The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

Background: Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Methods: Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular-and glomerular generation count at PND 35, clinical pathology parameters at 3-and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Results: Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 +/- 0.32 vs. 5.0 +/- 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 +/- 3,468 vs. 30,527 +/- 4,096; p = 0.026), higher creatinine clearance (0.84 +/- 0.1 vs. 0.77 +/- 0.09 ml/min/kg; p = 0.047) at - 3 months and lower plasma creatinine ( 25.7 +/- 1.8 vs. 27.5 +/- 2.8 mu mol/l; p = 0.043) at (months. Conclusion: Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. (C) 2016 S. Karger AG, Basel