Acute renal failure is a major complication in patients with increased oxalate serum concentration. To describe the metabolic mechanisms of oxalate-induced glomerular and tubular damage, we report a case of ethylene glycol intoxication as well as a case of xylitol infusion in a patient with previously unknown primary hyperoxaluria type 1. Both patients presented with acute renal failure associated with histologically proven renal oxalate accumulation. This excessive oxalate overloading resulted from elimination and metabolization of ethylene glycol or xylitol. Thus, key enzymes in the elimination pathway of these substances represent targets for pharmacological treatment. Simultaneous hemodialysis is often necessary to reduce oxalate serum concentration. Whereas renal function of the ethylene glycol-poisoned patient recovered, the second patient who received xylitol infusion required chronic hemodialysis due to the unmasked hyperoxaluria type 1. Our cases demonstrate that patients with excessive endogenous oxalate generation are at high risk to develop acute renal failure. Therefore, to prevent end-stage renal failure in these patients, important clinical factors should be considered as indicators for the underlying cause: history of alcohol abuse and severe high anion gap acidosis for ethylene glycol intoxication or history of long-lasting parenteral nutrition for xylitol-associated acute renal failure.