The LDH ratio as a marker for response to plasma exchange in HUS/TTP of the adult.

BACKGROUND: Plasma exchange improved the outcome of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) of the adult markedly, but a high number of non-responders remain. Identifying these patients at an early stage would help to optimize therapy. AIM: determine the value of serologic measures in predicting the response to plasma exchange. MATERIAL AND METHODS: We performed a retrospective chart review of 30 patients with HUS/TTP of the adult treated with plasma exchange. According to the treatment protocol, a mean of 42 +/- 8.2 ml plasma per kilogram of body weight was exchanged daily for 3 days and continued every second day thereafter. Prior to each session, clinical status and serologic markers for hemolysis and kidney function were obtained. To assess the early individual response to plasma exchange, the decline of LDH from the first to the third cycle was calculated as: LDH concentration before the third session/LDH concentration before the first session (LDH ratio). RESULTS: During the observation period (median 195, range 6-1500 days), 80% of the patients responded to therapy with plasmapheresis. None of the serologic measures or clinical signs obtained before initiation of plasma exchange showed a significant correlation with the outcome. After 2 sessions of plasma exchange, only LDH and platelet level had improved markedly in responding patients. The LDH ratio was the best predictive marker for the individual response. An LDH ratio < 0.6 predicted a favorable outcome with a sensitivity of 0.96 and a specificity of 0.83. CONCLUSION: The LDH ratio might be a useful marker for separating patients responding to plasma exchange from those not responding at an early stage.

Hypothyroidism as a cause of tacrolimus intoxication and acute renal failure: a case report.

The nephrotoxic side effects of cyclophilin-binding agents like cyclosporine A and tacrolimus are well characterized. In severe cases nephrotoxicity may profoundly deteriorate kidney function and even induce acute renal failure. In this report we describe the first case of excessive tacrolimus intoxication caused by hypothyroidism. The patient had undergone single-lung transplantation 6 months earlier, developed hypothyroidism, and was admitted with acute anuric renal failure. Thyroxin is a potent activator of the cytochrome P-450- CYP 3A enzyme system, which is crucial for tacrolimus metabolism. Hence, hypothyroidism reduces cytochrome P-450 activity and may result in drug accumulation. Rapid reversal of toxic drug levels could be achieved by reducing drug intake and increasing thyroxin levels by substitution therapy. In conclusion, it is important to consider thyroid function when prescribing medications with a narrow therapeutic range, which are metabolized by the cytochrome P-450 system such as tacrolimus, and the possible devastating effect of impaired drug metabolism during hypothyroidism.