"What do you think about nephrology?" A national survey of internal medicine residents.

BACKGROUND: Interest in nephrology has been declining among internal medicine residents but the reasons behind this observation are not well characterized. Our objective was to evaluate factors influencing residents' choice of subspecialty. METHODS: This is a mixed-method QUAL-QUAN design study that used the results of our previously published qualitative analysis on residents' perception of nephrology to create and pilot a questionnaire of 60 questions. The final questionnaire was distributed to 26 programs across the United States and a total of 1992 residents. We calculated response rates and tabulated participant characteristics and percentage of participant responses. We categorized choice of fellowship into 2 medical categories (Highly Sought After vs. Less Sought After) and fitted a logistic regression model of choosing a highly vs. less sought after fellowship. RESULTS: Four hundred fifteen out of 1992 (21%) US residents responded to the survey. Of the 268 residents planning to pursue fellowship training, 67 (25%) selected a less sought after fellowship. Female sex was associated with significantly higher odds of selecting a less sought after fellowship (OR = 2.64, 95% CI: 1.47, 4.74). Major factors deterring residents from pursuing nephrology were perception of inadequate financial compensation, broad scope of clinical practice and complexity of patient population. We observed a decline in exposure to nephrology during the clinical years of medical school with only 35.4% of respondents rotating in nephrology versus 76.8% in residency. The quality of nephrology education was rated less positively during clinical medical school years (median of 50 on a 0-100 point scale) compared to the pre-clinical years (median 60) and residency (median 75). CONCLUSION: Our study attempts to explain the declining interest in nephrology. Results suggest potential targets for improvement: diversified trainee exposure, sub-specialization of nephrology, and increased involvement of nephrologists in the education of trainees.

Cause-Specific Mortality in Patients with Chronic Kidney Disease and Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with death in patients with chronic kidney disease (CKD). We examined the associations between AF and cause-specific mortality in a large CKD population. METHODS: We included 62,459 patients with estimated glomerular filtration rate 15-59 mL/min/1.73 m2 (6,639 patients with AF and 55,820 without AF) followed in a large health care system. Outcomes included overall and cause-specific deaths (a) cardiovascular; (b) malignancy; and (c) non-cardiovascular/non-malignancy causes. Cox regression models for overall mortality and separate competing risk models for each major cause of death category were used to evaluate their respective associations with AF. RESULTS: During a median follow-up of 4.1 years, 19,094 patients died; cause of death was known for 18,854 patients. After multivariable adjustment (demographics, comorbidities, relevant laboratory data, medication use, and kidney function), AF was associated with 23% (95% CI 18-29%) higher risk of all-cause mortality, 45% (95% CI 31-61%) higher risk of cardiovascular mortality and 13% (95% CI 3-22%) lower risk of malignancy-related mortality. Exclusion of patients with malignancy yielded similar results except for a lack of association between AF and malignancy-related deaths. Results were consistent across various stages of CKD. CONCLUSIONS: In a non-dialysis-dependent CKD population, the presence of AF was associated with higher all-cause and cardiovascular mortality. These data suggest that patients with both CKD and AF are at high cardiovascular risk, and thus clinical practice (or trials) should aim at reducing the overall excess cardiovascular mortality (not stroke alone) in patients with AF and CKD.

Blood pressure parameters are associated with all-cause and cause-specific mortality in chronic kidney disease.

Previous observational studies reported J or U-shaped associations between blood pressure parameters and mortality in patients with chronic kidney disease (CKD). Here we examined the associations of different blood pressure levels with various causes of death in a CKD population that included patients with eGFR 15-59 ml/min/1.73 m2 with underlying hypertension receiving at least one antihypertensive agent. We obtained data on date and cause of death from State Department of Health mortality files and classified deaths into three categories: cardiovascular, malignancy-related, and non-cardiovascular/non-malignancy related. Cox models were fitted for overall mortality, and separate competing risk regression models for each major cause of death category, to evaluate their associations with various systolic and diastolic blood pressures. During a median follow-up of 3.9 years, 13,332 of 45,412 patients died. Systolic blood pressures under 100, 100-109, 110-119, and over 150 (vs. 130-139 mm Hg) were associated with higher all-cause and cardiovascular mortality. Systolic blood pressures under 100 mm Hg and 100-109 were associated with higher non-cardiovascular/non-malignancy related mortality. Diastolic blood pressures under 50 and 50-59 (vs. 70-79 mm Hg) were associated with higher all-cause and non-cardiovascular/non-malignancy-related mortality while diastolic blood pressures over 90 mm Hg was associated with higher cardiovascular but lower non-cardiovascular/non-malignancy related mortality. Thus, in a non-dialysis dependent CKD population, systolic blood pressures under 110 and over 150 mm Hg were associated with cardiovascular and non-cardiovascular/non-malignancy related deaths. However, diastolic blood pressure under 60 mm Hg was associated in contrast with all-cause mortality and non-cardiovascular/non-malignancy-related deaths.

