Ann M. O’Hare

Rates of Treated and Untreated Kidney Failure in Older vs Younger Adults

CONTEXT Studies of kidney failure in older adults have focused on receipt of dialysis, which may underestimate the burden of disease if older people are less likely to receive treatment. OBJECTIVE To determine the extent to which age is associated with the likelihood of treatment of kidney failure. DESIGN, SETTING, AND PARTICIPANTS Community-based cohort study of 1,816,824 adults in Alberta, Canada, who had outpatient estimated glomerular filtration rate (eGFR) measured between May 1, 2002, and March 31, 2008, with a baseline eGFR of 15 mL/min/1.73 m2 or higher and who did not require renal replacement therapy at baseline. Age was categorized as 18 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84, and 85 or more years and eGFR as 90 or higher, 60 to 89, 45 to 59, 30 to 44, and 15 to 29 mL/min/1.73 m2. MAIN OUTCOME MEASURES Adjusted rates of treated kidney failure (receipt of dialysis or kidney transplantation), untreated kidney failure (progression to eGFR <15 mL/min/1.73 m2 without renal replacement therapy), and death. RESULTS During a median follow-up of 4.4 years, 97,451 (5.36%) died, 3295 (0.18%) developed kidney failure that was treated and 3116 (0.17%) developed kidney failure that went untreated. Within each eGFR stratum the rate of treated kidney failure was higher in younger compared with older people. For example, in the lowest eGFR stratum (15-29 mL/min/1.73 m2), adjusted rates of treated kidney failure were more than 10-fold higher among the youngest (18-44 years) compared with the oldest (≥85 years) groups (adjusted rate, 24.00 [95% CI, 14.78-38.97] vs 1.53 [95% CI, 0.59-3.99] per 1000 person-years, respectively; P < .001). Rates of untreated kidney failure were consistently higher at older ages. In the eGFR stratum of 15 to 29 mL/min/1.73 m2, adjusted rates of untreated kidney failure were more than 5-fold higher among the oldest (≥85 years), compared with the youngest (18-44 years) groups (adjusted rate, 19.95 [95% CI, 15.79-25.19] vs 3.53 [95% CI, 1.56-8.01] per 1000 person-years, respectively; P < .001). Rates of kidney failure overall (treated and untreated combined) demonstrated less variation across age groups; eg, the adjusted rate per 1000 person years for those with eGFR of 15-29 mL/min/1.73 m2 was 36.45 (95% CI, 24.46-54.32) among participants aged 18 to 44 years and 20.19 (95% CI, 15.27-26.69) among those aged 85 years or older (P = .01). CONCLUSION In Alberta, Canada, rates of untreated kidney failure are significantly higher in older compared with younger individuals.

Whether and When to Refer Patients for Predialysis AV Fistula Creation: Complex Decision Making in the Face of Uncertainty

Patients who initiate chronic dialysis with a functional arteriovenous (AV) fistula survive longer and experience fewer complications after initiation of dialysis than those who require a catheter. However, more than 80% of patients in this country begin chronic dialysis with a catheter rather than a fistula, either because they do not have a permanent access or their permanent access is not ready for use. Increasing rates of predialysis AV fistula placement is thus considered a priority area for predialysis care in this country. However, achievement of a functional AV fistula by the time of dialysis initiation is not always an easy proposition. We here outline the limitations of currently recommended approaches toward timing of AV fistula placement. We also highlight the potential complexity of patient and clinician decision making in this area. Particularly in the presence of advanced age and a high burden of comorbidity and disability, it is often uncertain whether patients will need, want, or benefit from chronic dialysis. Adding to this uncertainty, it is often not known whether, when, and after how many revisions an AV fistula will be sufficiently mature to support dialysis. We argue that it is important to acknowledge the complexity of medical decision making in this area and the limitations of currently available prognostic tools to guide such decision making. We conclude that initiation of dialysis with a catheter is appropriate for patients in whom the perceived harms of preemptive fistula placement outweigh the expected benefit.

Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults.

IMPORTANCE Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention. OBJECTIVE To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease. EXPOSURE Level of estimated glomerular filtration rate (eGFR) and proteinuria. MAIN OUTCOMES AND MEASURES Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25. RESULTS The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses. CONCLUSIONS AND RELEVANCE Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.

