Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions.

Erythropoeitin dose variation in different facilities in different countries and its relationship to drug resistance.Background. The correction of anemia using erythropoeitin (EPO) is accorded high priority in the management of patients undergoing hemodialysis (HD). Target hemoglobin (Hb) levels have been established in many countries. Following an observation that the mean facility EPO dose in a chain of facilities in the United States varied by more than two-fold, an examination of the practice of anemia correction in other settings was carried out.Methods. We reviewed demographic and laboratory parameters in prevalent HD patients in 50 United States facilities and in a single HD facility in Vicenza, Italy. The mean EPO dose profile of the United States facilities was compared with the profiles in 10 facilities in the eastern United Kingdom (UKER) and in 20 facilities reporting to the United Kingdom Renal Registry (UKRR). Analysis of the factors that correlate with EPO resistance was carried out using the United States and Italian data.Results. The average EPO doses, by facility, in the 51 United States, the 10 UKER, and the 19 UKRR facilities were 19,569, 8,416, and 7,992 international units per week (IU/wk), respectively. While examination of the UKRR revealed a similar degree of inter-facility variation (2.6-fold), much larger doses of EPO were being administered in the United States patients, particularly in the low Hb group. Multivariate analysis of the United States data suggested that factors related to inflammation, including low albumin, the use of tunneled catheters for vascular access, and low protein catabolic rate (enPCR) correlated with low Hb and relative EPO resistance.Conclusion. Despite similar guidelines for anemia management, significant differences in practice are observed. While there seems to be a reluctance to administer large EPO doses to individual patients in Europe, this does not seem to apply in the United States, where more EPO is given. EPO resistance seems relative rather than absolute in many patients, allowing some to respond to the higher doses.The anemia of chronic kidney disease (CKD) has been well characterized and the intricacies of treatment, pri-

Uremia is associated with a state of immune dysfunction. Dysregulation of homeostasis may be directly related to abnormal apoptosis regulation in uremia, which is crucial for the maintenance of the biological system. We demonstrated that plasma from three groups of uremic subjects, i.e. hemodialysis (HD) patients, peritoneal dialysis (PD) patients and patients with predialysis chronic renal failure (CRF), has different apoptotic potential on U937 monocytes. The plasma of HD and CRF subjects when incubated with U937 cells induced higher levels of apoptosis compared with that of PD and control subjects (HD 26.08 ± 11.39, CRF 24.87 ± 9.07, PD 12.13 ± 4.51, controls 11.69 ± 4.02). Furthermore, the phagocytic ability of U937 cells incubated with the various plasma demonstrated an impaired response in the HD and CRF subjects (HD 27.56 ± 6.67, CRF 30.24 ± 9.08, PD 36.55 ± 9.80, controls 40.04 ± 6.98). These results suggest that continuous blood purification, such as in PD, may have advantages over intermittent therapies in removing uremic apoptotic molecules and potentially maintaining biological function and homeostasis.

Several patients undergoing chronic renal replacement therapy present problems related to their vascular access. Low blood flows and high rates of recirculation are common in such patients in which, for this reason, it becomes difficult to apply highly efficient techniques or techniques where diffusion and convection are combined as in hemodiafiltration. In these patients we studied the possibility of partially recirculating the blood in the extracorporeal circuit in order to increase the flow rate per single hollow fiber; we defined our system "double pass dialysis". We evaluated the system's efficiency in 12 patients during 24 dialysis sessions: 12 high flux dialysis sessions (without reinfusion) and 12 hemodiafiltration sessions (9 liters reinfusion). Different surfaces of polyacrylonitrile dialyzers were utilized (1.3-1.7-2.1 sqm) at 250 and 350 ml/min of blood flow with or without 100 ml/min of recirculation. During each dialysis session blood and dialysate samples were taken in order to calculate BUN, Creatinine, Phosphate and Inuline clearances from both the blood and dialysate side. The clearances of low molecular weight solutes were not really influenced by the artificial increase of the blood flow, but on the other hand, the clearances of higher molecular weight solutes increased from 10 to 30% during both high flux dialysis and hemodiafiltration with recirculation. This increase was evident mostly in hemodiafiltration suggesting that the cleaning effect on the membrane has a positive impact on the permeability. The good clinical results obtained with the double pass dialysis show that the system is safe and reliable and may become a valid support in critical situations in order to reach adequate dialysis treatment.

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients’ characteristics.