Background

Proteinuria in human immunodeficiency virus (HIV)-infected individuals has been associated with poorer outcomes. We examined risk factors associated with the development of proteinuria in a national registry of HIV-infected veterans.

Methods

A total of 21,129 HIV-infected veterans of black and white race without preexisting kidney disease were receiving health care in the Veterans' Health Administration (VHA) medical system between 1997 and 2011. Using the VHA electronic record system, we identified kidney-related risk factors (hypertension, diabetes, and cardiovascular disease) and HIV-related risk factors (CD4 lymphocyte count, HIV RNA level, hepatitis C virus, and hepatitis B virus) for developing proteinuria. Proteinuria was defined by 2 consecutive dipstick measures of 1 or higher. The Fine-Gray competing risk model was used to estimate association between clinical variables and incident proteinuria, while accounting for intervening mortality events.

Results

During follow-up (median = 5.3 years), 7031 patients developed proteinuria. Overall, black race compared with white race was associated with a higher risk of proteinuria {hazard ratio [95% confidence interval (CI)] = 1.51 [1.43 to 1.59]}, but the association was stronger at younger ages (P interaction <0.001). Age-stratified risk of proteinuria for blacks relative to whites was greatest among veterans <30 years [2.19 (1.66 to 2.89)] and the risk diminished with increasing age [1.14 (0.97 to 1.34) for >60 years]. We found the race difference to be stronger for the outcome of 2 or higher proteinuria [2.13 (1.89 to 2.39)]. Both HIV-related and traditional risk factors were also associated with incident proteinuria (P < 0.05).

Conclusions

Compared with whites, risk of proteinuria was higher in black veterans with HIV infection, particularly at younger ages. In both races, HIV- and kidney-related risk factors were associated with higher proteinuria risk.

Over the past decade, abiraterone and enzalutamide have largely replaced ketoconazole as oral treatments for castration-resistant prostate cancer (CRPC). We investigated the differential adoption of abiraterone and enzalutamide across facilities in a national healthcare system to understand the impact a facility has on the receipt of these novel therapies. Using data from the VA Corporate Data Warehouse, we identified a cohort of men with CRPC who received the most common first-line therapies: abiraterone, enzalutamide, docetaxel, or ketoconazole between 2010 and 2017. We described variability in the adoption of abiraterone and enzalutamide across facilities by time period (2010-2013 or 2014-2017). We categorized facilities depending on the timing of adoption of abiraterone and enzalutamide relative to other facilities and described facility characteristics associated with early and late adoption. We identified 4998 men treated with ketoconazole, docetaxel, abiraterone, or enzalutamide as first-line CRPC therapy between 2010 and 2017 at 125 national facilities. When limiting the cohort to oral therapies, most patients treated earlier in the study period (2010-2013) received ketoconazole. A dramatic shift was seen by the second half of the study period (2014-2017) with most men treated with first-line abiraterone (61%). Despite this shift and a new standard of care, some facilities persisted in the widespread use of ketoconazole in the later period, so-called late adopting facilities. After multivariable adjustment, patients who received treatment at a late adopting facility were more likely receiving care at a lower complexity, rural facility, with less urology and hematology/oncology workforce (all p < 0.01). Many facilities persisted in their use of ketoconazole as first-line CRPC therapy, even when other facilities had adopted the new standard of care abiraterone and enzalutamide. Further work is needed to identify the effect of this late adoption on outcomes important to patients.

Objective

Many societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults.

Research design and methods

Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999-2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if <1.4 mg/dL for women and <1.5 mg/dL for men) and eGFR categories: likely safe, ≥45 mL/min/1.73 m(2); contraindicated, <30 mL/min/1.73 m(2); and indeterminate, 30-44 mL/min/1.73 m(2)). Different eGFR equations were used: four-variable MDRD, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine (CKD-EPIcr), and CKD-EPI cystatin C, as well as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl). Diabetes was defined by self-report or A1C ≥6.5% (48 mmol/mol). We used logistic regression to identify populations for whom metformin was likely safe adjusted for age, race/ethnicity, and sex. Results were weighted to the U.S. adult population.

Results

Among adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m(2) was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4-151.5] vs. women) and non-Hispanic Blacks (aOR vs. whites 14.8 [4.27-51.7]). No individuals with sCr below conventional cutoffs had an MDRD eGFR <30 mL/min/1.73 m(2). All estimating equations expanded the population of individuals for whom metformin is likely safe, ranging from 86,900 (CKD-EPIcr) to 834,800 (CG). All equations identified larger populations with eGFR 30-44 mL/min/1.73 m(2), for whom metformin safety is indeterminate, ranging from 784,700 (CKD-EPIcr) to 1,636,000 (CG).

