Tenofovir-Induced Nephrotoxicity - Risk Factors, Complications, Diagnosis, and Treatment

Introduction

Drugs are a common cause of acute kidney injury. Compared to decades ago, the average patient nowadays is older, has more comorbidities, and is more likely to undergo diagnostic and therapeutic procedures that can impair kidney function. Drugs that are known to cause nephrotoxicity exert their toxic effects through one or more common pathogenic mechanisms. Drug-induced nephrotoxicity tends to occur more frequently in certain patients and in certain clinical settings. Successful prevention, therefore, requires knowledge of the pathogenic mechanisms of renal injury, patient-related risk factors, drug-related risk factors, and preventive measures, as well as vigilance and early intervention. Nephrotoxicity can cause acute kidney failure. Acute renal failure, also called acute kidney failure, develops rapidly, usually within a few days. Acute renal failure is most common in people already hospitalized, especially in critically ill patients who need urgent care.

What Is Tenofovir-Associated Nephrotoxicity?

Tenofovir is a prescription drug licensed in the United States by the Food and Drug Administration (FDA) for the treatment of HIV (human immunodeficiency virus) infection in adults and children over the age of 2 and weighing more than 10 killograms. Tenofovir is always used in combination with other HIV drugs. Nephrotoxicity is defined as the rapid deterioration of renal function due to the toxic effects of drugs or chemicals. It comes in many forms, and some drugs can affect kidney function in more than one way. Nephrotoxins are substances that exhibit nephrotoxicity. Proximal tubular cell secretion of Tenofovir in the kidney causes the accumulation of the drug in mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction and may be associated with acute kidney injury or chronic kidney disease.

What Are the Risk Factors of Tenofovir-Associated Nephrotoxicity?

Patient-related risk factors for drug-induced nephrotoxicity include the following:

• Decrease in intravascular volume (blood flow instability in the body).

• Age over 60 years.

• Diabetes mellitus (increased blood sugar).

• Exposure to multiple nephrotoxins.

• Heart failure.

• Sepsis (body’s extreme response to infection).

• Underlying renal dysfunction (glomerular filtration rate < 60 mL/min/1.73 square metres).

What Are the Symptoms of Tenofovir-Associated Nephrotoxicity?

Symptoms and signs of Tenofovir-associated kidney damage include:

• Difficulty breathing.

• Exhaustion.

• Nausea.

• Chest pain or chest tightness.

• Swelling of the legs, ankles, and feet due to fluid accumulation in the body.

• Decreased urine output.

• Irregular heartbeats.

What Are the Possible Complications of Tenofovir-Associated Nephrotoxicity?

The potential complications of Tenofovir- associated nephrotoxicity include:

• Fluid Accumulation- Acute renal failure can cause fluid to accumulate in the lungs, causing shortness of breath.

• Chest Pain- Inflammation of the pericardium (the membrane that covers the heart) can cause chest pain.

• Weakness- Muscle weakness occurs when the body's water and electrolytes (blood constituents) are out of balance.

• Permanent Kidney Damage- In some cases, nephrotoxicity causes acute renal failure, resulting in permanent loss of kidney function or end-stage renal disease. Patients with the end-stage renal disease require either permanent dialysis (a mechanical filtration process used to remove toxins and waste products from the body) or a kidney transplant to survive.

• Mortality- Nephrotoxicity can lead to loss of kidney function and eventual death.

When to Get Help for Tenofovir-Associated Nephrotoxicity?

A doctor's opinion should be immediately sought if symptoms of Tenofovir-associated nephrotoxicity listed below are noticed:

• Fluid retention in the legs and arms which causes swelling.

• Urinary flow is reduced.

• Feeling of weakness and tiredness.

• Hypertension (high uncontrollable blood pressure).

• Unbearable chest pain.

How Is Tenofovir-Associated Nephrotoxicity Diagnosed?

If signs and symptoms suggest nephrotoxicity, the physician may recommend certain tests and procedures to confirm the diagnosis. They include:

• Measurement of Urine Volume- Measuring urine output over 24 hours can help doctors identify the cause of kidney failure.

• Urinalysis- Analysis of a urine sample (urinalysis) may reveal abnormalities that indicate kidney failure.

• Blood Test- Blood tests may show rapidly elevated urea and creatinine levels - the two substances used to measure kidney function.

• Imaging Test- Imaging tests, such as ultrasound and computed tomography, help doctors visualize the kidneys.

• Biopsy of Kidney- In some circumstances, doctors may recommend a kidney biopsy to obtain a small sample of kidney tissue for laboratory tests. A needle is inserted through the skin into the kidney, and a sample is taken for further analysis.

How Is Tenofovir-Associated Nephrotoxicity Treated?

Treatment options of Tenofovir associated nephrotoxicity are listed below:

• The focus of treatment is to minimize nephrotoxic damage. Therefore, early detection of nephrotoxicity is essential.

• Drug treatment for severe nephrotoxicity.

• Dose adjustments are based on renal function.

• Dialysis removes waste products accumulated in the body.

How Can Tenofovir-Associated Nephrotoxicity Be Prevented?

Tenofovir nephrotoxicity can be prevented in the following ways-

• Use of effective but non nephrotoxic drugs.

• Estimation and improvement of potential risk factors of nephrotoxicity.

• Assessment of baseline renal function before starting the treatment.

• Adjustment of diet according to renal function.

• In at-risk patients, assessment of GFR (glomerular filtration rate) is mandatory before initiating treatment.

• Avoid prolonged intake or heavy dosage of the drug.

• Adequate hydration and treatment of underlying acute and chronic diseases.

• Good communication between experienced physicians and pharmacists for drug dose monitoring.

Some home remedies for the prevention of nephrotoxicity are -

• Choose Low-Potassium Foods- The nutritionist may recommend choosing low-potassium foods. Foods high in potassium include bananas, oranges, potatoes, spinach, and tomatoes. Examples of low-potassium foods include apples, cauliflower, bell peppers, grapes, and strawberries.

• Avoid Products With Added Salt- Reduce the amount of sodium one eats each day by avoiding products with added salt, including many convenience foods such as frozen foods, canned soups, and fast foods. Includes snacks, canned vegetables, processed meats, and cheeses.

• Limit Phosphorus in the Diet- Phosphorus is a mineral found in foods such as whole grain bread, oatmeal, bran cereal, dark cola, nuts, and peanut butter. Too much phosphorus in the blood can weaken bones and cause itchy skin. A nutritionist can give a specific meal plan.

Conclusion:

The kidney is a common site of drug toxicity due to frequent exposure to drugs and their toxic metabolites. Drug-induced nephrotoxicity is one of the leading causes of acute kidney injury worldwide. In addition to acute kidney injury, chronic drug toxicity can lead, in some cases, to chronic kidney disease and ultimately to end-stage renal disease. The drug can also interfere with the normal transport mechanisms of the kidneys and cause various electrolyte and acid-base disorders. If any symptoms of nephrotoxicity are noticed, a physician should be contacted for evaluation. Drug toxicity is reversible only if treated at the right time. Any delayed response to it may cause permanent damage and reduced quality of life.