Cyclosporin-Induced Renal Magnesium Leak in Renal Transplant Patients

Scoble, John E.; Freestone, Alyssa; Varghese, Z.; Fernando, O. N.; Sweny, P.; Moorheàd, J. F.

doi:10.1093/ndt/5.9.812

Cited by 20 publications

(9 citation statements)

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“…Most of our patients with chronic renal disease had mild to moderate renal failure, and normomagnesemia as expected [1]. The lower than normal values of serum tMg and Mg 2+ in renal transplant patients can be explained by cyclosporine-induced urinary magnesium wasting [3, 4]. Due to this magnesium leak, even magnesium substitution has been recommended for patients on cyclosporine [4, 13].…”

Section: Discussionmentioning

confidence: 83%

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Serum Ionized versus Total Magnesium in Patients with Chronic Renal Disease

Saha

Harmoinen

Nisula

et al. 1998

Nephron

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Background: Recent technology has made it possible to assess serum ionized magnesium with user-friendly ion-selective electrodes similar to measurement of the serum calcium concentration. Methods: We measured the serum ionized (Mg²⁺) and total magnesium (tMg) concentration in 69 patients with chronic kidney disease (38 men, 31 women, age 22–85 years) and in 75 control subjects. Results: In control subjects the reference ranges were as follows: serum Mg²⁺ 0.45–0.67 mmol/l, and tMg 0.67–0.96 mmol/l. In patients with chronic renal failure serum Mg²⁺ was 0.57 ± 0.05 mmol/l and tMg 0.80 ± 0.11 mmol/l, and in transplant recipients receiving cyclosporine 0.53 ± 0.05 and 0.71 ± 0.10 mmol/l, respectively. The correlation coefficient between serum Mg²⁺ and tMg was r = 0.73 (p < 0.001) in the patient group and r = 0.75 (p<0.001) in control subjects. Serum tMg was below the reference range in 15 of 69 measurements. However, serum Mg²⁺ was below the reference range in only 1 of these 15 samples. Hence, 14 of 69 cases with low tMg but normal Mg²⁺ were false-positive with respect to hypomagnesemia. Conclusion: We conclude that tMg may overestimate the incidence of hypomagnesemia, and the measurement of Mg²⁺ may be of benefit when studying patients with expected hypomagnesemia.

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Section: Discussionmentioning

confidence: 83%

“…Hypermagnesemia is common in advanced renal insufficiency, whereas serum magnesium levels are usually normal in mild to moderate renal function impairment due to compensatory decrease in tubular reabsorption [1, 2]. Subnormal magnesium levels have been reported in renal transplant recipients receiving cyclosporine [3, 4, 5]. …”

Section: Introductionmentioning

confidence: 99%

Serum Ionized versus Total Magnesium in Patients with Chronic Renal Disease

Saha

Harmoinen

Nisula

et al. 1998

Nephron

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“…The broad range can be the result of the fact that dietary Mg intake was not standardized, in view of the difficulty in enforcing strict nutritional restrictions in outpatients, and the fact that there are thus resultant broad day-to-day variations in Mg excretion. Peak serum Mg concentrations were lower in [20] related to a defective renal tubular system because of ischemia and the nephrotoxicity of various drugs especially ciclosporine [7,10,16]. The loading-test was applied to answer the question of whether there is magnesium deficiency or not.…”

Section: Discussionmentioning

confidence: 99%

“…Their mean Mg retention was 6.3 ± – 10.3% and the 0.025 and 0.975 fractiles were –19.5% and 27.5% of the loading dose, significantly less than the same investigative group found in the patients population [18]. Because even 8 hours infusion of the Mg load is unsuitably long for outpatients, we have undertaken studies of 1‐hour Mg infusion in healthy volunteers [19] and in patients who had undergone renal transplantation with (Mg wasting) immunosuppressive drug therapy [20]. Presented here are additional details on those studies, with the addition of comparative retention and bone Mg level data on hip replacement patients.…”

Section: Introductionmentioning

confidence: 99%

Can one really measure magnesium deficiency using the short‐term magnesium loading test?