Conclusions

The use of eGFR or CrCl to determine metformin eligibility instead of sCr can expand the adult population with diabetes for whom metformin is likely safe, particularly among non-Hispanic blacks and men.

Background

Approximately 4-6% of incident end stage renal disease (ESRD) patients in the U.S. recover enough kidney function to discontinue dialysis but there is considerable geographic variation. We undertook this study to investigate whether state-level variations in renal recovery among incident ESRD patients correlated with state-level variations in incidence of acute kidney injury requiring dialysis (AKI-D).

Methods

We conducted a national cross-sectional ecological study at the state-level using data from State Inpatient Databases and U.S. Renal Data System. All hospital admissions and all ESRD patients in 18 US states (AZ, AR, CA, FL, IA, KY, MA, MD, MI, NJ, NM, NY, NV, OR, RI, SC, VT, and WA) were included. Correlation between AKI-D incidence and rate of renal recovery across states was determined using Pearson's r (overall and in subgroups). We also calculated partial correlations adjusted for sex and age.

Results

AKI-D incidence ranged from 99.0 per million population (pmp) in Vermont to 490.4 pmp in Nevada. Rate of renal recovery among incident ESRD patients ranged from 8.8 pmp in Massachusetts to 29.3 pmp in Florida. A positive correlation between AKI-D incidence and rate of renal recovery among incident ESRD patients at state level was found overall (unadjusted r = 0.67; p = 0.002) and in age, sex, and race subgroups. The overall correlation persisted after adjusting for age (adjusted r = 0.62; p < 0.001) and sex (adjusted r = 0.65; p < 0.001).

Conclusion

Our findings suggest that AKI-D incidence is an important driver of renal recovery rates among incident ESRD patients.

Background

The feasibility of using health system data to estimate prevalence of chronic kidney disease (CKD) stages 3-5 was explored.

Study design

Cohort study.

Setting & participants

A 5% national random sample of patients from the Veterans Affairs (VA) health care system, enrollees in a managed care plan in Michigan (M-CARE), and participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).

Predictor

Observed CKD prevalence estimates in the health system population were calculated as patients with an available outpatient serum creatinine measurement with estimated glomerular filtration rate <60 mL/min/1.73 m(2), among those with at least one outpatient visit during the year.

Outcomes & measurements

A logistic regression model was fitted using data from the 2005-2006 NHANES to predict CKD prevalence in those untested for serum creatinine in the health system population, adjusted for demographics and comorbid conditions. Model results then were combined with the observed prevalence in tested patients to derive an overall predicted prevalence of CKD within the health systems.

Results

Patients in the VA system were older, had more comorbid conditions, and were more likely to be tested for serum creatinine than those in the M-CARE system. Observed prevalences of CKD stages 3-5 were 15.6% and 0.9% in the VA and M-CARE systems, respectively. Using data from NHANES, the overall predicted prevalences of CKD were 20.4% and 1.6% in the VA and M-CARE systems, respectively.

Limitations

Health system data quality was limited by missing data for laboratory results and race. A single estimated glomerular filtration rate value was used to define CKD, rather than persistence over 3 months.

Conclusions

Estimation of CKD prevalence within health care systems is feasible, but discrepancies between observed and predicted prevalences suggest that this approach is dependent on data availability and quality of information for comorbid conditions, as well as the frequency of testing for CKD in the health care system.

Background

The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population.

Methods

We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression.

Results

In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups.

Conclusion

Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study.

Background

Studies suggest an association between acute kidney injury (AKI) and long-term risk for chronic kidney disease (CKD), even following apparent renal recovery. Whether the pattern of renal recovery predicts kidney risk following AKI is unknown.

Study design

Retrospective cohort.

Setting & participants

Patients in the Veterans Health Administration in 2011 hospitalized (> 24 hours) with at least 2 inpatient serum creatinine measurements, baseline estimated glomerular filtration rate > 60 mL/min/1.73 m², and no diagnosis of end-stage renal disease or non-dialysis-dependent CKD: 17,049 (16.3%) with and 87,715 without AKI.

Predictor

Pattern of recovery to creatinine level within 0.3 mg/dL of baseline after AKI: within 2 days (fast), in 3 to 10 days (intermediate), and no recovery by 10 days (slow or unknown).

