Because large randomized clinical trials (RCTs) in dialysis have been relatively scarce, evidence-based dialysis care has depended heavily on the results of observational studies. However, when results from RCTs appear to contradict the findings of observational studies, nephrologists are left to wonder which type of study they should believe. In this editorial, we explore the key differences between observational studies and RCTs in the context of such seemingly conflicting studies in dialysis. Confounding is the major limitation of observational studies, whereas low statistical power and problems with external validity are more likely to limit the findings of RCTs. Differences in the specification of the population, exposure, and outcomes can also contribute to different results among RCTs and observational studies. Rigorous methods are required regardless of what type of study is conducted, and readers should not automatically assume that one type of study design is superior to the other. Ultimately, dialysis care requires both well-designed, well-conducted observational studies and RCTs to move the field forward.

End-stage kidney disease and earlier stages of chronic kidney disease (CKD) represent one of the most dramatic examples of racial/ethnic disparities in health in our nation. African Americans are 3 times more likely to require renal replacement therapy then their non-Hispanic white counterparts. This article describes CKD-related disparities linked to a variety of clinical, socioeconomic, and cultural factors, as well as to select social determinants of health that are defined by social positioning and often by race within the United States. Our advancing understanding of these issues has led to improvements in patient outcomes and is narrowing the gap in disparities across most aspects of CKD and CKD risk factors. There are also extensive data indicating similar improvements in quality measures for patients on dialysis therapy. This article also reviews the state of CKD in African Americans from a population perspective and provides recommendations for the way forward.

This paper develops two orthogonal contributions to scalable sparse regression for competing risks time-to-event data. First, we study and accelerate the broken adaptive ridge method (BAR), a surrogate ℓ ₀-based iteratively reweighted ℓ ₂-penalization algorithm that achieves sparsity in its limit, in the context of the Fine-Gray (1999) proportional subdistributional hazards (PSH) model. In particular, we derive a new algorithm for BAR regression, named cycBAR, that performs cyclic update of each coordinate using an explicit thresholding formula. The new cycBAR algorithm effectively avoids fitting multiple reweighted ℓ ₂-penalizations and thus yields impressive speedups over the original BAR algorithm. Second, we address a pivotal computational issue related to fitting the PSH model. Specifically, the computation costs of the log-pseudo likelihood and its derivatives for PSH model grow at the rate of O(n ²) with the sample size n in current implementations. We propose a novel forward-backward scan algorithm that reduces the computation costs to O(n). The proposed method applies to both unpenalized and penalized estimation for the PSH model and has exhibited drastic speedups over current implementations. Finally, combining the two algorithms can yields > 1, 000 fold speedups over the original BAR algorithm. Illustrations of the impressive scalability of our proposed algorithm for large competing risks data are given using both simulations and a United States Renal Data System data. Supplementary materials for this article are available online.

Purpose of review

We summarize the evidence for and against a target systolic blood pressure (SBP) < 130 mmHg in individuals with type 2 diabetes mellitus (T2DM).

Recent findings

The primary ACCORD trial pooled data from patients with more- and less-intense glycemic control and found no benefit to lowering SBP < 140 mmHg, findings consistent with multiple meta-analyses. However, a re-analysis of the ACCORD trial found that participants randomized to less-intense glycemic control (HbA1c 7.0-7.9%) benefited from targeting SBP < 120 vs. 140 mmHg. The SPRINT trial also found benefit for targeting SBP < 120 vs. 140 mmHg in participants at risk for cardiovascular events but excluded persons with T2DM. There is no consensus as to the optimal SBP target for patients with T2DM, though data suggest a benefit to targeting SBP < 130 mmHg in patients with less-intensive glucose control. Further research is also needed on BP control in the setting of newer anti-diabetic agents.

Background

Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S.

Methods

We conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users.

Results

Among 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73-1.02].

Conclusions

ACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.

Background

Data on the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in reducing cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD) are limited. We investigated the association between ACEI/ARB use and CV outcomes in patients initiating PD.