Diabetes Control and the Risks of ESRD and Mortality in Patients With CKD.

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD) and a significant contributor to mortality in the general population. We examined the associations of hemoglobin A1c (HbA1c) levels with ESRD and death in a population with diabetes and chronic kidney disease (CKD). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 6,165 patients with diabetes (treated with oral hypoglycemic agents and/or insulin) and CKD stages 1 to 5 at a large health care system. PREDICTOR: HbA1c level (examined as a categorical and continuous measure). OUTCOMES: All-cause and cause-specific mortality ascertained from the Ohio Department of Health mortality files and ESRD ascertained from the US Renal Data System. RESULTS: During a median 2.3 years of follow-up, 957 patients died (887 pre-ESRD deaths) and 205 patients reached ESRD. In a Cox proportional hazards model, after multivariable adjustment including for kidney function, HbA1c level < 6% was associated with higher risk for death when compared with HbA1c levels of 6% to 6.9% (HR, 1.23; 95% CI, 1.01-1.50). Similarly, HbA1c level ≥ 9% was associated with higher risk for all-cause death (HR, 1.34; 95% CI, 1.06-1.69). In competing-risk models, baseline HbA1c level was not associated with ESRD. For cause-specific mortality, diabetes accounted for >12% of deaths overall and >19% of deaths among those with HbA1c levels > 9%. LIMITATIONS: Small proportion of participants with advanced kidney disease; single-center population. CONCLUSIONS: In this cohort of patients with CKD with diabetes, HbA1c levels < 6% and ≥9% were associated with higher risk for death. HbA1c levels were not associated with ESRD in this specific CKD population. Diabetes-related deaths increased with higher HbA1c levels.

Impact of Uric Acid Levels on Kidney Disease Progression.

BACKGROUND: Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry. METHODS: We included 1,676 patients with CKD stages 3 and 4 from Ohio, who had measured their uric acid (UA) levels a year prior to the recording of the second eGFR <60 mL/min/1.73 m2, and follow-up eGFR, between 2005 and 2009. Our primary composite outcome included a 50% drop in eGFR or progression to ESRD. Secondary outcomes included the rate of decline in eGFR, all-cause mortality, progression to ESRD, and a composite measure of progression to ESRD or death. We assessed the association between UA, UALT, and outcomes using Cox models and competing risks regression models. RESULTS: In multivariable models, higher UA was associated with the composite endpoint, but it reached statistical significance only in the 4th quartile (≥8.9 mg/dL). Receipt of UALT was significantly associated with increased risk of the composite outcome. Neither UA nor UALT (considered a time-dependent covariate) was significantly associated with mortality. The inference was similar for UA as high vs. low, quartiles, or continuous. Similarly, neither high UA nor UALT were significantly associated with ESRD, the composite of ESRD and mortality, or eGFR decline. CONCLUSIONS: Hyperuricemia is associated with increased risk of progression to ESRD in patients with CKD stages 3 and 4, but UALT does not ameliorate the risk, suggesting that the relationship is not causal.

Associations of dysnatremias with mortality in chronic kidney disease.

