Severe vital depression as the presenting feature of cyclosporin-A-associated thrombotic microangiopathy.

were positive for Haemophilus influenzae. Renal ultraIntroduction sound showed no abnormalities. A renal biopsy showed Thrombotic microangiopathy (TMA) is a known a borderline interstitial rejection according to the Banff complication associated with cyclosporin A (CsA) classification. CsA trough levels were in the therapeutic therapy after renal transplantation, even in patients who range (150–200 mg/l ). The patient was again treated with do not have haemolytic uraemic syndrome (HUS) as 6×1 g methylprednisolone i.v., but renal function their original renal disease [1]. Manifestations caused by improved only marginally and did not return to baseline. the endothelial swelling and microvascular thrombi Two weeks after this treatment, the patient developed a include renal failure and neurological symptoms such as severe vital depression with lethargy, anorexia and sleepheadache, confusion, seizures and coma [2,3]. lessness. No focal neurological abnormalities were found. Psychiatric manifestations in the form of severe vital Laboratory investigation showed progressive anaemia depression have not been reported until now. We with a decrease in haemoglobin level from 7.2 to describe two patients with CsA-associated TMA 5.5 mmol/l, thrombocytopenia (50×109/l ), and rising several weeks after transplantation in whom the clinical LDH level (1441 U/l ) (Figure 1). In addition, abundant picture was dominated by a severe vital depression schistocytes were found on peripheral blood smear, the without other neurological findings as the sole sign of haptoglobin level was low (<0.1 g/l ) and coagulation possible cerebral localization. tests were normal. A diagnosis of TMA probably related to CsA was made. Cyclosporin A therapy was discontinued and Case 1 plasmapheresis instituted. During this treatment, the microangiopathic blood changes disappeared rapidly A 54-year-old woman with renal failure caused by chronic and there was a dramatic improvement of the vital pyelonephritis and treated with CAPD since May 1994 depression. Also, renal function improved with a underwent a cadaveric kidney transplantation in decrease of the serum creatinine-level to 145 mmol/l. December 1996. Immunosuppression consisted of CsA Immunosuppression was maintained with mycophenol(NeoralA, Novartis), mycophenolate mofetil and lowate mofetil and prednisolone. No recurrent episodes dose prednisolone. Renal graft function was good iniof depression of TMA have occurred since. Current tially, but a biopsy-proven interstitial rejection Banff graft function is excellent with a serum creatinine of grade I was diagnosed on day 20. After failure to respond 105 mmol/l and a creatinine clearance of 65 ml/min. to 6×1 g i.v. methylprednisolone, treatment with rabbit antithymocyte immunoglobulin with temporary discontinuation of CsA according to our local protocol was Case 2 instituted. Graft function improved to baseline-level and the patient was discharged in good clinical condition with A 63-year-old woman received a cadaveric kidney a creatinine clearance of 50 ml/min. transplant in February 1997. Renal failure from medulTwo months later she was readmitted with bronchitis lary polycystic disease and hypertension had led to the and sinusitis with fever up to 39°C. The serum creatinine initiation of CAPD treatment in November 1994, level had risen from 130 to 265 mmol/l. The maxillary which was changed to haemodialysis in May 1996. sinuses were drained and therapy with amoxycillin/clavulImmunosuppression consisted of CsA (NeoralA, anic acid was instituted. Sputum and sinus-fluid cultures Novartis) and low-dose prednisolone. Delayed graft function necessitating haemodialysis treatment Correspondence and offprint requests to: C. A. Stegeman MD PhD, occurred. While still oliguric a Banff grade I interstitial Department of Internal Medicine/Division of Nephrology University rejection was diagnosed by renal biopsy on the 10th Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. post-operative day. Since there was no response to