UOP typically remains above 1 liter/day (unless renal dysfunction is severe) due to induction of a concentrating defect, due to platinum induced damage to the loop of henle or decrease in aquaporin water channels in collecting tubules.
It is also believed that cisplatin treatment may lead to long term reduction in GFR as well.
Sodium thiosulphate- binds to cisplatin and render it non-toxic. Used in setting of IP cisplatin.
Amifostine: an organic thiophosphate, donates a thiol group selectively in normal tissues and not in malignant tissues, to bind to cisplatin. Major concerns are cost and possible interference with tumor efficacy.
Cimetidine-inhibitor of OCTs- could be used to decrease uptake.Imatinib, an anti-cancer agents also decreases uptake by affecting OCTs.
Antioxidants have been tried-unclear benefit.
Other agents that have been explored include N-acetylcysteine, theophylline,glycine,PPAR agonists,coreg etc.
A case report describes 2 patients with carboplatin toxicity developing acute renal failure.
Biopsy specimens showed focal and moderate interstitial nephritis with periglomerular fibrosis in one specimen and edematous interstitium with diffuse mononuclear infiltrate and toxic changes in tubules in the other.
Renal function improved with prednisone treatment @1 mg/kg/day for 4 weeks.
The American Journal of Medicine Volume 90, Issue 1 , January 1991, Pages 386-391
Renal pathological findings in cases of heavy proteinuria include 12 cases of thrombotic microangiopathy, 2 cases of collapsing glomerulopathy, one case of cryoglobulinemic glomerulonephritis, one case of immune complex associated focal proliferative glomerulonephritis and sorafenib-induced acute interstitial nephritis.
One case of Bevacizumab associated TMA which resolved once with discontinuation of drug and subsequently had relapse when was treated again with sunitinib responded to discontinuation of treatment and plasma exchange.
Another case of TMA responded to drug withdrawal, anti Hypertensive agents, steriods and plasma exchange.
However, role of plasma exchange still needs to be evaluated.
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