Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation.

OBJECTIVES: The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis. BACKGROUND: The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown. METHODS: In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities. RESULTS: The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations. CONCLUSIONS: In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Longer Predialysis ACEi/ARB Utilization Is Associated With Reduced Postdialysis Mortality.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) improve predialysis outcomes; however, ACEi/ARB are underused in patients transitioning to dialysis. We examined the association of different patterns of predialysis ACEi/ARB use with postdialysis survival and whether potentially modifiable adverse events are associated with lower predialysis ACEi/ARB use. METHODS: This was a historic cohort study of 34,676 US veterans with, and 10,690 without, ACEi/ARB exposure in the 3-year predialysis period who subsequently transitioned to dialysis between 2007 and 2014. Associations of different patterns of predialysis ACEi/ARB use with postdialysis all-cause mortality and with predialysis acute kidney injury and hyperkalemia events were examined using multivariable adjusted regression analyses. RESULTS: The mean age of the cohort was 70 years, 98% were males and 27% were African Americans. Compared to ACEi/ARB nonuse, continuous ACEi/ARB use was associated with lower postdialysis all-cause mortality (adjusted hazard ratio [aHR]; 95% confidence interval [95% CI] 0.87; 0.83-0.92). In analyses modeling the duration of predialysis ACEi/ARB use, ACEi/ARB use of 50%-74% and ≥75% were associated with lower mortality compared to nonuse (adjusted hazard ratio, 95% confidence interval 0.96, 0.92-0.99 and 0.91; 0.88-0.94, respectively), whereas no increase in postdialysis survival was observed with shorter predialysis ACEi/ARB use. Predialysis acute kidney injury was associated with shorter duration (<50%) of ACEi/ARB use and hyperkalemia was associated with interrupted and ACEi/ARB use of <75%. CONCLUSIONS: Longer predialysis ACEi/ARB exposure was associated with lower postdialysis mortality. Prospective studies are needed to evaluate the benefits of strategies enabling uninterrupted predialysis ACEi/ARB use.

Vancomycin-Associated Acute Kidney Injury in a Large Veteran Population.

BACKGROUND: To determine the association of vancomycin with acute kidney injury (AKI) in relation to its serum concentration value and to examine the risk of AKI in patients treated with vancomycin when compared with a matched cohort of patients receiving non-glycopeptide antibiotics (linezolid/daptomycin). METHODS: From a cohort of > 3 million US veterans with baseline estimated glomerular filtration rate ≥60 mL/min/1.73 m2, we identified 33,527 patients who received either intravenous vancomycin (n = 22,057) or non-glycopeptide antibiotics (linezolid/daptomycin, n = 11,470). We examined the association of the serum trough vancomycin level recorded within the first 48 h of administration with subsequent AKI in all patients treated with vancomycin and association of vancomycin vs. non-glycopeptide antibiotics use with the risk of incident AKI. RESULTS: The overall multivariable adjusted ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptides were 1.1 (1.1-1.2), 1.2 (1-1.4), and 1.4 (1.1-1.7), respectively. When examined in strata divided by vancomycin trough level, the odds of AKI were similar or lower in patients receiving vancomycin compared to non-glycopeptide antibiotics as long as serum vancomycin levels were ≤20 mg/L. However, in patients with serum vancomycin levels > 20 mg/L, the ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptide antibiotics were 1.5 (1.4-1.7), 1.9 (1.5-2.3), and 2.7 (2-3.5), respectively. CONCLUSIONS: Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L.

Changes With Lanthanum Carbonate, Calcium Acetate, and Phosphorus Restriction in CKD: A Randomized Controlled Trial.

