A single-center cohort study of kidney and kidneypancreas recipients was conducted to evaluate the association between new immunosuppressive regimens and risk of thrombotic microangiopathy (TMA). From January 1st,1996 to December 31, 2002, 368 patients received a kidney or kidney-pancreas transplant at our center. Four immunosuppressive regimens were evaluated as potential risk factors of TMA: cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA + SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus (FK + SRL). Thirteen patients developed biopsy-proven TMA in the absence of vascular rejection. The incidence of TMA was significantly different in the four immunosuppressive regimens studied (p < 0.001). The incidence of TMA was highest in the CsA + SRL group (20.7%). The relative risk of TMA was 16.1 [95% confidence interval (CI): 4.3-60.8] for patients in the CsA + SRL group as compared with those in the FK + MMF group. We also investigated in vitro the pathophysiological basis of this association. The CsA-SRL combination was found to be the only regimen that concomitantly displayed pro-necrotic and anti-angiogenic activities on arterial endothelial cells. We propose that this combination concurs to development of TMA through dual activities on endothelial cell death and repair.

In kidney transplant recipients, renal cell carcinoma (RCC) occurs either in the native kidney or, less frequently, in the grafted kidney. Here, we report a series of rare cases involving 5 patients from a single center who developed RCC in their grafts. The diagnosis was made serendipitously by ultrasound. The time lapse post-transplant varied from 4 to 17 years. Surgical treatment consisted of nephron-sparing surgery (NSS) in four cases and a secondary radical nephrectomy in one case. All tumors were less than 4 cm in diameter. The histopathology was clear cell type in four cases and papillary RCC in one case. Patients treated by NSS retained kidney function for 2 years or more, and none of them presented early neoplasia recurrence. In conclusion, NSS can be performed safely in grafted kidneys to treat incidental RCC. It prevents an immediate return to dialysis for patients.

The capacity of chronically hemodialyzed patients to metabolize acetate during conventional hemodialysis was evaluated using a retrospective study in 219 patients dialyzed for up to ten years under similar dialysis conditions. For each patient, and using all available data, a regression line relating the changes of plasma total CO2 during dialysis as a function of the pre-dialysis value was calculated. The intercept of this function indicates the plasma concentration where the losses of bicarbonate in the dialysate is matched by the generation of bicarbonate arising from the metabolism of acetate. This value therefore represents an individual index of the capacity of each patient to metabolize acetate. A value for this index smaller than 18.0 mM was considered abnormal. It was shown that around 10% of chronically hemodialyzed patients are clearly unable to metabolize acetate optimally. This defect is not related to the duration of dialysis, body weight or quality of hemodialysis treatments but is strongly related to sex, 19 of the 22 "acetate intolerant" patients being women. In a prospective study, all the 60 patients of the same population undergoing active dialysis were studied, and this index identified 12 abnormal (11 women, 1 man) patients and 48 normal patients. Plasma acetate measured at the end their dialysis treatments were significantly higher in abnormal than in normal patients. It is concluded: that this index is useful to identify the patients unable to metabolize acetate optimally; that only around 10% of hemodialyzed patients present a severe problem when dialyzed against acetate and should be dialyzed against bicarbonate; that dialysis against acetate does not fully correct the metabolic acidosis even in "normal" patients.