Pharmacokinetic monitoring of mycophenolate mofetil in kidney transplanted patients.

Mycophenolate mofetil (MMF) is a new immunosuppressant drug used in association with cyclosporin and oral corticosteroids to prevent acute rejection following renal allograft transplantation. MMF is an ester pro-drug of mycophenolic acid (MFA), the true active species, into which it is completely transformed after oral administration. The recommended initial dose to prevent kidney transplant rejection is 2 g/day irrespective of body weight, 1 g twice daily. The goal of this study was to correlate dosage (fixed or by body weight) and toxic effects to some non-compartmental values such as peak level (Cmax), time to peak level (Tmax) and trough level (Cmin). In a small number of patients who had already reached the plasma steady state, we found a large inter-patient variability, while the same qualitative pharmacokinetic profile (as Tmax) was conserved. At plasma trough level > 4 microg/ml some serious toxic effects were observed, whereas at Cmin < 2 microg/ml, there were some cases of interstitial rejection. There was also a negative correlation between dosage and body weight, suggesting that dosages related to body weight might be better than fixed ones. Finally, monitoring plasma level of drug from transplantation to at least 12 months after surgery, at fixed MFA dosage, a small but significant decline of MFA plasma levels was found.

[99mTc-DTPA scintigraphy in renal transplantation. Limitations related to the immunosuppressor used]. / La scintigrafia con 99mTc-DTPA nel trapianto renale. Limiti correlati all'immunodepressore usato.

The diagnostic tools used to achieve an assessment of allograft dysfunction should be as noninvasive as possible, because kidney graft recipients are fragile patients and quite often the need is for repeated investigations. In order to evaluate the reliability and accuracy of such a method, in this case scintigraphy with 99mTc-DTPA, the authors retrospectively studied 2 groups of kidney transplanted patients, having two different basic immunosuppressive regimens: group A--86 patients--taking steroids and azathioprine; group B--93 patients--taking steroids and cyclosporine. A total of 722 scans were retrospectively compared with scintigraphic information: 196 episodes of allograft dysfunction were due to acute rejection: 118 in group A, 78 in group B; 117 episodes were due to ATN: 75 in group A, 42 in group B; 11 episodes were ascribed to CyA acute nephrotoxicity. Group A and B behave differently in respect of the perfusion index. Only in group A were perfusion indexes statistically different in rejection, ATN and nephrotoxicity. Anyway, it must be stressed that, even if in group B, scintigraphy cannot be considered an accurate diagnostic method, it is somehow a helpful tool because it gives information about a worse perfusion of the graft, independently of the underlying pathology.

Antibodies to hepatitis C virus in kidney transplantation.

Ninety patients on dialysis, 241 cadaveric kidney donors and 27 cadaveric kidney recipients with a follow-up of 2 years, have been investigated as for anti-HCV positivity by means of 3 tests. As for patients on dialysis and cadaveric donors, the prevalence was 32 and 4%, respectively. As for transplanted patients, it must be noted that 4 negative recipients from positive donors seroconverted, but without any change in hepatic enzymes, while in 2 or 9 anti-HCV-positive recipients, hepatic enzymes increased after transplantation. Seroconversion in patients transplanted from a negative donor was not significantly different. We conclude that, according to their experience, anti-HCV positivity in the donors is not associated with a significant risk of infection in recipients of cadaveric grafts.

Echo-Doppler velocimetry in the diagnosis of renal artery stenosis on transplanted kidney.

Renal artery stenosis is one of the most important complications in the natural history of kidney transplantation. Particular care has to be taken in the use of angiography techniques because of the invasiveness and of the potential toxicity of radiopaque contrast material, even in the less invasive radiological tests, like endovenous sequential angiourography with image subtraction (SAU) and digital subtraction angiography (DSA). Fifty-one patients have been examined with echo-Doppler velocimetry (EDV) and also with SAU in order to verify the previous status of the artery. EDV exhibits a 100% sensitivity: all SAU detected stenosis have been formerly identified via EDV. The non-invasiveness and possibility of early repetition allows an early diagnosis capability for all transplanted patients. In this way, a surgical intervention may quite often be prevented by a precocious use of endoluminal angioplasty.

Muzolimine in chronic renal failure: a study in 16 patients.

