Beyond Survival: Assessing Renal and Cardiovascular Health in Fanconi Anemia Adolescents and Young Adults Post-Stem Cell Transplant

Fanconi anemia (FA) is an inherited DNA repair disorder resulting in bone marrow failure , cancer predisposition , and variable congenital abnormalities. One-third have a congenital abnormality of the kidney and urinary tract (CAKUT), and up to 30% have congenital cardiac anomalies . Due to improved stem cell transplant (SCT) survival, there is a new generation of adolescent and young adult (AYA) FA survivors with limited data on optimal long-term follow up. To assess the renal and cardiovascular health of AYA FA survivors. We prospectively assessed traditional and novel kidney and cardiovascular (CV) biomarkers using a convenience sample of FA patients in a single center survivorship clinic. Estimated glomerular filtration rate (eGFR) was assessed via creatinine (Cr) and cystatin C (CysC). Urine protein- or albumin-Cr ratio was used to assess for proteinuria . Office peripheral systolic (pSys), diastolic (pDia), and central systolic (cSys) blood pressures, along with pulse wave velocities (PWV) were assessed using Mobil-O-Graph. Kidney imaging and nearest corresponding echo were reviewed. We evaluated 21 patients between September 2019 and September 2021. Median age and years from transplant were 13.6 (5.7-26.5) and 5.5 (0.9-11.9) years, respectively. Seven of 21 (33%) had CAKUT and 2/21 (10%) had congenital cardiac anomalies. Prevalence of decreased kidney function identified by Cr eGFR or CysC eGFR <90 ml/1.73m 2 /min, was 5/21 (24%) and 8/14 (57%), respectively. Using age/height/sex population norms, 8/21 (38%) and 10/21 (48%) had pSys and pDia hypertension (HTN). However, 6/21 (29%) FA patients were <5 th % for height and were not represented in the age-based population data. Using just height/sex to determine prevalence of HTN, the rate of pSys and pDia HTN increased to 8/21 (38%) and 10/21 (48%), respectively. Only one subject was on antihypertensives at the time of evaluation. Of 19 patients who had cSys and PWV evaluation, 7/19 (37%) had HTN and 4/19 (21%) had elevated PWV. All had normal left ventricular (LV) ejection fraction [median: 62 (56-66)%], and none had elevated LV mass index [median: 26 (12-32) g/m 2.7 ]. LV end-diastolic volume was reduced in most patients, with 12/21 (57%) having Z-score ≤-2 and median cohort Z-score -2.3 (-3.7-1.25). Nearly half of AYA FA survivors had clinically significant CV and/or renal abnormalities at a median 5.5 years post-SCT. CysC, which is a predictive marker of CV morbidity and mortality, identified over twice as many survivors with an abnormal eGFR. Whether CysC is a more accurate GFR marker and/or is indicative of cardiovascular risks needs further study. Similarly, PWV, an indicator of vascular stiffness , was abnormal in a significant portion of AYA survivors. This unexpected stiffness in combination with the nearly ubiquitous reduced LV end-diastolic volumes merits further study.