Matthew B. Rivara

Sex Differences in Hospitalizations with Maintenance Hemodialysis

Hospitalization is a major source of morbidity among patients with ESRD undergoing maintenance hemodialysis and is a significant contributor to health care costs. To identify subgroups at the highest risk of hospitalization, we analyzed by sex, age, and race, adjusting for demographic and clinical characteristics, the hospitalization rates, and 30-day readmissions for 333,756 hospitalizations among 111,653 patients undergoing maintenance hemodialysis in facilities operated by a large dialysis organization in the United States (2007-2011). The overall hospitalization rate was 1.85 hospitalizations per person-year and was much higher among women than among men (2.08 versus 1.68 hospitalizations per year for women versus men, P<0.001). Age group-specific hospitalization rates were consistently higher for women than for men of the same race, and the differences were greatest in younger age groups (for example, women aged 18-34 years and ≥75 years had 54% [95% confidence interval, 42% to 67%] and 14% [95% confidence interval, 11% to 18%] higher hospitalization rates, respectively, than did men of respective ages). Women also had substantially higher risk for 30-day readmission, with the largest differences at younger ages. Women had a significantly lower serum albumin level than men, and stratification by serum albumin level attenuated sex differences in the age group-specific hospitalization and 30-day readmission rates. These findings suggest that women undergoing maintenance hemodialysis have substantially higher risks for hospitalization and 30-day readmission than men. In this cohort, the sex differences were greatest in the younger age groups and were attenuated by accounting for differences in health status reflected by serum albumin level.

Uncorrected and Albumin-Corrected Calcium, Phosphorus, and Mortality in Patients Undergoing Maintenance Dialysis

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.

The changing landscape of home dialysis in the United States.

Purpose of reviewTo discuss the changing landscape of home dialysis in the United States over the past decade, including recent research on clinical outcomes in patient undergoing peritoneal dialysis and home hemodialysis, and to describe the impact of recent payment reforms for patients with end-stage renal disease. Recent findingsAccumulating evidence supports the conclusion that clinical outcomes for patients treated with peritoneal dialysis or home hemodialysis are as good as or better than for patients treated with conventional in-center hemodialysis. The recent implementation of the Medicare-expanded prospective payment system for the care of end-stage renal disease patients has resulted in substantial growth in the utilization of peritoneal dialysis in the United States. Utilization of home hemodialysis has also grown, but the contribution of the expanded prospective payment system to this growth is less certain. SummaryHome dialysis, including peritoneal dialysis and home hemodialysis, represents an important alternative to in-center hemodialysis that is effective and patient-centered. Over the coming decade, the growth in the number of end-stage renal disease patient treated with home dialysis modalities should prompt further comparative and cost-effectiveness research, increased attention to racial and ethnic disparities, and investments in home dialysis education for both patients and providers. Video abstracthttp://links.lww.com/CONH/A13

Initiation of dialysis should be timely: neither early nor late.

Over the last decade, individuals with end‐stage renal disease (ESRD) in the United States are starting maintenance dialysis therapy at progressively higher estimated glomerular filtration rate (eGFR). Moreover, several observational studies have demonstrated an association of a higher risk of death with higher serum creatinine‐based estimates of GFR at the time of initiation of dialysis. In contrast, studies in which renal function has been measured by timed urinary collection show either a lower risk of death or no significant association with higher GFR at the time of initiation of dialysis. There are numerous potential sources of bias in such observational studies, particularly in those that use serum creatinine‐based eGFR. The only randomized controlled clinical trial to have examined this question did not demonstrate either benefit or harm with initiation of dialysis at higher level of renal function. Thus, the data to date suggest that eGFR should not be the sole consideration when assessing the need for initiating maintenance dialysis in patients with advanced chronic kidney disease. Given the high societal costs of starting renal replacement therapy earlier in the course of the disease, these considerations also suggest that dialysis can be safely be postponed in otherwise asymptomatic individuals with advanced chronic kidney disease. By the same token, dialysis should not be denied to individuals who could clearly benefit from renal replacement therapy simply because the GFR is too high (viz., volume overload, refractory hyperkalemia). Finally, there is a compelling need to reexamine the symptoms that could be attributed to uremia and clearly improve upon initiation of dialysis to better guide clinical decision‐making.

