Analgesic nephropathy overview

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Overview

Historical Perspective

Pathophysiology

Differentiating Analgesic nephropathy from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

CT

Treatment

Medical Therapy

Future or Investigational Therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]

Overview

The term analgesic nephropathy usually refers to damage induced by excessive use of combinations of these medications, specifically combinations that include phenacetin. For this reason, it is also called analgesic abuse nephropathy. Others prefer the less judgmental analgesic-associated nephropathy. Both terms are abbreviated to the acronym AAN, by which the condition is also commonly known.

Analgesic nephropathy is injury to the kidney caused by analgesic medications such as aspirin, phenacetin, and paracetamol. The term usually refers to damage induced by excessive use of combinations of these medications, especially combinations that include phenacetin. It may also be used to describe kidney injury from any single analgesic medication.

The specific kidney injuries induced by analgesics are renal papillary necrosis and chronic interstitial nephritis. They appear to result from decreased blood flow to the kidney, rapid consumption of antioxidants, and subsequent oxidative damage to the kidney. This kidney damage may lead to progressive chronic renal failure, abnormal urinalysis results, high blood pressure, and anemia. A small proportion of individuals with analgesic nephropathy may develop end-stage kidney disease.

Analgesic nephropathy was once a common cause of kidney injury and end-stage kidney disease in parts of Europe, Australia, and the United States. In most areas, its incidence has declined sharply since the use of phenacetin fell in the 1970s and 1980s.



Overview

Historical Perspective

In 1953, the association between analgesic drugs and chronic renal disease was first reported in German.[1] In 1977, phenacetin became legally banned in Australia.[2] In 1978 and 1983, phenacetin was withdrawn from the Canadian and US markets, respectively.[3][4]

Pathopysiology

Causes

Differentiating Analgesic nephropathy from other Diseases

Risk Factors

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.[5] 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).[5] Complications of analgesic nephropathy include: urinary tract infections, varying degrees of renal failure and End stage renal disease (ESRD).[6][7][5]

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.[8] Most patients with analgesic nephropathy have been reported to be middle age or older with a history of chronic pain.[9] Studies suggest that analgesic nephropathy is more conman in females than males.[10]

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.[11][12]

History and Symptoms

Common findings in patients with analgesic nephropathy include: headache, upper gastrointestinal disease (such as peptic ulcer), anemiaurinary tract infections, pyuria and hypertension.[6][7]

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), anemiaurinary tract infections, and hypertension.[6][7]

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).[6][7][5]

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.[11]

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).[5]

CT Scan

CT scan without contrast of the abdomen is usually preferred for diagnosing analgesic nephropathy, the findings include: decrease in renal size, bumpy contours and papillary calcifications.[12]

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.[6][5]

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.[13][6]

Surgery

Patients with analgesic nephropathy that progress to end stage renal disease (ESRD) may require renal replacement therapy with renal transplantation.[13]

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.[9]

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.

References

  1. Spühler O, Zollinger HU (1953). "Die chronisch-interstitielle Nephritis". Z Klin Med (in German). 151 (1): 1–50. PMID 13137299.
  2. Michielsen P, de Schepper P (2001). "Trends of analgesic nephropathy in two high-endemic regions with different legislation". J Am Soc Nephrol. 12 (3): 550–6. PMID 11181803.
  3. "Some pharmaceutical drugs". IARC Monogr Eval Carcinog Risk Chem Hum. 24: 1–337. 1980. PMID 6937434.
  4. "List of drug products that have been withdrawn or removed from the market for reasons of safety or effectiveness. Food and Drug Administration, HHS. Final rule". Fed Regist. 64 (44): 10944–7. 1999. PMID 10557618.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 "StatPearls". 2020. PMID 31082145.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 Nanra RS (1980). "Clinical and pathological aspects of analgesic nephropathy". Br J Clin Pharmacol. 10 Suppl 2: 359S–368S. doi:10.1111/j.1365-2125.1980.tb01824.x. PMC 1430193. PMID 7002190.
  7. 7.0 7.1 7.2 7.3 Nanra RS, Stuart-Taylor J, de Leon AH, White KH (1978). "Analgesic nephropathy: etiology, clinical syndrome, and clinicopathologic correlations in Australia". Kidney Int. 13 (1): 79–92. doi:10.1038/ki.1978.11. PMID 362034.
  8. Mihatsch MJ, Khanlari B, Brunner FP (2006). "Obituary to analgesic nephropathy--an autopsy study". Nephrol Dial Transplant. 21 (11): 3139–45. doi:10.1093/ndt/gfl390. PMID 16891638.
  9. 9.0 9.1 Yaxley J (2016). "Common analgesic agents and their role in analgesic nephropathy: A commentary of the evidence". Int J Risk Saf Med. 28 (4): 189–196. doi:10.3233/JRS-170735. PMID 28582877.
  10. Gault MH, Wilson DR (1978). "Analgesic nephropathy in Canada: clinical syndrome, management, and outcome". Kidney Int. 13 (1): 58–63. doi:10.1038/ki.1978.8. PMID 713269.
  11. 11.0 11.1 "Analgesic Nephropathy - StatPearls - NCBI Bookshelf".
  12. 12.0 12.1 de Broe ME, Elseviers MM (1998). "Analgesic nephropathy". N. Engl. J. Med. 338 (7): 446–52. PMID 9459649. Unknown parameter |month= ignored (help)
  13. 13.0 13.1 Linton AL (1972). "Renal disease due to analgesics. I. Recognition of the problem of analgesic nephropathy". Can Med Assoc J. 107 (8): 749–51. PMC 1941002. PMID 4638849. Unknown parameter |month= ignored (help)

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