BACKGROUND: Hyponatremia and hypernatremia are associated with death in the general population and those with chronic kidney disease (CKD). We studied the associations between dysnatremias, all-cause mortality and causes of death in a large cohort of Stage 3 and 4 CKD patients. METHODS: We included 45 333 patients with Stage 3 and 4 CKDs followed in a large healthcare system. Associations between hyponatremia (<136 mmol/L) and hypernatremia (>145), and all-cause mortality and causes of death (cardiovascular, malignancy related and non-cardiovascular/non-malignancy related) were studied using Cox proportional hazards and competing risk models. RESULTS: Dysnatremias were found in 9.2% of the study population. In separate multivariable Cox proportional hazards models using baseline serum sodium levels and time-dependent repeated measures, both hyponatremia and hypernatremia were associated with all-cause mortality. In the competing risk analyses, hyponatremia was significantly associated with increased risk for various cause-specific mortality categories [cardiovascular (hazard ratio, HR 1.16, 95% confidence interval, CI: 1.04, 1.30), malignancy related (HR 1.48, 95% CI: 1.33, 1.65) and non-cardiovascular/non-malignancy deaths (HR 1.25, 95% CI: 1.13, 1.39)], while hypernatremia was significantly associated with higher non-cardiovascular/non-malignancy mortality only (HR 1.36, 95% CI: 1.08, 1.72). CONCLUSIONS: In those with CKD, hyponatremia was associated with all-cause mortality, cardiovascular, malignancy and non-cardiovascular/non-malignancy-related deaths. Hypernatremia was associated with all-cause and non-cardiovascular/non-malignancy-related deaths. Further studies are needed to elucidate the mechanisms of differences in cause-specific death among CKD patients with hyponatremia and hypernatremia.

Body mass index and causes of death in chronic kidney disease.

In chronic kidney disease (CKD), a higher body mass index (BMI) is associated with a lower risk for death, but cause-specific death details are unknown across the BMI range. To define this, we studied 54,506 patients with CKD (stage 3 CKD- [91.5%]) from an institutional electronic medical record based-registry. We examined the associations among various causes of death (cardiovascular-, malignancy- and noncardiovascular/nonmalignancy-related deaths) across the BMI range using Cox proportional hazards and competing risks regression models. During a median follow-up of 3.7 years, 14,518 patients died. In the multivariable model, an inverted J-shaped association was noted between BMI and cardiovascular-related, malignancy-related, and noncardiovascular/nonmalignancy-related deaths. Similar associations were noted for BMI 25-29.9, 30-34.9, and 35-39.9 kg/m(2) categories. A BMI >40 kg/m(2) was not associated with cardiovascular-related and noncardiovascular/nonmalignancy-related deaths in CKD. Sensitivity analyses yielded similar results even after adjusting for proteinuria and excluding diabetes and hypertension from the models. In CKD, compared with a BMI of 18.5-24.9 kg/m(2), those who are overweight, with class 1 and 2 obesity have a lower risk for cardiovascular-related, malignancy-related, and noncardiovascular/nonmalignancy-related deaths. Future studies should examine the associations of other measures of adiposity with outcomes in CKD.

Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with higher mortality in the general population. We studied the associations between COPD and death among chronic kidney disease (CKD) patients along with reporting cause-specific death data. METHODS: We included 56,960 patients with stages 3 and 4 CKD who were followed in a large health care system. Associations between COPD and all-cause mortality and various causes of death (respiratory deaths, cardiovascular deaths, malignancy-related deaths and deaths due to other reasons) were studied using the Cox proportional hazards and competing risk models. RESULTS: Out of 56,960 CKD patients, 4.7% (n = 2,667) had underlying COPD. Old age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, and smoking were associated with higher risk for COPD. During a median follow-up of 3.7 years, 15,969 patients died. After covariate adjustment, COPD was associated with a 41% increased risk (95% CI 1.31-1.52) for all-cause mortality, and fourfold increased risk (sub-hazard ratio 4.36, 95% CI 3.54-5.37) for respiratory-related deaths. In a sensitivity analysis that was performed by defining COPD as the use of relevant International Classification of Diseases-9 codes and medications used to treat COPD, similar results were noted. CONCLUSIONS: COPD is associated with higher risk for death among those with CKD, and an underlying lung disease accounts for significant proportion of deaths. These data highlight the need for further prospective studies to understand the underlying mechanisms and potential interventions to improve outcomes in this population.

Cause-Specific Deaths in Non-Dialysis-Dependent CKD.

