Incidence and clinical course of de-novo malignancies in renal allograft recipients.

BACKGROUND: This study was designed to evaluate the development of malignancies after renal transplantation in a single centre. The outcome was studied in patients developing a malignant neoplasm after renal transplantation. METHODS: Malignancies are registered in a database containing relevant data about the patients with a renal transplant. This database and the files of the patients developing a malignant neoplasm, have been studied as to stage at presentation, therapy and outcome. RESULTS: In 1546 patients with 2075 renal transplantations, 240 malignancies developed in 231 recipients. Skin cancers often present with more than one lesion of the same histological type. After the first skin tumour, about half of the patients developed more lesions, of the same or a different histological type. The prognosis of skin tumours is relatively good, but most malignancies in all other categories have a poor prognosis. CONCLUSIONS: Cutaneous neoplasms tend to be multiple, but can be controlled by regular examination of the skin. Most malignant lymphomas do develop outside the lymphoproliferative system and have a poor prognosis. Patients with a solid tumour of the other tracts often present in an advanced stage of disease, which makes the outcome of treatment, if possible at all, disappointing.

A randomised, prospective study on the conversion from cyclosporine-prednisone to cyclosporine-azathioprine at 6 months after renal transplantation.

In a randomised prospective trial, we studied the effects of replacement of prednisone (Pred) by azathioprine (Aza), 6 months after transplantation, in stable renal allograft recipients on cyclosporine and prednisone (CsA + Pred). Out of 83 patients, 42 started treatment with CsA + Aza and 41 continued therapy with CsA + Pred. CsA was dosed to achieve a level of 150 ng/ml, the Aza dose was 3 mg/kg per day and the Pred dose was 0.15 mg/kg per day. Eighteen months after randomisation, in the CsA + Aza group 18 of the 42 patients were effectively treated with CsA + Aza. In the main, anaemia, leuco- and thrombocytopenia, and hypocorticism necessitated the reintroduction of Pred in the remaining 24 patients. Compared to the continuation of CsA + Pred, conversion of Pred to Aza resulted in a reduced number of antihypertensive drugs needed, and in lower serum total, LDL and HDL cholesterol levels; the incidence of acute rejections and graft losses was no different. In conclusion, conversion of CsA + Pred to CsA + Aza is a safe option in renal transplant patients with contraindications to long-term corticosteroid treatment.

Pneumocystis carinii pneumonia in renal transplant recipients.

In 1991 and 1992 Pneumocystis carinii pneumonia (PCP) was diagnosed in 28 renal transplant recipients. The incidence of PCP in our renal transplant centre was remarkably increased from 1.1% before 1991 to 11.5% in 1991-1992. We compared 28 PCP patients with a control group of 27 renal transplant recipients, matched for transplantation day and without an episode of PCP. The mean age was significantly higher in the PCP group (50 +/- 13 versus 38 +/- 13 years). We observed no differences in basic immunosuppressive and rejection treatment nor in antibiotic consumption, number of hospitalization days, and incidence of CMV infection. In March 1993 we introduced PCP prophylaxis. More than 140 renal transplant recipients received co-trimoxazole, starting 1 day after transplantation and continued for a period of 4 months. To the time of writing no one in this group had developed PCP.

Intraperitoneal administration of recombinant human erythropoietin.

OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable.

Mannitol as an indispensable constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric transplantation.

With its incidence of about 40%, acute renal failure (ARF) is a major problem after cadaveric renal transplantation. We have previously shown that, with moderate hydration (2.5 L) of the recipient, together with rapid infusion of 250 ml of mannitol 20% just before clamp removal, the incidence of ARF decreased to below 10%. Administration of mannitol without hydration was not effective. In a prospective randomized trial we have now investigated whether hydration without mannitol is sufficient to prevent ARF. For this purpose patients were randomly allocated to treatment with moderate hydration with or without mannitol. Furthermore, in both treatment groups recipients were randomized to treatment with cyclosporine or azathioprine. The allocation method used guaranteed an even distribution for 10 important prognostic factors. In the cyclosporine group, the percentage of ARF was significantly lower in mannitol-treated (n = 32) than in glucose-treated patients (n = 32) (19% vs. 54%, P less than 0.01). In the azathioprine group the percentage of ARF was also lower in mannitol-treated (n = 33) than in glucose-treated patients (n = 34) (18% vs. 44%, P less than 0.05). Overall incidence of ARF in both groups was significantly lower in mannitol-treated patients (P less than 0.001). Thus, moderate hydration and administration of 250 ml mannitol 20% just before arterial clamp removal are both indispensable for optimal prevention of ARF after cadaveric renal transplantation.

Prevention of acute tubular necrosis in cadaveric kidney transplantation by the combined use of mannitol and moderate hydration.

Recent studies have indicated that maximal hydration of the transplant recipient can substantially reduce the incidence of acute tubular necrosis (ATN). However, this policy requires invasive hemodynamic monitoring, prolonged mechanical ventilation, and bears the risk of overhydration. In a prospective trial we studied the incidence of ATN in recipients of cadaveric kidneys after restricted fluid infusion (Group 1, N = 21), after restricted fluid infusion along with 250 ml of mannitol 20% (Group 2, N = 19), and after a moderate hydration policy together with 250 ml mannitol 20% (Group 3; N = 21). Donor- and preoperative recipient parameters were comparable in all three groups. The total amount of fluid administered and the incidence of ATN were as follows: Group 1-1059 +/- 371 ml and 43%; Group 2-1548 +/- 622 ml and 53%; and Group 3-2529 +/- 675 ml and 4.8%. The moderate hydration policy in Group 3 resulted in a significantly higher peroperative systolic blood pressure compared to Groups 1 and 2. We did not observe any problems related to overhydration. The reduction of ATN incidence led to a substantial decrease in the number of hemodialysis treatments, radionuclide scans, ultrasound investigations, transplant biopsies, and rejection episodes in the first 3 months after transplantation. It is concluded that moderate fluid administration of 2.5 liters during the transplant procedure together with infusion of 250 ml of mannitol 20% immediately before vessel clamp release reduces the incidence of postoperative ATN below five per cent. The procedure is safe, simple, and does not require invasive hemodynamic monitoring.

Cimetidine prophylaxis after renal transplantation.

Over an 18 month period 66 consecutive kidney transplant patients at risk of gastrointestinal bleeding were treated prophylactically with the histamine H2-blocker cimetidine, without antacids. The incidence of gastrointestinal bleeding, the number of rejection episodes, and graft survival were compared with those of 66 patients, who had received a transplant in the period immediately preceding the start of the study, and who had never received cimetidine. The incidence of gastrointestinal hemorrhage was significantly reduced in the cimetidine-treated patients (P less than 0.05). In addition, cimetidine treatment neither increased the total number of rejection episodes nor did it impair long-term graft survival.

Inhibition of frusemide-induced natriuresis by indomethacin in patients with the nephrotic syndrome.

1. In four patients with nephrotic syndrome indomethacin not only reduced proteinuria but also inhibited the natriuretic effect of high doses of frusemide. 2. The inhibition of natriuresis by indomethacin could not be antagonized by albumin infusions. 3. Only the combined use of spironolactone and frusemide induced a natriuresis during indomethacin treatment. Spironolactone alone was ineffective. 4. It is suggested that inhibition of prostaglandin synthesis by indomethacin, in the presence of a stimulated renin-angiotensin system and hyperaldosteronism, may cause this strong tendency to sodium retention.