Low serum magnesium is associated with decreased graft survival in patients with chronic cyclosporin nephrotoxicity.
BACKGROUND
Hypomagnesaemia is a common side effect of cyclosporin A (CsA) therapy. Animal studies suggest that magnesium (Mg) supplementation inhibits chronic CsA nephropathy.


METHODS
To determine if low Mg levels correlate with true CsA-induced nephrotoxicity in humans, we examined kidney transplant biopsy records at our centre for all transplant biopsies performed between 1990 and 2002. We simultaneously reviewed the medical records to determine whether serum Mg levels were checked at the time of biopsy. Those individuals with histologically proven CsA nephrotoxicity were studied.


RESULTS
Serum total Mg levels were available for 320 patients, 60 of whom were diagnosed with chronic CsA-mediated nephropathy. Patients were divided in two groups, a low Mg [n = 29, 1.8 (1.67-1.9) mg/dl or 0.74 (0.68-0.78) mmol/l] and a normal Mg group [n = 31, 2.2 (2.0-2.4) mg/dl or 0.9 (0.82-0.98) mmol/l, P<0.05] based on the median Mg level in the entire cohort (2 mg/dl or 0.82 mmol/l). Both groups were analysed for disease progression and graft loss using the slope of creatinine clearance (CCR) and multivariate analyses. Although the CCR at the time of biopsy was greater in the low Mg group [44.3 (36.3-64.3) ml/min vs 37.8 (25.2-47.3) ml/min, P<0.05), the decline in graft function was faster in this group (-8.9+/-3.5 vs 1+/-2.7 ml/min/year; P = 0.02) compared with the normal Mg cohort. Using Cox proportional hazards analyses, the adjusted graft survival was significantly reduced in the low Mg group 5 years after biopsy.


CONCLUSIONS
Our study demonstrates that low serum Mg levels were associated with a faster rate of decline in kidney allograft function and increased rates of graft loss in renal transplant recipients with chronic CsA nephropathy. This suggests that hypomagnesaemia could potentiate CsA-mediated nephropathy.
Holzmacher
Ryan
R
Department of Medicine, University of Wisconsin, Madison, WI, USA.
Kendziorski
Christina
C
Michael Hofman
R
R
Jaffery
Jonathan
J
Becker
Bryan
B
Djamali
Arjang
A
D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000097:blood* / Q000139:chemically induced*; D016030:Kidney Transplantation; D008274:Magnesium / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008274:Magnesium