Lithium nephropathy

Introduction

Chronic use of lithium in patients with affective disorders is associated with different forms of kidney damage. Nephrogenic diabetes insipidus is the most common renal side effect of lithium treatment. In addition, lithium use can lead to chronic interstitial nephritis (CIN) and will, in rare cases, lead to end-stage kidney failure.

Clinical presentation

40% of lithium users will developed reduced ability to concentrate urine, and a smaller number will develop renal diabetes insipidus. Lithium use can affect ADH sensitivity in the collecting ducts and result in a diminished response to ADH. Reduced presentation of aquaporines luminally will therefore lead to weakened ability to concentrate urine. The changes can become irreversible after prolonged usage. Nocturia in lithium users should lead to suspicions of the condition. Renal tubular acidosis can also occur due to defects in the distal parts of the nephron. Chronic interstitial nephritis is also a known delayed effect of lithium use, the presentation of the disease and histopathological finds are then as with other CIN. (see chronic interstitial nephritis). In addition, nephrotic syndromes with histopathological finds like in minimal change nephropathy and FSGS are also related to lithium use. The mechanism behind this is not well understood.

Prognosis and treatment

Lithium is often a necessary treatment for psychiatric disorders. It is therefore not always advisable to stop the medication even if desired. Further treatment should be discussed with the attending psychiatrist and other alternatives should be considered if advisable. If further lithium use is necessary, amiloride can improve the symptoms of diabetes insipidus. Lithium competes with Na for luminal Na-channels to enter the cells. Since the toxic effects of lithium in the collecting ducts are intracellular, blocking luminal Na channels will reduce the intracellular lithium and improve the senstitivity to ADH. Thiazid diuretics and NSAIDs are also used as treatment of renal diabetes insipidus. It is very important that lithium concentrations are monitored when amiloride, NSAIDs or thiazide diuretics are started, as renal clearance of lithium can decrease and the patient can develop severe lithium poisoning.

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