key: cord-0975834-7bmatg2m
authors: Laessle, Claudia; Schneider, Johanna; Pisarski, Przemyslaw; Fichtner-Feigl, Stefan; Jänigen, Bernd
title: Experiences and short-term outcome of kidney transplantation during Covid-19 pandemic from a medium volume transplantation and supraregional Covid-19 treatment center.
date: 2021-01-20
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2021.01.036
sha: 4f01741cc5e802469976bff6f7040fb47d86e46f
doc_id: 975834
cord_uid: 7bmatg2m

Introduction The coronavirus, which appeared in 2019, developed into a pandemic during 2020. It remains unclear to what extent the pandemic endangers the safety of kidney transplantation programs. In this study, we evaluate the short-term outcome of our patients receiving a kidney transplant during the first phase and comparing them with patients who received a kidney transplant immediately before the corona pandemic. Material and Methods Our retrospective study includes 34 kidney transplant recipients between October 1st, 2019, and April 30th, 2020. 19 patients from the phase immediately prior to the first corona wave (pre-corona group) and 15 patients from the phase of the first corona wave (corona group). We retrospectively evaluated demographic data, postoperative short-term outcome and complications, immunosuppression regime, corona infection status and behavior during the first phase of the pandemic. Results There were no differences between the two groups with regard to short-term outcomes and postoperative complications or in immunosuppressive medication. After the introduction of intensified hygienic conditions and routine swabs prior to transplantation, no nosocomial SARS-CoV-2 infections occurred. In the outpatient setting, none of the patients developed a SARS-CoV-2 infection. The majority of patients performed voluntary quarantine. Conclusion The short-term outcome after kidney transplantation during the first phase of the coronavirus pandemic was comparable to pre-pandemic patients and no SARS-CoV-2 associated death or transplant failure occurred in our small cohort. We consider patient compliance with hygiene and self-isolation measures to be very high. Nevertheless, in further phases of the pandemic, the continuation of the life kidney donation program must be critically evaluated.

The short-term outcome after kidney transplantation during the first phase of the coronavirus pandemic was comparable to pre-pandemic patients and no SARS-CoV-2 associated death or transplant failure occurred in our small cohort. We consider patient compliance with hygiene and self-isolation measures to be very high. Nevertheless, in further phases of the pandemic, the continuation of the life kidney donation program must be critically evaluated.

The Corona virus is a very infective virus first identified in December 2019 and was declared as a global pandemic by the World Health organization on March 11 th , 2020. (1,2) The global coronavirus pandemic creates major challenges for national and international health systems. Not only must the management of the acute Covid-19 disease be organized and ensured, but also other equally urgent diseases must be treated and therapies performed at the same time. In this field of conflict, it is necessary to consider for each individual patient whether therapy is necessary and whether the increased risk of becoming infected with SARS-CoV-2 during treatment and afterwards is justifiable. Elective therapies must also be considered in view of the limited resources of medical staff, intensive care units and medical equipment. (3, 4) However, kidney transplantation is the most effective and cost-effective treatment for terminal renal failure.(5) Transplanted patients require a lifelong immune suppression and intensive medical care, especially in the first weeks after transplantation. During the first time after transplantation, patients are highly immunosuppressed and thus have an increased risk to viral diseases such as cytomegalovirus or Epstein- Barr virus.(6, 7) Consequently, this group of recently transplanted patients also represents a high-risk group for a severe case of There were no national or international guidelines for kidney transplantation during the first wave of the Covid-19 pandemic. First protocols for standardized procedures in J o u r n a l P r e -p r o o f organizational and hygiene processes around organ transplantation are only in the initial phase of development.(9) The pandemic is expected to continue until the successful introduction of a vaccine. The question arises for us as a medium volume kidney transplantation center and as a supraregional Covid-19 treatment center; what are the outcomes after kidney transplantation during the pandemic? And is there an increased number of Covid-19 infections in the vulnerable first phase after kidney transplantation?

To answer the questions, we have compared the patients who got kidney transplantation during the first wave of the Covid-19 pandemic with the patients who were transplanted just before the appearance of Covid-19 in Germany.

In Germany, the first case of SARS-CoV-2 was reported on the 24 th of January, 2020. During the pandemic period, we continued our kidney transplantation program, interrupting only the living donor kidney transplant program from the middle of March until the middle of May. We retrospectively identified 15 recipients, who were transplanted in this period of the first wave of pandemic in Germany and compared them with 19 renal transplant recipients of the direct pre-corona time period (between October 23 rd , 2019 and January, 2020).( fig.1 ) Follow up was finished by the end of July, 2020. The donors in our living kidney transplant program were not from prison, not paid or coerced. In all recipients, we applied the immunosuppression after our standard protocol, including a triple maintenance immunotherapy with tacrolimus, mycophenolate acid and steroids. Induction therapy was applied risk adjusted: none: low risk as defined in a former report, basiliximab: standard risk and thymoglobulin: immunized recipients.(10) All recipients were only treated in two-bed rooms in our transplant ward and only shared the room with other transplanted patients to J o u r n a l P r e -p r o o f reduce the contact to other patients and staff. Visitors were restricted to 2 persons per recipient and from the middle of March, completely prohibited. After discharge, we suggested voluntary quarantine. After the advice of the German Transplant Society (DTG) from the 23 rd of March, all recipients were tested for SARS-CoV-2 before transplantation.

The kidney was transplanted using the established technique, typically comprising implantation into the right iliacal fossa. Until postoperative day 5, all recipients received a fixed dose of 12,500 units of heparin intravenously per day, starting 6 h after the end of surgery.