Systolic BP and Mortality in Older Adults with CKD

BACKGROUND AND OBJECTIVES Optimal BP targets for older adults with CKD are unclear. This study sought to determine whether a nonlinear relationship between BP and mortality-as described for the broader CKD population and for older adults in the general population-is present for older adults with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cohort of 21,015 adults age 65-105 years with a moderate or severe reduction in eGFR (<60 ml/min per 1.73 m(2)) were identified within the Kaiser Permanente Northwest Health Maintenance Organization population. The relationship between baseline systolic BP (SBP; ≤120, 121-130, 131-140, 141-150, >150 mmHg; referent, 131-140 mmHg) and all-cause mortality across age groups (65-70, 71-80, and >80 years) was examined; patients were followed for up to 11 years after cohort entry. RESULTS The median times at risk were 3.15 years, 3.53 years, and 2.76 years for adults age 65-70, 71-80, and >80 years, respectively. Mortality during follow-up was 19.6% for those age 65-70 years, 33.4% for those age 71-80 years, and 55.7% for those age >80 years. The relationship between SBP and mortality varied as a function of age. The risk of death was highest for patients with the lowest SBP in all age groups. Only among adults age 65-70 years was an SBP>140 mmHg associated with a higher risk of death compared with the referent category. Patterns of age modification of the relationship between SBP and mortality were consistent in all sensitivity analyses. CONCLUSIONS In a cohort of older adults, the relationship between SBP and mortality varied systematically with age. A relationship between higher SBP and mortality was present only for younger members of this cohort and not for those older than 70. These results raise the question of whether the relative benefits and harms of lowering BP to recommended targets for older adults with CKD may vary as a function of age.

Trends in the Timing and Clinical Context of Maintenance Dialysis Initiation

Whether secular trends in eGFR at dialysis initiation reflect changes in clinical presentation over time is unknown. We reviewed the medical records of a random sample of patients who initiated maintenance dialysis in the Department of Veterans Affairs (VA) in fiscal years 2000-2009 (n=1691) to characterize trends in clinical presentation in relation to eGFR at initiation. Between fiscal years 2000-2004 and 2005-2009, mean eGFR at initiation increased from 9.8±5.8 to 11.0±5.5 ml/min per 1.73 m(2) (P<0.001), the percentage of patients with an eGFR of 10-15 ml/min per 1.73 m(2) increased from 23.4% to 29.9% (P=0.002), and the percentage of patients with an eGFR>15 ml/min per 1.73 m(2) increased from 12.1% to 16.3% (P=0.01). The proportion of patients who were acutely ill at the time of initiation and the proportion of patients for whom the decision to initiate dialysis was based only on level of kidney function did not change over time. Frequencies of documented clinical signs and/or symptoms were similar during both time periods. The adjusted odds of initiating dialysis at an eGFR of 10-15 or >15 ml/min per 1.73 m(2) (versus <10 ml/min per 1.73 m(2)) during the later versus earlier time period were 1.43 (95% confidence interval [95% CI], 1.13 to 1.81) and 1.46 (95% CI, 1.09 to 1.97), respectively. In conclusion, trends in eGFR at dialysis initiation at VA medical centers do not seem to reflect changes in the clinical context in which dialysis is initiated.

Creatinine clearance, walking speed, and muscle atrophy: a cohort study.

