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
Dehydration due to increased loss of water through urine
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
- ACE Inhibitors
- Thiazide diuretics
Frequently asked questions
How do you treat lithium induced nephropathy?
The signs and symptoms can be treated with the use of diuretics and NSAIDS, Anticonvulsants
Discontinuation of lithium or lessening the dosage can be an alternative to prevent the damage
How does lithium affects potassium levels
As lithium interferes with the k+and Na + during filtration process leading to intracellular hypokalemia and extracellular hyperkalemia.usually it can be noticed in chronic lithium intoxication
Is lithium to toxicity is reversible
Lithium toxicity can be reversible in certain conditions of acute kidney damage but it is irreversible when the neurological and other chronic nephrogenic symptoms are noticed.Some patients do require hemodialysis
At what GFR should lithium be discontinued?
eGfr 40 ml/min and below are the the levels are considered to to cease the lithium usage and the studies have shown that it improved the condition in patients who discontinued the usage at eGFR level 40 ml per minute
What are the other organs that can be affected by lithium?
Apart from kidneys the other organs that get affected by the lithium usage are thyroid glands and parathyroid glands. The organs might be different but negative effects can be directly or indirectly affecting the kidneys in some way or the other
How dehydration and Salt intake shows its impact on patients on lithium therapy?
Dehydration can increase the risk of getting toxicity even more severe and decreased sodium intake can also results in the severity as well
Consuming as per the medical officer instructions regarding the diet and liquids intake is highly recommended
At what lithium levels dialysis is recommended?
many major guidelines recommend dialysis for asymptomatic patients if the lithium levels is greater than 4 mM, or above 2.5 mM with renal disease or impairment
Few other guidelines suggest if levels are greater than 5 mM, or above 4 mM
Does lithium affect blood cells count on usage ?
Yes ,it increases the White blood cell ,red blood cells counts and the other cell counts in both acute and chronic conditions of renal diseases.The reason is not completely known
This can be corrected by lithium carbonate
The blood tests are taken for every week but at least 3 months to 6 months until the levels are normalized
What foods should be avoided when in lithium therapy ?
Excessive intake of caffeine, energy saving drinks ,tea ,sodas,colas must be avoided in mentally sick patients as they may interfere with its mechanism of action by lowering its effectiveness
What anti inflammatory drugs can be taken on lithium therapy
Drugs such as Tylenol and clinoril are used as a pain relievers
What is the lithium belly?
Increased weight gain can results in lithium belly
This can be due or increased thirst constipation, fatigue, hormonal imbalance ,fluid retention etc
Is the best time to go check for lithium levels ?
The Best time is usually after 10 to 12 hours after the first usage of lithium.
Samples collected during mornings shows the precise and best results