INTRODUCTION: Abnormal phosphorus homeostasis develops early in chronic kidney disease (CKD). It is unclear if its correction results in improved clinical outcomes in non-dialysis dependent CKD. METHODS: We conducted a randomized controlled, parallel design clinical trial in 120 patients with estimated glomerular filtration rate 15 to 59 ml/min per 1.73 m2 and abnormal phosphorus homeostasis (serum phosphorus >4.6 mg/dl, parathyroid hormone [PTH] >70 pg/ml or tubular reabsorption of phosphorus [TRP] <80%). Patients were randomized to open-label lanthanum carbonate versus calcium acetate versus dietary intervention over 1 year. The co-primary outcomes were month 12 (vs. baseline) biochemical (serum phosphorus, TRP, PTH, calcium, bone-specific alkaline phosphatase [bALP], and fibroblast growth factor 23 [FGF23]) and vascular parameters (coronary artery calcium score, pulse wave velocity, and endothelial dysfunction) in all patients. Secondary outcomes were between-treatment differences in change for each parameter between month 12 and baseline. All analyses were intention to treat. RESULTS: Baseline characteristics were similar in the 3 groups. A total of 107 patients (89%) completed 12 months of follow-up. Differences were not significant at month 12 (vs. baseline) for any of the outcomes except bALP (median [25th, 75th] percentile at month 12 versus baseline: 13.8 [10.6, 17.6] vs. 15.8 [12.1, 21.1], P < .001) and FGF23 (132 [99, 216] vs. 133 [86, 189], P = .002). Changes for all outcomes were similar in the 3 arms except for PTH, which was suppressed more effectively by calcium acetate (P < .001). CONCLUSION: A 1-year intervention to limit phosphorus absorption using dietary restriction or 2 different phosphorus binders resulted in decreased bALP suggesting improved bone turnover, but no other significant changes in biochemical or vascular parameters in patients with CKD stage 3/4. (ClinicalTrials.gov: NCT01357317).

Abrupt Decline in Kidney Function Precipitating Initiation of Chronic Renal Replacement Therapy.

INTRODUCTION: Abrupt declines in kidney function often occur in patients with advanced chronic kidney disease and may exacerbate the need to initiate dialysis treatment. It is unclear how frequently such events occur in patients transitioning to chronic dialysis therapy, and what outcomes they are associated with. METHODS: We examined a national cohort of 23,349 US veterans with incident end-stage renal disease (ESRD) and with available pre-ESRD estimated glomerular filtration rate (eGFR) to identify abrupt declines in kidney function, defined as an unexpected >50% decrease in eGFR at the time of chronic dialysis transition. Associations with all-cause mortality and with renal recovery were examined in Cox proportional hazard and competing risk regression models. RESULTS: A total of 4804 (21%) patients experienced an abrupt decline in kidney function at dialysis transition. Renal recovery occurred in 586 (12.2%) and 297 (1.6%) patients with and without an abrupt decline, respectively (adjusted subhazard ratio: 4.42; 95% confidence interval [CI]: 3.72-5.27; P < 0.001). In the first 6 months after dialysis transition 1178 patients (24.5%) with abrupt decline died (annualized mortality rate 574/1000 patient-years), compared with 2354 deaths (12.7%) in patients without abrupt decline (274 deaths/1000 patient-years). An abrupt decline was associated with 45% higher mortality after multivariable adjustments (hazard ratio: 1.45; 95% CI: 1.33-1.57). CONCLUSION: Abrupt declines in kidney function are common in patients transitioning to chronic dialysis, and are associated with higher mortality. Patients with abrupt declines also experience a higher rate of renal recovery; hence, careful attention to residual kidney function is warranted in these patients.

Primary Aldosteronism: Diagnosis and Management.

Primary aldosteronism (PA) is an important and commonly unrecognized cause of secondary hypertension. Idiopathic hyperaldosteronism and aldosterone-producing adenomas account for more than 95% of PA and are characterized, respectively, by bilateral or unilateral involvement of the adrenal glands. When there is suspicion for the presence of PA, a plasma aldosterone to renin ratio should be obtained initially. Localization to determine adrenal gland involvement is done by imaging, with computerized tomography or magnetic resonance imaging. After imaging, adrenal vein sampling is done to establish treatment options. Patients with unilateral disease, who are good surgical candidates, are most appropriately managed with adrenalectomy. A biochemical cure is almost certain following adrenalectomy; however, only 30-50% of patients would show adequate blood pressure improvement. Patients with bilateral adrenal disease and those believed not to be surgical candidates are managed with mineralocorticoid antagonists.

