Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups

Comparison of outcome and characteristics between 6343 COVID-19 patients and 2256 other community-acquired viral pneumonia patients admitted to Dutch ICUs

Purpose: Describe the differences in characteristics and outcomes between COVID-19 and other viral pneumonia patients admitted to Dutch ICUs. Materials and methods: Data from the National-Intensive-Care-Evaluation-registry of COVID-19 patients admitted between February 15th and January 1th 2021 and other viral pneumonia patients admitted between January 1st 2017 and January 1st 2020 were used. Patients' characteristics, the unadjusted, and adjusted in-hospital mortality were compared. Results: 6343 COVID-19 and 2256 other viral pneumonia patients from 79 ICUs were included. The COVID-19 patients included more male (71.3 vs 49.8%), had a higher Body-Mass-Index (28.1 vs 25.5), less comorbidities (42.2 vs 72.7%), and a prolonged hospital length of stay (19 vs 9 days). The COVID-19 patients had a significantly higher crude in-hospital mortality rate (Odds ratio (OR) = 1.80), after adjustment for patient characteristics and ICU occupancy rate the OR was respectively 3.62 and 3.58. Conclusion: Higher mortality among COVID-19 patients could not be explained by patient characteristics and higher ICU occupancy rates, indicating that COVID-19 is more severe compared to other viral pneumonia. Our findings confirm earlier warnings of a high need of ICU capacity and high mortality rates among relatively healthy COVID-19 patients as this may lead to a higher mental workload for the staff. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Inferior results with basis immunosuppression with sirolimus in kidney transplantation.

Contains fulltext : 53188.pdf (publisher's version ) (Open Access)BACKGROUND: The introduction of sirolimus has provided the opportunity to develop an immunosuppressive regimen without the nephrotoxic calcineurin inhibitors. METHODS: We conducted a first trial in 30 renal allograft recipients. Ten patients were followed prospectively and received sirolimus, to achieve a target blood level of 10 to 15 ng/ml, induction therapy with one dose of daclizumab, low-dose steroids and mycophenolate mofetil. We compared this group with a historical control group of 20 patients who received our standard treatment consisting of tacrolimus, low-dose steroids, and mycophenolate mofetil. RESULTS: After a mean follow-up of 15 weeks, seven patients developed an acute rejection in the sirolimus group (70%) compared with three patients in the tacrolimus group (15%) (p.<0.01). Because of this unacceptable high rate of acute rejections we conducted a second prospective pilot study in nine patients. These patients received sirolimus in combination with two doses of daclizumab, high-dose steroids and mycophenolate mofetil. No rejections occurred under this immunosuppressive regimen; however, many immunosuppression-related adverse events were seen. CONCLUSION: The present study demonstrates an unacceptably high rate of acute rejections (70%) in patients treated with sirolimus, daclizumab, mycophenolate mofetil and low-dose prednisolone. No rejections but many adverse events were seen when sirolimus was given in combination with high-dose steroids

'Nieuwe wegen naar orgaandonatie'; een advies van de Gezondheidsraad.

De Nederlandse situatie op het gebied van orgaandonatie en transplantatie is zorgwekkend. Er is al jaren een flinke achteruitgang merkbaar in het aantal hersendode donoren. Om de lange wachtlijsten te bekorten moeten twee andere vormen van donatie ook optimaal benut worden: donatie door levende donoren en door donoren die aan een hartstilstand zijn overleden. De stagnatie in het aanbod van organen wordt op dit moment al voor een deel goedgemaakt doordat meer mensen bij leven een orgaan afstaan. Ook donororganen van mensen die aan een hartstilstand zijn overleden kunnen echter helpen om de wachtlijsten te bekorten, gezien de sterk verbeterde resultaten. Om deze vormen van donatie verder te stimuleren is gericht beleid noodzakelijk. Dit schrijft de Gezondheidsraad in een advies dat vandaag wordt aangeboden aan de minister van Volksgezondheid, Welzijn en Sport

Two doses of daclizumab are sufficient for prolonged interleukin-2Ralpha chain blockade.

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Oral ulcers in kidney transplant recipients treated with sirolimus and mycophenolate mofetil.

BACKGROUND: In an attempt to reduce calcineurin inhibitor toxicity, transplant patients treated with tacrolimus can be switched to maintenance treatment with sirolimus. METHODS: In a prospective, randomized, multicenter trial, 33 kidney transplant recipients on steroid-free maintenance treatment with tacrolimus and mycophenolate mofetil continued tacrolimus and mycophenolate mofetil (control group, n=18) or were converted from tacrolimus to sirolimus (study group, n=15) at 1 year after transplantation. RESULTS: The study was prematurely stopped as a result of a cluster of nine patients suffering from painful oral ulcerations in the study group. Oral ulcerations did not occur in the control group. The authors here report on the individual cases suffering from this side effect of the instituted immunosuppressive regimen. CONCLUSIONS: The authors review the literature with respect to the occurrence of oral ulcers associated with the use of sirolimus or mycophenolate mofetil and speculate on the causes of the high incidence of oral ulcers in their study group. Possible explanations are overimmunosuppression during the period of the conversion from tacrolimus to sirolimus without antiviral prophylaxis, the use of the oral emulsion instead of tablets, or the lack of corticosteroid co-administration

Randomized trial of misoprostol in patients with chronic renal transplant rejection

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Preservation of non-heart-beating donor kidneys: a clinical prospective randomised case-control study of machine perfusion versus cold storage.

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