Analgesic nephropathy overview

# Overview
Analgesic nephropathy is a disorder caused by long-term use of analgesic drugs, mainly phenacetin and combinations containing phenacetin. This resulted in the withdrawal of phenacetin from most markets around the world since over 30 years ago, which has led to the disappearance of classic analgesic nephropathy caused by phenacetin. The main findings in analgesic nephropathy are renal papillary necrosis and chronic interstitial nephritis. The kidney injury may progress to end stage renal disease (ESRD). Although non-phenacetin analgesics (such as NSAIDs, aspirin and acetaminophen) or their combinations have been reported in some studies as causes to analgesic nephropathy, but there is insufficient evidence that suggests these drugs cause analgesic nephropathy.

# Historical Perspective
In 1953, the association between analgesic drugs and chronic renal disease was first reported in German. In 1977, Australia was first to legally ban phenacetin. In 1983, phenacetin was withdrawn from the US markets.

# Pathopysiology
The pathogenesis of analgesic nephropathy caused by phenacetin may be due to several reasons. Toxic metabolites of phenacetin cause capillary sclerosis in the renal medulla, which results in renal papillary necrosis, tubulointerstitial nephropathy and cortical atrophy. Renal ischemia and renal papillary necrosis may be result from the methemoglobinemia caused by phenacetin. Additionally, It has been reported that the concentration of phenacetin is higher at the papillary which is suggestive of direct damage to the renal papillary cells.  Although non-phenacetin analgesics (such as NSAIDs, aspirin and acetaminophen) or their combinations have been reported in some studies as causes to analgesic nephropathy, but there is insufficient evidence that suggests these drugs cause analgesic nephropathy.

# Causes
There is a strong association between phenacetin and analgesic nephropathy which has led to the disappearing of classic analgesic nephropathy after the removal of phenacetin from the markets over 30 years ago. Although non-phenacetin analgesics (such as NSAIDs, aspirin and acetaminophen) or their combinations have been reported in some studies as causes to analgesic nephropathy, but there is insufficient evidence that suggests these drugs cause analgesic nephropathy.

# Differentiating Analgesic nephropathy from other Diseases
Analgesic nephropathy should be differentiated with other disorders that cause renal papillary necrosis, such as: diabetic nephropathy, renal crisis in sickle cell disease, pyelonephritis, obstructive uropathy, renal tuberculosis, alcohol-induced nephropathy, systemic vasculitis and renal vein thrombosis.

# Risk Factors
Risk factors for renal insufficiency from NSAIDs include: history of renal disorder, older age, congestive heart failure (CHF), cirrhosis with ascites, nephrotic syndrome, history of hemorrhage or surgery, vomiting and  diarrhea.

# Screening
There is insufficient evidence to recommend routine screening for analgesic nephropathy.

# Natural History, Complications and Prognosis
The prognosis of analgesic nephropathy depends on the scarring and damage to the renal tissue. Most patients in early stages recover to normal renal function after stopping the analgesic drug, however some may progress to end stage renal disease (ESRD). Complications of analgesic nephropathy include: urinary tract infections, varying degrees of renal failure and end stage renal disease (ESRD).

# Epidemiology and Demographics
There is insufficient evidence about the incidence, prevalence and racial predilection of analgesic nephropathy. However, the classic analgesic nephropathy is disappearing after the removal of phenacetin from the markets over 30 years ago. Most patients with analgesic nephropathy have been reported to be middle age or older with a history of chronic pain. Studies suggest that analgesic nephropathy is more conman in females than males.

# Diagnosis

## Diagnostic Study of Choice
Renal biopsy is the diagnostic study of choice, however, since it is an invasive procedure, CT scan without contrast of the abdomen is usually preferred.

## History and Symptoms
Common findings in patients with analgesic nephropathy include: headache, upper gastrointestinal disease (such as peptic ulcer), anemia, urinary tract infections, pyuria and hypertension.

## Physical Examination
In physical examination of patients with analgesic nephropathy checking for the followings should be considered: headache, upper gastrointestinal disease (such as peptic ulcer), anemia, urinary tract infections, and hypertension.

## Laboratory Findings
The laboratory tests and findings in analgesic nephropathy may include: urinary examination (sterile pyuria, hematuria, proteinuria and bacteriuria) and blood tests (anemia and renal failure).

## Electrocardiogram
There are no ECG findings associated with analgesic nephropathy.

## X-ray
A pyelogram is not helpful in the diagnosis of analgesic nephropathy and may worsen the renal injury due to contrast utilization.

## Ultrasound
There are no ultrasound findings associated with analgesic nephropathy. However, ultrasound of the abdomen, kidneys and the urinary bladder could be helpful in ruling out other causes of nephropathy (obstruction or infection).

## CT Scan
CT scan without contrast of the abdomen is usually preferred for diagnosing analgesic nephropathy, the findings include: decrease in renal size, irregular contours and papillary calcifications.

## MRI
There is insufficient evidence suggesting MRI findings associated with analgesic nephropathy.

## Other Imaging Findings
There are no other imaging findings associated with analgesic nephropathy.

## Other Diagnostic studies
There are no other diagnostic studies associated with analgesic nephropathy.

# Treatment

## Medical therapy
Medical treatment of analgesic nephropathy may include: discontinuation of analgesics, adequate hydration with normal saline and treatment of infections with antibiotics.

## Interventions
Patients with analgesic nephropathy that present with acute renal failure or progression to end stage renal disease (ESRD) may require renal replacement therapy with dialysis.

## Surgery
Patients with analgesic nephropathy that progress to end stage renal disease (ESRD) may require renal replacement therapy with renal transplantation.

## Prevention
It has been suggested that in clinical practice, non-opioid analgesics, when possible, should be avoided for long-term use due to their nephrotoxicity.

## Cost-Effectiveness of Therapy
There is insufficient evidence about the cost-effectiveness of therapy in analgesic nephropathy.

## Future or Investigational Therapies
No further or investigational therapies have been suggested in analgesic nephropathy.