Analgesic Nephropathy: pain killers killing kidneys

Analgesic nephropathy is chronic tubulointerstitial nephritis. It is caused by long-term use of high doses (>1-2 Kgs) of certain analgesics, especially if taken in combinations.

The combinations of the following analgesics are most commonly associated with AN-

phenacetin, aspirin, and caffeine
phenacetin-acetaminophen
NSAIDs and acetaminophen

High-risk groups

Women in the sixth and seventh decades of life.
People with chronic pain
Elderly and people with renal disease are at high risk of developing AN.
Volume contracted states – CHF, Ascites, excessive diuretic use.

Pathophysiology

Following are the hypothesized causes behind renal damage associated with Analgesic nephropathy-

Reduced blood flow to the kidney-most analgesics (including NSAIDs) reduce pain by inhibiting prostaglandin (PG) synthesis. Prostaglandins have a vasodilatory effect which helps in the maintenance of renal blood flow. In patients with normal renal function and normal volume state, the renal synthesis of PG is low, and it does not play a significant role in the maintenance of renal blood flow.

But in decreased renal perfusion, the local synthesis of vasodilator prostaglandins is increased. And renal perfusion is maintained. This autoregulatory mechanism is crucial for adequate renal blood flow: in cases with volume contracted states (congestive heart failure, ascites, hepatic failure, and chronic kidney disease, diuretic users, and the elderly with vascular damage/atherosclerosis).

Mechanism of renal injury, prostaglandin is blocked by analgesics -

Analgesics in high doses → inhibition of prostaglandin synthesis → less prostaglandin for renal vasodilation→ reduced renal blood flow → increased chances of ischemic and hypoxic injury to tubules and interstitial tissue→ acute kidney injury

Oxidative damage of kidney tissue-

High doses of analgesics → increased concentration of reactive intermediates → reactive intermediates are detoxified, by antioxidants like glutathione → consumption of antioxidants→ rapid depletion of antioxidants → renal tissue becomes susceptible for oxidative damage in the antioxidant depleted state → increased oxidative free radicles injury → chronic tubulointerstitial nephritis and tubular injury

Direct injury to the kidney tissue - accumulated reactive intermediates of analgesic, especially phenacetin and acetaminophen

Untreated AN leads to progressive chronic kidney failure and ESRD. Chronic kidney injury → reduced erythropoietin production → decreased erythropoiesis →anemia.

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Symptoms and Signs

Clinical presentation can be variable. The patient may be asymptomatic or may present with signs and symptoms of kidney failure.

asymptomatic hematuria
sterile pyuria
non-nephrotic proteinuria
anemia
chronic kidney failure
urinary tract infection
flank pain

Diagnosis

History of chronic analgesic use (cases with chronic pain)
Urine analysis- shows microscopic hematuria, proteinuria, sterile pyuria, and tubular cast. In case of urinary infection, pyuria can be present.
Non-enhanced CT of the abdomen shows-

decreased renal size (shrunken kidney)
renal scarring
irregular renal surfaces- >3 indentations in renal contour
papillary calcifications (micro calcifications at the papillary tips)

Renal biopsy is the confirmatory diagnostic test but is not always appropriate due to its invasive nature.

Treatment

The first line of treatment is the discontinuation of the associated drug to prevent further damage.
Adequate hydration to achieve restoration of blood perfusion to the kidney.
Treatment of infections, especially pyelonephritis, is essential for the prevention of complications and sepsis.

Revision for today Acute Tubular Necrosis/Injury - Creative Med Doses

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