Background

Prior studies have shown the association of low serum magnesium levels with adverse health outcomes in patients undergoing hemodialysis. There is a paucity of such studies in patients undergoing peritoneal dialysis (PD).

Study design

Cohort study.

Setting & participants

10,692 patients treated with PD from January 1, 2007, through December 31, 2011, in facilities operated by a single large dialysis organization in the United States.

Predictor

Baseline serum magnesium levels, examined as 5 categories (<1.8, 1.8-<2.0, 2.0-<2.2 [reference], 2.2-<2.4, and ≥2.4mg/dL).

Outcomes

Time to first hospitalization and time to death using competing-risks regression models.

Results

The distribution of baseline serum magnesium levels in the cohort was <1.8mg/dL, 1,928 (18%); 1.8 to <2.0mg/dL, 2,204 (21%); 2.0 to <2.2mg/dL, 2,765 (26%); 2.2 to <2.4mg/dL, 1,765 (16%); and ≥2.4mg/dL, 2,030 (19%). Of 10,692 patients, 6,465 (60%) were hospitalized at least once and 1,392 (13%) died during follow-up (median, 13; IQR, 7-23 months). Baseline serum magnesium level < 1.8mg/dL was associated with higher risk for hospitalization and all-cause mortality after adjustment for demographic and clinical characteristics (adjusted HRs of 1.23 [95% CI, 1.14-1.33] and 1.21 [95% CI, 1.03-1.42], respectively). The higher risk for hospitalization persisted upon adjustment for laboratory variables, whereas that for all-cause mortality was attenuated to a nonsignificant level. The greatest risk for hospitalization was in patients with low serum albumin levels (<3.5g/dL; P for interaction < 0.001).

Limitations

Possibility of residual confounding by unmeasured variables cannot be excluded.

Conclusions

Lower serum magnesium levels may be associated with higher risk for hospitalization in incident PD patients, particularly those with hypoalbuminemia. Additional studies are needed to confirm these findings and investigate whether correction of hypomagnesemia reduces these risks.

Objectives

To compare the mortality of elderly adults with end-stage renal disease (ESRD) treated with home hemodialysis (HD) with that of those receiving a kidney transplant (KTx).

Design

Prospective cohort.

Setting

Pertinent data for the two groups were obtained from electronic medical records from a large dialysis provider and the U.S. Renal Data System.

Participants

Using data from elderly adults (aged ≥65) who started home HD and underwent KTx in the US between 2007 and 2011, a 1:1 propensity score (PS)-matched cohort of 960 elderly adults was created, and the association between treatment modality and all-cause mortality was examined using Cox proportional hazards and competing risk regression survival models using modality failure as a competing event.

Measurements

Modality of renal replacement therapy.

Results

The baseline mean age ± standard deviation of the PS-matched individuals undergoing home HD was 71 ± 6, and that of KTx recipients was 71 ± 5, 69% of both groups were male, 81% of those undergoing home HD and 79% of KTx recipients were white, and 11% and 12%, respectively, were African American. Median follow-up time was 205 days (interquartile range (IQR) 78-364 days) for those undergoing home HD and 795 days (IQR 366-1,221 days) for KTx recipients. There were 97 deaths (20%, 253/1,000 patient-years, 95% confidence interval (CI) = 207-309/1,000 patient-years) in the home HD group and 48 deaths (10%, 45/1,000 patient-years, 95% CI = 34-60/1,000 patient-years) in the KTx group. Elderly adults undergoing home HD had a risk of mortality that was almost five times as high as that of KTx recipients (hazard ratio = 4.74, 95% CI = 3.25-6.91). Similar results were seen in competing risk regression analyses (subhazard ratio = 4.71, 95% CI = 3.27-6.79). Results were consistent across different types of kidney donors and subgroups divided according to various recipient characteristics.

Conclusion

Elderly adults with ESRD who receive a KTx have greater survival than those who undergo home HD. Further studies are needed to assess whether KTx receipt is associated with other benefits such as better quality of life and lower hospitalization rates.

