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Primary causes of kidney disease and mortality in dialysis-dependent children

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Abstract

Background

Congenital anomalies of the kidney and urinary tract (CAKUT) is associated with a slower progression to end-stage renal disease (ESRD) in pre-dialysis patients. However, little is known about the associated mortality risks after transitioning to dialysis.

Methods

This retrospective cohort study included 0–21 year-old incident dialysis patients from the United States Renal Data System starting dialysis between 1995 and 2016. We examined the association of CAKUT vs. non-CAKUT with all-cause mortality, using Cox regression adjusted for case mix variables. We also examined the mortality risk associated with 14 non-CAKUT vs. CAKUT ESRD etiologies and under stratification by estimated glomerular filtration rate (eGFR).

Results

Among 25,761 patients, the median (interquartile range) age was 17 (11–19) years, and 4780 (19%) had CAKUT. CAKUT was associated with lower mortality, with an adjusted hazard ratio (aHR) of 0.72 (95%CI, 0.64–0.81) (reference: non-CAKUT). In age-stratified analyses, CAKUT vs. non-CAKUT aHRs (95%CI) were 0.66 (0.54–0.80), 0.56 (0.39–0.80), 0.66 (0.50–0.86), and 0.97 (0.80–1.18) among patients < 6, 6–< 13, 13–< 18, and ≥ 18 years at dialysis initiation, respectively. Among non-CAKUT ESRD etiologies, the risk of mortality associated with primary glomerulonephritis (aHR, 0.93; 95%CI 0.80–1.09) and focal segmental glomerulosclerosis (aHR, 0.89; 95%CI, 0.75–1.04) were comparable or slightly lower compared to CAKUT, whereas most other primary causes were associated with higher mortality risk. While the CAKUT group had lower mortality risk compared to the non-CAKUT group patients with eGFR ≥5 mL/min/1.73m2, CAKUT was associated with higher mortality in patients with eGFR < 5 mL/min/1.73 m2.

Conclusions

CAKUT is associated with lower mortality among children < 18 years old, but showed comparable mortality with non-CAKUT among patients ≥ 18 years old. ESRD etiology should be considered in risk assessment for children initiating dialysis.

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Acknowledgments

The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government.

Funding

The authors are supported by the research grants from the NIH/NIDDK including T32-DK104687 (M.L.), K23-DK102903 (C.M.R), R03-DK114642 (C.M.R), K24 DK091419 (K.K. Z), U01 DK102163 (K.K. Z), and philanthropist grants from H. Simmons, L. Chang and J. Lee. Y.T. is supported by the grant from Shengjing Hospital of China Medical University.

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Authors and Affiliations

  1. Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine Medical Center, 101 The City Drive South, City Tower, Suite 400, Orange, CA, 92868, USA

    Yusuke Okuda, Melissa Soohoo, Ying Tang, Yoshitsugu Obi, Connie M. Rhee, Elani Streja & Kamyar Kalantar-Zadeh

  2. Department of Pediatrics, Kitasato University School of Medicine, 1 Chome-15-1 Kitazato, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan

    Yusuke Okuda & Kenji Ishikura

  3. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Marciana Laster

  4. Division of Pediatric Nephrology, Mattel Children’s Hospital at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095, USA

    Marciana Laster

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  1. Yusuke Okuda
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  2. Melissa Soohoo
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  3. Kenji Ishikura
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  4. Ying Tang
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  5. Yoshitsugu Obi
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  7. Connie M. Rhee
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  9. Kamyar Kalantar-Zadeh
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Corresponding author

Correspondence to Kamyar Kalantar-Zadeh.

Ethics declarations

This study was approved by the Institutional Review Board of University of California Irvine with waiver of informed consent because the USRDS contains only deidentified information.

Conflict of interest

K.K.-Z. has received honoraria and/or support from Abbott, Abbvie, Alexion, Amgen, American Society of Nephrology, Astra-Zeneca, AVEO Oncology, Chugai, DaVita, Fresenius, Genentech, Haymarket Media, Hofstra Medical School, International Federation of Kidney Foundations, International Society of Hemodialysis, International Society of Renal Nutrition and Metabolism, Japanese Society of Dialysis Therapy, Hospira, Kabi, Keryx, Novartis, National Institutes of Health, National Kidney Foundation, OPKO, Pfizer, Relypsa, Resverlogix, Sandoz, Sanofi, Shire, Vifor, UpToDate, and ZSPharma. K.I. has received grants from Asahi Kasei Pharma, Astellas Pharma, Chugai Pharmaceutical, Fuso Pharmaceutical Industries, JMS, Novartis Pharma and Zenyaku Kogyo; personal fees from Chugai Pharmaceutical, Zenyaku Kogyo, Novartis Pharma and Vifor Pharma and other funding from Alexion Pharmaceuticals, Astellas Pharma, Novartis Pharma and Otsuka Pharmaceutical.

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Okuda, Y., Soohoo, M., Ishikura, K. et al. Primary causes of kidney disease and mortality in dialysis-dependent children. Pediatr Nephrol 35, 851–860 (2020). https://doi.org/10.1007/s00467-019-04457-7

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