CKD is associated with higher risk of death, but details regarding differences in cause-specific death in CKD are unclear. We examined the leading causes of death among a non-dialysis-dependent CKD population using an electronic medical record-based CKD registry in a large healthcare system and the Ohio Department of Health mortality files. We included 33,478 white and 5042 black patients with CKD who resided in Ohio between January 2005 and September 2009 and had two measurements of eGFR<60 ml/min per 1.73 m(2) obtained 90 days apart. Causes of death (before ESRD) were classified into cardiovascular, malignancy, and non-cardiovascular/non-malignancy diseases and non-disease-related causes. During a median follow-up of 2.3 years, 6661 of 38,520 patients (17%) with CKD died. Cardiovascular diseases (34.7%) and malignant neoplasms (31.8%) were the leading causes of death, with malignancy-related deaths more common among those with earlier stages of kidney disease. After adjusting for covariates, each 5 ml/min per 1.73 m(2) decline in eGFR was associated with higher risk of death due to cardiovascular disease (hazard ratio [HR], 1.10; 95% confidence interval [95% CI], 1.08 to 1.12) and non-cardiovascular/non-malignancy diseases (HR, 1.12; 95% CI, 1.09 to 1.14) but not to malignancy. In the adjusted models, blacks had overall-mortality hazard ratios similar to those of whites but higher hazard ratios for cardiovascular deaths. Further studies to confirm these findings and explain the mechanisms for differences are warranted. In addition to lowering cardiovascular burden in CKD, efforts to target known risk factors for cancer at the population level are needed.

Renal failure requiring dialysis complicating slow continuous ultrafiltration in acute heart failure: importance of systolic perfusion pressure.

BACKGROUND: Recent reports have raised concerns regarding renal outcomes in patients with decompensated acute heart failure (HF) treated with slow continuous ultrafiltration (SCUF). The purpose of this study was to identify risk factors for renal failure (RF) requiring dialysis in patients with acute HF initiated on SCUF. METHODS AND RESULTS: We studied 63 consecutive patients with acute HF who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. Median serum creatinine at SCUF initiation was higher in patients who developed RF requiring dialysis [2.5 (interquartile range 1.8-3.3) vs 1.6 (1.2-2.3) mg/dL; P < .001]. Weight loss within 48 hours of SCUF initiation was larger in patients who did not progress to RF [-6 (-10 to -2) vs -4 (-6 to -2) kg; P = .03]. Systolic perfusion pressure had a nonlinear association with RF requiring dialysis, with a threshold effect noted at 90 mm Hg. Twelve-month mortality in patients who were moved to dialysis versus those who were not was 95% versus 35%, respectively (P < .001). CONCLUSIONS: In patients with acute HF initiated on SCUF, onset of RF requiring dialysis is associated with high mortality. Systolic perfusion pressure which incorporates both perfusion and venous congestion parameters may present a modifiable risk factor for worsening RF during SCUF in acute HF patients.

Serum Potassium, End-Stage Renal Disease and Mortality in Chronic Kidney Disease.

BACKGROUND/AIMS: Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population. METHODS: Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m(2) and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models. RESULTS: Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality. CONCLUSION: In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.

Development of a chronic kidney disease patient navigator program.

BACKGROUND: Chronic Kidney Disease (CKD) is a public health problem and there is a scarcity of type 2 CKD translational research that incorporates educational tools. Patient navigators have been shown to be effective at reducing disparities and improving outcomes in the oncology field. We describe the creation of a CKD Patient Navigator program designed to help coordinate care, address system-barriers, and educate/motivate patients. METHODS: The conceptual framework for the CKD Patient Navigator Program is rooted in the Chronic Care Model that has a main goal of high-quality chronic disease management. Our established multidisciplinary CKD research team enlisted new members from information technology and data management to help create the program. It encompassed three phases: hiring, training, and implementation. For hiring, we wanted a non-medical or lay person with a college degree that possessed strong interpersonal skills and experience in a service-orientated field. For training, there were three key areas: general patient navigator training, CKD education, and electronic health record (EHR) training. For implementation, we defined barriers of care and created EHR templates for which pertinent study data could be extracted. RESULTS: We have hired two CKD patient navigators who will be responsible for navigating CKD patients enrolled in a clinical trial. They have undergone training in general patient navigation, specific CKD education through directed readings and clinical shadowing, as well as EHR and other patient related privacy and research training. CONCLUSIONS: The need for novel approaches like our CKD patient navigator program designed to impact CKD care is vital and should utilize team-based care and health information technology given the changing landscape of our health systems.