BACKGROUND AND OBJECTIVES:Patients undergoing hemodialysis with a frequency other than thrice weekly are not included in current clinical performance metrics for dialysis adequacy. The weekly standard Kt/Vurea incorporates treatment frequency, but there are limited data on its association with clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We used multivariable regression to examine the association of dialysis standard Kt/Vurea with BP and metabolic control (serum potassium, calcium, bicarbonate, and phosphorus) in patients incidental to dialysis treated with home (n=2373) or in-center hemodialysis (n=109,273). We further used Cox survival models to examine the association of dialysis standard Kt/Vurea with mortality, hospitalization, and among patients on home hemodialysis, transfer to in-center hemodialysis. RESULTS:After adjustment for potential confounders, patients with dialysis standard Kt/Vurea <2.1 had higher BPs compared with patients with standard Kt/Vurea 2.1 to <2.3 (3.4 mm Hg higher [P<0.001] for home hemodialysis and 0.9 mm Hg higher [P<0.001] for in-center hemodialysis). There were no clinically meaningful associations between dialysis standard Kt/Vurea and markers of metabolic control, irrespective of dialysis modality. There was no association between dialysis standard Kt/Vurea and risk for mortality, hospitalization, or transfer to in-center hemodialysis among patients undergoing home hemodialysis. Among patients on in-center hemodialysis, dialysis standard Kt/Vurea <2.1 was associated with higher risk (adjusted hazard ratio, 1.11; 95% confidence interval, 1.07 to 1.14) and standard Kt/Vurea ≥2.3 was associated with lower risk (adjusted hazard ratio, 0.97; 95% confidence interval, 0.94 to 0.99) for death compared with standard Kt/Vurea 2.1 to <2.3. Additional analyses limited to patients with available data on residual kidney function showed similar relationships of dialysis and total (dialysis plus kidney) standard Kt/Vurea with outcomes. CONCLUSIONS:Current targets for standard Kt/Vurea have limited utility in identifying individuals at increased risk for adverse clinical outcomes for those undergoing home hemodialysis but may enhance risk stratification for in-center hemodialysis.

Background

Among the general population, low circulating testosterone levels are associated with higher risk of cardiovascular disease and death. While testosterone deficiency is common in dialysis patients, studies of testosterone and mortality in this population are ambiguous and overlapping. We hypothesized that lower testosterone levels are associated with higher mortality in male dialysis patients.

Methods

We examined a nationally representative cohort of male dialysis patients from a large US dialysis organization who underwent one or more total testosterone measurements from 1/2007 to 12/2011. The association between total testosterone categorized as quartiles and all-cause mortality was studied using Cox models adjusted for expanded case-mix and laboratory covariates. We also examined total testosterone as a continuous predictor of all-cause mortality using restricted cubic splines.

Results

Among 624 male dialysis patients, 51% of patients demonstrated testosterone deficiency (total testosterone <300 ng/dL); median (IQR) total testosterone levels were 297 (190-424) ng/mL. In expanded case-mix + laboratory adjusted Cox analyses, we observed a graded association between lower testosterone levels and higher mortality risk (ref: quartile 3): adjusted hazard ratios (95% CI) 2.32 (1.33-4.06), 1.80 (0.99-3.28), and 0.68 (0.32-1.42) for Quartiles 1, 2, and 4, respectively. In adjusted spline analyses, the lower testosterone-higher mortality risk association declined with higher testosterone levels until the value reached a threshold of 400 ng/dL above which risk plateaued.

Conclusion

Lower testosterone levels were independently associated with higher mortality risk in male dialysis patients. Further studies are needed to determine underlying mechanisms, and whether testosterone replacement ameliorates death risk in this population.

