Acute humoral rejection (AHR) is currently perceived as an immunological reaction against donor antigens mediated by complement-binding antibodies. C4d, a split product of complement activation and bound to endothelial cells of the peritubular capillaries, is used as a diagnostic marker for AHR. We report on three patients with biopsyproven acute humoral rejection who were treated initially with plasmapheresis (PS). As two of the patients did not recover renal function, and biopsy showed persistent C4d staining after PS, immunoadsorption (IAS) was additionally performed on them. In all patients, renal function recovered, and follow-up biopsies in two patients showed complete disappearance of C4d, 29 days and 58 days after transplantation and only minimal residual C4d deposits in one patient 48 days after transplantation. We conclude that successful treatment of AHR is followed by complete resolution of serological and histological markers of AHR, displayed by the disappearance of C4d.

Our results suggest that the acceleration of PMN apoptosis in the presence of CU is mediated via an antibody-dependent activation of the classical complement pathway mobilizing both caspase-dependent and -independent pathways.

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To the Editors:Ruf et al. report hyponatremia to be an excellent predictor of outcome in patients with advanced cirrhosis and that the presence of hyponatremia significantly increases the efficacy of the Model for End-Stage Liver Disease (MELD) to predict waitlist mortality. 1 Furthermore, they suggest hyponatremia to be incorporated into the MELD formula.However, we believe that with the emergence of aquaretics (i.e., V2-receptor antagonists) for treatment of hyponatremia these suggestions should be viewed with caution. These drugs, which are expected to be approved by the FDA this year, have been shown to reverse hyponatremia efficiently in patients with advanced liver disease. 2,3 While it has yet to be shown that treatment with aquaretics increases survival in this patient population, the prevalence of hyponatremia will certainly decrease with the more widespread use of these drugs. Furthermore, it can be assumed that the management of ascites will also be affected due to the aquaretic effect of these drugs. With the emergence of these new drugs and the anticipated change of the incidence of hyponatremia in this patient population, we believe that the suggestion to incorporate serum sodium into the MELD score might be premature and will need to be reconsidered after the full impact of these drugs have been evaluated. To the Editors:We agree with Dr. Koller that the advent of effective and safe aquaretic drugs may potentially reduce the incidence of dilutional hyponatremia and thus the usefulness of incorporating serum sodium into the Model for End-Stage Liver Disease (MELD) formula to increase its prognostic power. However, for a number of reasons we believe that at the present time this should be regarded more as an optimistic theory than as a fact. First, only a total of 125 patients with cirrhosis and hyponatremia were enrolled in the 4 reported phase II clinical trials using VPA-985, a selective vasopressin V2-receptor antagonist. [1][2][3][4] Second, although the use of VPA-985 for a maximum of only 7 days was associated with increased free-water clearance, normalization of serum sodium in the European multicenter study occurred in 50% of patients treated with 200 mg/day and in only 27% of the 100 mg/day group. 4 An increase of Ն5 mEq/L of serum sodium was observed in 67% and 45%, respectively. However, how clinically significant is a short-term increase in natremia from 120 to 125 mEq/L in a given patient? How efficacious are aquaretics in the long term? How many patients will escape from the aquaretic effects of VPA-985 during continuous administration? Third, safety of aquaretic drugs is still largely unknown, especially when considering long-term therapy. In the North American multicenter trial, 24% of patients with cirrhosis developed adverse effects such as worsening encephalopathy and dehydration with systemic postural hypotension. 3 Of major concern is the synergic interaction between aquaretic and natriuretic agents in patients with endstage cirrhosis and circulatory dysfunction. Finally, Dr...

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