Publications

Randomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney disease and the exorbitant costs of their health care. Observational studies of CKD frequently yield seemingly paradoxic associations of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials conducted in people with normal kidney function to patients with CKD. However, many completed trials in CKD have been limited by intermediate outcomes of unclear clinical significance or narrow eligibility criteria that limit external validity, and implementation of proven therapies remains a challenge. It is therefore imperative that the nephrology community capitalize on recent interest in novel approaches to trial design, such as pragmatic clinical trials. These trials are meant to promote research within real world settings to yield clinically relevant results with greater applicability than those of traditional trials, while maintaining many advantages, such as controlling for potential sources of bias. We provide a description of pragmatic clinical trials and a discussion of advantages, disadvantages, and practical challenges inherent to this study design, in the context of specific scientific questions relevant to patients with CKD.

STUDY OBJECTIVE

Previous reviews of emergency department (ED) visit reduction programs have not required that studies meet a minimum quality level and have therefore included low-quality studies in forming conclusions about the benefits of these programs. We conduct a systematic review of ED visit reduction programs after judging the quality of the research. We aim to determine whether these programs are effective in reducing ED visits and whether they result in adverse events.

METHODS

We identified studies of ED visit reduction programs conducted in the United States and targeted toward adult patients from January 1, 2003, to December 31, 2014. We evaluated study quality according to the Grading of Recommendations Assessment, Development, and Evaluation criteria and included moderate- to high-quality studies in our review. We categorized interventions according to whether they targeted high-risk or low-acuity populations.

RESULTS

We evaluated the quality of 38 studies and found 13 to be of moderate or high quality. Within these 13 studies, only case management consistently reduced ED use. Studies of ED copayments had mixed results. We did not find evidence for any increase in adverse events (hospitalization rates or mortality) from the interventions in either high-risk or low-acuity populations.

CONCLUSION

High-quality, peer-reviewed evidence about ED visit reduction programs is limited. For most program types, we were unable to draw definitive conclusions about effectiveness. Future ED visit reduction programs should be regarded as demonstrations in need of rigorous evaluation.

BACKGROUND

The capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net.

METHODS

We conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996-2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies.

RESULTS

Overall, 1730 persons progressed to end-stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83-94 %, 74-95 %, and 75-82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42-71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC ≥0.80) when evaluated using traditional criteria.

CONCLUSIONS

Recently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations.

BACKGROUND

Tenofovir disoproxil fumarate (TDF) can cause proximal tubular damage and chronic kidney disease in human immunodeficiency virus (HIV)-infected individuals. Urine α1-microglobulin (A1M), a low-molecular-weight protein indicative of proximal tubular dysfunction, may enable earlier detection of TDF-associated tubular toxicity.

STUDY DESIGN

Cross-sectional.

SETTING & PARTICIPANTS

883 HIV-infected and 350 -uninfected men enrolled in the Multicenter AIDS Cohort Study.

PREDICTORS

HIV infection and TDF exposure.

OUTCOME

Urine A1M level.

RESULTS

Urine A1M was detectable in 737 (83%) HIV-infected and 202 (58%) -uninfected men (P<0.001). Among HIV-infected participants, 573 (65%) were current TDF users and 112 (13%) were past TDF users. After multivariable adjustment including demographics, traditional kidney disease risk factors, and estimated glomerular filtration rate, HIV infection was associated with 136% (95% CI, 104%-173%) higher urine A1M levels and 1.5-fold (95% CI, 1.3- to 1.6-fold) prevalence of detectable A1M. When participants were stratified by TDF exposure, HIV infection was associated with higher adjusted A1M levels, by 164% (95% CI, 127%-208%) among current users, 124% (95% CI, 78%-183%) among past users, and 76% (95% CI, 45%-115%) among never users. Among HIV-infected participants, each year of cumulative TDF exposure was associated with 7.6% (95% CI, 5.4%-9.9%) higher A1M levels in fully adjusted models, a 4-fold effect size relative to advancing age (1.8% [95% CI, 0.9%-2.7%] per year). Each year since TDF treatment discontinuation was associated with 4.9% (95% CI, -9.4%--0.2%) lower A1M levels among past users.

LIMITATIONS

Results may not be generalizable to women.

CONCLUSIONS

HIV-infected men had higher urine A1M levels compared with HIV-uninfected men. Among HIV-infected men, cumulative TDF exposure was associated with incrementally higher A1M levels, whereas time since TDF treatment discontinuation was associated with progressively lower A1M levels. Urine A1M appears to be a promising biomarker for detecting and monitoring TDF-associated tubular toxicity.