Rob

Dick

Bley

et al. 1999

Journal of Internal Medicine

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. Rob PM, Dick K, Bley N, Seyfert T, Brinckmann CH, Höllriegel V, Friedrich HJ, Dibbelt L, Seelig MS (Medizinische Uniersität zu Lübeck, Freie Universität Berlin, Germany and University of North Carolina, Chapel Hill, USA). Can one really measure magnesium deficiency using the short‐term magnesium loading test? J Intern Med 1999 246: 373–378. Objective. To compare a 1‐h‐version of a magnesium‐loading‐test (MLT) designed for outpatients in healthy controls with the 8‐h standard; to establish the test in patients after renal transplantation prone to develop magnesium (Mg) deficiency; to correlate femur Mg‐concentration and percentage retention of the given load. Design. Comparision of mean values from healthy controls with respective from the literature; a prospective, randomized, controlled 4‐month study; an intra‐individual correlation of Mg‐serum values and loading‐test data with femur‐Mg concentrations. Setting. One centre study in a medical university; outpatients from the transplant unit; inpatients from the orthopedic unit. Subjects. Twenty‐four healthy controls aged 36.7 ± 7.4 years; 34 patients after renal transplantation (46.5 ± 14.3 years); 41 patients with hip replacement therapy (63.9 ± 18.6 years). Intervention. Baseline Mg values were measured by atomic absoprtion spectroscopy (AAS) in serum and urine. An intravenous Mg load with 0.1 mmol Mg‐aspartate hydrochloride per kilogram bodyweight was given during 1 h. In 24 h‐urine, the amount of excreted Mg was measured by AAS and the percentage retention of the given load calculated according to the formula: 1 −[Mg 24 h‐urine/Mg test dose] × 100. Femur Mg was measured by AAS in a peace of the femur neck. Patients after renal transplantation were randomized after the first Mg load to either obtain daily 5 mmol Mg‐aspartate hydrochloride per kilogram bodyweight, or placebo. Four months later a second loading‐procedure was performed. Main outcome measure. Serum Mg, percentage retention of the given Mg load (%Ret) and femur Mg concentration. Results. Mean serum Mg values were within the normal range. In controls, %Ret was –18 ± 21 and not different from the literature. In the first MLT after renal transplantation, %Ret was 47 ± 43. In patients under Mg medication it decreased significantly to 16 ± 26, but was 58 ± 27 in the placebo group. Femur Mg concentration was 62.6 ± 20.9 mmol kg–1 dry substance and the corresponding %Ret was 14 ± 28 with r = – 0.7093. Conclusion. The short‐term version of the MLT is as good as the standard and was easily applied in outpatients. The indication from the good correlation between bone‐Mg and %Ret and a marked decrease in %Ret in patients after Mg medication was that one can really measure magnesium deficiency.

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“…Most investigators assume that hypomagnesemia is a conse quence of a higher urinary fractional excretion rate [6][7][8]12], but some others believe that it is due to a shift of magnesium (Mg) into Mg-rich organs such as skeletal muscles, liver or kidney [5,9,10]. Only a few authors reported no significant alterations in serum Mg levels fol lowing long-term Ci treatment [13][14][15], but a decrease during the first week of treatment [13,14].…”

Section: Introductionmentioning

confidence: 99%

Magnesium Metabolism: Basic Aspects and Implications of Ciclosporine Toxicity in Rats

Rob

Lebeau

Nobiling

et al. 1996

Nephron

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In rapidly growing male Sprague-Dawley rats with an initial body weight of 100 ± 10 g, we investigated how alimentary magnesium (Mg) supply, Mg metabolism and ciclosporine (Ci)-associated nephrotoxicity are interrelated. Food with 100 ppm Mg (lMg) or 1,000 ppm Mg (stMg) or 10,000 ppm Mg (rMg), Ci 20 mg/kg body weight daily or olive oil were applied for 3 months (n = 10/group). Mg concentrations in various compartments were measured by atomic absorption spectrophotometry. Creatinine clearance (Jaffé), urinary N-acetyl-β-D-glucosaminidase (NAG) activity (fiuorometrically), urinary sodium excretion (flame photometry) and osmolality were measured. Histomorphological examination was done and renal renin expression was studied by monoclonal antibodies. Ci reduced the Mg concentration of the femur under lMg(72.6 ± 9.7 vs. 112.6 ± 14.3 mmol/kg dry substance, p < 0.05) and under stMg (150.6 ± 16.6 vs. 194.1 ± 10.2 mmol/kg dry substance, p < 0.05), thus indicating Ci-related Mg deficiency. This was due to a significant increase in Mg excretion in Ci treatment compared to dietary controls. Under rMg, there was no difference between Ci-treated and control animals. Ci treatment lowered creatinine clearance in lMg (1.42 ± 0.05 vs. 3.02 ± 0.58 ml/min) and in stMg (1.04 ± 0.45 vs. 2.18 ± 0.51 ml/min), NAG/creatinine and urinary sodium excretion were negatively affected by Ci under lMg and stMg. Histomorphology showed macrocalcifications due to Mg deficiency and Ci-specifïc findings, which were markedly enhanced in lMg and stMg. Animals with plentiful Mg supply had no functional alterations due to Ci and no or weakly expressed histomorphological lesions. Renin-positive stained cells were higher in Ci-treated animals. This seems to be functionally relevant under lMg and stMg, since it was associated with sodium retention and elevated relative heart weight, indicating hypertension. Alimentary or drug-induced Mg deficiency plays a relevant role in the pathophysiology of chronic Ci nephrotoxicity. Our data suggest that Mg supplementation is helpful to reduce Ci toxicity, even if there is ‘normal’ alimentary Mg intake.

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Cyclosporin-Induced Renal Magnesium Leak in Renal Transplant Patients

Cited by 20 publications

References 0 publications

Serum Ionized versus Total Magnesium in Patients with Chronic Renal Disease

Serum Ionized versus Total Magnesium in Patients with Chronic Renal Disease

Can one really measure magnesium deficiency using the short‐term magnesium loading test?

Magnesium Metabolism: Basic Aspects and Implications of Ciclosporine Toxicity in Rats

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