Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes.

BACKGROUND: Whether the benefits of phosphorus binders extend to those without end stage renal disease is uncertain. Among a large diverse non-dialysis chronic kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate phosphorus binder use and compare mortality risk between patients prescribed and not prescribed binders. METHODS: A retrospective cohort study within an integrated health system (January 1, 1998 - December 31, 2012) among CKD patients (age ≥18) was performed. Non-dialysis CKD patients with 2 separate estimated glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus ≥5.0 mg/dL within 180 days of eGFR were included. Multivariable cox proportional hazards and inverse probability of treatment-weighted models were used to estimate mortality hazard ratios (HRs) for patients who received phosphorus binders compared to no binders. RESULTS: Among 10,165 study patients, 2,733 subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86 (0.80-0.93) using traditional multivariable and inverse probability of treatment-weighted models respectively. Sensitivity analyses removing patients who were prescribed binders >180 days after index date revealed no difference in mortality between those with binders and with no binders. CONCLUSION: Our findings from a real-world clinical environment revealed that 27% of hyperphosphatemic non-dialysis CKD patients were prescribed binders. They also had lower risk of mortality compared to those not prescribed phosphorus binders. However, the lower mortality risk was not observed when we accounted for immortal time bias. Whether phosphorus binder use in CKD improves survival remains to be determined.

Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system.

OBJECTIVE: To evaluate the prevalence of and characterize resistant hypertension in a large representative population with successful hypertension management and reliable health information. PATIENT AND METHODS: We performed a cross-sectional study using clinical encounter, laboratory, and administrative information from the Kaiser Permanente Southern California health system between January 1, 2006, and December 31, 2007. From individuals older than 17 years with hypertension, resistant hypertension was identified and prevalence was determined. Multivariable logistic regression was used to calculate odds ratios (ORs), with adjustments for demographic characteristics, clinical variables, and medication use. RESULTS: Of 470,386 hypertensive individuals, 60,327 (12.8%) were identified as having resistant disease, representing 15.3% of those taking medications. Overall, 37,061 patients (7.9%) had uncontrolled hypertension while taking 3 or more medicines. The ORs (95% CIs) for resistant hypertension were greater for black race (1.68 [1.62-1.75]), older age (1.11 [1.10-1.11] for every 5-year increase), male sex (1.06 [1.03-1.10]), and obesity (1.46 [1.42-1.51]). Medication adherence rates were higher in those with resistant hypertension (93% vs 89.8%; P<.001). Chronic kidney disease (OR, 1.84; 95% CI, 1.78-1.90), diabetes mellitus (OR, 1.58; 95% CI, 1.53-1.63), and cardiovascular disease (OR, 1.34; 95% CI, 1.30-1.39) were also associated with higher risk of resistant hypertension. CONCLUSION: In a more standardized hypertension treatment environment, we observed a rate of resistant hypertension comparable with that of previous studies using more fragmented data sources. Past observations have been limited due to nonrepresentative populations, reliability of the data, heterogeneity of the treatment environments, and less than ideal control rates. This cohort, which was established using an electronic medical record-based approach, has the potential to provide a better understanding of resistant hypertension and outcomes.

Phosphorus and risk of renal failure in subjects with normal renal function.

PURPOSE: Whether higher serum phosphorus levels increase risk for kidney disease onset and progression to end-stage renal disease in those with normal renal function is largely unknown. We sought to determine whether higher serum phosphorus levels increase risk for end-stage renal disease within a large ethnically diverse population with normal kidney function. METHODS: A retrospective longitudinal cohort study was performed in the period January 1, 1998 through December 31, 2008 of adults within a vertically integrated health plan (3.4 million members). The primary objective was to determine risk of incident end-stage renal disease. Baseline and time-averaged phosphorus were used for Cox regressions analyses to calculate hazard ratios (HR) adjusting for age, sex, race, pre-existing hypertension, and diabetes. RESULTS: A total of 94,989 subjects were identified in the 11-year observation period. Mean age of the cohort was 50 years, with 61% female, 38% white, 14% black, and 25% Hispanic. Population-based phosphorus quartile ranges were 1.9-3.0 mg/dL, 3.1-3.4 mg/dL, 3.5-3.8 mg/dL, and 3.9-5.7 mg/dL. End-stage renal disease occurred in 130 (0.1%) subjects. Every 0.5-mg/dL phosphorus increase demonstrated an adjusted HR of 1.40 (95% confidence interval [CI], 1.06-1.84) and HR for mortality of 1.09 (95% CI, 1.06-1.13). Adjusted HRs were 0.64 (95% CI, 0.37-1.11), 0.83 (95% CI, 0.50-1.39), and 1.48 (95% CI, 0.96-2.28) in the 2nd, 3rd, and 4th quartile, respectively, compared with the first phosphorus quartile. Time-averaged serum phosphorus demonstrated a similar relationship across quartiles and as a continuous variable. CONCLUSION: In our large, ethnically diverse cohort of non kidney disease subjects, higher serum phosphorus levels were associated with greater risk for end-stage renal disease and mortality.

