Cyclosporin and tacrolimus have improved survival figures in organ transplantation. However, both drugs are potentially nephrotoxic. The immunosuppressive and nephrotoxic effects of both drugs appear to depend on the inhibition of calcineurin. Cyclosporin and tacrolimus cause acute (functional changes) and chronic nephrotoxicity (structural lesions in the kidney). These last important lesions include arteriolar hyalinosis, stripped interstitial fibrosis and tubular atrophy. It is possible that repeated episodes of renal ischaemia contribute to the development of chronic nephrotoxicity and then chronic allograft nephropathy. Cyclosporin and tacrolimus also induce arterial hypertension. Therefore, the beneficial effects of immunosuppression have been limited due to nephrotoxicity and arterial hypertension. Rapamycin, a novel immunosuppressive agent, that does not inhibit calcineurin, provides immunosuppression without nephrotoxicity. In fact, in the trials performed in Europe, sirolimus-treated immunosuppression patients exhibited a much better renal function than cyclosporin-treated patients. However, sirolimus can potentiate the nephrotoxic effect of cyclosporin. Therefore, when cyclosporin and sirolimus are used in combination, a reduction of the cyclosporin dose is desirable.

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Dear Sir, Yanagisawa and Wada [1] recently reported a signifi cant increase in carcinogenic heterocyclic amines in the plasma of patients with uremia just before induction of hemodialysis (HD) treatment. Uremic patients receiving maintenance H D treatment showed lower levels of those compounds and it could not be detected in normal sub jects. Several reports have shown the patients with chronic renal failure exhibit a higher incidence of malig nancy [2-5] and a hypothetical relationship can be sug gested.We reviewed the incidence of malignancies among patients treated with chronic HD in our center between 1977 and 1988. 474 patients were investigated and malig nant neoplasms were diagnosed in 20 cases (4.21%). This indicates a 2.76 times greater risk of suffering from cancer than the general population at the same age [6]. 14 pa tients were males (4.6% of males treated with HD) and 6 were females (3.4% of females treated with HD). The mean age of the patients was 56.2 ± 12.0 years, 9 (45%) of the diagnosed cases were older than 60 years. The age at which the neoplasm was discovered was lower in women than in men (47.6± 15.6 vs. 59.8±8.2 years; p<0.005), with 3 cases younger than 40 years (50%) versus none of the men. Six cases (30%) were diagnosed just before starting HD treatment, 2 more cases were detected less than 6 months after induction of HD treatment, and the rest (n = 12) a long time after beginning dialysis. In 7 (35%) patients the malignancy was detected when the patient had been on HD for more than 5 years. The mean time of uremia before the diagnosis of neoplasm was 51.2 ±38.4 months (2-140 months) and the mean time of treatment with dialysis before detection of cancer was 52.7 ± 37.6 months (5-126 months).Other authors have observed that most of the neo plasms diagnosed in their series were found in the early phase after the induction of HD treatment [4,5]. It is possible that the novice agent works during the period of uremia and it disappears or decreases after H D treatment has begun. Our data also suggest that the agent could persist a long time after HD treatment has been induced, perhaps at a lower concentration, and it could produce the same effect some years later.Several factors could be involved in the pathogenia of the increased incidence of cancer in uremia [2,3,7,8]: T-lymphocyte dysfunction; acquired renal cystic dis ease; etiology of chronic renal failure; the extracorporeal elements used in HD, and increased concentrations of nitrosamines in natural water, among others. Until now, no clear demonstration of the involvement of one or more of these factors has been offered. Especially, T-lymphocyte and natural killer activity have been suggested to play an important role in this item [7,9], but HD treatment does not enhance cellular immunity at all [9] and so, this hypothesis cannot be supported by our data.The work of Yanagisawa and Wade [1] suggests an interesting hypothesis to explain the high incidence of cancer around the moment of induction of H D treatment in our patients. We ha...

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow. Fractional sodium and potassium excretions were similar to those of control dogs. Renal production or extraction of glutamine, glutamate, alanine, ammonium, and oxygen (all expressed by 100 ml of GFR) was not significantly different in basal conditions or 2 days after ischemia, but lactate extraction was reduced in postischemic kidneys (-101 +/- 29 vs -204 +/- 38 mumol/100 ml GFR in control dogs). The cortical concentrations of glutamine and glutamate were lower in postischemic than in control kidneys. No differences were found in cortical concentration of alpha-ketoglutarate, aspartate, lactate, pyruvate, or ATP, but total nucleotides and inorganic phosphate were decreased in postischemic kidneys. It is concluded that in the recovery phase of the ischemia, a decreased lactate uptake is the main metabolic change, and total ATP production is adapted to the decrease of GFR and sodium reabsorption.

Despite poorer renal function at 3 months in 1998 than in 1990, renal allograft survival has improved in Spain between 1990 and 1998. This result is partly explained by a slower deterioration of renal function during the first year of follow-up.