Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term

Clinical Study Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENCE Study 3-Year Follow Up

Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term

Early initiation of continuous renal replacement therapy improves survival of elderly patients with acute kidney injury: a multicenter prospective cohort study

BACKGROUND: Continuous renal replacement therapy (CRRT) is essential in the management of critically ill patients with acute kidney injury (AKI). However, the optimal timing for initiating CRRT remains controversial, especially in elderly patients. Therefore, we investigated the outcomes of early CRRT initiation in elderly patients with AKI. METHODS: A total of 607 patients ≥65 years of age who started CRRT due to AKI between August 2009 and December 2013 were prospectively enrolled. They were divided into two groups based on the median 6-hour urine output immediately before CRRT initiation. Propensity score matching was used to compare the overall survival rate, CRRT duration, and hospitalization duration. RESULTS: The median age of both groups was 73.0 years, and 60 % of the patients were male. The most common cause of AKI was sepsis. In the early CRRT group, the mean arterial pressure was higher, but the prothrombin time and total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels were lower. The overall cumulative survival rate was higher in the early CRRT group (log-rank P < 0.01). Late CRRT initiation was associated with a higher mortality rate than early initiation after adjusting for age, sex, the Charlson comorbidity index, systolic arterial pressure, prothrombin time, the total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels, cumulative fluid balance and diuretic use (hazard ratio, 1.35; 95 % confidence interval 1.06, 1.71, P = 0.02). Following propensity score matching, patient survival was significantly better in the early CRRT group than in the late CRRT group (P < 0.01). The total duration of hospitalization from the start of CRRT was shorter among the survivors when CRRT was started earlier (26.7 versus 39.1 days, P = 0.04). CONCLUSION: A better prognosis can be expected if CRRT is applied early in the course of AKI in critically ill, elderly patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1437-8) contains supplementary material, which is available to authorized users