25-hydroxyvitamin D levels and hypertension rates.

Vitamin D deficiency has been linked to cardiovascular disease and risk factors including hypertension. The authors sought to determine prevalence rates of hypertension in adults tested for 25-hydroxyvitamin D categorized by their levels and evaluate odds ratios for hypertension at lower 25-hydroxyvitamin D levels compared with optimal levels. A cross-sectional study was conducted January 1, 2004, through December 31, 2006, of patients aged 18 years and older within a large ethnically diverse population. Diagnosis of hypertension was determined by International Statistical Classification of Diseases and Related Health Problems codes. Patients were categorized into quartiles according to 25-hydroxyvitamin D levels: ideal (≥40 ng/mL), adequate (30-39 ng/mL), deficient (15-29 ng/mL), and severely deficient (<15 ng/mL). Prevalence rates of hypertension and odds ratios were calculated for each 25-hydroxyvitamin D quartile, adjusting for age, sex, race, and renal insufficiency. A total of 2722 individuals met the inclusion criteria for the study. The overall prevalence of hypertension in the study population was 24%. Hypertension rates were 52%, 41%, 27%, and 20% in 25-hydroxyvitamin D quartiles <15 ng/mL, 15 to 29 ng/mL, 30 to 39 ng/mL, and ≥40 ng/mL, respectively (P<.001). Odds ratios (95% confidence intervals) for hypertension adjusting for age, sex, race, and renal insufficiency were 2.7 (1.4-5.2), 2.0 (1.5-2.6), and 1.3 (1.2-1.6) for 25-hydroxyvitamin D levels <15 ng/mL, 15 to 29 ng/mL, and 30 to 39 ng/mL, respectively, compared with the ≥40 ng/mL group. This study demonstrates increased rates of hypertension in individuals who tested for lower levels of 25-hydroxyvitamin D starting at levels <40 ng/mL. This retrospective analysis raises the question of whether supplementing to optimal vitamin D levels can prevent or improve hypertension.

Incidence of end-stage renal disease and death among insured African Americans with chronic kidney disease.

African Americans have the highest incidence of end-stage renal disease (ESRD) in the United States. To understand the basis of this disparity, we examined data from a prepaid, integrated health system for this retrospective cohort study of members who had one or more serum creatinine tests performed over a 9-year period. The cohort included 182,959 adults (8% black) with stage 3 or 4 chronic kidney disease based on their estimated glomerular filtration rate (eGFR). Competing-risk methods were used to determine the incidence of ESRD and death prior to ESRD. At all follow-up times and from any entry eGFR, the cumulative incidence of ESRD was significantly greater in blacks. The age and gender-adjusted hazard ratios for ESRD and death prior to ESRD in blacks compared to non-blacks were 1.83 and 1.15, respectively. Increased survival free of ESRD was found in blacks 70 years and older with eGFR stage 4. The hazard ratio for the combined outcomes of ESRD or death was 1.31 in blacks as compared to non-blacks. Despite equivalent health insurance benefits, blacks with chronic kidney disease were at increased risk for ESRD and death prior to ESRD. Compared to non-blacks, blacks with chronic kidney disease were twice as likely to enter into ESRD as to die prior to ESRD.

Sleep apnea in early and advanced chronic kidney disease: Kaiser Permanente Southern California cohort.

BACKGROUND: Sleep apnea (SA) has been reported to be highly prevalent in the dialysis population. The reported rates of SA in dialysis are severalfold greater than the 2 to 4% estimated in the general population. This study sought to determine whether an association exists between SA and early stages of chronic kidney disease (CKD) where SA may represent an important comorbidity and potential risk factor in kidney disease. METHODS: Cross-sectional study of adults from an integrated health plan with documented serum creatinine levels in the period January 1, 2002, through December 31, 2004. SA diagnosis determined by International Classification of Diseases, ninth revision, coding for SA and Current Procedural Terminology coding for positive airway pressure devices. Kidney function was determined by the estimated glomerular filtration rate (eGFR). Logistic was regression used to estimate the relative risk for SA. RESULTS: The overall prevalence of SA was 2.5% in the study population that included subjects with normal renal function and those with CKD. The odds ratios (ORs) for SA by eGFRs of 75 to 89, 60 to 74, 45 to 59, 30 to 44, and 15 to 29 mL/min per 1.73 m(2), respectively, compared to normal kidney function, after adjustment for age, sex, and number of visits, were as follows: 1.22 (95% confidence interval [CI], 1.18 to 1.25); 1.32 (95% CI, 1.27 to 1.37); 1.42 (95% CI, 1.35 to 1.50); 1.37 (95% CI, 1.25 to 1.50); and 1.32 (95% CI, 1.13 to 1.55). The increased ORs for eGFRs > 45 mL/min per 1.73 m(2) were sustained even after controlling for diabetes, heart failure, and hypertension. CONCLUSION: This study demonstrated an increased risk of SA in patients with early CKD. Further evidence of a causal relationship should be sought in the hope that the detection and management of SA may improve the course of CKD.