Lithium-induced kidney problems

Published: October, 2009

Serious problems are unusual, but monitoring is key.

Lithium is one of the most effective treatments for bipolar disorder, not only helping to prevent relapse, but also reducing risk of suicide in these patients. But clinicians and patients may be concerned about risks of using lithium for bipolar disorder, including damage to the kidneys.

Doctors primarily worry about two types of kidney problems in patients who take lithium for bipolar disorder.

Excess thirst and urination

The most common lithium-induced kidney problem is impaired ability to concentrate urine, which may affect up to 60% of people with bipolar disorder during the first weeks or months of taking lithium. The problem persists in about 20% to 25%. The main symptoms — excessive thirst (polydipsia) and urination (polyuria) — are sometimes dismissed as unavoidable and even minor side effects of lithium treatment.

But these symptoms are evidence that the kidneys are not responding to the antidiuretic hormone that normally signals the kidneys to concentrate urine, a condition called nephrogenic diabetes insipidus.

Healthy people produce about one to two liters of urine per day. Anything more than three liters of urine output per day is considered polyuria. In patients with nephrogenic diabetes insipidus, urine output may reach up to 15 liters per day. If fluid intake does not match output, people may become so dehydrated that they develop neurological symptoms such as fatigue, headache, or lethargy. Furthermore, dehydration can also lead to toxic lithium levels, which in turn can damage the kidneys and other organs. (This is one reason clinicians advise patients taking lithium to ingest adequate amounts of liquid.)

Initial treatments. If a patient becomes excessively thirsty or urinates frequently while on lithium, the first step is to switch to a once-daily dose of the drug taken at bedtime, when urine production naturally slows. If this doesn't help, patients can increase fluid intake to avoid dehydration, while taking a lower dose of lithium.

Switch drugs. Patients can also try switching from lithium to a more kidney-friendly mood-stabilizing drug such as valproic acid (Depakote) or carbamazepine (Tegretol). Except in cases of lithium toxicity or acute kidney failure, it's important to reduce the lithium dose slowly rather than stopping it abruptly, to reduce risk of relapse and suicide.

Take a diuretic. If the benefits of lithium for bipolar disorder are so clear that it is desirable to manage a persistent urine-concentrating problem, patients can take a diuretic in addition to lithium. Although diuretics usually increase urine output, certain diuretics can affect how the kidneys handle lithium in a way that actually reduces urine output in people with nephrogenic diabetes insipidus.

The thiazide diuretic hydrochlorothiazide is one of these. If it is prescribed, the lithium dose is typically cut by half, because thiazide diuretics boost lithium levels in the blood and could cause toxicity. It's also important to monitor for imbalances of electrolytes, the salts that travel in the bloodstream. In particular, clinicians look out for low potassium levels — a potassium supplement may be necessary.

For this reason, the first choice is usually amiloride (Midamor), a potassium-sparing diuretic that may help patients avoid needing a potassium supplement. Another advantage to this drug is that it does not affect levels of lithium, reducing risk of toxicity.

The role of NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce excess urination, but — as with some diuretics — this class of drugs also can boost the lithium in the blood, sometimes to toxic levels. The NSAID most often discussed in nephrogenic diabetes insipidus is indomethacin (Indocin). It inhibits prostaglandins, compounds that are involved with regulation of urine flow (among numerous other functions). Because of the risk of toxicity, using NSAIDs to control lithium-induced nephrogenic diabetes insipidus is worthwhile only when lithium is uniquely beneficial for managing a patient's psychiatric symptoms.

Declining kidney function

Each kidney contains a million nephrons, tiny processing units that filter waste and produce urine. Nephrons have a complex structure, and — in a small proportion of patients — lithium causes enough damage to nephrons to gradually decrease function. Rarely, kidney failure occurs.

Kidney impairment is diagnosed with a combination of blood and urine tests. A standard measure of overall kidney function is the glomerular filtration rate (GFR). One frequently cited study analyzed reports of kidney function in 1,172 patients on lithium who had taken part in studies published from 1979 to 1986. It found that GFR was in the normal range in 85% of the patients, while it was only mildly decreased in the remaining 15%. But other researchers have noted that some patients on lithium experience a slow progressive decline in GFR or other subtle kidney damage that may elude clinical detection for years.

Taking lithium for bipolar disorder is not the only reason kidney function may become impaired. Kidney capacity gradually decreases with age, even in healthy people. And two common chronic conditions — high blood pressure and diabetes — can further impair kidney function by damaging blood vessels.

The first sign of kidney deterioration is the detection of tiny amounts of the protein albumin in the urine. As kidney deterioration worsens, larger amounts of albumin and other proteins are found in urine. The next stage is chronic kidney disease, or gradually decreasing function. Those most at risk are patients taking lithium continually for at least 20 years. Untreated, chronic kidney disease could eventually lead to kidney failure.

Patients' kidney function should be evaluated before they take lithium and monitored regularly. The American Psychiatric Association recommends testing kidney function every two to three months for the first six months of lithium treatment, and then following up with kidney function tests at least annually or semiannually afterward, unless more frequent testing is indicated medically. This can be done with simple blood tests taken at the same time as checking the lithium level.

If kidney function becomes moderately impaired (defined as a GFR of 45–59 ml/min/1.73m2), or seems to be declining steadily, it may be wise for patients to see a kidney specialist (nephrologist). Sometimes changes in diet can help reduce the kidneys' workload, but other steps may be necessary — including stopping lithium treatment and switching to another drug. It's also important to keep blood pressure under control and take other steps to guard heart health, because high blood pressure is associated with worsening kidney function, and vice versa.

Image: Mohammed Haneefa Nizamudeen/iStock

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