BACKGROUND:The prevalence of severe obesity, often considered a contraindication to peritoneal dialysis (PD), has increased over time. However, mortality has decreased more rapidly in the PD population than the hemodialysis (HD) population in the United States. The association between obesity and clinical outcomes among patients with end-stage kidney disease remains unclear in the current era. STUDY DESIGN:Historical cohort study. SETTING & PARTICIPANTS:15,573 incident PD patients from a large US dialysis organization (2007-2011). PREDICTOR:Body mass index (BMI). OUTCOMES:Modality longevity, residual renal creatinine clearance, peritonitis, and survival. RESULTS:Higher BMI was significantly associated with shorter time to transfer to HD therapy (P for trend < 0.001), longer time to kidney transplantation (P for trend < 0.001), and, with borderline significance, more frequent peritonitis-related hospitalization (P for trend = 0.05). Compared with lean patients, obese patients had faster declines in residual kidney function (P for trend < 0.001) and consistently achieved lower total Kt/V over time (P for trend < 0.001) despite greater increases in dialysis Kt/V (P for trend < 0.001). There was a U-shaped association between BMI and mortality, with the greatest survival associated with the BMI range of 30 to < 35kg/m2 in the case-mix adjusted model. Compared with matched HD patients, PD patients had lower mortality in the BMI categories of < 25 and 25 to < 35kg/m2 and had equivalent survival in the BMI category ≥ 35kg/m2 (P for interaction = 0.001 [vs < 25 kg/m2]). This attenuation in survival difference among patients with severe obesity was observed only in patients with diabetes, but not those without diabetes. LIMITATIONS:Inability to evaluate causal associations. Potential indication bias. CONCLUSIONS:Whereas obese PD patients had higher risk for complications than nonobese PD patients, their survival was no worse than matched HD patients.

Background

End stage kidney disease and hemodialysis dependence are associated with impairments in health-related quality of life (HRQOL), which may be related to vascular access (VA). Few HRQOL measures are VA-specific and none differentiate HRQOL impact by VA type. We developed a VA-targeted HRQOL measure to distinguish the impact of fistulas, grafts and catheters.

Methods

We created an initial item pool based on literature review and then conducted focus groups at 4 US sites with 37 adults and interviews with nine dialysis clinicians about VA's impact on HRQOL. We then drafted the Hemodialysis Access-Related Quality of Life (HARQ) measure and cognitively tested it with 17 hemodialysis patients. Focus group and cognitive interview participants were diverse in age, gender, years on dialysis, and VA.

Results

We identified six domains for the HARQ: symptoms, physical functioning, emotional impacts, social and role functioning, sleep, and care-related burdens. Cognitive interviews indicated that items were easily understood and supported content validity. Attributing HRQOL impact to VA as opposed to other hemodialysis burden was challenging for some items. Some items were dropped that were considered redundant by patients, limitations while dressing was added, and reference to VA-specific impact was included for each item. The average Flesch-Kincaid reading grade level for the revised 47-item HARQ was 5.3.

Conclusions

The HARQ features VA-specific content not addressed in other HRQOL measures, making it ideal for comparisons of different VA types and new VA technologies. The psychometric properties of the HARQ will be evaluated in future research.

Uncorrected serum calcium concentration is the first mineral metabolism metric planned for use as a quality measure in the United States ESRD population. Few studies in patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) have assessed the association of uncorrected serum calcium concentration with clinical outcomes. We obtained data from 129,076 patients on dialysis (PD, 10,066; HD, 119,010) treated in DaVita, Inc. facilities between July 1, 2001, and June 30, 2006. After adjustment for potential confounders, uncorrected serum calcium <8.5 and ≥10.2 mg/dl were associated with excess mortality in patients on PD or HD (comparison group uncorrected calcium 9.0 to <9.5 mg/dl). Additional adjustment for serum albumin concentration substantially attenuated the all-cause mortality hazard ratios (HRs) associated with uncorrected calcium <8.5 mg/dl (HR, 1.29; 95% confidence interval [95% CI], 1.16 to 1.44 for PD; HR, 1.17; 95% CI, 1.13 to 1.20 for HD) and amplified the HRs associated with calcium ≥10.2 mg/dl (HR, 1.65; 95% CI, 1.42 to 1.91 for PD; HR, 1.59; 95% CI, 1.53 to 1.65 for HD). Albumin-corrected calcium ≥10.2 mg/dl and serum phosphorus ≥6.4 mg/dl were also associated with increased risk for death, irrespective of dialysis modality. In summary, in a large nationally representative cohort of patients on dialysis, abnormalities in markers of mineral metabolism, particularly high concentrations of serum calcium and phosphorus, were associated with increased mortality risk. Additional studies are needed to investigate whether control of hypercalcemia and hyperphosphatemia in patients undergoing dialysis results in improved clinical outcomes.

