4CPS-259 Usefulness of cystatin c as a biomarker of renal function in drug dosing in a haematologic patient with protein malnutrition

Background Serum cystatin C (CysC) is a marker that could be useful in haematologic adult patients with protein malnutrition (hypoalbuminaemia) secondary to oral mucositis and gut graft-vs-host-disease, because it detects acute renal failure (ARF) earlier than serum creatinine, the standard marker, and is not affected by sex, age or muscle mass. Purpose To describe the usefulness of CysC as a predictor of glomerular filtration rate (GFR) in a haematologic patient with low serum creatinine concentration (CrC) and protein malnutrition, where the value of creatinine clearance (CrCl) to evaluate ARF is limited. Material and methods A 62-year-old patient with acute myeloid leukaemia was admitted for donor haematopoietic progenitor allogeneic transplant not related with myeloablative conditioning. Tacrolimus and methotrexate were administrated as graft-vs-host-disease prophylaxis. Patient weight, albumin, CrC and CysC, and tacrolimus dosage were obtained from medical records. Tacrolimus levels were measured in the autoanalyser Architect i1000 (Abbott). CrCl and CysC clearance (CysCl) were estimated by the Cockcroft–Gault and Larsson formulas respectively. The influence of ARF in the clearance of tacrolimus and dose requirements was assessed by the level/dose ratio. Results At the start of treatment, tacrolimus was initiated at a dose of 1.3 mg (0.02 mg/kg) IV daily, since renal function was normal (CrCl=89.22 mL/min). No interactions with tacrolimus or other nephrotoxic drugs were found. After determining tacrolimus trough levels (TTL), the individual dose to reach therapeutic range was adjusted to 0.6 mg/day IV (level/dose: 12.5 mg/mL*mg). On +10 day post-transplant, radiologic diagnosis suggested invasive fungal infection, and treatment with amphotericin B liposomal was started. An increase in TTL was detected and a dose adjustment was necessary (level/dose: 29.10 mg/mL*mg). CrCL was 75.27 mL/min, not reflecting severe ARF. Other evidence suggestive of renal failure such as hyperphosphataemia and dermal toxicity secondary to amphotericin were observed. A CysCl control of 34.58 mL/min confirmed a worsening of kidney function and explained the increase in level/dose for tacrolimus. Conclusion Given that CrCl presents major limitations in adult haematologic patients with protein malnutrition, CysCl could be a useful marker for ARF to guide dose adjustments of drugs with renal elimination. Pharmacokinetic studies evaluating the relationship between CysCl and drug clearance would be desirable. No conflict of interest