The role of lithium carbonate and lithium citrate in regulating urinary citrate level and preventing nephrolithiasis

Abstract

Background and purpose: Urinary Citrate is an inhibitor of Calcium oxalate stone formation. It is reabsorbed in the proximal kidney through sodium dicarboxylate co-transporters (NaDC-1, NaDC-3) present in the renal tubular epithelium. Lithium (Li) is a known potent inhibitor of these transporters. We investigated the effect of lithium carbonate (LiC) and lithium citrate (LiCit) in regulating urinary citrate levels and preventing nephrolithiasis (NL) in the rat model.

Experimental approach: We took 220 Wistar rats and induced nephrolithiasis in 130 of them by administering high doses of 5% ammonium oxalate (AmOx) for seven days and labeled them as Group B. Rest were labeled as Group A. Each group was then divided into 3 subgroups. First sub-group acted as control while other two were treated with either lithium carbonate (LiC) or lithium citrate (LiCit) for 21 days. Ten rats from each of the six sub-groups were randomly selected for sacrifice on 3(rd), 7(th) and 14(th) day and additional 10(th) and 21(st) day from Li treated groups. Blood and urine samples were collected and analyzed on these days. The kidneys of the sacrificed rats were dissected and studied under light microscopy for crystal deposition (left kidney) and histological changes (right kidney).

Key results: Urinary citrate levels were significantly increased in response to either LiC (p<0.001) or LiCit (p<0.001). Increased urinary citrate levels resulted in the reduction of calcium oxalate (CaOx) crystal deposition, kidney tubular dilatation and infiltration of inflammatory cell in the tubulo-interstitium.

Conclusions and implications: Use of lithium salts might be a potentially useful approach in the prevention of recurrent NL.

Keywords: kidney calculi; lithium; nephrolithiasis; urinary citrate levels; urolithiasis.

Figure 1

Urinary citrate Levels after administration of LiC and LiCit in group A rats. Urinary Citrate levels are increased with administration of LiC and LiCit as compared to untreated controls.

Figure 2

Urinary Citrate Levels after administration of LiC and LiCit in group B rats. Urinary Citrate levels increased significantly after 3 days of administration of LiC and LiCit compared to untreated NL model rats.

Figure 3

Plasma citrate levels when LiC and LiCit were given in Group A rats. Plasma citrate levels are significantly increased with administration of LiC or LiCit.

Figure 4

Plasma citrate levels in NL model rats (Group B). Plasma citrate levels increased after a week of Lithium therapy in both Group B2 and B3.

Figure 5

Plasma Lithium levels corresponding to 36.9 mg/d and 94 mg/d of LiC and LiCit respectively as compared to control.

Figure 6

Renal morphological alterations of experimental nephrolithiasis in rats (A), Normal kidney (×200). (B), Renal morphological alterations of rats at 14th day after 5% AmOx contained forge administration, showing obviously dilated renal tubules and marked inflammatory cell infiltration in the tubulointerstitium (×200). (C) and (D), Renal morphological alterations of rats of experimental NL after LiC or LiCi treatment for 7 days, displaying mildly dilated renal tubules and less inflammatory cells infiltration (×200). (E) and (F), Renal morphological alterations of experimental NL rats treated with LiC or LiCi for 14 days respectively, displaying above mentioned lesions caused by AmOx administration were further alleviated.