Renal Complications in Kidney Transplant Recipients After Whole-virus Inactivated COVID-19 Vaccination : Transplantation

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Renal Complications in Kidney Transplant Recipients After Whole-virus Inactivated COVID-19 Vaccination

Yin, Saifu MD1; Ma, Ming MD1; Zhong, Qiang MD1; Lin, Tao MD, PhD1; Song, Turun MD, PhD1

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doi: 10.1097/TP.0000000000004330

Despite the efficacy and safety of the COVID-19 vaccine in the general population, for solid organ transplants, there is a theoretical concern regarding vaccination-triggered immunologic complications. In fact, several rejection episodes have been reported after mRNA COVID-19 vaccination.1,2 Contrary to mRNA vaccines that synthesize specific antigens to generate neutralizing antibody, whole-virus inactivated vaccines can activate the immunologic system more extensively as it used entire viral capsid. Additionally, new-onset and relapsed kidney pathological changes have been reported following COVID-19 vaccination in the general population, including minimal change disease, IgA nephrology, and membranous nephropathy.3,4

Thus, we conducted a prospective study in kidney transplants (KTs) to evaluate the safety of whole-virus inactivated COVID-19 vaccine, especially renal graft complications. This study has been registered in Clinical Trials.gov (NCT04969614). Between September 1, 2021, and January 31, 2022, 290 kidney recipients received inactivated whole-virus COVID-19 vaccine (Table S1, SDC, https://links.lww.com/TP/C546), including BBIBP-CorV (Vero cell) and Coronavac (Vero cell). The median age was 41 y with 2 adolescents, and the majority were male. 278 received 2 doses of inactivated COVID-19 vaccine and 12 received 1 dose only. Among 290 patients, 56.9% received living-donor KT, 39.3% received antithymocyte immunoglobulin as the induction therapy and 97.6% received tacrolimus plus mycophenolic acid and steroids as the maintenance therapy. The median duration from transplantation to vaccination was 38 mo. During the last year, 5 patients received high-dose steroid pulse therapy, 2 received antithymocyte immunoglobulin, and 3 received rituximab because of rejection events.

The median follow-up was 4.2 mo after vaccination. After vaccination, 11% patients experienced a serum creatinine increment >10% and 0.7% had an increment >30% (Table 1). Seven patients (4.0%) had new-onset proteinuria after vaccination. Eight patients were diagnosed with acute rejection (AR) clinically (2.8%) with 4 biopsy-confirmed AR (1.4%, 2 antibody-mediated, 1 T-cell mediated, and 1 mixed) in a median follow-up of 34 d after vaccination. Additionally, 1 patient developed multiple myeloma after vaccination, confirmed by bone marrow and kidney biopsy, and experienced graft failure in 3 mo. No death was observed after vaccination. No severe local symptoms were observed, whereas 2 had severe fever, 2 severe chills, 6 severe fatigue, 3 severe headache, 2 severe myalgias, and 2 had severe diarrhea (Table S2, SDC, https://links.lww.com/TP/C546).

TABLE 1. - Renal complications of 290 kidney transplant recipients after receiving inactivated COVID-19 vaccine
Renal complications No. Events (proportion)
Prevaccination eGFR, mL/min/1.73m2 282 68.4 (±19.3)/67.2 (14.2–134.7)
Prevaccination creatinine, µmol/L 290 115 (±33.7)/110 (49–321)
eGFR within 1–2 mo after vaccination, mL/min/1.73m2 267 68 (±18.9)/67.6 (8.9–128.8)
Creatinine within 1–2 mo after vaccination, µmol/L 267 115 (±32.6)/110 (57–579)
<10% increase 235 (89%)
10%–20% increase 25 (9.4%)
20%–30% increase 5 (1.9%)
>30% increase 2 (0.7%)
New-onset of proteinuria 174
No 167 (96.0%)
Yes 7 (4.0%)
Acute rejection 290
No 278 (95.8%)
Yes 8 (2.8%)
Biopsy-confirmed acute rejection 4 (1.4%)
Graft loss 290
No 289 (99.6%)
Yes 1 (0.4%)
Patient death 290
No 290 (100%)
Yes 0 (0%)
eGFR, estimated glomerular filtration rate.

Boyarsky et al reported that 1 of 176 experienced AR after receiving 2 doses of mRNA vaccines.5 Vaiciuniene et al reported 6 biopsy-confirmed ARs in 167 fully vaccinated KT recipients with mRNA vaccine in 9 mo follow-up.2 Our results provided the safety profile of the whole-virus inactivated COVID-19 vaccine in KTs, suggesting that more intensive monitoring of graft function after vaccination was necessary. Notably, due to lack of matched control group and ascertainment bias, it remains unclear whether there is casual association between renal complications and vaccination. Also, the role of immunosuppression modifications remains unclear. Well-designed prospective studies are still wanted to confirm this association.

REFERENCES

1. Del Bello A, Marion O, Delas A, et al. Acute rejection after anti-SARS-CoV-2 mRNA vaccination in a patient who underwent a kidney transplant. Kidney Int. 2021;100:238–239.
2. Vaiciuniene R, Sitkauskiene B, Bumblyte IA, et al. Immune response after SARS-CoV-2 vaccination in kidney transplant patients. Medicina (Kaunas). 2021;57:1327.
3. Carr EJ, Kronbichler A, Graham-Brown M, et al. Review of early immune response to SARS-CoV-2 vaccination among patients with CKD. Kidney Int Rep. 2021;6:2292–2304.
4. Holzworth A, Couchot P, Cruz-Knight W, et al. Minimal change disease following the Moderna mRNA-1273 SARS-CoV-2 vaccine. Kidney Int. 2021;100:463–464.
5. Ou MT, Boyarsky BJ, Chiang TPY, et al. Immunogenicity and reactogenicity after SARS-CoV-2 mRNA vaccination in kidney transplant recipients taking belatacept. Transplantation. 2021;105:2119–2123.

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