Lithium nephrotoxicity

Markowitz GS, Radhakrishnan J, Kambham N, et al Lithium nephrotoxicity a progressive combined glomerular and mbulointerstitial nephropathy. J Am Soc Nephrol 11 1439-1448,2000 Myers DH, Carter RA, Bums BH, et al A prospective study of the effects of lithium on thyroid function and on the prevalence of antithyroid antibodies. Psychol Med 15 55-61, 1985... 

Markowitz GS, Radhakrishnan , Kambham N, Valeri AM, Hines WH, D Agati VD Lithium nephrotoxicity a progressive combined glomerular and tubulointerstitial nephropathy. Am Soc Nephrol 2000 11 1439-48. 

Walker RG, Davies BM, Holwill BJ. A chronic pathological study of lithium nephrotoxicity. J Chro Dis 1982 35 655-695. 

Walker RG. Lithium nephrotoxicity. Kidney Int Suppl 1993 42 S93-S98. LamSS, Kjellstrand C. Emergency treatment of lithium-induced diabetes insipidus with nonsteroidal anti-inflammatory drugs. Ren Eail 1997 19 183-188. 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Lithium-induced nephrotoxicity is rare if patients are maintained on the lowest effective dose, if once-daily dosing is used, if good hydration is maintained, and if toxicity is avoided. 

Urinary aikaiinization In the treatment of certain drug intoxications (eg, salicylates, lithium) and in hemolytic reactions requiring aikaiinization of the urine to diminish nephrotoxicity of blood pigments. 

Before the introduction of specific vasopressin receptor antagonists, pharmacological treatments for hyponatremia centered on the use of loop diuretics and nonspecific inhibitors of vasopressin signaling, such as lithium carbonate and demeclocycline.11 The utility of such therapies has been limited by a range of sideeffects. Loop diuretic use can result in electrolyte imbalances and suffers from poor response predictability.11 Lithium carbonate suffers from a low therapeutic index and a risk of renal damage as well as limited effectiveness in many patients. Lithium carbonate has therefore been nearly completely supplanted by demeclocycline, a tetracycline antibiotic, in the treatment of chronic hyponatremia.12 Demeclocycline use is itself limited by its nephrotoxicity (particularly in cirrhotic patients), ability to cause reversible uremia, and ability to induce photosensitivity.1,11... 

Etodolac This drug has effects similar to those of the other NSAIDs. Gastrointestinal problems may be less common. However, other adverse effects such as fluid retention and abnormal kidney and liver function have been reported. Etodolac may increase the serum levels and thus raise the risk of adverse reactions caused by digoxin, lithium, methotrexate, and enhance the nephrotoxicity of cyclosporine. 

Two studies in rats have potential implications for humans. In rats with mild to severe lithium-induced nephropathy, urine TV-acetyl-p-D-glucosaminidase was an early indicator of renal insufficiency (369). Both 6Li and 7Li caused reduced urine concentrating ability and increased urine volume and renal tubular lesions, but 6Li was more nephrotoxic (370). The authors suggested that eliminating 6Li from pharmaceutical products might reduce nephrotoxicity (although 6Li accounts for only about 7% of the lithium in such products). 

Hemodialysis (383,552,553), sometimes with additional continuous venovenous hemofiltration dialysis (554,555), continues to be described as a successful intervention for lithium poisoning. Peritoneal dialysis is a far less efficient way to clear lithium from the body. One patient treated in this way had permanent neurological abnormalities and another died a third toxic patient who also had diabetic ketoacidosis died after treatment with hydration and insulin (556). On the other hand, a 51-year-old woman who took 50 slow-release lithium carbonate tablets (450 mg) had a serum lithium concentration of 10.6 mmol/1 13 hours later, but no evidence of neurotoxicity or nephrotoxicity. She was treated conservatively with intravenous fluids and recovered fully (557). Acute lithium overdose is often better tolerated than chronic intoxication. 

Both lithium and rofecoxib have been associated with nephrotoxicity, and it is likely that lithium intoxication was caused by concomitant administration of rofecoxib, causing a reversible reduction in renal function. 

Tariq M, Morais C, Sobki S, A1 Sulaiman M, A1 Khader A. Effect of lithium on cyclosporin induced nephrotoxicity in rats. Ren Fail 2000 22(5) 545-60. 

Teicher MH, Altesman RI, Cole JO, Schatzberg AF. Possible nephrotoxic interaction of lithium and metronidazole. JAMA 1987 257(24) 3365-6. 

Porter, G. A., and Bennett, W. M. 1989. Drug-induced renal effects of cyclosporine, aminoglycoside antibiotics and lithium Extrapolation of animal data to man. In Nephrotoxicity Extrapolation from in vitro to in vivo, and animals to man, ed. Bach, P. H. and Lock, E. A., 147-170. New York, London Plenum Press. 

Loop diuretics (especially as i.v. boluses) potentiate ototoxicity of aminoglycosides and nephrotoxicity of some cephalosporins. NSAIDs tend to cause sodium retention which counteracts the effect of diuretics the mechanism may involve inhibition of renal prostaglandin formation. Diuretic treatment of a patient taking lithium can precipitate toxicity from this drug (the increased sodium loss is accompanied by reduced lithium excretion). Reference is made above to drug treatments which, when combined with diuretics, may lead to hyper-kalaemia, hypokalaemia, hyponatraemia, or glucose intolerance. 

Lithium carbonate 0.9-1.2gq.24hr Renal 100% 50-75% 25-50% Nephrotoxic adverse effects include nephrogenic diabetes insipidus, nephrotic syndrome, renal tubular acidosis, and interstitial fibrosis acute toxicity when serum levels > 1.2 mEq/L serum levels should be measured periodically 12 hr after dosing half life does not reflect extensive tissue accumulation plasma levels rebound after dialysis toxicity enhanced by volume depletion, NSAIDs, and diuretics Dose after dialysis NC Dose for GFR 10-50 ml/min... 

Metals A wide range of metals induce nephrotoxicity in humans and/or in animal models (Table 5). Some of these metals (e.g., iron, cobalt, copper) are essential elements required for normal body function, while others can be useful in treating diseases. For example, gold salts are useful in treating rheumatoid arthritis lithium salts are indicated for the treatment of manic-depressive illness and aluminum and bismuth salts are available to treat indigestion and stomach aches. However, exposure to these and other metals can occur from environmental sources and in excessive concentrations, can lead to nephropathy. 

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