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Background Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia. Methods We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations Results Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab. Conclusions Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials.

Pre-transplant dialysis is known to affect kidney graft survival. Here, we report the impact of pre-transplant dialysis on patient and graft survival of type 1 diabetic recipients of either a simultaneous pancreas-kidney (SPK) or living donor kidney (LDK) transplant.Using the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database, 6822 adult type 1 diabetic recipients transplanted through 2000-2011 were identified. Patients were categorized based on pre-transplant dialysis time (DT): preemptive recipients (P-LDK, n = 498; P-SPK, n = 1529), recipients with1 year of DT (0-1 year DT; LDK n = 582, SPK n = 1700), and those with 1-2 years DT (1-2 year DT; LDK n = 301, SPK n = 2212). Seven-year patient and kidney survival were examined.Compared with the P-SPK group, both 0-1 year DT and 1-2 year DT SPK recipients had lower 7-year patient survival (89, 8484% respectively; log-rank P-value versus P-SPK = 0.010.001). For LDK groups, DT1 year was associated with inferior patient survival (7-year survival 76% versus 87% for P-LDK, P-value versus P-LDK = 0.009). Comparing P-LDK to all other SPK groups, there was no significant difference in 7-year patient or kidney survival.Preemptive transplantation is associated with the highest patient survival in both LDK and SPK. Compared with the P-LDK group, DT1 year is associated with lower patient survival among LDK recipients, but there is no difference in survival with dialysis up to 2 years with SPK. These results highlight the differential impact of DT on LDK and SPK transplantation.

Author(s): Molnar, Miklos Z; Bunnapradist, Suphamai; Huang, Edmund; Krishnan, Mahesh; Nissenson, Allen R; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar | Abstract: BackgroundThe role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear.MethodsLinking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively.ResultsPatients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected.ConclusionsHigher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.