#2623 Homeostatic Model Assessment (HOMA) in pediatric patients with nephrotic syndrome receiving tacrolimus

Abstract

Abstract Background and Aims Children with nephrotic syndrome (NS) receive diabetogenic drugs like tacrolimus (TAC) and steroids. TAC is toxic to pancreatic β-cells and suppresses insulin production in a time and dose dependent manner. This is well documented in renal transplant patients who develop post-transplant diabetes mellitus (PTDM). Although overt diabetes is uncommon in children receiving TAC for NS, the subclinical effect on β cell function has not been studied. Our aim was to study pancreatic beta cell function as assessed by homeostasis model assessment (HOMA) indices in children with NS who received TAC therapy for at least 1 year duration. Method We performed a prospective descriptive study where we followed children (1-18 years) with NS who received TAC therapy for at least 1 year. We noted patient demographics, clinical and histologic pattern of NS, cumulative steroid dose (mg/kg/day) received 90 days prior and TAC C0 levels. Fasting insulin, blood sugar to calculate HOMA indices for IR (insulin resistance), HOMA % β for beta cell function, HOMA-IS (insulin sensitivity), C-peptide and HbA1C were done once at study inclusion and yearly intervals when required. Statistical analysis included Pearson's correlation, paired t test and regression analysis. Results We performed HOMA indices in 37 children (19 males, 18 females) between September 2021-February 2023. Six patients had 2 measurements during the study period. The mean age of onset of NS was 28 months (95% CI [20; 36]) and mean age at HOMA indices measurement was 69 months (95% CI [59; 79]). Of the 37 patients, 54% (20/37) had late steroid resistance, 32% (12/37) had early steroid resistance, 8% (3/37) had steroid dependent NS, 6% (2/37) had frequently relapsing NS. Kidney biopsy performed in 36 children showed minimal change disease in 55.5% (20/36) and focal segmental glomerulosclerosis in 44.5% (16/36). The mean TAC duration, TAC Co level and mean cumulative steroid dose received in last 90 days were 27 months (95% CI [22;32]), 4.54 ng/ml (95% CI [4.12;4.97]) and 0.36 mg/kg/d (95% CI [0.28;0.44]) respectively. Eleven (30%) patients had cutaneous signs of insulin resistance like acanthosis nigricans and 9 (24%) patients had fasting blood sugar of >100 mg/dl. In Pearson's correlation analysis we found positive correlation between TAC Co level, HOMA IR (r = 0.4, P = 0.008) and TAC Co, HOMA %β (r = 0.44, P = 0.003) and cumulative steroid dose, fasting blood glucose (r = 0.3, P = 0.46). There was negative correlation between TAC Co level, HOMA IS (r = −0.4, P = 0.007). In regression analysis, only TAC Co level significantly influenced all HOMA indices including insulin resistance, insulin sensitivity and beta cell function. A HbA1C of > 5.7 (pre-diabetes range) was found in 32.4% (12/37) patients which warrants further monitoring. C-peptide levels were significantly higher after 12 months of TAC therapy in 6 patients who had two measurements (p = 0.032). Conclusion Tacrolimus therapy for nephrotic syndrome in children can affect pancreatic beta cell function as assessed by HOMA indices. Long term monitoring of pancreatic beta cell function in children with NS on TAC is needed to assess the full extent of these subclinical alterations.