[Effect of PTH, phosphate, and metabolic acidosis on the progression of renal insufficiency in the azotemic rat]. / Efecto de la PTH, fosfato y acidosis metabólica en la progresión de la insuficiencia renal en la rata azotémica.

In a previous study we have observed that NH4Cl-induced metabolic acidosis halted the progression of renal disease in azotemic rats with a high phosphate diet. We hypothesized that NH4Cl-induced metabolic acidosis may exert its protective effect by decreasing renal calcium content independent of serum levels of PTH and phosphate loading. To test this hypothesis we studied azotemic rats with very low phosphate diet or parathyroidectomy. Rats with low phosphate diet and parathyroidectomized rats developed renal failure after 5/6 nephrectomy, and in both groups the acid loading significantly decreased the progression of renal disease. Calcium renal content increased in both groups, even in rats with low phosphate diet, and this effect was also significantly decreased after an acid loading. Rats with acid loading developed greater hypertrophy of renal tissue than rats without acid loading. We conclude that NH4Cl-induced metabolic acidosis halted the progression of renal disease by decreasing calcium precipitation on renal tissue. Parathyroidectomy did not prevent progression of renal disease nor calcium precipitation, and a low phosphate diet in azotemic rats did not prevent increased calcium content on remnant renal tissue.

Efecto de la PTH, fosfato y acidosis metabólica en la progresión de la insuficiencia renal en la rata azotémica / Role of PTH, phosphate, and metabolic acidosis in the progresión of renal disease in azotemic rats

Se ha demostrado que la acidosis metabólica (AM) inducida por cloruro de amonio (NH4Cl) enlentece la progresión del daño renal en ratas con nefrectomía 5/6 (NFX) y dieta alta en fósforo (P). Objetivo: Evaluar el rol de una dieta restringida en fósforo, 0,05%P (DBP) y de la paratiroidectomía (PTX) en el efecto protector de la AM inducida por NH4Cl sobre la progresión del daño renal en ratas azotémicas. Resultados: Las ratas azotémicas sometidas a una DBP tuvieron niveles de PTH más bajos que ratas normales con 0,6%P en la dieta (39,0 ± 12 vs 64,6 ± 12 pg/ml; p < 0,05). La administración de ácido por 30 días a ratas con DBP o PTX disminuyó la creatinemia (DBP: 0,67 ± 0,03 vs 0,54 ± 0,02 mg/dl, p < 0,05; PTX: 0,80 ± 0,06 vs 0,6 ± 0,04 mg/dl, p < 0,05) y mejoró el aclaramiento de creatinina (DBP: 2,6 ± 0,2 vs 3,5 ± 0,2 ml/min, p < 0,05; PTX: 2,4 ± 0,2 vs 3,5 ± 0,2 ml/min, p < 0,05). La PTX no evitó la progresión del daño renal y el contenido de calcio renal (KCa) fue el doble del observado en ratas azotémicas con DBP y 100 veces mayor al de ratas normales (103 ± 18 vs 48 ± 13 y 0,80 ± 0,09 μmol/g respectivamente, p < 0,01). La carga de ácido disminuyó el KCa en ratas con DBP o PTX (32 ± 9,0 vs 48 ± 13 μmol/g y 53,9 ± 9,8 vs 103 ± 18 μmol/g respectivamente; p < 0,05). El peso del tejido renal remanente (kWt) fue significativamente mayor en las ratas que recibieron ácido (DBP: 5,4 ± 0,3 vs 4,1 ± 0,2 mg/g; p < 0,05; PTX: 8,9 ± 0,5 vs 4,8 ± 0,4 mg/g; p < 0,05). Conclusiones: 1) la AM mejoró la función renal, disminuyó el contenido de calcio renal (KCa) y aumentó el peso del riñón remanente (kWt) en ratas azotémicas con DBP o PTX; 2) la PTX no evitó la progresión del daño renal ni el depósito de calcio renal; 3) una DBP en ratas azotémicas no evitó del aumento de contenido de calcio renal (AU)

In a previous study we have observed that NH4Cl-induced metabolic acidosis halted the progression of renal disease in azotemic rats with a high phosphate diet. We hypothesized that NH4Cl-induced metabolic acidosis may exert its protective effect by decreasing renal calcium content independent of serum levels of PTH and phosphate loading. To test this hypothesis we studied azotemic rats with very low phosphate diet or parathyroidectomy. Rats with low phosphate diet and parathyroidectomized rats developed renal failure after 5/6 nephrectomy, and in both groups the acid loading significantly decreased the progression of renal disease. Calcium renal content increased in both groups, even in rats with low phosphate diet, and this effect was also significantly decreased after an acid loading. Rats with acid loading developed greater hypertrophy of renal tissue than rats without acid loading. We conclude that NH4Cl-induced metabolic acidosis halted the progression of renal disease by decreasing calcium precipitation on renal tissue. Parathyroidectomy did not prevent progression of renal disease nor calcium precipitation, and a low phosphate diet in azotemic rats did not prevent increased calcium content on remnant renal tissue (AU)