Context

Neither uncorrected- nor albumin-corrected total calcium reliably predict ionized calcium in patients with end-stage renal disease. However, little is known about the consequences of inaccurate assessment of calcium concentration using total calcium.

Objective

We hypothesized that hidden hypercalcemia (ie, elevated ionized calcium with normal total calcium) and apparent hypercalcemia (ie, elevated ionized calcium with elevated total calcium) are both associated with increased mortality risk.

Design, setting, and patients

We identified 874 incident hemodialysis patients with measured serum ionized calcium, total calcium, albumin, phosphorus, and bicarbonate from October 2007 to December 2011, using data from a large dialysis organization in the United States.

Exposures

Serum concentrations of ionized calcium and total calcium were measured.

Main outcome measure

The primary outcome was all-cause mortality.

Results

There was only fair interindex agreement with calcium status between ionized calcium and uncorrected or corrected total calcium (κ = 0.32 and 0.27, respectively). Among patients with high ionized calcium (>1.32 mmol/liter), 88% and 70% patients were incorrectly categorized as being normocalcemic using uncorrected and corrected total calcium, respectively, and were thus considered to have "hidden hypercalcemia." Compared to patients with low-normal ionized calcium (1.16-1.24 mmol/liter), patients with high ionized calcium had a significantly higher mortality risk (adjusted hazard ratio, 1.77; 95% confidence interval, 1.13-2.75). Furthermore, compared to patients with normocalcemia (ionized calcium 1.16-1.32 mmol/liter), those with hidden hypercalcemia by uncorrected and corrected total calcium also had a higher risk for death (adjusted hazard ratio 1.75 [95% confidence interval 1.11-2.75] and 1.80 [95% confidence interval, 1.11-2.90], respectively).

Conclusion

The majority of end-stage renal disease patients with elevated ionized calcium are incorrectly categorized as normocalcemic using conventional total calcium measurements; these patients have a higher death risk. Future research is needed to establish whether reducing ionized calcium concentrations in these patients improves clinical outcomes.

Conventional albumin-corrected calcium is inaccurate in predicting ionized calcium, and hidden hypercalcemia, characterized as high ionized calcium with normal total calcium, is associated with higher mortality in hemodialysis patients. By using a national cohort of hemodialysis patients in the Unites States, a novel laboratory-specific prediction equation composed of total calcium, albumin, and phosphorus was derived from 242 patients in the South Atlantic division (adjusted R² = 0.80 versus 0.71 for the conventional equation) and then validated among 566 patients in the other divisions (adjusted R² = 0.79 versus 0.68 for the conventional equation). Compared with the conventional equation, the novel equation showed a greater correlation with intact parathyroid hormone. Its relative performance against the conventional equation was consistent across subgroups based on medications related to calcium metabolism. The novel equation also had a higher sensitivity (57% versus 34%) and an equivalent specificity (99% versus 100%) against ionized hypercalcemia at a cut-off value of 10.2 mg/dL. Sensitivity and specificity at 9.4 mg/dL was 94% and 76% (versus 87% and 82% for the conventional equation), respectively. A survival analysis in 87,779 incident hemodialysis patients showed that among patients who were categorized as having a high-normal calcium status (ie, >9.4 to 10.2 mg/dL) by the conventional equation, there appeared a trend toward higher adjusted mortality risk across higher calcium status defined according to the novel equation. Meanwhile, the mortality risk was consistent across calcium strata defined according to the conventional equation within the categories defined by the novel equation. In conclusion, in comparison to the conventional equation, a novel laboratory-specific correction equation derived for correction of total calcium performs significantly better in ascertaining hidden hypercalcemia in hemodialysis patients, and aids in identifying patients at higher risk for mortality. © 2016 American Society for Bone and Mineral Research.