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NDT Advance Access published online on June 1, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh311
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received March 25, 2004
Accepted April 16, 2004

Original Article

Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. I. Renal function and biochemical changes

Aquiles Jara 1*, Cecilia Chacón 1, Magdalena Ibaceta 1, Andres Valdivieso 1, Arnold J. Felsenfeld 2

1 Department of Nephrology, Pontificia Universidad Católica de Chile, Santiago, Chile
2 Department of Medicine, West Los Angeles VA Medical Center and UCLA, Los Angeles, California, USA

* To whom correspondence should be addressed. E-mail: ajara{at}med.puc.cl.



  Abstract

Background. Both dietary phosphorus restriction and the ingestion of ammonium chloride (NH4Cl) given to rats on a high-phosphorus diet have been shown to preserve renal function in the azotaemic rat. Parathyroidectomy also has been reported to preserve renal function and, in addition, to prevent kidney hypertrophy in the remnant kidney model. Our goals were (i) to evaluate in azotaemic rats the effect of dietary phosphorus on renal function in a shorter time frame than previously studied and (ii) to determine whether NH4Cl administration (a) enhances the renoprotective effect of dietary phosphorus restriction and (b) improves renal function in the absence of parathyroid hormone (PTH).

Methods. High (H; 1.2%), normal (N; 0.6%) and low (L; <0.05%) phosphorus diets (PD) were given for 30 days to 5/6 nephrectomized rats. In each dietary group, one-half of the rats were given NH4Cl in the drinking water. The six groups were HPD + NH4Cl, HPD, NPD + NH4Cl, NPD, LPD + NH4Cl and LPD. The effect of NH4Cl administration was also evaluated in 5/6 nephrectomized, parathyroidectomized (PTX) rats on NPD.

Results. In each of the three dietary phosphorus groups, creatinine and urea clearances were greater (P<0.01) in rats receiving NH4Cl. Neither creatinine nor urea clearance was reduced by high dietary phosphorus. Urine calcium excretion was greatest in the LPD group and was increased (P <= 0.001) in all three groups by NH4Cl ingestion. An inverse correlation was present between plasma calcium and phosphorus in the parathyroid intact (r = -0.79, P<0.001) and PTX groups (r = -0.46, P = 0.02). In PTX rats, NH4Cl ingestion increased (P <= 0.01) creatinine and urea clearances and both an increasing plasma calcium concentration (r = 0.67, P<0.001) and urine calcium excretion (r = 0.73, P<0.001) increased urine phosphorus excretion.

Conclusions. At 30 days of renal failure (i) NH4Cl ingestion increased creatinine and urea clearances, irrespective of dietary phosphorus; (ii) high urine calcium excretion, induced by dietary phosphorus restriction and NH4Cl ingestion, did not adversely affect renal function; (iii) high dietary phosphorus did not decrease renal function; (iv) the absence of PTH did not preserve renal function or prevent NH4Cl from improving renal function; and (v) both an increasing plasma calcium concentration and urine calcium excretion resulted in an increase in urine phosphorus excretion in PTX rats.

Keywords: ammonium chloride; calcium; dietary phosphorus; phosphorus; renal failure


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