A case control analysis investigating risk factors and outcomes for nephrocalcinosis and renal calculi in neonates

SummaryIntroductionStudies on outcomes and risk factors for neonatal nephrocalcinosis (NC) and renal calculi (RC) are limited, and often do not include controls for comparison. We conducted a case-control analysis to identify risk factors associated with NC and/or RC in neonates and studied the natural course of these anomalies.Study designInfants diagnosed with NC/RC on ultrasound within the first year of life and corresponding gestational age- and gender-matched controls were identified from the neonatal intensive care unit database at our institution over a 10-year period. Risk factors assessed included: low birth weight, small for gestational age, nephrotoxic drugs, respiratory support therapy, use of total parental nutrition (TPN), surgeries, history of UTIs, creatinine at presentation, and history of maternal hypertension. Unadjusted odds ratios were estimated. Chi square analysis was performed for binary variables and the Mann-Whitney U test for continuous variables. Outcomes examined include time to resolution of NC/RC, renal function, and hypertension.ResultsWe identified 22 cases of NC/RC with corresponding matched controls. Median follow-up was 28 months (IQR 0-122 months). History of urinary tract infections (UTI) was the only variable significantly associated with the presence of NC/RC (OR 5.62, 95% CI 1.12-31.1, p < 0.013) (Table). All other known risk factors were comparable in both groups. There was no difference in the incidence of hypertension (OR 2.94, 95% CI 0.40-33.82, p = 0.216) at diagnosis or last follow-up between the groups. Resolution of NC/RC was observed in 72.7%, during a median follow-up of 12.1 months. Mean urinary calcium/creatinine ratio for the NC/RC group was 2.3 ± 1.5 at diagnosis and 0.96 ± 0.8 at last follow-up.DiscussionMost NC/RC in infants resolve without surgical intervention but some infants require medical therapy and follow-up. Risk factors for NC/RC in neonates continue to be poorly defined because of the quality of studies available. Our study provides further adjustment for confounders but has a small sample size and is restricted to neonates from an intensive care unit.ConclusionMost cases of NC/RC resolve spontaneously without surgical intervention. The mean time to resolution is 12.1 months, without untoward consequences in terms of hypertension. A history of UTIs is the only identified risk factor identified in this study which is associated with a significant increased risk of neonatal nephrocalcinosis and/or renal calculi. Larger prospective studies are warranted to confirm these findings.Summary Table. Selected risk factors for NC/RC.Controls (n = 22)Cases (n = 22)OR (95% CI)p-ValueVentilator support, days, median (IQR)2 (0-38)2.5 (0-28)-0.883Nephrotoxic drug exposure15 (68.1)16 (72.7)1.24 (0.28-5.61)0.741Small for gestational age8 (36.3)6 (27.2)0.65 (0.14-2.81)0.517Previous urinary tract infection4 (18.1)10 (45.4)5.62 (1.12-31.1)0.013Chi-square test for binary variables. Mann-Whitney U test for continuous variables.