Electrolyte Blood Press.  2020 Dec;18(2):31-39. 10.5049/EBP.2020.18.2.31.

Association of Proteinuria with Urinary Concentration Defect in Puromycin Aminonucleoside Nephrosis

• Jo CH
• Kim S
• Kim GH

• KMID: 2511871
• DOI: http://doi.org/10.5049/EBP.2020.18.2.31

Abstract

Background
Puromycin aminonucleoside (PA) can induce nephrotic syndrome in rats, and proteinuria is an important mediator of tubulointerstitial injury in glomerulopathy. We assumed that glomerular proteinuria may affect tubular function, such as urinary concentration, and investigated whether a urinary concentration defect is associated with proteinuria in puromycin aminonucleoside nephrosis (PAN). We also investigated the defect response to enalapril.
Methods
Glomerular proteinuria was induced by a single intraperitoneal injection of PA (150 mg/kg BW) in male Sprague-Dawley rats. In a half of these rats, enalapril (35 mg/kg BW) was administered daily in a food mixture for two weeks. After the animal experiment, kidneys were harvested for immunoblot analysis and histopathologic examination.
Results
Compared with the control group, PA-treated rats had severe proteinuria, polyuria, and a lower urine osmolality. PA treatment induced remarkable tubulointerstitial injury and significant reductions in protein abundances of aquaporin-1 and Na-K-2Cl co-transporter type 2 (NKCC2). Proteinuria significantly correlated with osteopontin expression in the kidney and inversely correlated with renal expression of aquaporin-1, aquaporin-2, and NKCC2. The degree of tubulointerstitial injury significantly correlated with proteinuria, urine output, and osteopontin expression and inversely correlated with urine osmolality and renal expression of aquaporin-1, aquaporin-2, and NKCC2. No significant differences in parameters were found between PA-treated rats with and without enalapril.
Conclusion
In PAN, glomerular proteinuria was associated with tubulointerstitial injury and water diuresis. Downregulation of aquaporin-1 and NKCC2 can impair countercurrent multiplication and cause a urinary concentration defect in PAN.

Keyword

Enalapril; Proteinuria; Puromycin aminonucleoside; Tubulointerstitial injury; Urinary concentration