A wearable artificial kidney for patients with end-stage renal disease

BACKGROUND Stationary hemodialysis machines hinder mobility and limit activities of daily life during dialysis treatments. New hemodialysis technologies are needed to improve patient autonomy and enhance quality of life. METHODS We conducted a FDA-approved human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine, based on dialysate-regenerating sorbent technology. We aimed to determine the efficacy of the wearable artificial kidney in achieving solute, electrolyte, and volume homeostasis in up to 10 subjects over 24 hours. RESULTS During the study, all subjects remained hemodynamically stable, and there were no serious adverse events. Serum electrolytes and hemoglobin remained stable over the treatment period for all subjects. Fluid removal was consistent with prescribed ultrafiltration rates. Mean blood flow was 42 ± 24 ml/min, and mean dialysate flow was 43 ± 20 ml/min. Mean urea, creatinine, and phosphorus clearances over 24 hours were 17 ± 10, 16 ± 8, and 15 ± 9 ml/min, respectively. Mean β2-microglobulin clearance was 5 ± 4 ml/min. Of 7 enrolled subjects, 5 completed the planned 24 hours of study treatment. The trial was stopped after the seventh subject due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows. CONCLUSION Treatment with the wearable artificial kidney was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis. These results serve as proof of concept that, after redesign to overcome observed technical problems, a wearable artificial kidney can be developed as a viable novel alternative dialysis technology. TRIAL REGISTRATION ClinicalTrials.gov NCT02280005. FUNDING The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.

Racial and Ethnic Disparities in Use of and Outcomes with Home Dialysis in the United States

Home dialysis, which comprises peritoneal dialysis (PD) or home hemodialysis (home HD), offers patients with ESRD greater flexibility and independence. Although ESRD disproportionately affects racial/ethnic minorities, data on disparities in use and outcomes with home dialysis are sparse. We analyzed data of patients who initiated maintenance dialysis between 2007 and 2011 and were admitted to any of 2217 dialysis facilities in 43 states operated by a single large dialysis organization, with follow-up through December 31, 2011 (n =: 162,050, of which 17,791 underwent PD and 2536 underwent home HD for ≥91 days). Every racial/ethnic minority group was significantly less likely to be treated with home dialysis than whites. Among individuals treated with in-center HD or PD, racial/ethnic minorities had a lower risk for death than whites; among individuals undergoing home HD, only blacks had a significantly lower death risk than whites. Blacks undergoing PD or home HD had a higher risk for transfer to in-center HD than their white counterparts, whereas Asians or others undergoing PD had a lower risk than whites undergoing PD. Blacks irrespective of dialysis modality, Hispanics undergoing PD or in-center HD, and Asians and other racial groups undergoing in-center HD were significantly less likely than white counterparts to receive a kidney transplant. In conclusion, there are racial/ethnic disparities in use of and outcomes with home dialysis in the United States. Disparities in kidney transplantation evident for blacks and Hispanics undergoing home dialysis are similar to those with in-center HD. Future studies should identify modifiable causes for these disparities.

Extended-hours hemodialysis is associated with lower mortality risk in patients with end-stage renal disease.

Extended-hours hemodialysis offers substantially longer treatment time compared to conventional hemodialysis schedules and is associated with improved fluid and electrolyte control and favorable cardiac remodeling. However, whether extended-hours hemodialysis improves survival remains unclear. Therefore, we determined the association between extended-hours compared to conventional hemodialysis and the risk of all-cause mortality in a nationally representative cohort of patients initiating maintenance dialysis in the United States from 2007 to 2011. Survival analyses using causal inference modeling with marginal structural models were performed to compare mortality risk among 1206 individuals undergoing thrice weekly extended-hours hemodialysis or 111,707 patients receiving conventional hemodialysis treatments. The average treatment time per session for extended-hours hemodialysis was 399 minutes compared to 211 minutes for conventional therapy. The crude mortality rate with extended-hours hemodialysis was 6.4 deaths per 100 patient-years compared with 14.7 deaths per 100 patient-years for conventional hemodialysis. In the primary analysis, patients treated with extended-hours hemodialysis had a 33% lower adjusted risk of death compared to those who were treated with a conventional regimen (95% confidence interval: 7% to 51%). Additional analyses accounting for analytical assumptions regarding exposure and outcome, facility-level confounders, and prior modality history were similar. Thus, in this large nationally representative cohort, treatment with extended-hours hemodialysis was associated with a lower risk for mortality compared to treatment with conventional in-center therapy. Adequately powered randomized clinical trials comparing extended-hours to conventional hemodialysis are required to confirm these findings.

