Magnesium wasting

The irreversible form of amphotericin nephrotoxicity usually occurs in the setting of prolonged administration (> 4 g cumulative dose). Renal toxicity commonly presents with renal tubular acidosis and severe potassium and magnesium wasting. There is some evidence that the prerenal component can be attenuated with sodium loading, and it is common practice to administer normal saline infusions with the daily doses of amphotericin B. 

Barton CH, Vaziri ND, Martin DC et al. (1987) Hypomagnesemia and renal magnesium wasting in renal transplant recipients receiving cyclosporine. Am J Med 83 693-699... 

Lam M, Adelstein DJ (1986) Hypomagnesemia and renal magnesium wasting in patients treated with cisplatin. Am J Kidney Dis 8 164-169... 

Tuso PJ, Nortman D (1992) Renal magnesium wasting associated with acetaminophen abuse. Conn Med 56 421 —423... 

In five healthy volunteers gentamicin 5 mg/kg caused immediate but transient renal calcium and magnesium wasting (78). 

Renal magnesium wasting occurred in 24% of a series of renal transplant patients taking ciclosporin other indicators of renal function were normal (66,67). 

Renal magnesium wasting is the main mechanism responsible for the hypomagnesemia associated with cisplatin (172), and it can be associated with enhanced tubular reabsorption of calcium and consequent hypocalciuria (173). This dissociation in the renal handling of calcium and magnesium is similar to what is found in Bartter s syndrome. The site of the renal tubular defect in these conditions is not known, but there is evidence that active renal tubular transport systems are disrupted. 

Mavichak V, Coppin CM, Wong NL, Dirks JH, Walker V, Sutton RA. Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man. Chn Sci (Lond) 1988 75(2) 203-7. 

The most restrictive adverse effect associated with AmB therapy is its potential to induce nephrotoxicity, manifested as disturbances in both glomerular and tubular function. The clinical manifestations usually include azotemia, renal tubular acidosis, decreased concentrating ability of the kidney, and electrolyte disturbances such as urinary potassium wasting leading to hypokalemia, and magnesium wasting to result in hypomagnesemia [17]. 

The mechanisms for the observed AmB induced renal magnesium wasting remain unclear. Increased... 

Barton CH, Pahl M, Vazirl ND,CesarloT. Renal magnesium wasting associated with amphotericin B therapy. Am J Med 1984 77 471 -4. 

Symptomatic hj/pocalcenda and hj/pomagnesenda with rend magnesium wasting associated with pentamidine therapy was described in a patient with AIDS [183]. Three other cases have been reporte [184-186]. 

Another previous report [187] described severe hypocalcemia with tetany in patients with AIDS concomitantly receiving pentamidine and foscarnet. The hypocalcemia, however, was attributed to the administration of foscarnet. Despite magnesium replacement, magnesium wasting may persist up to two months after the discontinuation of pentamidine, suggesting that anatomic renal tubular injury may be responsible [183,185]. Both abnormalities developed within 6 to 10 days of pentamidine administration. Because life-threatening arrhythmias can develop, especially at serum magnesium levels less than 1.6 mg/dl, early replacement therapy is clinically warranted. 

In summary, parenteral pentamidine administration for the treatment of PCP can be associated with the development of usually mild, reversible acute kidney injury. Compounding risk factors, of which volume depletion is the most important, are found in the majority of cases of pentamidine nephrotoxicity. There is no convincing evidence that the aerosol route of pentamidine administration for PCP prophylaxis results in nephrotoxicity. Hypocalcemia and hypomagnesemia with renal magnesium wasting, and particularly, hyperkalemia are seen with pentamidine therapy. 

Shah GM, Alvarado P, Kirschenbaum MA. Symptomatic hypocalcemia and hypomagnesemia with renal magnesium wasting associated with pentamidine therapy in a patient with AiDS.The American journal of medicine. 1990 Sep 89(3) 380-2. 

Mani S. Pentamidine-induced renal magnesium wasting. AiDS (London, England). 1992 Jun 6(6) 594-5. 

Excessive urinary losses of magnesium from the kidneys are important causes of magnesium deficiency. Clinically important causes include alcohol, diabetes meUitus (osmotic diuresis), loop diuretics (furosemide), and aminoglycoside antibiotics. Increased sodium excretion (parenteral fluid therapy) and increased calcium excretion (hypercalcemic states) also result in renal magnesium wasting. 

Toxicity is often initially manifest by abnormahties of renal tubular function including potassium, sodium, and magnesium wasting, impaired urine concentrating ability, and distal renal tubular acidosis due to a leak of hydrogen ions back out of the tubular lumen. Substantial potassium and magnesium replacement may be necessary. Renal blood flow and GFR decreases are common, and result in a rise in serum creatinine and blood urea nitrogen concentrations. 

Hypomagnesemia is commonly caused by excessive gastrointestinal or renal magnesium wasting. 

Hypomagnesemia Diarrhea, malabsorption, anabolism magnesium-wasting drug therapy Increase magnesium intake... 

---