Journal Article

Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. Part II–kidney hypertrophy and calcium deposition

Aquiles Jara, Cecilia Chacón, Magdalena Ibaceta, Andres Valdivieso and Arnold J. Felsenfeld

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 8, pages 1993-1998
Published in print August 2004 | ISSN: 0931-0509
Published online May 2004 | e-ISSN: 1460-2385 | DOI:
Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. Part II–kidney hypertrophy and calcium deposition

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Background. Kidney hypertrophy is stimulated by both partial nephrectomy and NH4Cl administration. Also, parathyroidectomy (PTX) has been reported to prevent kidney hypertrophy induced by a high protein diet. Our goal was to determine in the azotaemic rat: (i) the combined effects of NH4Cl administration and dietary phosphorus on the development of kidney hypertrophy and calcium deposition in the kidney and (ii) whether the absence of parathyroid hormone (PTH) affected the development of kidney hypertrophy and calcium deposition.

Methods. High (HPD, 1.2%), normal (NPD, 0.6%) or low (LPD, <0.05%) phosphorus diets were given to 5/6 nephrectomized rats for 30 days. In each dietary group, one-half of the rats were given NH4Cl in the drinking water. The six groups of rats were: (i) HPD + NH4Cl; (ii) HPD; (iii) NPD + NH4Cl; (iv) NPD; (v) LPD + NH4Cl and (vi) LPD. In a separate study, PTX was performed to determine whether PTH affected renal hypertrophy in 5/6 nephrectomized rats given NH4Cl.

Results. Both with and without NH4Cl (+/−NH4Cl), kidney weight was greatest (P<0.05) in the HPD groups. In each dietary phosphorus group, kidney weight was greater (P<0.05) in the NH4Cl group. In both the +/−NH4Cl groups, kidney calcium content was greatest (P<0.05) in the HPD group, but was less (P<0.05) in the NPD and HPD groups given NH4Cl. An inverse correlation was present between creatinine clearance and kidney calcium content (r = −0.51, P<0.001). When factored for kidney weight, creatinine clearance was less (P<0.05) in the HPD group in both the +/−NH4Cl groups, but was greater in the HPD + NH4Cl than in the HPD group. In PTX rats, kidney weight was greater (P<0.05) and kidney calcium deposition was less (P<0.05) in rats given NH4Cl.

Conclusions. In azotaemic rats studied for 30 days, NH4Cl administration induced kidney hypertrophy. A HPD also induced kidney hypertrophy. The effects on kidney calcium deposition were divergent for which NH4Cl administration decreased and a HPD increased calcium deposition. The inverse correlation between kidney calcium content and creatinine clearance suggests that kidney calcium deposition is harmful to renal function. When factored for kidney weight, the lower creatinine clearance in the high phosphorus group suggests that kidney hypertrophy does not completely compensate for the harmful effects of a HPD. This result also suggests that a longer study would probably result in more rapid deterioration in the high phosphorus group. In PTX rats, the absence of PTH did not prevent NH4Cl from inducing kidney hypertrophy and reducing kidney calcium deposition. In conclusion, NH4Cl and dietary phosphorus each independently affect kidney growth and calcium deposition in the growing rat with renal failure.

Keywords: ammonium chloride; dietary phosphorus; kidney hypertrophy; nephrocalcinosis

Journal Article.  3935 words.  Illustrated.

Subjects: Nephrology

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