Methods

In this observational cohort study, we identified from the United States Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We applied Cox regression to an inverse probability of treatment weighted cohort to estimate the hazard ratios (HRs) for the combined outcome of death, ischemic stroke or myocardial infarction (MI) and each outcome individually.

Results

Among 4879 patients, 2063 (42%) used an ACEI/ARB. Patients were followed up for a median of 1.2 years. We recorded 1771 events, for a composite rate of 25 events per 100 person-years. ACEI/ARB use (versus nonuse) was associated with a reduced risk of the composite outcome {HR 0.84 [95% confidence interval (CI) 0.76-0.93]}, all-cause mortality [HR 0.83 (95% CI 0.75-0.92)] and CV death [HR 0.74 (95% CI 0.63-0.87)], but not MI [HR 0.88 (95% CI 0.69-1.12)] or ischemic stroke [HR 1.06 (95% CI 0.79-1.43)]. Results were similar in as-treated analyses. In a subgroup analysis, we did not find any effect modification by residual renal function.

Conclusions

ACEI/ARB use is common in patients initiating PD and is associated with a lower risk of fatal CV outcomes.

Background

There is evidence that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) may reduce cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD), but no studies have compared the effectiveness between these drug classes. In this observational cohort study, we compared the association of ARB vs. ACEI use on CV outcomes in patients initiating PD.

Methods

We identified from the US Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We excluded patients who used both ACEI and ARB. We applied Cox proportional hazards regression to an inverse probability of treatment-weighted cohort to estimate the hazard ratios (HR) for the combined outcome of all-cause death, ischemic stroke, or myocardial infarction; all-cause mortality; and CV death.

Results

Among 1892 patients using either drug class, 39 % were ARB users. We observed 624 events over 2,898 person-years of follow-up, for a composite event rate of 22 events per 100 person-years. We observed no differences between ARB vs. ACEI users: composite outcome HR 0.94, 95 % confidence interval (CI) 0.79-1.11; all-cause mortality HR 0.92, 95 % CI 0.76-1.10; CV death HR: 1.06, 95 % CI 0.80-1.41.

Conclusion

We identified no significant difference in the risks of CV events or death between users of ARBs vs. ACEIs in patients initiating PD, thus supporting their mostly interchangeable use in this population.

Rationale & objective

Home dialysis has been underused in the United States, especially among minority groups. We investigated whether adjustment for socioeconomic factors would attenuate racial/ethnic differences in the initiation of home dialysis.

Study design

Retrospective observational cohort study.

Setting & population

Adult patients in the US Renal Data System who initiated dialysis on day 1 with either in-center hemodialysis (HD), home HD (HHD), or peritoneal dialysis (PD) from 2005 to 2013.

Predictor

Race/ethnicity: non-Hispanic white, Hispanic, black, or Asian.

Outcome

Initiating dialysis with PD versus in-center HD and HHD versus in-center HD for each minority group compared with non-Hispanic whites.

Analytical approach

Odds ratios and 95% CIs estimated by logistic regression.

Results

Of 523,526 patients, 55% were white, 28% were black, 13% were Hispanic, and 4% were Asian; 8% started dialysis on PD, and 0.1%, on HHD. In unadjusted analyses, blacks and Hispanics were 30% and 19% less likely and Asians were 31% more likely to start on PD than whites. The differences narrowed when fully adjusted for demographic, medical, and socioeconomic factors. Adjustment for socioeconomic factors reduced these differences between white and black, Hispanic, and Asian patients by 13%, 28%, and 1%, respectively. Blacks were just as likely and Hispanics and Asians were less likely to start on HHD than whites. This did not change appreciably when fully adjusted for demographic, medical, and socioeconomic factors.

Limitations

No data for physician and patient preferences or modality education.

Conclusions

Black and Hispanic patients are less likely to start on PD than white patients, attributable partly, though not completely, to socioeconomic factors. Hispanics and Asians are less likely to start on HHD than whites. This was materially unaffected by socioeconomic factors. More research is needed to determine whether urgent-start PD programs and transitional care units in socioeconomically disadvantaged areas might reduce these disparities and increase home dialysis use among all groups.