Nephrotic Syndrome Induced by Dibasic Sodium Phosphate Injections for Twenty-eight Days in Rats

Abstract

Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.

Hyperglycemic environment disrupts phosphate transporter function and promotes calcification processes in podocytes and isolated glomeruli

“…Dense granules that were stained with von Kossa dye (which is used to visualize calcium complexes) were observed in podocytes (Tsuchiya et al, 2004). This led to the fusion and detachment of foot processes, thickening of the glomerular basement membrane, and consequently overt proteinuria that resembled nephrotic syndrome (Tsuchiya et al, 2009). These abnormalities may result from the influx of Pi into podocytes, with the participation of phosphate cotransporters.…”

Urinary Tract

“…141,142 Lesions were characterized by the presence of granular basophilic deposits in the glomerular and parietal epithelium associated with PAS positive nodules on the glomerular basement membrane. However, it has been induced in rats in a dose-related manner following bolus injection of dibasic sodium phosphate solution for 14 or 28 days.…”

Preparo do intestino grosso para a coloscopia: usos, abusos e idéias controversas

“…Os três parecem ser igualmente efetivos; pouca diferença de resultado relativo à limpeza há entre a solução NaP e a solução PEG, mas as duas soluções tem defeitos relativamente sérios e limitantes 63 . Apesar da reconhecida eficácia, o NaP tem sido incriminado em decorrência dos efeitos colaterais indesejáveis 9,63 , mormente os distúrbios eletrolíticos e as lesões renais [64][65][66][67][68][69] motivos pelos quais há vários alertas, por iniciativa do FDA, nos últimos 5 anos 70 , ou por estudos que salientam sua ação deleté-ria mesmo quando se trata de rins normais 71,72 . Embora as soluções com sais de fosfato seja um atrativo por causa do pequeno volume a ser ingerido -seja na forma de solução ou de comprimidos -e haja considerações de segurança no que diz respeito ao risco de hiperfosfatemia, hipernatremia, hipocalemia ou de hipocalcemia, deve-se observar, com insistência, que esses efeitos têm potencial para causar desidratação, acidose metabólica, insuficiência renal, tetania ou mesmo morte 9,[73][74][75][76][77][78][79][80][81] , além do que, também há um descuido geral no que diz respeito aos riscos para os pacientes com doenças cardíacas, renais e hepáticas 82,83 .…”