Part 2: Recovery Of Kidney Function After Dialysis Initiation in Children And Adults in The US: A Retrospective Study Of United States Renal Data System Data

Contact: emily.li@wecistanche.com

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Temporal trends in the recovery of kidney function in adults versus children

When we examined temporal trends in the recovery of kidney function among adults, recovery of kidney function was noted to peak qualitatively in 2010 and began to decline in the last 5-year calendar period (Fig 1A). In children, similar trends were noted qualitatively, but the magnitude of the improvement in recovery rates before 2010 was qualitatively less pronounced than that observed in adults (Fig 1B). When we examined temporal trends in the recovery of kidney function among adult and pediatric patients with a diagnosis of ATN (Fig 1C), trends were qualitatively similar to that observed in the overall cohort (Fig 1A and 1B), but at the peak rate of recovery around 2009, 36% (N=1,370 out of 3,786) of patients were recovering kidney function within 1 year of starting dialysis. In AIN, rates of recovery exceeded 40% (N=135 out of 312) around 2010 and then began to decline thereafter as seen qualitatively in Fig 1D.

Trends in recovery of kidney function were statistically significantly different in adults (sub-HR 1.90; 95% CI 1.86 to 1.95, p<0.001) versus children (sub-HR 1.49; 95% CI 1.15 to 1.92, p=0.002) in the 2006 to 2010 period (Table 3) as well as in the 2011 to 2015 period (sub HR 1.75; 95% CI 1.71 to 1.79, p<0.001 in adults versus sub-HR 1.05; 95% CI 0.80 to 1.38, p=0.73 in children). In particular, children in the most recent 5-year period (2011 to 2015) did not have a statistically significantly higher hazard of recovery of kidney function (sub-HR 1.05; 95% CI 0.80 to 1.38; p=0.73) compared with children starting dialysis between 1996 and 2000 (the reference comparator).

Relation between temporal trends in recovery and timing of dialysis initiation at higher versus lower eGFR

We further explored qualitatively whether the temporal trends in the recovery of kidney function would differ among those who were started on dialysis at higher versus lower eGFR. As shown in Fig 2A and 2B, recovery was qualitatively lower in those who had an eGFR <10 mL/min/ 1.73 m2 at dialysis initiation compared with those with earlier dialysis initiation (eGFR 10 mL/min/1.73 m2, Fig 2C, and 2D). Recovery rates improved initially for adults regardless of whether they underwent early or late initiation and subsequently declined over time as seen qualitatively in Fig 2A and 2C. In contrast, recovery rates were stably low for children who started dialysis late and did not improve as substantially over time compared to children who started dialysis early as seen qualitatively in Fig 2B and 2D.

Discussion

Many patients who start outpatient dialysis therapy inquire about their chances of discontinuing dialysis over time. However, few studies have focused on understanding the incidence, predictors, and temporal trends of recovery among patients receiving outpatient dialysis treatment. In this study, we examined the incidence of recovery of kidney function among persons starting outpatient dialysis treatment over the last 2 decades. We found that overall, 4% of the population who started outpatient dialysis recovered sufficient kidney function to discontinue maintenance dialysis within 1 year. Recovery rates ranged between 10% and 15% within the first 30 days of dialysis initiation, but nearly half of patients who recovered kidney function did so within 90 days after dialysis initiation. Few patients recovered after 180 days of outpatient chronic dialysis. Adults were more likely to recover and become dialysis independent compared with children, but in both populations, ATN and AIN were associated with the highest recovery rates, and these recovery rates were as high as 25% to 45% depending on the calendar year of study. However, rates of recovery differed by etiology of kidney disease.

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Although we had hypothesized that children would have a better potential for recovery of kidney function given their lower prevalence of age-related comorbidities and a lower likelihood of long-standing CKD, we found lower rates of recovery in the outpatient setting among children compared with adults. Differences in practice patterns among adult and pediatric practitioners may explain the observed differences in the risk of recovery in the adult versus pediatric population. In pediatrics, there may be a greater tendency to monitor patients with dialysis-requiring AKI in the inpatient setting for recovery (rather than discharge these patients to outpatient dialysis units), as it can be logistically challenging to identify outpatient dialysis units that are willing to treat younger children (outside of large academic centers) [26]. There may also be less pressure to discharge children from inpatient to outpatient care, especially given the complexities of ESKD care in the outpatient setting and training required for pediatric caregivers. In addition, a larger proportion of children with ESKD in our cohort were treated with peritoneal dialysis, which was a risk factor for non-recovery in both the pediatric and adult populations. Because peritoneal dialysis catheters may be more difficult to place

and remove than tunneled hemodialysis catheters, providers may be more conservative about using peritoneal dialysis as a treatment modality unless patients have strong evidence of endstage disease. We acknowledge, however, that some pediatric centers do offer peritoneal dialysis as an acute treatment modality in the setting of AKI (which is less common in adult practice in the US) [27].

We also noted differences in recovery by race in the adult and pediatric populations. In adults, NHB individuals had a lower probability of recovery compared with NHW individuals, but this racial disparity was not observed in children. Likely, socioeconomic factors such as access to insurance and routine healthcare before ESKD may contribute to these observations, as children typically have universal healthcare coverage and better access to care [28, 29]. The steady decrease in recovery of kidney function after 2012 is consistent with policy clarifications that may have further disincentivized the acceptance of patients with AKI for dialysis treatment at outpatient facilities between 2012 and 2017. However, the decline in recovery rates began even before the onset of this policy change in 2012, the reasons for which are unclear.

A steady increase in the number of patients who are receiving dialysis after AKI in the US population [30] has been noted over time [21]. Given improvements in the survival of patients with AKI-requiring dialysis to hospital discharge [31], to the better rates of recovery of kidney function up until 2010 [11]. However, this trend was noteworthy among those starting dialysis with an eGFR above 10 mL/min/1.73 m2 in both children and adults. The frequently unpredictable nature of CKD progression may lead some practitioners to conservatively start dialysis early, and a smaller degree of recovery in these patients may be necessary to be able to discontinue dialysis. We do acknowledge that policy clarifications which emphasized that Medicare patients receiving treatment at outpatient dialysis facilities in the US for AKI would not be reimbursed for their outpatient treatments were released in 2012 [11,12]. This clarification to Medicare payment policies may have delayed hospital discharge of inpatients who otherwise were ready for outpatient care while awaiting recovery of kidney function and could potentially contribute to a decrease in the rate of recovery of kidney function in outpatient facilities thereafter.

Our study has practice and policy implications. First, nephrology providers may need to consider earlier and more frequent in-person visits at dialysis units, more vigilant assessments of residual kidney function, and changes in practice patterns (such as avoidance of excessive ultrafiltration and intradialytic hypotension) for the subset who may recover kidney function [32–34]. In addition, the frequent pressure to determine whether an individual has ESKD may lead to misclassification of patients and inappropriate resource utilization, such as transportation and insurance benefits that may come with the diagnosis of ESKD. Whether more recent policy changes which now allow for the reimbursement of dialysis provisions for AKI in outpatient facilities have influenced temporal and practice pattern changes remains to be determined [34].

The strengths of our study include the large size of the national cohort, the contemporary nature of the data, and the inclusion of a racially and ethnically diverse group of adults and children. Our follow-up of participants is also longer than most prior studies which have been primarily single-center studies and may have limited data on the long-term outcomes of patients after the start of dialysis in the outpatient setting. Limitations include potential errors in data and missing data from the CMS-2728 forms that may have led to potential misclassification of predictors of recovery and lack of data surrounding whether nephrotoxic agents were used following AKI which may have delayed recovery of kidney function. We lack substantial data surrounding care of patients before dialysis initiation, and we are unable to delineate whether patients had baseline CKD and subsequently developed AKI or the exact nature of the trajectory of kidney function before the initiation of dialysis. We believe our study population includes patients with more severe AKI who continued to require dialysis in the outpatient setting, and thus our results do not generalize to patients who may have developed AKI and recovered kidney function before hospital discharge or to patients in other countries where dialysis care may differ from that in the US. We also acknowledge that changes to care of patients with AKI may have occurred with most recent policy changes surrounding reimbursement for the dialysis of patients with AKI, which may limit the applicability of our findings following such policy changes. Finally, given the observational nature of our data, residual confounding may be present.

In conclusion, we note that recovery of adequate kidney function for discontinuation of outpatient dialysis occurs in 4% of patients who were noted to have ESKD. Close monitoring of patients within the first 6 months of dialysis initiation may be prudent, especially among those with ATN, AIN, or in children, glomerulonephritis. Further studies are needed to understand factors that may improve the chances of recovery of kidney function in the outpatient setting, and strategies are needed to maximize the potential for recovery.

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Supporting information

S1 STROBE Checklist. STROBE checklist for the manuscript. STROBE, Strengthening the Reporting of Observational Studies in Epidemiology.

(DOC)

S1 Table. Adjusted Fine and Gray models for time to recovery from maintenance dialysis at any point during follow-up after ESKD onset. ESKD, end-stage kidney disease.

(DOCX)

S2 Table. Adjusted Fine and Gray models for time to recovery from maintenance dialysis at any point during follow-up after ESKD onset with a focus on factors that differed between children and adults. ESKD, end-stage kidney disease.

(DOCX)

S1 Fig. Percent of children and adults recovering kidney function within different time intervals of interest.

(TIF)

Acknowledgments

We thank Timothy Copeland for his assistance in executing competing risk analyses.

Disclaimer

The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government.

Author Contributions

Conceptualization: Elaine Ku, Raymond K. Hsu, Kirsten L. Johansen.

Data curation: Elaine Ku, Barbara A. Grimes.

Formal analysis: Elaine Ku, Kirsten L. Johansen, Charles E. McCulloch, Barbara A. Grimes, Kathleen D. Liu.

Investigation: Elaine Ku, Raymond K. Hsu, Charles E. McCulloch, Mark Mitsnefes, Barbara A. Grimes, Kathleen D. Liu.

Methodology: Elaine Ku, Raymond K. Hsu, Kirsten L. Johansen, Charles E. McCulloch, Barbara A. Grimes, Kathleen D. Liu.

Supervision: Kathleen D. Liu.

Validation: Charles E. McCulloch.

Writing – original draft: Elaine Ku.

Writing – review & editing: Raymond K. Hsu, Kirsten L. Johansen, Charles E. McCulloch, Mark Mitsnefes, Barbara A. Grimes, Kathleen D. Liu.

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