Lithium renal function effects

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

Polyuria, polydipsia, tremor, ataxia, nausea, diarrhea, weight gain, drowsiness, acne, hair loss Possible effects on thyroid and renal functioning with longterm administration Children prone to dehydration are at higher risk for acute lithium toxicity... 

Lithium should not be administered to patients with fluctuating or unstable renal function. Because hthium may affect functioning of the cardiac sinus node, patients with sinus node dysfunction (e.g., sick sinus syndrome) should not receive hthium. Although hthium also has acute and chronic effects on the thyroid, patients with hypothyroidism may receive hthium if the thyroid disease is adequately treated and monitored. Laboratory tests that should be performed before initiation of hthium are listed in Table 5-1. 

In this context, the first role of the laboratory is to detect specific adverse effects to target organs (see Role of the Laboratory later in this chapter). Monitoring will generally be tailored to the specific therapy used because of its known potential for causing certain problems. Examples include periodic blood counts with carbamazepine or clozapine and thyroid and renal function studies with long-term maintenance lithium. 

Hetmar O, Bolwig TG, Brun C, et al. Lithium long-term effects on the kidney I. Renal function in retrospect. Acta Psychiatr Scand 1986 73 574-581. 

In a cross-sectional study of 12 octogenarians (average age 84 years) who had taken lithium for an average of 54 months (mean serum concentration 0.42 mmol/1), none became toxic and none had to stop treatment because of adverse effects. Transient renal function abnormalities were noted one patient developed nephrogenic diabetes insipidus and one became hypothyroidic (510). For lithium therapy in very old people, the authors advised close monitoring in a specialized setting. 

A review of the psychiatric effects of NSAIDs included a section on renal function and lithium clearance (666). 

Stoll PM, Stokes PE, Okamoto M. Lithium isotopes differential effects on renal function and histology. Bipolar Disord 2001 3(4) 174-80. 

I The long-term effects of lithium on renal function are controversial ... 

Clinical effects of lithium are slow in onset and may not be apparent before a week or two of daily treatment. Lithium is cleared exclusively by the kidney at a rate 20% of that of creatinine. Clearance is influenced by many factors, including renal function, serum sodium concentration, hydration state, pregnancy, and the presence of other drugs. High urinary levels of sodium inhibit renal tubular reabsorption of lithium, thus decreasing its plasma levels. By decreasing blood volume, thiazides may increase lithium plasma levels. Any drug that can cross the blood-brain barrier can cross the placental barrier The answer is (C). 

A woman taking lithium carbonate developed signs of lithium toxicity (ataxia, dysarthria, tremor, confusion) within 2 to 3 weeks of starting to take enalapril 20 mg daily. After 5 weeks her plasma-lithium levels had risen from 0.88 to 3.3 mmol/L, and moderate renal impairment was noted. No toxicity occurred when the enalapril was later replaced by nifedipine. Lithium toxicity following the use of enalapril, and associated in some cases with a decrease in renal function, has been seen in another 5 patients, " and a reduced lithium dosage was found adequate in another patient. Enalapril 5 mg daily for 9 days had no effect on the mean serum-lithium levels of 9 healthy male subjects. However, one subject had a 31% increase in lithium levels. "... 

In a double-blind study, 13 patients with normal renal function were given a single 600-mg dose of lithium either with or without gabapentin at steady state. Gabapentin did not significantly alter the pharmacokinetics of the lithium, and no increase in adverse effects was noted. More longterm studies will be needed to confirm this lack of interaction, especially in patients with impaired renal function as both drugs are eliminated by renal excretion. ... 

Tredget J, Kirov A, Kirov G. Effects of chronic lithium treatment on renal function. J Affect Disord 2010 126(3) 436 0. 

Rej S, Herrmann N, Shulman K. The effects of lithium on renal function in older adults - a systematic review. J Geriatric Psychiatry Neurol... 

There is no final consensus on whether normal use of lithium, without any episode of toxicity (the vast majority of patients), may result in permanent renal impairment. Polyuria occurs in 20-40% and is due to inhibition of antidiuretic hormone (ADH) by lithium. It usually resolves on cessation of lithium as do any effects on glomerular function. Interference with thyroid function is due to inhibition of the action of thyroid stimulating hormone (TSH) and is easily managed by administration of thyroxine. Lithium is contraindicated during pregnancy (major vessel anomalies in fetus) and breastfeeding. 

To what extent long-term treatment with lithium impairs GFR is a matter of continued study (360). Lithium does not appear to impair GFR consistently, especially if correction is made for age-related changes in kidney function, although in one study there was an age-related reduction in 21% of 142 patients who had taken lithium for at least 15 years (366). There have been a few case reports of progressive renal insufficiency attributed to lithium, but it has not been possible to establish a cause-and-effect relation with absolute certainty. 

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