Suboptimal kidney: the experience of a single transplant unit.

Not all kidneys are suitable for transplantation. In 2001 in Italy, only 1530 of 1748 organs were transplanted. This difference (-12.5%) not only represents organs harvested from marginal donors considered not suitable, but also kidneys that, although collected from standard donors, had a vascular, parenchymal, or urologic anomaly that made them unsuitable for transplantation. In our center, we established a procedure that defined the characteristics of suboptimal kidneys and allowed us to specifically select the appropriate recipient. We considered as suboptimal all organs with complex arterial anomalies (more than 2 arteries although on a single patch or separated such as to need a double anastomosis or a bench reconstruction); organs with noticeable parenchymal damage (macroscopic sclerosis areas or sutured polar branches accidentally damaged during removal), and organs with complex anomalies of the excretory tract (complete double district). The organs were not considered as suboptimal if they had venous anomalies revised on the bench or if they had a double artery with a single patch <2.5 cm. Such organs were transplanted to recipients who were between 55 and 60 years of age with a body weight of at least 20% less than the donor, and female.

Effects of simvastatin and pravastatin on hyperlipidemia and cyclosporin blood levels in renal transplant recipients.

Thirty-one renal transplant recipients, submitted to treatment with cyclosporin in association with other immunosuppressive agents, were also treated for 9 months with two hydroxymethylglutaryl coenzyme A reductase inhibitors, simvastatin (10 mg/day) or pravastatin (20 mg/day), for concomitant hypercholesterolemia and hypertriglyceridemia. Both drugs significantly decreased total cholesterol and triglyceride serum levels, but they did not modify whole-blood trough concentrations of polyclonal and monoclonal cyclosporin or polyclonal/monoclonal cyclosporin ratio. No alterations of the clinical and laboratory parameters investigated were found. The results of this study show the efficacy and safety of hydroxymethylglutaryl coenzyme A reductase inhibitors in the treatment of hyperlipidemia in kidney transplant patients.

Polyclonal/monoclonal ratio in kidney and bone marrow transplanted patients treated with cyclosporine.

On 296 blood samples obtained from 22 bone marrow and 21 kidney transplanted patients, the concomitant measurements of polyclonal and monoclonal cyclosporine (CsA) were performed and the relative polyclonal/monoclonal (P/M) ratios were calculated. Biochemical profiles of kidney and liver functions were also determined in all patients. For each type of transplant, biochemical data were divided into two subgroups on the basis of P/M ratio: A) data obtained in patients with P/M ratio > 3.0; B) data obtained in patients with P/M ratio < or = 3.0. While in kidney transplanted patients no difference of biochemical profiles was found between two subgroups, in bone marrow transplant recipients the subgroup A showed a worsening of hepatic function parameters as compared to subgroup B. Therefore, it appears that P/M ratio could represent in bone marrow transplantation an index of hepatic CsA toxicity.

Lack of effect of gemfibrozil on cyclosporine blood concentrations in kidney-transplanted patients.

Forty kidney-transplanted patients with hypertriglyceridemia, under treatment with cyclosporine alone or associated with other immunosuppressive drugs, were treated with gemfibrozil. This drug, for a long-term treatment (ranging from 4 to 6 months), was able to decrease hypertriglyceridemia and did not modify either polyclonal (P) and monoclonal (M) cyclosporine blood levels or P/M ratio. These data seem to exclude an effect of gemfibrozil on cyclosporine blood concentrations. Therefore, the use of gemfibrozil in kidney-transplanted patients does not require modifications of cyclosporine dose.

Drug interaction between cyclosporine and two antimicrobial agents, josamycin and rifampicin, in organ-transplanted patients.

In the post-transplant period, antimicrobial agents are often coadministered with cyclosporine (CsA) to treat the infections occurring in the immunosuppressed patients. These agents produce drug interactions with cyclosporine and can increase or reduce the blood concentration of the immunosuppressant. We report two cases of drug interaction between cyclosporine and two antimicrobial agents, josamycin and rifampicin, coadministered in a kidney-transplanted and a liver-transplanted patient, respectively. Josamycin increased the CsA blood levels by inhibiting the CsA metabolism through the hepatic cytochrome P450 enzymes. Conversely, rifampicin decreased the CsA blood levels by stimulating the same enzymatic system. When using these agents it is necessary to adjust the CsA doses to avoid risks of CsA toxicity or allograft rejection.