Muzolimine is a diuretic with chemical features different from all other known diuretics, and its use seem to be particularly interesting in patients with chronic renal failure. In fact, similarly to furosemide, muzolimine presents a strong action on Henle's loop but with a slower and more lasting effect, as experimentally demonstrated in both animals and man. We used high doses muzolimine (240, 480, 720 mg/die) in 16 patients with chronic renal failure (creatinine clearance less than 20 ml/min) and clinical pattern of important hydrosaline retention (6 primitive glomerulonephritis, 3 interstitial nephrites, 1 vascular nephropathy, 1 diabetic nephropathy, 1 lupus nephritis, 1 amyloidosis, 1 polycystic nephropathy and 2 nephropathies of unknown diagnosis). Muzolimine diuretic action was compared with furosemide 500 mg/die. The schedule employed was: furosemide 500 mg/die for 5 days followed by 6 days of muzolimine treatment at increasing doses (240 mg on 1st and 2nd day, 480 mg on 3rd and 4th, 720 mg on 5th and 6th). In all patients (undergoing a diet constant in water, sodium, potassium and protein content) body weight, blood pressure, heart rate, serum and urinary electrolyte concentration, serum and urinary uric acid, BUN, creatinine clearance, glycaemia, hematocrit and hemoglobin were daily controlled. A clinical and laboratory investigation of the possible side effects was also assessed; in particular liver enzymes, bilirubin and total serum proteins were considered. In our study muzolimine increased the renal excretion of water, sodium and chloride in all cases. This effect is more evident during the treatment with the highest dose (720 mg/die) but already appears with the 480 mg/die dose and is higher than that obtained with comparable doses of furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemofiltration in diabetic uremic patients.

The increasing number of Diabetic Uremic Patients (DUP) starting the substitutive treatment (ST) constitutes a difficult and often disappointing problem in terms of efforts, clinical results and side-effects. While treatment of these patients by C.A.P.D. is well documented, the adoption of Hemofiltration (HF), has been, up to now scarcely considered. In order to define the potentialities of a HF policy in the treatment of these patients, data from 6 DUP treated with postdilutional HF for a 10.6 months/patient period were collected on a multi-center basis and retrospectively examined. Good results were achieved in terms of vascular stability, control of arterial hypertension and of retinopathy, clinical complications and hospitalization rate. Although C.A.P.D. may represent a first choice treatment for DUP with residual function, satisfactory glicemic control, difficult blood access and a motivation to full autonomization, HF may constitute a logical alternative when C.A.P.D. should be unmanageable (visus impairment, history of repeated peritonitis and dismetabolism, considerable weight gain): an integration of HF and C.A.P.D. can assure PDU with a continuative treatment.

[Renal tolerance for aminoglycosides]. / Tollerabilità renale agli aminoglicosidi.

Tissue pharmakinetics, morphology of renal lesions and clinical picture of aminoglycoside-induced tubulopathy are described. Almost completely filtered by the glomerulus, they are eliminated in active form and about a third are reabsorbed along the proximal convoluted tubule, thus reaching maximum concentration in the renal cortex in the sixth hour as the drug disappears from the circulation. They are located inside the lysosomes of the convoluted tubule cells where some typical formations called myeloid bodies are present. Cellular lesions are, however, only produced by high doses after, first, clinical manifestations of tubular disturbance such as polyuria, tubular proteinuria, enzymuria, followed, if the toxic insult persists, by renal insufficiency. This can present clinically as progressive renal function deterioration dependent on the dose-time factor. This deterioration is usually not oliguric and it may also present as a sudden oliguric renal insufficiency. The now fully documented risk factors are discussed as well as the duration of treatment (not more than 11 days), the dosage (3 mg/kg/die), the dosage intervals, the age factor (the elderly being shown to be more highly sensitive to the drug), the association with other aminoglycosides or diuretics or cephalosporin. It is very important to diagnose already existing nephropathies or renal insufficiency, in which case dosages must be appropriately reduced. The nephrological history of the patient and control of urea and creatinine clearances before the start of treatment (in addition, obviously, to functional control of the eighth pair of cranial nerves) are essential for all patients receiving courses of aminoglycoside therapy. It is also necessary to check renal function by daily measurements of creatinaemia and urine. These precautions are valid for all aminoglycosides including those that have come on to the market most recently.