BACKGROUND Chronic kidney disease is associated with malnutrition and inflammation. These processes may lead to loss of skeletal muscle and reduced physical performance. Associations of kidney function with muscle composition and longitudinal measures of physical performance are unknown. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS We evaluated 826 community-dwelling older adults enrolled in the Invecchiare in Chianti (InCHIANTI) Study who were free of baseline stroke or activities of daily living disability. PREDICTOR Baseline creatinine clearance (Clcr) based on 24-hour urine collection. OUTCOMES Cross-sectional and longitudinal trajectories of physical performance measured by 7-m usual gait speed, 400-m fast gait speed, and knee extension strength using isometric dynamometry. Calf muscle composition assessed by quantitative computed tomography. RESULTS Mean age of participants was 74 ± 7 (SD) years, with 183 having Clcr < 60 mL/min/1.73 m(2). After adjustment, each 10-mL/min/1.73 m(2) decrement in Clcr was associated with 0.01 (95% CI, 0.004-0.017) m/s slower 7-m usual walking speed and 0.008 (95% CI, 0.002-0.014) m/s slower 400-m walking speed. Each 10-mL/min/1.73 m(2) decrement in Clcr was associated with 28 (95% CI, 0.8-55) mm(2) lower muscle area and 0.15 (95% CI, 0.04-0.26) mg/cm(3) lower muscle density. After adjustment, lower Clcr was associated with slower mean 7-m (P=0.005) and 400-m (P=0.02) walk and knee extension strength (P=0.001) during the course of follow-up. During a mean follow-up of 7.1 ± 2.5 years, each 10-mL/min/1.73 m(2) lower baseline Clcr was associated with 0.024 (95% CI, 0.01-0.037) kg/y greater decline in knee strength. LIMITATIONS Single baseline measurement of Clcr and 3-year interval between follow-up visits may lead to nondifferential misclassification and attenuation of estimates. CONCLUSIONS Among older adults, lower Clcr is associated with muscle atrophy, reduced walking speed, and more rapid declines in lower-extremity strength over time.

Trends in Timing of Dialysis Initiation within Versus Outside the Department of Veterans Affairs

BACKGROUND AND OBJECTIVES The secular trend toward dialysis initiation at progressively higher levels of eGFR is not well understood. This study compared temporal trends in eGFR at dialysis initiation within versus outside the Department of Veterans Affairs (VA)-the largest non-fee-for-service health system in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study used linked data from the US Renal Data System, VA, and Medicare to compare temporal trends in eGFR at dialysis initiation between 2000 and 2009 (n=971,543). Veterans who initiated dialysis within the VA were compared with three groups who initiated dialysis outside the VA: (1) veterans whose dialysis was paid for by the VA, (2) veterans whose dialysis was not paid for by the VA, and (3) nonveterans. Logistic regression was used to estimate average predicted probabilities of dialysis initiation at an eGFR≥10 ml/min per 1.73 m(2). RESULTS The adjusted probability of starting dialysis at an eGFR≥10 ml/min per 1.73 m(2) increased over time for all groups but was lower for veterans who started dialysis within the VA (0.31; 95% confidence interval [95% CI], 0.30 to 0.32) than for those starting outside the VA, including veterans whose dialysis was (0.36; 95% CI, 0.35 to 0.38) and was not (0.40; 95% CI, 0.40 to 0.40) paid for by the VA and nonveterans (0.39; 95% CI, 0.39 to 0.39). Differences in eGFR at initiation within versus outside the VA were most pronounced among older patients (P for interaction <0.001) and those with a higher risk of 1-year mortality (P for interaction <0.001). CONCLUSIONS Temporal trends in eGFR at dialysis initiation within the VA mirrored those in the wider United States dialysis population, but eGFR at initiation was consistently lowest among those who initiated within the VA. Differences in eGFR at initiation within versus outside the VA were especially pronounced in older patients and those with higher 1-year mortality risk.

Utilization of Acute Care among Patients with ESRD Discharged Home from Skilled Nursing Facilities

