Kidney Coach

Lithium Toxicity & Kidney Disease

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Contents

  1. What is Lithium
  2. What is Lithium used for
  3. What are the dosage and side effects of lithium
  4. Lithium & its impact on the kidneys
  5. Lithium & Nephrogenic Diabetes Insipidis
  6. Lithium induced CKD
  7. How to prevent Lithium Toxicity

 

Lithium Toxicity & Kidney Disease
Lithium Toxicity & Kidney Disease

What is Lithium

Lithium is a well-known medication used in the treatment of bipolar and other psychiatric disorders, and it has helped many patients since its introduction. However, its therapeutic benefits are challenged due to significant adverse effects, particularly lithium toxicity. Among the various organs at risk, the kidneys are especially vulnerable due to their role in lithium excretion.

Lithium is a mood stabiliser used for certain mental illnesses such as;

  • Mania: a feeling of being highly overactive, distracted or excited
  • Hypomania: Like mania, but it is less severe
  • Bipolar disorder: Mood changes between feeling very high (mania) and very low (depression)

For behaviour to be classified as manic, three of the following signs/symptoms need to be present, and they must cause a significant disturbance to a person’s social or occupational functioning;

  • Inflated self-esteem or grandiosity
  • Increased quantity of speech or pressured speech
  • Decreased need for sleep
  • Racing thoughts
  • Difficulty concentrating
  • Increase in goal-directed behaviour
  • Engaging in activities that may have detrimental outcomes, such as excessive spending

It also treats symptoms of depressive episodes such as:

  • Indifference
  • Low energy
  • Loss of interest in activities
  • Feelings of extreme sadness
  • Periods of hopelessness
  • Suicidal thoughts

Lithium: Uses, side effects, dosage and more (medicalnewstoday.com)

Lithium can also be used to treat;

  • Schizophrenia
  • Some types of depression

Bipolar disorder is a condition where a person will experience rapid shifts in mood, energy, activity levels and concentration. It can affect a person’s ability to carry out everyday tasks. Lithium is used as a long-term treatment for bipolar disorder as it helps to decrease the intensity of manic and depressive episodes and will help to make the symptoms less severe.

Lithium is taken orally as a pill or liquid form and is found as;

  • extended-release (ER) tablets, which are long-acting
  • immediate-release (IR) tablets, which are short-acting
  • capsules
  • liquid solution

Lithium toxicity and renal disease

Lithium: Side Effects, Uses, Dosage, and More | Psych Central

Lithium: Uses, side effects, dosage and more (medicalnewstoday.com)

Although lithium is an effective medication used for mood disorders, it has a narrow therapeutic window and is associated with a number of significant side effects and toxicities.  Disturbances associated with lithium salts were first documented by Garfinkel et al. in 1973, where cases of hypothyroidism and hyperparathyroidism were observed. Frequently, lithium is prescribed as a chronic, long-term medication. Therefore, regular monitoring of calcium homeostasis, as well as thyroid and kidney function, is required. In addition, patients using lithium salts may experience other side effects such as nephrogenic diabetes insipidus and decline in renal function.

Dosage & Side Effects of Lithium

If the prescribed dose of lithium is too low, the medication will not work properly; however, if the dose is too high, patients can experience more severe side effects (lithium toxicity) such as;

  • Increased stomach pain, vomiting or diarrhoea
  • Increased muscle weakness, shaking or twitching
  • Severe drowsiness, dizziness
  • Staggering or trouble walking or slurred speech
  • Dry mouth, very thirsty
  • Ringing in the ears
  • Blurred vision
  • Swelling of your face, mouth, or tongue that may cause trouble breathing or swallowing

Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management – PMC (nih.gov)

Not all of these side effects will occur with this medication, but if they do, please contact and discuss them with your medical doctor.

Less common
  • Confusion, poor memory, or lack of awareness
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • frequent urination
  • slow heartbeat
  • stiffness of the arms or legs
  • troubled breathing (especially during hard work or exercise)
  • unusual tiredness or weakness
  • weight gain

Lithium (Oral Route) Side Effects – Mayo Clinic

Lithium & its Effect on Kidneys

Following are the key ways lithium can impact kidney function;

Nephrogenic Diabetes Insipidus

Nephrogenic diabetes insipidus (NDI) is the most common side effect seen with lithium therapy and is seen in 50-73% of patients using it long-term. NDI can be reversable when lithium treatment is discontinued, however, persisting cases have been reported after the cessation of lithium.

The most common symptoms experienced by adults include:

  • excessive thirst
  • excessive urination
  • frequent urination at night

* NDI is unrelated to diabetes mellitus, commonly known as diabetes.