Changes in Symptom Burden and Physical Performance with Initiation of Dialysis in Patients with Chronic Kidney Disease

hypocalcemic state may be more prolonged in some patients. Congestive heart failure is a rare complication of chronic hypocalcemia, and has been previously described; most adult cases were secondary to either idiopathic or surgical hypoparathyroidism. Despite improving clinical status, PTX could be associated with myocardial dysfunction, as indicated by elevated NT-proBNP, mainly in the hypocalcemic patients. In such conditions, a significant decrease in serum calcium would lead to myocardial dysfunction and decrease in blood pressure, reflecting more cardiovascular morbidity. This information should be taken into account mainly in patients with a history of cardiac disease who are to be submitted to PTX.

Timing of Dialysis Initiation: What Has Changed Since IDEAL?

The optimal timing of initiation of maintenance dialysis in patients with end-stage renal disease currently is unknown. This transition period is one of exceptionally high vulnerability for patients; annual mortality rates in stage 5 chronic kidney disease through the first year of maintenance dialysis exceed 20%. The results of the Initiating Dialysis Early and Late (IDEAL) study, a randomized trial that tested the impact of dialysis initiation at two different levels of kidney function on outcomes, showed no significant difference in survival or other patient-centered outcomes between treatment groups. These data have challenged the established paradigm of using estimates of glomerular filtration as the primary guide for initiation of maintenance dialysis and illustrate the compelling need for research to optimize the high-risk transition period from chronic kidney disease to end-stage renal disease. This article reviews the findings of the IDEAL study and summarizes the evolution of research findings, updated clinical practice guidelines, and trends in dialysis initiation practices in the United States in the 6 years since the publication of the results from IDEAL. Complementary strategies to the use of estimated glomerular filtration rate to optimally time the initiation of maintenance dialysis and potentially improve patient-centered outcomes also are considered.

Diurnal and Long-term Variation in Plasma Concentrations and Renal Clearances of Circulating Markers of Kidney Proximal Tubular Secretion

BACKGROUND The renal proximal tubule is essential for removing organic solutes and exogenous medications from the circulation. We evaluated diurnal, prandial, and long-term biological variation of 4 candidate endogenous markers of proximal tubular secretion. METHODS We used LC-MS to measure plasma and urine concentrations of hippurate (HA), cinnamoylglycine (CMG), indoxyl sulfate (IS), and p-cresol sulfate (PCS) in 25 healthy adults. We measured plasma concentrations of secreted solutes at 13 time points over a 24-h period, and again after 2 weeks and 14 weeks of follow-up. We further measured 24-h renal clearances of secreted solutes at baseline, 2 weeks, and 14 weeks. RESULTS Plasma concentrations of secreted solutes varied over the 24-h baseline period. Diurnal variation was greatest for HA, followed by CMG, IS, and PCS. Plasma concentrations of HA (P = 0.002) and IS (P = 0.02), but not CMG and PCS, increased significantly following meals. Long-term intraindividual biological variation (CVI) in plasma concentrations of secreted solutes over 14 weeks varied from 21.8% for IS to 67.3% for PCS, and exceeded that for plasma creatinine (CVI, 7.1%). Variation in 24-h renal clearances was similar among the secreted solutes [intraindividual variation (CVA+I), 33.6%-47.3%] and was lower using pooled plasma samples from each study visit. CONCLUSIONS Plasma concentrations of HA, CMG, IS, and PCS fluctuate within individuals throughout the day and over weeks. Renal clearances of these secreted solutes, which serve as estimates of renal proximal tubule secretion, are also subject to intraindividual biological variation that can be improved by additional plasma measurements.