Reduced erythrocyte and leukocyte magnesium is associated with cyclosporin treatment and hypertension in renal transplant patients

Al-Khursany, I. A. M.; Thomas, Travis; Harrison, Karen; Wilkinson, Robert H.

doi:10.1093/oxfordjournals.ndt.a092115

Cited by 23 publications

(16 citation statements)

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“…These results contrast with the findings of Andoh et al (4) who reported that sirolimus, along with CsA and tacrolimus, causes significant hypomagnesemia in a rat model. The hypomagnesemia commonly observed in CsA-treated patients has been implicated in the pathophysiology of neurotoxicity and hypertension (24), and it is proposed to be an important factor in the pathogenesis of CsA nephrotoxicity (25). In the present study, significantly…”

mentioning

confidence: 57%

Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients

Morales

Wramner

Kreis

et al. 2002

American Journal of Transplantation

178

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Sirolimus and cyclosporine (CsA) prevent acute rejection in man when used as primary therapies in triple drug regimens. Sirolimus does not act via the calcineurin pathway and therefore is not expected to produce the same renal side-effects. This paper presents the pooled 2-year data analysis of renal function parameters from two open-label, randomized, multicenter studies. Patients (18-68 years) receiving a primary renal allograft were randomized to receive concentration-controlled sirolimus (n Ω 81) or CsA (n Ω 80), in combination with azathioprine and steroids (n Ω 83), or mycophenolate mofetil (MMF) and steroids (n Ω 78). From week 10 through year 2, calculated glomerular filtration rate (GFR) was significantly higher in sirolimus-than in CsA-treated patients (69.3 vs. 56.8 mL/min, at 2 years, p Ω0.004). Serum uric acid was significantly higher in the CsA-treated patients and magnesium was significantly lower; these parameters were more likely to be within normal limits in the sirolimus group. Mean serum potassium and phosphorus were lower in sirolimus-treated patients. In conclusion, sirolimus, when administered as primary therapy in combination with azathioprine or MMF, has a favorable safety profile compared to CsA with regards to renal function.

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mentioning

confidence: 57%

Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients

Morales

Wramner

Kreis

et al. 2002

American Journal of Transplantation

178

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“…It has been reported to increase the magnesium concentration in kidney, skeletal muscle, liver and leucocytes [15,16], but there are also contradictory findings, e.g. decreased magnesium in erythrocytes and leucocytes [19,20] and no change in skeletal muscle [21]. If the hypomagnesaemia was not caused by movement of extracellular magnesium into cells, then the medium-to long-term consequence of the hypomagnesaemia is likely to be loss of magnesium from bone to the extracellular fluid.…”

Section: Discussionmentioning

confidence: 99%

The hypomagnesaemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone

et al. 2000

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A side-effect of the immunosuppressive drug FK506 (Prograf; tacrolimus) is hypomagnesaemia. We have investigated the effects of short-term (7-day) treatment of rats with FK506, using a protocol designed to indicate whether there are modifications in the renal tubular handling of magnesium and other electrolytes, or in the tissue deposition of magnesium, which may account for the hypomagnesaemia. We have also investigated whether parathyroid hormone has a role in the observed hypomagnesaemia. Two studies have been performed; in the first we administered FK506 (0.5 mg x kg(-1) body weight x day(-1)) or vehicle by intraperitoneal injection for 7 days, and then housed the rats in metabolic cages for the 24 h collection of urine. At the end of the metabolic cage period, the animals were anaesthetized, and blood and tissue samples were taken for analysis. In the second set of experiments the dosage regime was identical, but at the end of the treatment period the animals were anaesthetized for implantation of arterial and venous cannulae, and then received a saline (plus inulin) infusion for 6 h, during which time blood and urine samples were collected. The dose of FK506 employed did not decrease the glomerular filtration rate. FK506 elicited hypomagnesaemia in both sets of experiments, accompanied by inappropriately high fractional excretion of magnesium. There was also evidence of disruption of the normal renal reabsorption of calcium, but this did not result in hypocalcaemia. Plasma parathyroid hormone activity was not significantly different between the two groups, and there was no evidence of altered tissue content of magnesium in kidney, liver, heart, skeletal muscle or bone. The study confirms that hypomagnesaemia is a significant side-effect of FK506, even at a relatively low dose which did not decrease the glomerular filtration rate. The effect is not due to a decrease in parathyroid hormone release, or to translocation of magnesium from plasma to tissues, but does reflect decreased renal tubular magnesium (and calcium) reabsorption.

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“…A diminished PGI 2 production may be caused by the hypomagnesaemia, a common ¢nding in CsAtreated patients [42]. During short-term use of CsA, a shift of plasma Mg 2z to mononuclear white blood cells is initiated [43], while after long-term use further plasma (but also cellular) Mg 2z depletion occurs due to renal Mg 2z loss based on the tubular resorption defect [44,45]. In our study on patients with severe psoriasis, low doses of CsA were used and over a relatively short period.…”

Section: Discussionmentioning

confidence: 99%

Red blood cell rigidification during cyclosporin therapy: a possible early warning signal for adverse reactions

Hardeman

Meinardi

İnce

et al. 1998

Scandinavian Journal of Clinical and Laboratory Investigation

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In a previous retrospective study with kidney-transplant patients, immunosuppressive treatment with Cyclosporin A (CsA) was found to be associated with impaired red blood cell (RBC) deformability. The aim of the present study was to evaluate and substantiate a possible causal relationship between the use of CsA and its effect on RBC deformability in a prospective study on non-transplant patients. Blood samples of 12 patients with psoriasis were taken before and after 2, 4, 8, 12 and 16 weeks of treatment with CsA (3-5 mg/day). Red cell deformability, expressed as Elongation Index (EI), was measured with the Laser-assisted Optical Rotational Cell Analyzer (LORCA), a new ektacytometric instrument. Mean values +/- SD for EI found after 16 weeks of treatment with cyclosporin (0.570 +/- 0.008) were significantly (p < 0.001) lower than the value before treatment (0.589 +/- 0.011). A dose-response relation could not be established within the small range of CsA doses used in this study. Irrespective of the dose, however, a significant correlation (r = -0.55; p = 0.0001) between duration of treatment and decrease in EI was demonstrated. In vitro incubation of blood with cyclosporin was not able to reproduce this effect, suggesting that a direct effect of the drug on RBCs is unlikely. Despite its use in relatively low doses, CsA causes a reduction in RBC deformability, an effect that increases during the course of treatment. It is suggested that this slow, but continuously increasing, RBC rigidification plays a role in the early pathogenesis of the adverse nephrotoxic complications frequently associated with this immunosuppressive regimen.

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Reduced erythrocyte and leukocyte magnesium is associated with cyclosporin treatment and hypertension in renal transplant patients

Cited by 23 publications

References 0 publications

Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients

Sirolimus Does Not Exhibit Nephrotoxicity Compared to Cyclosporine in Renal Transplant Recipients

The hypomagnesaemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone

Red blood cell rigidification during cyclosporin therapy: a possible early warning signal for adverse reactions

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