All recipients received prednisone starting with 250 mg intraoperatively, 125 mg on the 1 st postoperative day and 50 mg on postoperative day 2 with a quick taper to 15 mg on day 12.

Tacrolimus trough levels were targeted at 8-10 ng/ml and mycophenolate acid started with a fixed dose of 2 g daily initiated at the evening prior to transplantation. If receiving induction therapy, a dose of 20 mg basiliximab was administered intraoperatively and on day 4, respectively. In immunized recipients 1.5 mg/kg body weight antithymocyte globulin was administered intraoperatively.

Clinical data collection, definitions, and statistical analysis Clinical data were retrospectively collected from clinical records. Follow-up data were collected from the responsible nephrologists throughout Germany and from the patients itself. Delayed graft function was defined by the need of at least one dialysis treatment during the first postoperative week. Postoperative complications were categorized using 12) In the high phase in calendar week 19, 12 Covid-19 positive patients and 3 newly kidney transplanted patients were treated simultaneously in our Surgical Clinic.

From the first of April 2020 onwards, all patients who were admitted to NTX were room isolated and swabbed for Covid-19 before the transplantation.( fig.2 ) If the swab was negative, the transplantation was performed. However, the transplanted patients were monitored directly postoperatively in our Surgical Intensive Care Unit, which also took care of patients with SARS-CoV-2 infection. Patients were isolated in their rooms and the nursing staff was not allowed to handle patients with Covid-19 at the same time.

J o u r n a l P r e -p r o o f Baseline characteristics:

The two patient groups do not differ statistically in the parameters collected (table 1) . The donor age, donor and recipient gender distribution and donor and recipient BMI are balanced. The ASA score, as a score for preoperative physical status, does not differ between the two groups. Both groups have the same amount of pulmonary predisposition (26.3% vs. 13.3%). In the Pre-Corona group (Pre-C), 5 patients abused nicotine while in the Corona group (C), 2 patients abused nicotine. In the Corona group, one patient had suffered from COPD.

Immunosuppression is the same in both groups. There is also no statistical difference in induction therapy, 47.4% had basiliximab induction in the Pre-C Group and 73.3% in the Cgroup (p=0.1706). The cold and warm ischemia times also show no significant difference, although the cold ischemia time in the pre-C group (395.5 ± 260.8 minutes) was markedly lower than in the Corona group (532.2 ± 349.8 minutes). This is due to the higher rate of living donation in the pre-C group. There are also no significant differences in CMV status. Among these, 2 patients received surgical treatment of the lymphocele, one patient showed a urine leakage which was treated with a percutaneous nephrostomy. In the C group, 2 patients have suffered from a complication which needed intervention. 2 patients got a lymphocele, one of them had to be relieved laparoscopically and one patient was treated with a percutaneous drainage.

The rate of any internistic deviations was also identical in both groups (31.6% vs. 46.7%, p=0.4836). In the pre-C group, 2 patients developed bacterial pneumonia and one patient developed a cellular rejection, which made this patient require dialysis again. Another cellular rejection was successfully treated with cortisone therapy. One patient developed esophagitis, which was also treated conservatively.

In the C group, 3 patients developed NODAT (new onset diabetes after kidney transplantation) and 2 patients a suspected rejection, which regressed after cortisone therapy. One patient developed segmental colitis.

In both patients with Covid-19 positive swabs occurred prerenal kidney failure (maximum creatinine 2.1 mg/dl), which was completely regressive on volume therapy. Postoperative blood transfusion was balanced in both groups as well.

Serum creatinine 30 days after transplantation was also not statistically significantly different in both groups and was 2.05 ± 2.23 (0.86 -9.97) mg/dl in the pre-Corona group and 1.49 ± 0.45 (0.91 -2.71) mg/dl in the Corona group.

Corona status in the cohort:

In both groups there was no significant difference in the incidence of Covid-19 diseases (table 3) . Only two patients (13%) had Covid-19 disease after transplantation while the hospital stay in the C group, neither of the two patients needed ICU care. In both patients the first positive swab was taken during the initial postoperative phase (12 and infections.(28) The two positive patients described in our study tested positive the week before the intensified screening with a routine swab and strict room isolation was started.

The nosocomial path of infection in these two patients was not retrospectively detectable, but was probably caused by leaving the room and the transplantation area. In a review that collected intercontinental data, Kumar et al. discussed describes equally in her study in which they examined whether a worse postoperative outcome is related to immunosuppression or to existing chronic diseases, that severe complications of a Covid-19 infection are more related to pre-existing diseases rather than to chronic immunosuppression.(36) In our cohort we could not confirm this observation. In both J o u r n a l P r e -p r o o f groups we have an identical cardiac preload of the patients. We did not have a single case of prolonged ICU stay or ICU resumption after discharge from postoperative monitoring. But we need to mention that the significance of our observations is certainly limited by the small cohort.

With regard to postoperative complications, there are no differences between the two groups before and during the pandemic and there is no association with regard to a Covid-19

infection. There is also no evidence in the literature for increased surgical complications after NTX and Covid-19 infection. (24) Another question we want to answer with this study is whether our patients have an increased rate of Covid-19 infections in in the ambulant setting after in-patient discharge.

The two infections in our cohort are nosocomial infections in the early stages during the first wave. After the first two nosocomial infections no nosocomial or ambulant infections have occurred due to strict adherence to hygiene and self-quarantine measures of the patients. 

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