NDI occurs when the kidneys are unable to concentrate urine. For most of us, the body balances the fluids we drink with the amount of urine excreted. People with NDI produce an excessive amount of urine (polyuria), which causes insatiable thirst (polydipsia). Vasopressin, or antidiuretic hormone (ADH), is a hormone that regulates the balance of fluid intake and urine excretion. When the intake of fluid is low, the body’s levels of ADH increase, signalling the body to make less urine. In contrast, when fluid intake is high, ADH levels decrease, causing the kidneys to produce more urine.

Lithium & Nephrogenic Diabetes Insipidus

Lithium causes NDI by interfering with the ADH signalling pathway in the kidneys and interferes with the normal function of the collecting ducts within the kidneys, which are critical for water reabsorption. Lithium enters the cells of the collecting duct through the epithelial sodium channel. Here it inhibits the action of ADH, glycogen synthase kinase-3 (GSK-3) activity, and the generation of cAMP.1. Research shows it also induces cyclooxygenase-2 expression in renal interstitial cells and the production of prostaglandin E2 (PGE2). Polymorphisms of the GSK-3 beta gene can occur causing an issue, this may be related to the differences in the extent of lithium induced renal concentrating defect among patients who take lithium.

Lithium-induced nephrogenic diabetes insipidus (NDI), is reversible in early treatment, however, it may become irreversible over time. It all depends on the stage of kidney disease and the duration of lithium treatment; even once lithium has been discontinued, symptoms can still persist.

CP02204037.pdf (mdedge.com)

Nephrogenic Diabetes Insipidus (NDI): What is it? (healthline.com)

LITHIUM-INDUCED NEPHROGENIC DIABETES INSIPIDUS RESPONSIVE TO DESMOPRESSIN – PMC (nih.gov)

 

Lithium and kidney failure

Lithium-Induced Chronic Kidney Disease

Chronic Tubulointerstitial Nephropathy (CTIN)

Kidney disease due to lithium can occur as acute (sudden) or chronic kidney disease and cysts. Renal failure is a risk factor for cardiovascular disease, making it necessary to weigh up the pros and cons associated with lithium therapy. There is uncertainty in the prevalence of CKD related to lithium intake, and some studies suggest between 10-35% of patients are impacted.

Closely monitoring lithium levels and renal functioning can prevent the occurrence of chronic kidney disease stage 4 and end-stage renal failure.

Risk factors for renal failure have been found to be;

  • Higher lithium levels
  • Duration of lithium therapy
  • Lower initial eGFR
  • Older age and medical comorbidity

The predominant form of chronic renal disease associated with long-term lithium treatment is chronic tubulointerstitial nephropathy (CTIN). Findings in patients with CTIN include;

  • Tubular atrophy
  • Interstitial fibrosis
  • Sclerotic glomeruli
  • Tubular dilation
  • Nephron atrophy with cyst formation

How to Help Prevent Lithium Toxicity

Healthcare providers recommend regular blood and urine testing to monitor your health when taking lithium long-term. Suggestions are as follows;

  • Check blood lithium levels three to five days after starting or adjusting the dose.
  • Checking blood lithium levels every three to six months for people on long-term therapy.
  • Checking electrolyte, urea and creatinine levels every three to six months.
  • Checking calcium and thyroid-stimulating hormone (TSH) levels every six to 12 months.
  • Kidney function should be assessed before and during lithium treatment.

Lithium Toxicity: What It Is, Causes, Symptoms & Treatment (clevelandclinic.org)

Lithium: Package Insert – Drugs.com

Chronic kidney disease in lithium-treated patients, incidence and rate of decline | International Journal of Bipolar Disorders | Full Text (springeropen.com)

Lithium is eliminated primarily via the kidneys, the clearance of lithium is decreased in patients with abnormal renal function, therefore the risk of lithium toxicity increases under these circumstances. ‘Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine, creatinine clearance, or proteinuria). During lithium treatment, progressive or sudden changes in renal function, even within the normal range, indicate the need for re­-evaluation of treatment’.

.Lithium: Package Insert – Drugs.com

Image via https://psychscenehub.com/psychinsights/lithium-prescribing-monitoring-clinical-practice/

While effective, long-term use of lithium poses a risk for the development of renal complications, including nephrogenic diabetes insipidus, chronic kidney disease, and acute kidney injury. Early detection of lithium toxicity through regular testing is crucial in mitigating long-term damage. It is critical patients are aware of the signs and symptoms and seek medical advice as required.

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