Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations
A. Schmiedl et al., Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations, UROL RES, 29(4), 2001, pp. 229-237
Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etio
logy. Using highly inbred (syngeneic) male Lewis rats, we describe the spon
taneous occurrence of histologically detectable C-NC in sham operated contr
ol rats (Sham; n=12), its aggravation following grafting of the ascending t
horacic aorta from a donor rat to the infrarenal aorta of a recipient (ATx;
n=12), and differences in C-NC inhibition after 12 weeks of oral administr
ation of magnesium (Mg), citrate and alkali. C-NC is characterized by Kossa
-positive areas located in cells of the proximal tubule close to blood vess
els and also, to a lesser extent, within glomeruli. After ATx there was vas
cular overproduction of endothelin (ET-1) but decreased production of nitra
te; in renal cortical tissue there was an excess of calcium over Mg and pho
sphorus and oxalate over citrate. In plasma there was an increase in calciu
m and creatinine within the normal range. Calcification of tubular cells wa
s eliminated by a preparation containing potassium, sodium and bases (from
citrate degradation and bicarbonate) in addition to Mg. Less effective than
the latter was Mg-potassium citrate and least effective, Mg citrate. The f
ormer treatment also normalized calcemia and urinary nitrate, but only inco
mpletely suppressed ET-1 and had no significant effect on glomerular calcif
ication or tissue and urinary oxalate. Urinary ET-1 excess appeared directl
y related to the cortical tissue calcium/Mg ratio, and urinary excretion of
Mg, citrate and total protein appeared to be inversely related to the seve
rity of C-NC. It was concluded that (1) the highly inbred rat is prone to p
recipitation of calcium phosphate in the renal cortex; (2) this type of C-N
C occurs in close proximity to and within renal vascular tissue and is asso
ciated with an imbalance of vasoconstrictors and vasodilators of endothelia
l origin; (3) effective inhibition of C-NC can be achieved by an alkalinizi
ng combination of Mg, potassium, sodium and citrate, underscoring its utili
ty in the prophylaxis of pathological calcium phosphate deposition. The sig
nificance of these findings for the etiology and treatment of clinical diso
rders with renal and vascular calcification is uncertain and requires furth
er investigation.