Authors :
Presenting Author: Tuhina Govil-Dalela, MD – Michigan Medicine
Erika Mann, MD – Michigan Medicine; Russell Derry, MPH – Michigan Medicine; Samantha Choi Choi, MS, RDN, CSP – Michigan Medicine; Stephanie Rau, BS, CCRP – Michigan Medicine; Brittany Nordhaus, BA, ACRP-CP – Michigan Medicine; Julie Ziobro, MD, PhD – Michigan Medicine; Sucheta Joshi, MD, FAES – Michigan Medicine
Rationale:
The ketogenic diet (KD) is adjunctive treatment for pharmacoresistant epilepsies with positive outcomes, often resulting prolonged use. Studies have shown that prolonged treatment with the KD can result in kidney stones and/or skeletal fractures. Despite theoretical risks/anecdotal evidence of such long-term effects, clinical studies evaluating these issues are scarce. There are no well-defined or standard clinical pathways to routinely test and risk-stratify children on the KD for renal and bone health. Our study aimed to identify markers for early detection of risk for poor bone health and kidney stones in children on the KD for more than 2 years at a level 4 epilepsy center.
Methods:
An institutional KD database was used to identify patients (0-21 years) between 2014 to 2021 treated with the KD or Modified Atkins diet (MAD) for
> 2 years, regardless of indication. Data related to bone and kidney health were collected and analyzed through retrospective chart review. Analysis was done using SPSS22 for descriptive statistics, Fisher’s exact, and Mann-Whitney U tests.
Results:
Forty patients were identified as on the KD or MAD for > 2 years (18 females, median age at initiation 2.5 years, median duration of dietary therapy 3.5 years). Thirty-eight were on KD and 2 on MAD. Nineteen (47.5%) had generalized epilepsy, 8 (20%) focal and 13 (32.5%) mixed epilepsy, and 29 (72.5%) were on 1-3 anti-seizure medications concurrently (Table 1). Thirty six (90%) reported a reduction in seizure frequency, with 10 (25%) weaning some medications after two years on the diet.
One patient developed a uric acid kidney stone nine months after starting the diet, while on sodium bicarbonate and without exposure to other stone-forming medications. Six (15%) underwent renal ultrasounds (two screening, or for hematuria, flank pain, hypertension and hydronephrosis).
Two patients had bone fractures (one with multiple, and later diagnosed with scurvy).
Both were referred to Orthopedics and Endocrinology. Thirteen (32.5%) had osteopenia diagnosed on x-rays; one had osteoporosis. Two patients underwent Dual Energy X-ray Absorptiometry (DEXA) scans (one with multiple fractures, one for screening). Skeletal health was not significantly associated with weight or BMI percentiles, KD ratio, urinary ketone counts or number of anti-seizure medications. Osteopenia was significantly associated with beta-hydroxybutyrate values (median 4.4 for those with osteopenia vs to 3.0 for those without).
Conclusions:
Our study represents a contemporary cohort of patients with prolonged KD use. Our results suggest that close monitoring of renal and bone health for prolonged KD therapy is necessary, as risk cannot be predicted by diet or patient parameters alone, except for beta-hydroxybutyrate.
Given the high prevalence of osteopenia, routine screening DEXA scans after two years on the KD and early engagement with endocrinology may be beneficial. These data are important for patient counseling, follow-up and risk stratification. Limitations of our study include retrospective chart review, small sample size and lack of serial lab measurements.
Funding: None