BACKGROUND AND OBJECTIVES Older adults with ESRD often receive care in skilled nursing facilities (SNFs) after an acute hospitalization; however, little is known about acute care use after SNF discharge to home. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study used Medicare claims for North and South Carolina to identify patients with ESRD who were discharged home from a SNF between January 1, 2010 and August 31, 2011. Nursing Home Compare data were used to ascertain SNF characteristics. The primary outcome was time from SNF discharge to first acute care use (hospitalization or emergency department visit) within 30 days. Cox proportional hazards models were used to identify patient and facility characteristics associated with the outcome. RESULTS Among 1223 patients with ESRD discharged home from a SNF after an acute hospitalization, 531 (43%) had at least one rehospitalization or emergency department visit within 30 days. The median time to first acute care use was 37 days. Characteristics associated with a shorter time to acute care use were black race (hazard ratio [HR], 1.25; 95% confidence interval [95% CI], 1.04 to 1.51), dual Medicare-Medicaid coverage (HR, 1.24; 95% CI, 1.03 to 1.50), higher Charlson comorbidity score (HR, 1.07; 95% CI, 1.01 to 1.12), number of hospitalizations during the 90 days before SNF admission (HR, 1.12; 95% CI, 1.03 to 1.22), and index hospital discharge diagnoses of cellulitis, abscess, and/or skin ulcer (HR, 2.59; 95% CI, 1.36 to 4.45). Home health use after SNF discharge was associated with a lower rate of acute care use (HR, 0.72; 95% CI, 0.59 to 0.87). There were no statistically significant associations between SNF characteristics and time to first acute care use. CONCLUSIONS Almost one in every two older adults with ESRD discharged home after a post-acute SNF stay used acute care services within 30 days of discharge. Strategies to reduce acute care utilization in these patients are needed.

Advance Directives and End-of-Life Care among Nursing Home Residents Receiving Maintenance Dialysis

BACKGROUND AND OBJECTIVES Little is known about the relation between the content of advance directives and downstream treatment decisions among patients receiving maintenance dialysis. In this study, we determined the prevalence of advance directives specifying treatment limitations and/or surrogate decision-makers in the last year of life and their association with end-of-life care among nursing home residents. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using national data from 2006 to 2007, we compared the content of advance directives among 30,716 nursing home residents receiving dialysis to 30,825 nursing home residents with other serious illnesses during the year before death. Among patients receiving dialysis, we linked the content of advance directives to Medicare claims to ascertain site of death and treatment intensity in the last month of life. RESULTS In the last year of life, 36% of nursing home residents receiving dialysis had a treatment-limiting directive, 22% had a surrogate decision-maker, and 13% had both in adjusted analyses. These estimates were 13%-27%, 5%-11%, and 6%-13% lower, respectively, than for decedents with other serious illnesses. For patients receiving dialysis who had both a treatment-limiting directive and surrogate decision-maker, the adjusted frequency of hospitalization, intensive care unit admission, intensive procedures, and inpatient death were lower by 13%, 17%, 13%, and 14%, respectively, and hospice use and dialysis discontinuation were 5% and 7% higher compared with patients receiving dialysis lacking both components. CONCLUSIONS Among nursing home residents receiving dialysis, treatment-limiting directives and surrogates were associated with fewer intensive interventions and inpatient deaths, but were in place much less often than for nursing home residents with other serious illnesses.

Association Between Hospice Length of Stay, Health Care Utilization, and Medicare Costs at the End of Life Among Patients Who Received Maintenance Hemodialysis

Importance Patients with end-stage renal disease are less likely to use hospice services than other patients with advanced chronic illness. Little is known about the timing of hospice referral in this population and its association with health care utilization and costs. Objective To examine the association between hospice length of stay and health care utilization and costs at the end of life among Medicare beneficiaries who had received maintenance hemodialysis. Design, Setting, and Participants This cross-sectional observational study was conducted via the United States Renal Data System registry. Participants were all 770 191 hemodialysis patients in the registry who were enrolled in fee-for-service Medicare and died between January 1, 2000, and December 31, 2014. The dates of analysis were April 2016 to December 2017. Main Outcomes and Measures Hospital admission, intensive care unit (ICU) admission, and receipt of an intensive procedure during the last month of life; death in the hospital; and costs to the Medicare program in the last week of life. Results Among 770 191 patients, the mean (SD) age was 74.8 (11.0) years, and 53.7% were male. Twenty percent of cohort members were receiving hospice services when they died. Of these, 41.5% received hospice for 3 days or fewer. In adjusted analyses, compared with patients who did not receive hospice, those enrolled in hospice for 3 days or fewer were less likely to die in the hospital (13.5% vs 55.1%; P < .001) or to undergo an intensive procedure in the last month of life (17.7% vs 31.6%; P < .001) but had higher rates of hospitalization (83.6% vs 74.4%; P < .001) and ICU admission (54.0% vs 51.0%; P < .001) and similar Medicare costs in the last week of life (