QW59-January 2026

Question: Select each option to validate with explanations

Clinical Case Scenario

A 70 kg 56- yr old female with acute myeloid leukaemia on induction chemotherapy with VCR- daunorubicin regimen is neutropenic day 11 following chemotherapy and admitted to ICU with confusion, facial swelling and diplopia. CECT brain reveals rhino cerebral mucormycosis and he is commenced on liposomal Amphotericin B ( LAMB) at 5mg/kg intravenous. He develops ST segment depression and T wave inversions in ECG. The following changes are noted on blood and urine parameters day 7 of therapy:

Urine output: 7500 ml/ day
Serum creatinine e: 88-242 µmol/L
Serum potassium: 4.3->3.6->2.8mmol /L
Serum magnesium :0.45 mmol /L
Serum bicarbonate 18 mol/L
Urinalysis: bland; nil casts
Renal ultrasound: normal

Question: Which of the following statements are false regarding the mechanism of nephrotoxicity:

A) The hydrophobic part of LAMB binds with sterol and induces pore formation in renal tubules allowing extravasation of electrolytes into the ECF space of tubular cells and hence urinary loss by diffusion down a concentration gradient

B) LAMB causes resistance to arginine vasopressin and hence concentrating ability of the collecting ducts is lost precipitating nephrogenic diabetes insipidus

C) LAMB induced hypokalaemia is partially mediated through upregulation of aldosterone receptors in the distal tubules and collecting ducts causing inability to reabsorb sodium and facilitating renal potassium loss

D) LAMB mediated AKI is partly due to the reduction in glomerular filtration GFR associated with renal vasoconstriction

Wrong Answer: AMP – B induced formation of pores and extravasation of ions , thereby causing cell death is the mechanism of action against fungal cell wall ; In addition to fungal cell wall , it causes substantial toxicity to mammalian kidney , heart and hematologic cells The use of lipid based formulations can minimize although not eliminate the risk of nephrotoxicity; The incidence of AKI further worsens with cumulative accumulation of doses ; This is promptly seen in the above scenario where the patient had already received >2000 mg

Wrong Answer: Initially it was thought that amphotericin induced hypokalaemia mediated the polyuria and hypernatremia. Now there is increasing evidence to suggest that LAMB can cause polyuria due to resistance to AVP . This is evidenced by the fact that patients with serum K of >3 still can experience polyuria and hypernatremia with LAMB and such patients respond well to desmopressin , amiloride and thiazide therapy

Right Answer: LAMB causes hypokalaemia similar to hyperaldosteronism; However it is associated with distal renal tubular acidosis and not alkalosis as found in hyper aldosteronism. Excess aldosterone causes kidneys to excrete both H+ and K + ions and the kidneys in turn reabsorb HCO3- causing metabolic alkalosis. LAMB on the other hand causes distal tubular loss of potassium and back diffusion of H + across a concentrating gradient precipitating distal renal tubular acidosis..

Salt loading or volume expansion with 500 ml of normal saline is recommended in patients who are not hypervolemic as salt loading has been shown to reduce the sensitivity of TGF system . Thus, saline administration can protect against the LAMB induced GFR decline but not the signs of tubular dysfunction

Wrong Answer: LAMB mediates extravasation of sodium and chloride in the medullary tubules; Increased concentration of chloride in the cells of macula densa located in the early part of distal tubules activates tubule-glomerular feedback and afferent arteriolar constriction ; This inappropriate activation of TGF along with direct renal vasoconstriction by LAMB both contribute to fall in GFR.

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