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

Ruud R.G. Bueters, Annelies Jeronimus-Klaasen, Nuria Maicas, Sandrine Florquin, Lambertus P. van den Heuvel, Michiel F. Schreuder
2016 Nephron  
3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 μmol/l; p = 0.043) at 9 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. Abstract Background: Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney
more » ... s 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
doi:10.1159/000442674 pmid:26807737 fatcat:is4gzticxvd67nvrylakgmcbhu