Analgesic Nephropathy - Causes, Symptoms, Diagnosis and Treatment

Introduction:

Analgesics nephropathy is commonly caused due to the long-term use of analgesic medications such as Paracetamol, Aspirin, and Nonsteroidal anti-inflammatory drugs (NSAIDs). The evidence of analgesics causing chronic kidney disease was reported in the year 1950. Analgesics nephropathy is characterized by chronic damage to the tubular interstitium of the kidneys. Subsequently, developing the symptoms of chronic kidney disease, over time, leads to an end-stage renal disease needing dialysis for survival.

What Is Analgesics Nephropathy?

Analgesics nephropathy is also known as analgesic abuse nephropathy or analgesic-associated nephropathy. It is a type of chronic tubulointerstitial nephritis that develops as a response to the prolonged use of analgesic medications. The most common analgesics reported being involved in causing this condition are namely Acetaminophen (Paracetamol), Ibuprofen, Aspirin, NSAIDs, Phenacetin, and combination drugs.

What Is the Epidemiology and Etiology of Analgesics Nephropathy?

Epidemiology- The incidence of analgesic nephropathy is reported to be more in females as compared to males, with an average estimation of 50 to 80 percent in females. Patients with preexisting kidney.

disease and old age are considered to be at high risk. The more common age group includes 30 to 70 years.

Etiology- The proposed etiology for the development of analgesic nephropathy is the chronic usage of the analgesics such as,

• Paracetamol.

• Ibuprofen.

• Aspirin.

• NSAIDs.

• Combination of these drugs.

The above-said drugs are known to inhibit prostaglandins which in turn reduces the blood supply to the components of the kidneys, causing injury and affecting the functional status of the kidneys.

What Is the Pathogenesis of Analgesics Nephropathy?

The pathogenesis of this condition is that these drugs reduce the synthesis of prostaglandins by inhibiting cyclooxygenase. Drugs such as Aspirin and NSAIDs are the main inhibitors of cyclooxygenase, thereby reducing the levels of prostaglandin E2 (PGE2). Prostaglandin E2 (PGE2) is responsible for maintaining adequate blood supply to the kidneys. Reduction in the amount of PGE2, in turn, reduces the blood supply to the kidneys, causing capillary sclerosis.

The innermost part of the kidney, called the renal papilla, exclusively depends on the PGE2 for maintaining the proper blood flow. This reduced PGE2 will affect the renal papilla causing renal papillary necrosis. This, in turn, would result in chronic interstitial nephritis and subsequently develops into an end-stage renal disease. Alternative pathogenesis has been proposed for the drugs such as Paracetamol and Phenacetin. The metabolites of these drugs deplete the antioxidant glutathione, thus making the kidneys prone to oxidative damage and causing further complications.

What Are the Symptoms of Analgesics Nephropathy?

It is usually asymptomatic in its initial stages; as the disease progresses, it may show up symptoms like,

• Anemia (decrease in red blood cell (RBC) count).

• Hematuria (passage of blood in the urine).

• Pyuria (presence of white blood cells (WBC) in the urine).

• Flank pain (pain may be due to any obstruction in the urinary tract).

• Proteinuria (presence of protein in the urine).

• Frequent urinary tract infections.

• Presence of urinary sediments in the urine.

• Hypertension (the increased blood pressure as a result of diminished kidney function).

What Is the Diagnosis and Differential Diagnosis of Analgesics Nephropathy?

Diagnosis: The steps in the diagnosis of analgesic nephropathy include,

• History: Proper medical history, the history of chronic painkiller usage, and the clinical symptoms of the disease would provide a major clue in diagnosing this condition.

• Urine Analysis: This may reveal the presence of pyuria (white blood cells in urine), hematuria (blood in the urine), and proteinuria (protein in the urine).

• Blood Test:

1. Complete Metabolic Profile- To measure the electrolyte levels in the body, such as sodium, potassium, etc., and the fluid balance in the body. Basically, this test helps to indicate the functioning status of the kidney.

2. Complete Blood Count- This may indicate the presence of anemia (decreased red blood cell count) and the presence of infection if any.

• Kidney Ultrasound: This may be helpful to rule out other causes of nephropathy, such as any obstruction or infection.

• Non-contrast Computed Tomography (CT) Scan: It is the most preferred method as it is non-invasive and less time-consuming. The findings include,

1. Reduction in kidney size and volume.

2. Scarring of the kidneys (caused due to sclerosis).

3. Irregularity on the kidney surface (caused due to necrosis).

4. Renal calcifications may be noticed.

• Histopathology: The microscopic examination would reveal the presence of interstitial fibrosis, papillary necrosis with inflammatory changes, papillary calcifications, and deposition of metabolites in the medullary zone.

Differential Diagnosis:

Some conditions that show similar features as analgesic nephropathy should be differentiated that including,

• Obstructive neuropathy.

• Pyelonephritis.

• Nephropathy is associated with diabetes mellitus.

• Sickle cell disease with the renal crisis.

• Nephropathy induced by alcohol use.

• Systemic vasculitis.

How Is Analgesics Nephropathy Managed?

1. Stoppage of Analgesic Use: The first line of treatment is to quit or stop the analgesic to prevent further damage to the kidney tissues.

2. Adequate Hydration: Patients who are at the initial stage of the disease are advised to take plenty of water to restore the blood flow to the affected areas of the renal tissue.

3. Treating Infection: Infections should be treated with prior antibiotics to prevent further complications and sepsis.

4. Dialysis: Patients who progressed to end-stage renal disease had to undergo dialysis to compensate for the functional loss of kidneys.

5. Kidney Transplantation: Renal transplantation can be advised in patients affected at a young age.

What Is the Prognosis and Complications of Analgesics Nephropathy?

Prognosis:

The prognosis of this condition varies with each person based on the amount of renal injury, scarring, and time of diagnosis. Usually, patients opting for treatment in the early stages of the disease show a better prognosis than the ones presenting at the later phase. It is worrisome that, in some cases, even after stopping the causative drug, the condition does not improve. Most of the cases progress to end-stage renal disease and require dialysis and replacement surgeries.

Complications:

Complications of this condition may include;

• Pyelonephritis -It is the inflammation of the kidneys caused due to the presence of bacterial infection. Bacterial infection may occur as a result of frequent urinary tract infections.

• Renal Failure - Renal failure may develop as a consequence of renal papillary necrosis and oxidative damage to the renal tissues altering the functional capacity of the kidney. This, in turn, may lead to the total shutdown of kidney function and the development of end-stage renal disease.

• Transitional Cell Carcinoma - Studies report that patients with analgesic nephropathy are at greater risk of developing transitional cell carcinoma of the urinary tract.

Conclusion:

Analgesic nephropathy was one of the most common causes of renal failure in the 1990s. At present, the incidence is decreasing because of the awareness created among medical professionals and the general population. The only effective way to control analgesic nephropathy is through prevention. More awareness should be created among the public about the side effects of long-term usage of analgesics.