Association of age and BMI with kidney function and mortality: a cohort study.

BACKGROUND: Compared with normal weight, obesity might be associated with worse clinical outcomes, including chronic kidney disease. Whether this association is modified by age is not known. We investigated the association of BMI with progressive loss of kidney function and all-cause mortality in US veterans. METHODS: In a national cohort of 3,376,187 US veterans with an estimated glomerular filtration rate (eGFR) of more than 60 mL/min per 1·73 m(2), we assessed the association of BMI in patients of different ages (<40 years, 40 years to <50 years, 50 years to <60 years, 60 years to <70 years, 70 years to <80 years, and ≥80 years) with loss of kidney function and with all-cause mortality in logistic regression models and Cox proportional hazards models adjusted for ethnic origin, sex, comorbidities, medications, and baseline eGFR. FINDINGS: 274,764 (8·1%) of 3,376,187 veterans had a rapid decline in kidney function (decrease in slope of >5 mL/min per 1·73 m(2)). The lowest risk for loss of kidney function was noted in patients with BMI of at least 25 kg/m(2) but less than 30 kg/m(2). A generally consistent U-shaped association was noted between BMI and rapid loss of kidney function that was more prominent with increasing age, except in the patients younger than 40 years, in whom BMI did not seem to be predictive of renal function impairment. 672,341 veterans died (28·7 per 1000 patient-years, 95% CI 28·6-28·7) over a median follow-up of 6·8 years (IQR 6·5-7·7). BMI also showed a U-shaped association with mortality, which was similar in all age groups. INTERPRETATION: A BMI of 30 kg/m(2) or more is associated with rapid loss of kidney function in patients with eGFR of at least 60 mL/min per 1·73 m(2), and this association is accentuated in older patients. A BMI of 35 kg/m(2) or more is also associated with high mortality. A BMI of at least 25 kg/m(2) but less than 30 kg/m(2) is associated with the best clinical outcomes. FUNDING: National Institute of Health, Memphis VA Medical Center, Long Beach VA Healthcare System, Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, and VA Information Resource Center.

"Black"-Appearing Peritoneal Effluent.

When encountering unusually appearing dialysate effluent from a patient doing peri- toneal dialysis, it is important to review the patient's recent exposures. In the case of "black"-appearing dialysate effluent, consideration needs to be given to the possibility of someone having undergone a colonoscopy and having tattooing with India ink. Nephrology nurses are frequently the first to be notified when there has been a change in the character of a patient's peritoneal dialysis dialysate effluent. This article describes a case of "black"-appearing dialysate and includes some of the potential differentials that were considered in the evaluation process. Even though "black"-appearing dialysate is a rare occurrence, nephrology nurses need to be aware of some of the potential etiologies, including exposure to India ink.

Multiple myeloma with hypercalcemia and chloride resistant metabolic alkalosis.

This report describes a novel presentation of chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM). A 51-year-old male with newly diagnosed MM presented with widespread skeletal involvement, calcium (Ca(+2)) of 18 mg/dL, phosphorous (PO4) of 6 mg/dL, serum bicarbonate (HCO3) of 37 mEq/L, and serum creatinine (Cr) of 2.6 mg/dL Other causes of metabolic alkalosis such as vomiting, diuretics, alkali ingestion, mineralocorticoid excess and hypokalemia were excluded. Hypercalcemia and metabolic alkalosis were only partially corrected after rehydration, calcitonin and steroids. Subsequent treatment with zoledronic acid resulted in resolution of hypercalcemia and correction of metabolic alkalosis.The chloride resistant component of metabolic alkalosis was most likely related to extensive release of Ca(+2), carbonate and phosphate from bone by activated osteoclasts with inhibited osteoblastic activity. The additional reduction in glomerular filtration rate due to MM, contributed to a triad mimicking Calcium-Alkali syndrome.