Lithium is an essential trace element required for health and is used as a drug of choice for the treatment of bipolar affective disorders. It is also used as a mood stabilizer for migraine and cluster headaches. Lithium has been successfully used to treat various diseases like arthritis, leucopenia (decrease in white blood cells), neurodegenerative diseases, and more. Such diseases require lifelong treatment, and the long-term effects of lithium are harmful to organs such as the kidneys. Lithium in the form of lithium carbonate is used as a psychiatric medication. However, the use of lithium has been reduced in the past few years due to its adverse effects, such as nephrotoxicity.

What Is Lithium Nephropathy?

Lithium is a drug to treat psychiatric diseases, and almost 50 % of patients develop polyuria. 15 to 20 % of patients develop nephrogenic diabetes insipidus (NDI). It is characterized by a loss of the ability of the kidney to concentrate urine due to resistance to vasopressin. Long-term use of lithium in patients with psychiatric disorders can cause nephrotoxicity, including kidney dysfunction and urinary abnormalities such as proteinuria. Despite lithium nephrotoxicity, the overall incidence of significant chronic lithium nephrotoxicity is low. The average latency duration from the start of lithium intake to the presence of end-stage renal disease is at least 20 years.

How Does Lithium Cause Nephropathy?

Kidney damage due to lithium can include acute or chronic kidney disease and kidney systems. The amount of damage depends on the period of time of lithium intake. The most common problem associated with lithium is a type of diabetes due to kidney damage called nephrogenic diabetes insipidus. This type of diabetes differs from diabetes mellitus caused by elevated blood sugar. In nephrogenic diabetes insipidus, the kidneys do not respond to antidiuretic hormone, a chemical messenger that controls fluid balance. This results in greater than normal urine output and excessive thirst.

What Are the Symptoms of Lithium Nephropathy?

Estimated Glomerular Filtration Rate - A fall in estimated GFR is found to be associated with increased lithium dosage in clinical practice.
Polyuria - Greater than normal urine output.
Polydipsia - Greater than normal fluid intake or excessive thirst.
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Orthostatic Hypotension - Drop in blood pressure during standing.
Tachycardia - Increased heartbeat.
Xerostomia - Dry mouth.
Hypernatraemia - Increased levels of sodium in the blood.
Delerium - Change in mental status.
Electrolyte Imbalance - Excessive loss of fluid can cause electrolyte imbalance. Electrolytes in the body are minerals with an electric charge. Examples of electrolytes are potassium and sodium. Symptoms of electrolyte imbalance or feeling of weakness, tiredness, irritability, and muscle pain.

What Is Acquired Nephrogenic Diabetes Insipidus?

Lithium is considered to be one of the most common causes of acquired nephrogenic diabetes insipidus. It is seen in almost 12 % of patients treated with lithium for more than 15 years. The patients with nephrogenic diabetes insipidus have renal impairment with polyuria or impaired renal concentrating ability. The development of NDI is characterized by polydipsia, the production of excessive amounts of urine, and dilute urine osmolality. The defect in urinary concentrating ability is seen within two to three months of commencement of the lithium therapy and disappears after cessation of the therapy. The most effective therapy to treat NDI is by using Amiloride, a potassium-sparing diuretic that acts on the distal tubule epithelial sodium channels and is effective in mild to moderate cases. Hydrochlorothiazide is also another diuretic used to treat NDI.

How to Prevent Kidney Damage Due to Lithium?

Avoiding levels of rhythm that are toxic to the kidneys can be a preventive step.
Monitoring levels of lithium to make sure the lowest amount gives the best results.
Checking the levels of creatinine in serum once or twice a year. If the level stays above 1.6 mg/dL, consult a physician.
If possible, avoid lithium intake twice a day and limit it to a once-a-day regimen.

How Is Lithium Nephropathy Diagnosed?

Blood Analysis - A blood profile to check the presence of serum creatinine can be done.
Urinalysis - The presence of protein in urine can be detected using urine tests.
Magnetic Resonance Imaging (MRI) - The presence of small cystic lesions can be detected on MRI screening.
Kidney Biopsy - Changes in the renal tissue and function are detected using biopsy.

How Is Lithium Nephropathy Treated?

The treatment of lithium-induced nephropathy depends upon the severity of the symptoms. The treatment modality lies in the severity of the toxicity and chronicity, as well as the presence of pertinent abnormalities. A short-term dose of lithium-induced renal changes is reversible, but the damage caused by long-term use is irreversible. Hydration to minimize lithium clearance is done. An isotonic solution of 0.9 % saline, depending upon the fluid status and cardiac function, is given. Gastrointestinal decontamination with whole bowel irrigation using polyethylene glycol solution is given.

What Are the Risks Associated With Lithium-Induced Nephropathy?

Lithium causes chronic kidney disease with increased dosage and advanced age.
A fall in the estimated glomerular filtration rate can be found, and the value is greater in women.
Other concomitant risks for chronic kidney disease such as hypertension and diabetes mellitus, the use of other nephrotoxic medication such as angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory agents, and Thiazide diuretics, and nephrogenic diabetes insipidus can increase the risk.
Lithium-induced nephrogenic diabetes insipidus also has its risk factors that include non-responsiveness of the mood disorder to lithium, and its continuous dosage twice daily implies increased risk.
Earlier secession of the lithium therapy reverses the renal conditions to normal. However, extended use of lithium can lead to irreversible changes in renal structure and function.
The poor prognosis of lithium nephropathy includes the degree of interstitial fibrosis and the presence of heavy proteinuria.

Conclusion :

Lithium is the most effective therapy for bipolar disorder. However, there are some significant toxicities associated with its long-term use. A low dose of lithium for the short term can cause minimal damage to the renal tissues and is reversible with cessation. Long-term effects of lithium can cause reversible kidney damage and pose a high risk for chronic kidney disease, end-stage renal disease, and renal failure. Therefore, a collaborative decision should be made regarding the dosage of lithium and the period of time for the management of bipolar disorders.