Serum testosterone levels and mortality in men with CKD stages 3-4.

BACKGROUND: Hypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD). STUDY DESIGN: Retrospective, cohort study. SETTING & PARTICIPANTS: 2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH. PREDICTORS: Total testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL). OUTCOMES: Factors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. RESULTS: Hypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16). LIMITATIONS: Single-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias. CONCLUSIONS: Low total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed.

Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD.

BACKGROUND: Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias. STUDY DESIGN: Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10mL/min/1.73m(2)). SETTING & PARTICIPANTS: Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30mL/min/1.73m(2) measured at least 180 days apart. PREDICTORS: Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation≥10mL/min/1.73m(2)) or later (eGFR < 10mL/min/1.73m(2)) and was time-varying. OUTCOMES: Death from any cause occurring from the time that eGFR was equal to 20mL/min/1.73m(2) through September 15, 2009. RESULTS: The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n=465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10mL/min/1.73m(2). Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11). LIMITATIONS: Interpolated eGFR, moderate sample size, and likely unmeasured confounders. CONCLUSIONS: In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias.

Chronic kidney disease in an electronic health record problem list: quality of care, ESRD, and mortality.

BACKGROUND: Whether chronic kidney disease (CKD) recognition in an electronic health record (EHR) problem list improves processes of care or clinical outcomes of end-stage renal disease (ESRD) and death is unclear. METHODS: We identified patients who had at least 1 year of follow-up (2005-2009) in our EHR-based CKD registry (n = 25,742). CKD recognition was defined by having ICD-9 codes for CKD, diabetic kidney disease, or hypertensive kidney disease in the problem list. We calculated proportions of patients with and without CKD recognition and examined differences by demographics, clinical factors, and development of ESRD or mortality. We evaluated differences in the proportion of patients with CKD-specific laboratory results checked before and after recognition among cases and propensity-matched controls. RESULTS: Only 11% (n = 2,735) had CKD recognition in the problem list and they were younger (68 vs. 71 years), a higher proportion were male (61 vs. 37%) and African-American (21 vs. 10%) compared to those unrecognized. CKD-specific laboratory results for patients with estimated glomerular filtration rate (eGFR) 30-59 including intact parathyroid hormone (23 vs. 6%), vitamin D (22 vs. 18%), phosphorus (29 vs. 7%), and a urine check for proteinuria (55 vs. 36%) were significantly more likely to be done among those with CKD recognition (all p < 0.05). Similar results were found for eGFR <30 except for proteinuria and in our propensity score-matched control analysis. There was no independent association of CKD recognition with ESRD or mortality. CONCLUSIONS: CKD recognition in the EHR problem list was low, but translated into more CKD-specific processes of care; however ESRD or mortality were not affected.

Practice patterns of phosphate binder use and their associations with mortality in chronic kidney disease.

BACKGROUND: Higher serum phosphorus is associated with an increased mortality among those with chronic kidney disease (CKD). We examined the practice patterns of phosphate binder use to lower serum phosphorus levels and their associations with mortality in the non-dialysisdependent CKD population. METHODS: We examined the factors associated with the use of calcium and non-calcium phosphate binders in those with stage 3 and 4 CKD (eGFR 15 - 59 mL/min/1.73 m2) using logistic regression models. The associations between phosphate binder use and mortality were studied using propensity based analysis. RESULTS: Out of 57,928 patients with eGFR 15 - 59 mL/min/1.73 m2, 13,325 (23%) patients had serum phosphorus levels measured. 945 patients were prescribed phosphate binders, with 238 (25%) of them prescribed non-calcium-based phosphate binders and the rest calcium-based phosphate binders. Higher BMI, higher serum phosphorus, and higher serum calcium were associated with higher odds of being prescribed a non-calcium-based binder. Phosphate binder use was not significantly associated with mortality in either the entire cohort or the matched cohort in the analysis limited to those who were treated for at least 6 months. In the matched cohort, those who were treated for 1 year with a phosphate binder had a non-significant lower mortality rate (hazard ratio (HR): 0.85, 95% CI 0.66, 1.10). CONCLUSIONS: Phosphate binder use for 6 months and 1 year was not associated with reduced mortality in those with stage 3 and stage 4 CKD.