Outcome

CKD stage 3 or higher, defined as 2 outpatient estimated glomerular filtration rates < 60 mL/min/1.73m² at least 90 days apart or CKD diagnosis, dialysis therapy, or transplantation.

Measurements

Risk for CKD was modeled using modified Poisson regression and time to death-censored CKD was modeled using Cox proportional hazards regression, both stratified by AKI stage.

Results

Most patients' AKI episodes were stage 1 (91%) and 71% recovered within 2 days. At 1 year, 18.2% had developed CKD (AKI, 31.8%; non-AKI, 15.5%; P < 0.001). In stage 1, the adjusted relative risk ratios for CKD stage 3 or higher were 1.43 (95% CI, 1.39-1.48), 2.00 (95% CI, 1.88-2.12), and 2.65 (95% CI, 2.51-2.80) for fast, intermediate, and slow/unknown recovery. A similar pattern was observed in subgroup analyses incorporating albuminuria and sensitivity analysis of death-censored time to CKD.

Limitations

Variable timing of follow-up and mostly male veteran cohort may limit generalizability.

Conclusions

Patients who develop AKI during a hospitalization are at substantial risk for the development of CKD by 1 year following hospitalization and timing of AKI recovery is a strong predictor, even for the mildest forms of AKI.

Background

Longer nephrology care before end-stage renal disease (ESRD) has been linked with better outcomes.

Methods

We investigated whether longer pre-end-stage renal disease (ESRD) nephrology care was associated with lower mortality at both the patient and state levels among 443 761 incident ESRD patients identified in the USA between 2006 and 2010.

Results

Overall, 33% of new ESRD patients had received no prior nephrology care, while 28% had received care for >12 months. At the patient level, predictors of >12 months of nephrology care included having health insurance, white race, younger age, diabetes, hypertension and US region. Longer pre-ESRD nephrology care was associated with lower first-year mortality (adjusted hazard ratio = 0.58 for >12 months versus no care; 95% confidence interval 0.57-0.59), higher albumin and hemoglobin, choice of peritoneal dialysis and native fistula and discussion of transplantation options. Living in a state with a 10% higher proportion of patients receiving >12 months of pre-ESRD care was associated with a 9.3% lower relative mortality rate, standardized for case mix (R (2) = 0.47; P < 0.001).

Conclusions

This study represents the largest cohort of incident ESRD patients to date. Although we did not follow patients before ESRD onset, our findings, both at the individual patient and state levels, reflect the importance of early nephrology care among those with chronic kidney disease.

Background

Poor access to food among low-income adults has been recognized as a risk factor for chronic kidney disease (CKD), but there are no data for the impact of food insecurity on progression to end-stage renal disease (ESRD). We hypothesized that food insecurity would be independently associated with risk for ESRD among persons with and without earlier stages of CKD.

Study design

Longitudinal cohort study.

Setting & participants

2,320 adults (aged ≥ 20 years) with CKD and 10,448 adults with no CKD enrolled in NHANES III (1988-1994) with household income ≤ 400% of the federal poverty level linked to the Medicare ESRD Registry for a median follow-up of 12 years.

Predictor

Food insecurity, defined as an affirmative response to the food-insecurity screening question.

Outcome

Development of ESRD.

Measurements

Demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. Dietary acid load was estimated from 24-hour dietary recall. We used a Fine-Gray competing-risk model to estimate the relative hazard (RH) for ESRD associated with food insecurity after adjusting for covariates.

Results

4.5% of adults with CKD were food insecure. Food-insecure individuals were more likely to be younger and have diabetes (29.9%), hypertension (73.9%), or albuminuria (90.4%) as compared with their counterparts (P<0.05). Median dietary acid load in the food-secure versus food-insecure group was 51.2 mEq/d versus 55.6 mEq/d, respectively (P=0.05). Food-insecure adults were more likely to develop ESRD (RH, 1.38; 95% CI, 1.08-3.10) compared with food-secure adults after adjustment for demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. In the non-CKD group, 5.7% were food insecure. We did not find a significant association between food insecurity and ESRD (RH, 0.77; 95% CI, 0.40-1.49).

Limitations

Use of single 24-hour diet recall; lack of laboratory follow-up data and measure of changes in food insecurity over time; follow-up of cohort ended 10 years ago.

Conclusions

Among adults with CKD, food insecurity was independently associated with a higher likelihood of developing ESRD. Innovative approaches to address food insecurity should be tested for their impact on CKD outcomes.