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

Nephrol Dial Transplant. 2004 Aug;19(8):1993-8. doi: 10.1093/ndt/gfh301. Epub 2004 May 25.


Background: Kidney hypertrophy is stimulated by both partial nephrectomy and NH(4)Cl 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 NH(4)Cl 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 NH(4)Cl in the drinking water. The six groups of rats were: (i) HPD + NH(4)Cl; (ii) HPD; (iii) NPD + NH(4)Cl; (iv) NPD; (v) LPD + NH(4)Cl and (vi) LPD. In a separate study, PTX was performed to determine whether PTH affected renal hypertrophy in 5/6 nephrectomized rats given NH(4)Cl.

Results: Both with and without NH(4)Cl (+/-NH(4)Cl), 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 NH(4)Cl group. In both the +/-NH(4)Cl 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 NH(4)Cl. 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 +/-NH(4)Cl groups, but was greater in the HPD + NH(4)Cl 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 NH(4)Cl.

Conclusions: In azotaemic rats studied for 30 days, NH(4)Cl administration induced kidney hypertrophy. A HPD also induced kidney hypertrophy. The effects on kidney calcium deposition were divergent for which NH(4)Cl 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 NH(4)Cl from inducing kidney hypertrophy and reducing kidney calcium deposition. In conclusion, NH(4)Cl and dietary phosphorus each independently affect kidney growth and calcium deposition in the growing rat with renal failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Chloride / pharmacology*
  • Animals
  • Calcium / metabolism*
  • Creatinine / metabolism
  • Disease Progression
  • Diuretics / pharmacology*
  • Hypertrophy
  • Kidney / metabolism*
  • Kidney / pathology*
  • Male
  • Nephrectomy
  • Parathyroidectomy
  • Phosphorus / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / metabolism
  • Renal Insufficiency / pathology*
  • Uremia / metabolism
  • Uremia / pathology*


  • Diuretics
  • Ammonium Chloride
  • Phosphorus
  • Creatinine
  • Calcium