortality and slopes of estimated glomerular filtration rate, eGFR) associated with serum potassium in 1,227 males with CKD. Mortality was examined in time-dependent Cox models, and slopes of eGFR in linear mixed effects models with adjustments for case mix and laboratory values.

Results

Both hypo- and hyperkalemia were associated with mortality overall and in 933 white patients, but in 294 blacks hypokalemia was a stronger death predictor. Hypokalemia was associated with loss of kidney function independent of race: a 1 mEq/l lower potassium was associated with an adjusted difference in slopes of eGFR of -0.13 ml/min/1.73 m(2)/year (95% CI: -0.20 to -0.07), p < 0.001.

Conclusion

Hypo- and hyperkalemia are associated with higher mortality in CKD patients. Blacks appear to better tolerate higher potassium than whites. Hypokalemia is associated with faster CKD progression independent of race. Hyperkalemia management may warrant race-specific consideration, and hypokalemia correction may slow CKD progression.

Background and objectives

Elevated serum calcium has been associated with increased mortality in dialysis patients, but it is unclear whether the same is true in non-dialysis-dependent (NDD) chronic kidney disease (CKD). Outcomes associated with low serum calcium are also not well-characterized.

Design, setting, participants, & measurements

We examined associations of baseline, time-varying, and time-averaged serum calcium with all-cause mortality in a historic prospective cohort of 1243 men with moderate and advanced NDD CKD by using Cox models.

Results

The association of serum calcium with mortality varied according to the applied statistical models. Higher baseline calcium and time-averaged calcium were associated with higher mortality (multivariable adjusted hazard ratio (95% confidence interval): 1.31 (1.13, 1.53); P < 0.001 for a baseline calcium 1 mg/dl higher). However, in time-varying analyses, lower calcium levels were associated with increased mortality.

Conclusions

Higher serum calcium is associated with increased long-term mortality (as reflected by the baseline and time-averaged models), and lower serum calcium is associated with increased short-term mortality (as reflected by the time-varying models) in patients with NDD CKD. Clinical trials are warranted to determine whether maintaining normal serum calcium can improve outcomes in these patients.

Background

Serum alkaline phosphatase (ALP) increases in patients with chronic kidney disease (CKD) and high-turnover bone disease. ALP may represent an adjunct marker of high bone turnover devoid of drawbacks of serum parathyroid hormone (PTH), and it may also be associated with cardiovascular calcification in CKD. Higher ALP has been recently associated with increased mortality and coronary calcification in dialysis patients. In pre-dialysis CKD patients, this association is not clear.

Methods

We examined the association of baseline, time-varying and time-averaged ALP with all-cause mortality and the composite of pre-dialysis mortality or end-stage renal disease in a historical prospective cohort of 1158 male veterans with pre-dialysis CKD from a single institution by using multivariable-adjusted Cox models.

Results

Higher ALP was associated with increased mortality irrespective of the statistical model. Time-averaged ALP displayed a consistent linear association with mortality: a 50-U/L higher serum ALP was associated with a multivariable-adjusted death hazard ratio (95% confidence interval) of 1.17 (1.08-1.28), P < 0.001. Baseline and time-varying ALP showed non-linear associations with mortality, with serum levels above 70 U/L in all models and with lower levels in time-varying models. Associations between ALP levels and the composite outcomes were similar. However, compared to serum PTH, mortality predictability of ALP appeared more incremental.

Conclusions

Elevated ALP is associated with increased mortality in patients with pre-dialysis CKD. Low ALP appears to be associated with short-term mortality.

Background

The efficacy of 25-hydroxyvitamin D (25[OH]D) supplementation versus vitamin D receptor activators for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stages 3 or 4 and vitamin D deficiency is unclear.

Study design

Randomized controlled trial.

Setting & participants

80 patients with CKD stages 3 or 4, 25(OH)D level <30 ng/mL, and SHPT in a single medical center.

Intervention

Ergocalciferol, 50,000 units, titrated to achieve serum levels ≥30 ng/mL versus paricalcitol, 1 or 2 μg/d, for 16 weeks.

Outcomes

The occurrence of 2 consecutive parathyroid hormone (PTH) levels decreased by at least 30% from baseline. All analyses were intention to treat.

Results

Baseline characteristics in the 2 groups were similar. 21 patients (53%) on paricalcitol and 7 patients (18%) on ergocalciferol treatment achieved the primary outcome measure (P = 0.002). After 16 weeks, PTH levels did not decrease significantly in patients receiving ergocalciferol, but were decreased significantly in those treated with paricalcitol (mean estimate of between-group difference over 16 weeks of therapy, 43.9 pg/mL; 95% CI, 11.2-76.6; P = 0.009). Serum 25(OH)D levels increased significantly after 16 weeks in only the ergocalciferol group, but not the paricalcitol group (mean estimate of between-group difference over 16 weeks of therapy, 7.08 ng/mL; 95% CI, 4.32-9.85; P < 0.001). Episodes of hyperphosphatemia and hypercalcemia were not significantly different between the 2 groups.

Limitations

Lack of blinding and use of surrogate end points.

Conclusions

Paricalcitol is more effective than ergocalciferol at decreasing PTH levels in patients with CKD stages 3 or 4 with vitamin D deficiency and SHPT.

Unlabelled

An estimated 4 million Americans have been exposed to the hepatitis C virus (HCV). The risks of incident and progressive chronic kidney disease and of mortality in patients with normal kidney function infected with HCV are unclear. In a nationally representative cohort of 100,518 HCV(+) and 920,531 HCV(-) US veterans with normal baseline estimated glomerular filtration rate (eGFR), we examined the association of HCV infection with (1) all-cause mortality, (2) incidence of decreased kidney function (defined as eGFR <60 mL/min/1.73 m(2) and 25% decrease in eGFR), (3) end-stage renal disease, and (4) rate of kidney function decline. Associations were examined in naive and adjusted Cox models (for time-to-event analyses) and logistic regression models (for slopes), with sequential adjustments for important confounders. Propensity-matched cohort analysis was used in sensitivity analyses. The patients' age was 54.5 ± 13.1 (mean ± standard deviation) years, 22% were black, 92% were male, and the baseline eGFR was 88 ± 16 mL/min/1.73 m(2) . In multivariable adjusted models HCV infection was associated with a 2.2-fold higher mortality (fully adjusted hazard ratio = 2.17, 95% confidence interval [CI] 2.13-2.21), a 15% higher incidence of decreased kidney function (adjusted hazard ratio = 1.15, 95% CI 1.12-1.17), a 22% higher risk of steeper slopes of eGFR (adjusted odds ratio = 1.22, 95% CI 1.19-1.26), and a 98% higher hazard of end-stage renal disease (adjusted hazard ratio = 1.98, 95% CI 1.81-2.16). Quantitatively similar results were found in propensity-matched cohort analyses.

Conclusions

Infection with HCV is associated with higher mortality risk, incidence of decreased kidney function, and progressive loss of kidney function; randomized controlled trials are warranted to determine whether treatment of HCV infection can prevent the development and progression of chronic kidney disease and improve patient outcomes.