Lithium Nephrotoxicity 

1. What is lithium?

• Lithium is an monovalent cation,usually indicated in the treatment of bipolar disorders or other manic diseases,cluster headaches and in migraine headaches

• Being a mood stabilizing drug ,it can be used in treatment of anxiety and depression with or without other antidepressant drugs 
• Being an active cation it can easily displaces the sodium and potassium ions during reabsorption through kidneys 
• So, One  to one and half percentage of population May develop nephrogenic toxicity or the kidney damage
• Lithium is considered as a narrow therapeutic class of drug ,which means overdose can cause toxicity

2. How does lithium cause negative effects on the kidneys ?

• About 30 to 40% of patients on lithium therapy can experience the renal  toxicity that resulting in nephrogenic diabetes insipidus
• Usually affects distal tubules of  glomeruli of kidney
• To explain, the mechanism of action in under normal conditions is that sodium enters via epithelial sodium channels get exported through sodium potassium ATPase pump
• So Patients  on lithium therapy has lithium ions which interferes with the sodium and crosses the membrane enters the sodium channel and then prevents sodium from entering and disrupts the normal flow of sodium imbalances  the filtrate
• lithium inhibits GSK 3 beta intracellularly 
• As GSK 3 decreases  or get inhibited by lithium ,the sensitivity of  cells to the antidiuretic hormone or ADH happens  resulting in renal diabetes insipidus which usually  unbalancing to  control the osmolality of the kidneys and fails to reabsorption the water, resulting in polyuria and polydipsia 
• The toxic effects of lithium can be acute ,chronic ,acute on chronic
• Therapeutic dosage of lithium is not toxic to kidneys but above that can create severe issues  and permanent damage over time.
• Chronic kidney disease can show  chronic tubulointerstitial nephropathy, tubular atrophy, renal cyst tubular micro cysts  found in areas of damage, interstitial fibrosis where the kidney shrinks resulting in decreased GFR focal segmental sclerosis which is very rare
• Negative effects of lithium on kidneys can be accelerated by certain factors such as the duration of treatment ,the dosages of drug, the serum levels of lithium in the blood, frequency of use, frequency of acute lithium intoxication
• Specifically ,Acute effects can be determined by volume depletion ,obtundation cardiovascular collapse
• The chronic effects can be determined by polyuria, chronic kidney diseases 

3. What are the side effects of using lithium as a therapeutic drug?

• The therapeutic dosages range between 0.6-1.2 mEq/L,>1.5mEq/L more serious toxicity,>2.5mEq/L can cause death.
• Few of the major  side effect of using lithium on renal system  is nephrogenic diabetes insipidus, chronic kidney disease ,acute kidney injury, interstitial nephritis ,End stage renal disease (ESRD),interstitial fibrosis ,focal nephron atrophy,Chronic tubulointerstitial nephropathy,Medullary  tubular cyst,Tubular dilatation ,Interstitial fibrosis,Focal segmental glomerulosclerosis

4. What are the signs and symptoms?

• Signs and symptoms are classified into mild,moderate and severe

Polyuria -increased urine output than usual 

Polydipsia -increased thirst

Nocturia

Nausea 

Vomiting

Lethargy 

Tremors 

Confusion 

Agitation

Delirium 

Hypertonia

Coma

Seizures

Hypothermia

Swelling 

Renal insufficiency

Dehydration due to increased loss of water through urine 

Dry mouth

Tachycardia 

Hypertension(postural)

Hypernatremia 

Mood swings 

Irritability 

Fatigue

Tiredness

Blurred vision 

Muscle spasms 

Muscle Ache/spasms 

Hypotension

Death

5. How is it diagnosed ?

• Blood test to know the creatinine levels shows a decrease  levels due to poor kidney function,serum Na+levels ,GFR levels ,,BUN
• Urinary test to check the osmolality,urine volume 
• Interventional radiology to look for any masses or cysts 

6. Precautions to take from lithium to not get affected by it?

• Avoid taking more than therapeutic dosages of lithium when toxicity is detected 
• Checking and maintaining the blood levels of lithium as lower as possible
• Keeping track on creatinine levels / eGFR levels /BUN 
• Dialysis is used for cases of Li+ toxicity in few 
• Amiloride is prescribed for toxicity to inhibit the entrance of lithium 
• Take medication as suggested by the medical advisor only
• Fluid correction and electrolytes balance is taken care of  
• Health check up should be done for every 6 months 
• Withdraw on advice when necessary  by calibrated levels with caution 

7. Lithium usage with kidney disease?

• To protect the kidneys from the lithium  over usage  the toxicity can be inhibited by N-acetyl cysteine which is an antioxidant supplement which can be used as an additional way to protect the kidneys 
• 1800 mg / day for BID are mentioned to be benefited 

• Can be taken 2000 mg/day single dose per day or 1000mg/day twice a day 
• Even though there are possible concerns of kidney damage or nephritis ,however there are possible contributions of lithium usage resulting in decreased risk of stroke, cancer dementia, heart diseases and other neurological diseases
• The  symptoms and signs are manifested within one month of usage of lithium
• Can be ruled out by accessing the long-term use decrease The glomerular filtration rate
• Or might take around 25-30 years to express the severe damage 

How does it impaires?

• Hampers GFR rates 
• Leads to end stage renal disease (ESRD)
• Toxicity sometimes leading to renal cell death if dosage exceeds 0.8mmol/liter 
• Higher doses are recommended if acute stage of bipolar is existed (1.2mmol/lit)
• The dosage of inversely proportional to the age ,for 60 years -0.4-0.6 mg/day,young adults -0.6-0.8 mg/day

Contraindications of lithium therapy 

• Cardiac disease 
• Untreated hypothyroidism
• Pregnant women /breast feeding women 
• Addison disease
• Hypersensitive patients
• Severe renal impaired patients 
• Patient on low sodium /salt restricted diet 

How do we monitor patients on lithium toxicity?

• As mentioned above there is no specific treatment but the supportive treatment is indicated
• And it includes careful monitoring for 24 hours and the ECG study is done the treatment should be initiated, if hypertension is present
• Renal and thyroid tests are initiated for every 6 months and continues till the impairment is resolved
• Calcium function tests  are done for every 12 months as lithium causes hypoparathyroidism 
• Weight and body mass index is monitored regularly
• An ECG studies should be done regularly
• Hemodialysis should be done until there is no serum lithium levels

Drug interactions 

• ACE Inhibitors
• Thiazide diuretics
• NSAIDS

Frequently asked questions