Acute renal and immunological effects of low-dose cyclosporin in humans.

BACKGROUND: In recent years a reduction of oral cyclosporin A (CsA) dose has been adopted to minimize its adverse renal effects. To date, however, little is known about the intrinsic renal and immunological effects of low-dose CsA. METHODS: Four oral doses of the drug (2, 3, 4 and 5 mg/kg body wt) and placebo (P) were randomly administered in two half-doses to seven healthy subjects. Studies were performed during water diuresis 4 h after administration of the 2nd half-dose, i.e. when the biological activity of the drug is considered maximal. Renal function was evaluated after all doses. In the same subjects, the levels of interleukin-2 (IL-2) and IL-2 receptor (IL-2R), that are the main immunological targets of CsA, were measured in the supernatant of peripheral blood mononuclear cells cultured with phytohaemagglutinin (PHA) after P, 3 and 5 mg/kg of the drug. RESULTS: CsA induced a dose-dependent and proportional decrease of GFR and RPF associated with increasing renal vascular resistances (RVR) in presence of unmodified blood pressure. Similarly, Na+ urinary excretion decreased in a dose-dependent manner due to both GFR reduction and to an higher tubular reabsorption mainly localized at the level of the proximal nephron. All these changes were significant only after 4 and 5 mg/kg. A significant suppression of PHA-stimulated IL-2 and IL-2R cell release was observed following 5 mg/kg only. CONCLUSIONS: This study suggests that nephrotoxic and immunosuppressive effects of low-dose CsA are strictly linked.

Evaluation of monoclonal/polyclonal ratio in kidney-transplanted patients treated with cyclosporine.

Fifty-seven kidney-transplanted outpatients, treated with cyclosporine alone or associated with azathioprine, prednisone, or methylprednisolone, were submitted to a monthly follow-up in order to determine cyclosporine blood levels and the monoclonal/polyclonal (M/P) ratio. Only methylprednisolone was able to modify the M/P ratio. This drug increased the M/P ratio, suggesting a cyclosporine metabolic inhibition. This effect disappeared in a few months in spite of the continuation of methylprednisolone treatment.

Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure.

These studies were performed in patients with chronic renal failure to understand the mechanism(s) of hyperkalemia secondary to hypertonic NaCl infusion. In 10 patients, after intravenous infusion of either 5% or 2.5% NaCl (6 mEq per kg body wt for 120 minutes in both solutions), the maximum increase in plasma potassium averaged 0.6 (range 0.3 to 1.3) mmol/liter (P less than 0.01) or 0.3 (range 0.2 to 0.6) mmol/liter (P less than 0.01), respectively. The rise of both plasma potassium and osmolality was significantly higher during 5% NaCl than during 2.5% NaCl infusion (P less than 0.01). A significant linear correlation (P less than 0.01) between plasma potassium and osmolality was observed. Urinary potassium excretion was increased to a similar extent by 5% NaCl and 2.5% NaCl infusion. The observed hyperkalemia, secondary to NaCl infusion, was independent of venous pH, plasma bicarbonate, anion gap, insulin levels, and urinary norepinephrine and epinephrine excretion, and was associated with a fall in plasma aldosterone concentration. In separate studies, nine patients were treated with desoxycorticosterone acetate (DOCA; 20 mg i.m. for three days) before receiving saline (5%) infusion. DOCA did not prevent the level increase in plasma potassium that remained significantly correlated with plasma osmolality (P less than 0.01). In conclusion, hypertonic NaCl infusion in patients with renal failure causes a clinically relevant hyperkalemia despite increased renal excretion of potassium. This hyperkalemia is independent of acid-base or hormonal mechanisms known to regulate extrarenal homeostasis of potassium, and is strictly correlated with a rise in plasma osmolality.