Background Cystic fibrosis (CF) is a multisystem autosomal recessive disease caused by mutations in the cystic fibrosis transduction regulator (CFTR). The CFTR is expressed in all renal tubular segments. Tubular functional abnormalities as well as renal histologic changes are recognized in people with cystic fibrosis (CF). Chronic kidney disease (CKD) occurs in CF at greater frequency than in the non-CF population. The prevalence and characteristics of end stage kidney disease (ESKD) in the cystic fibrosis population have not previously been described.

Methods We used data supplied by the US Renal Data System (USRDS) to compare persons with ESKD and CF with those with ESKD who did not have a diagnosis of CF. We used linear and logistic regression, propensity score-matched Kaplan-Meier survival curves, and log-rank tests.

Results The prevalence of ESKD was approximately thirty times higher than predicted in the general US population. Diabetes was more frequently a diagnosis in people with CF, but was approximately half as frequently the primary cause of ESKD than in those without CF. Complications of transplantation, particularly of lung, were rarely the cause of ESKD in those without CF but were the second most frequent etiology of ESKD in people with CF. Drugs and medications, interstitial nephritis and acute kidney injury (AKI) were more frequent primary causes in those with CF. Hypertension, cystic kidney disease, and glomerulonephritis were less frequent in those with CF. Mortality and survival with ESKD were not significantly different between those with CF and ESKD and those with ESKD who did not have CF. Diabetes mellitus and complications of lung transplantation as the primary cause of ESKD, but not lung transplant status, were associated with significantly shorter survival with ESKD in people with CF.

Conclusions People living with CF have a markedly higher prevalence of ESKD than the general United States population. The profile of primary causes of ESKD differed significantly from that of the non-CF population. Diabetes mellitus was approximately half as frequently the primary cause of ESKD in those with CF. Complications of solid organ transplant, particularly lung, were the second most frequent primary cause of ESKD in people with CF. Survival with ESKD was not significantly different between those who did and did not have CF. The diagnosis of diabetes mellitus, and complications of lung transplantation as the primary cause of ESKD, but not lung transplant status, were associated with significantly shorter survival with ESKD in people with CF. It is our aim that these findings will promote awareness of kidney disease in persons living with CF and will encourage prevention of acute kidney injury (AKI), early detection and intervention in CKD, and preemptive referral to nephrology and transplant centers.

The authors have declared no competing interest.

This study was funded by a pilot study subaward to Dr Graber. The Prime grant is at Dartmouth College, PI Dean Madden DartCF P30DK117469

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB review (copy on file with USRDS CC): The study was reviewed by the Dartmouth Hitchcock (Dartmouth Hitchcock Medical Center, Lebanon, NH 03756) IRB on 10.5.21. IRB ID STUDY02000769. The IRB determined that the study is not research involving human subjects as defined by DHHS and FDA regulations, and that IRB review is not required. IRB contact telephone 603 650-1846.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes