Association of hypercalciuria with vitamin D supplementation in patients undergoing ketogenic dietary therapy

Abstract

BackgroundKetogenic dietary therapy (KDT) is used as an effective treatment for epilepsy. However, KDT carries the risk of bone health deterioration; therefore, vitamin D supplementation is required. Vitamin D replacement therapy in KDT has not been established because it may be related to hypercalciuria/urolithiasis, which are common adverse effects of KDT. Hence, this study aimed to evaluate the dose-dependent association between vitamin D3 and hypercalciuria/urolithiasis in patients undergoing KDT and dose optimization for renal complications.Materials and methodsOverall, 140 patients with intractable childhood epilepsy started 3:1 KDT (lipid to non-lipid ratio) at the Severance Children’s Hospital from January 2016 to December 2019. Regular visits were recommended after KDT initiation. Participants were assessed for height, weight, serum 25-hydroxyvitamin D (25-OH-D3) level, parathyroid hormone level, and ratio of urinary excretion of calcium and creatinine (Uca/Ucr). Kidney sonography was conducted annually. Patients who already had urolithiasis and were taking hydrochlorothiazide before KDT, failed to maintain KDT for 3 months, did not visit the pediatric endocrine department regularly, did not take prescribed calcium and vitamin D3 properly, or needed hospitalization for > 1°month because of serious medical illness were excluded. Data from patients who started diuretic agents, e.g., hydrochlorothiazide, were excluded from that point because the excretion of calcium in the urine may be altered in these patients.ResultIn total, 49 patients were included in this study. Uca/Ucr ratio significantly decreased with increasing levels of 25-OH-D3 (p = 0.027). The odds ratio for hypercalciuria was 0.945 (95% confidence interval, 0.912–0.979; p = 0.002) per 1.0 ng/mL increment in 25-OH-D3 level. Based on findings of receiver operating characteristic curve analysis and Youden’s J statistic, the cut-off 25-OH-D3 level for preventing hypercalciuria was > 39.1 ng/mL at 6 months. Furthermore, the vitamin D3 supplementation dose cut-off was > 49.5 IU/kg for hypercalciuria prevention.ConclusionAn inverse relationship between Uca/Ucr ratio and 25-OH-D3 level was noted, which means that vitamin D supplementation is helpful for preventing hypercalciuria related to KDT. We suggest that the recommended 25-OH-D3 level is > 40 ng/mL for hypercalciuria prevention and that KDT for children with epilepsy can be optimized by vitamin D3 supplementation at 50 IU/kg.

Prevelance of Kidney Stones to the Human Populaton of District Buner and Nonpharmacologic Treatment of Kidney Stone

“…This distribution contrasts with the prevalence patterns in the United States and the East region of Algeria, where urate stones are less prevalent, contributing to 8-10% and 17% of kidney stones respectively, as reported in previous studies. Notably, the current analysis revealed urate stones constituted a significant 17% of cases, underscoring a regional dietary influence potentially rich in purine sources (7,13).…”

“…Given the rising prevalence and recurrence of kidney stones, a comprehensive understanding of the disease, its risk factors, and effective non-pharmacological management strategies is crucial. This includes the exploration of dietary modifications, fluid intake adjustments, and lifestyle changes to mitigate the risk and manage the condition effectively (13,14). The increasing global burden of nephrolithiasis necessitates an integrated approach to prevention and management, combining medical insights with lifestyle and dietary interventions to reduce the incidence and recurrence of this painful and prevalent condition (15,16).…”

Ketogenic Diet and Vitamin D Metabolism: A Review of Evidence

“…Human studies that investigated the effects of KDs on vitamin D in patients with epilepsy are shown in Table 2. In total, seven studies were conducted on subjects with epilepsy [7,[55][56][57][58][59][60]. Most of the participants were children who followed a KD for a long period (12-15 months) for medical purposes [7,[55][56][57][58]60].…”

“…In total, seven studies were conducted on subjects with epilepsy [7,[55][56][57][58][59][60]. Most of the participants were children who followed a KD for a long period (12-15 months) for medical purposes [7,[55][56][57][58]60]. Only one study was conducted on adults [59].…”

“…The exact supplemental dose of vitamin D was not reported in most studies. Circulating vitamin D was increased in the first 3 months of treatment and then stabilized [55,58,60] or decreased [56]. The baseline levels of vitamin D were quite heterogenous and ranged from a high percentage of deficiency [7,55,56] to values closer to normal ones (8% of subjects had an insufficient 25(OH)D level) [58].…”