This is a randomized trial (ATHENA study) in de novo kidney transplant patients to compare everolimus versus mycophenolic acid (MPA) with similar tacrolimus exposure in both groups, or everolimus with concomitant tacrolimus or cyclosporine (CsA), in an unselected population. In this 12-month, multicenter, open-label study, de novo kidney transplant recipients were randomized to everolimus with tacrolimus (EVR/TAC), everolimus with CsA (EVR/CsA) or MPA with tacrolimus (MPA/TAC), with similar tacrolimus exposure in both groups. Non-inferiority of the primary end point (estimated glomerular filtration rate [eGFR] at month 12), assessed in the per-protocol population of 338 patients, was not shown for EVR/TAC or EVR/CsA versus MPA/TAC. In 123 patients with TAC levels within the protocol-specified range, eGFR outcomes were comparable between groups. The mean increase in eGFR during months 1 to 12 post-transplant, analyzed post hoc, was similar with EVR/TAC or EVR/CsA versus MPA/TAC. The incidence of treatment failure (biopsy proven acute rejection, graft loss or death) was not significant for EVR/ TAC but significant for EVR/CsA versus MPA/TAC. Most biopsy-proven acute rejection events in this study were graded mild (BANFF IA). There were no differences in proteinuria between groups. Cytomegalovirus and BK virus infection were significantly more frequent with MPA/TAC. Thus, everolimus with TAC or CsA showed comparable efficacy to MPA/TAC in de novo kidney transplant patients. Non-inferiority of renal function, when pre-specified, was not shown, but the mean increase in eGFR from month 1 to 12 was comparable to MPA/TAC.
Late switch to sirolimus and impaired renal function are risk factors for pneumonitis. A sirolimus blood trough level above 12 mug/l may increase the risk, but pneumonitis may also occur at blood trough levels as low as 6 mug/l. Since pneumonitis may recur during low-dose sirolimus treatment, discontinuation of sirolimus appears to be the safest treatment option.
Severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) preferentially affects epithelia of the upper and lower respiratory tract. Thus, impairment of kidney function has been primarily attributed until now to secondary effects such as cytokine release or fluid balance disturbances. We provide evidence that SARS‐CoV‐2 can directly infiltrate a kidney allograft. A 69‐year‐old male, who underwent pancreas‐kidney transplantation 13 years previously, presented to our hospital with coronavirus disease 2019 (COVID‐19) pneumonia and impaired pancreas and kidney allograft function. Kidney biopsy was performed showing tubular damage and an interstitial mononuclear cell infiltrate. Reverse transcriptase polymerase chain reaction from the biopsy specimen was positive for SARS‐CoV‐2. In‐situ hybridization revealed SARS‐CoV‐2 RNA in tubular cells and the interstitium. Subsequently, he had 2 convulsive seizures. Magnetic resonance tomography suggested meningoencephalitis, which was confirmed by SARS‐CoV‐2 RNA transcripts in the cerebrospinal fluid. The patient had COVID‐19 pneumonia, meningoencephalitis, and nephritis. SARS‐CoV‐2 binds to its target cells through angiotensin‐converting enzyme 2, which is expressed in a broad variety of tissues including the lung, brain, and kidney. SARS‐CoV‐2 thereby shares features with other human coronaviruses including SARS‐CoV that were identified as pathogens beyond the respiratory tract as well. The present case should provide awareness that extrapulmonary symptoms in COVID‐19 may be attributable to viral infiltration of diverse organs.
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