Prognostic importance of serum alkaline phosphatase in CKD stages 3-4 in a clinical population.

BACKGROUND: Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2)) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m(2) drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. PREDICTOR: ALP levels measured using the calorimetric assay were examined as quartiles (quartile [Q]1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure. OUTCOMES & MEASUREMENTS: All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System. RESULTS: After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively. LIMITATIONS: Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias. CONCLUSIONS: Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD.

Electronic health records: a new tool to combat chronic kidney disease?

Electronic health records (EHRs) were first developed in the 1960s as clinical information systems for document storage and retrieval. Adoption of EHRs has increased in the developed world and is increasing in developing countries. Studies have shown that quality of patient care is improved among health centers with EHRs. In this article, we review the structure and function of EHRs along with an examination of its potential application in CKD care and research. Well-designed patient registries using EHRs data allow for improved aggregation of patient data for quality improvement and to facilitate clinical research. Preliminary data from the United States and other countries have demonstrated that CKD care might improve with use of EHRs-based programs. We recently developed a CKD registry derived from EHRs data at our institution and complimented the registry with other patient details from the United States Renal Data System and the Social Security Death Index. This registry allows us to conduct a EHRs-based clinical trial that examines whether empowering patients with a personal health record or patient navigators improves CKD care, along with identifying participants for other clinical trials and conducting health services research. EHRs use have shown promising results in some settings, but not in others, perhaps attributed to the differences in EHRs adoption rates and varying functionality. Thus, future studies should explore the optimal methods of using EHRs to improve CKD care and research at the individual patient level, health system and population levels.

Serum triglycerides and risk for death in Stage 3 and Stage 4 chronic kidney disease.

BACKGROUND: An elevated triglyceride level is associated with cardiovascular and all-cause mortality in the general population. The associations between serum triglyceride and all-cause mortality among patients with chronic kidney disease (CKD) are unclear. METHODS: Patients with Stage 3 and Stage 4 CKD (estimated glomerular filtration rate 15-59 mL/min/1.73 m(2)) who had serum triglycerides measured prior to being classified as CKD were included. We examined the associations of serum triglyceride levels with all-cause mortality among 25 641 Stage 3 and Stage 4 CKD patients using Cox proportional hazard models and Kaplan-Meier survival curves. RESULTS: In the Cox model, after adjusting for relevant covariates including other lipid parameters, serum triglyceride level 150-199 mg/dL was not associated with death [hazard ratio (HR) 1.00, 95% confidence interval (95% CI) 0.92-1.10] relative to serum triglyceride <150 mg/dL while serum triglyceride ≥ 200 mg/dL was associated with a 11% increased hazard for death (95% CI 1.01-1.22). Age modified the association between serum triglyceride levels ≥ 200 mg/dL and mortality with patients <65 years having a 38% higher hazard for death (95% CI 1.15-1.65) and ≥ 65 years with no increased risk for death (HR 0.97, 95% CI 0.88-1.08, P for interaction <0.001). When serum triglycerides were examined as a continuous log-transformed variable, similar associations with mortality were noted. CONCLUSIONS: Serum triglyceride ≥ 200 mg/dL was independently associated with all-cause mortality in Stage 3 and Stage 4 CKD patients aged <65 years but not among patients of age ≥ 65 years. Future studies should confirm these findings and examine the mechanisms that may explain these associations.

Low 25-hydroxyvitamin D levels and mortality in non-dialysis-dependent CKD.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) levels are common in patients with non-dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in non-dialysis-dependent patients with CKD are unclear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2); n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System. PREDICTOR: 25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL. OUTCOMES: We examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. MEASUREMENTS: 25(OH)D was measured using chemiluminescence immunoassay. RESULTS: Of 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL. LIMITATIONS: Single-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias. CONCLUSIONS: 25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non-dialysis-dependent patients with CKD.