Methods: The study included KTR adults at a single transplant institute who were diagnosed with COVID-19 and required hospitalization between March 15, 2020 and January 15, 2021. We analyzed patient demographics, comorbid risk factors, and clinical series of clinical patients who were able to to recover from the infection. Renal function was analyzed before infection, during initial hospitalization and up to 12 months after infection. Results: We identified 48 KTRs diagnosed with COVID-19 infection during the study period. Eighteen KTRs among them required hospitalization for symptoms of fever and respiratory distress. Four patients died of complications related to the COVID-19 infection and were excluded from the study. The 14 remaining patients in the study were predominantly Black (85.7%), with a median time since transplant of four years. Of the patients, 64.3% developed acute kidney injury (AKI), with a mean peak serum creatinine (sCr) of 2.6 mg/dl and a glomerular filtration rate (GFR) of 35. The group mean sCr and GFR were 2 mg /dl and 44 at baseline (before infection). This represented an increase in their sCr and GFR of 34% and 29%, respectively. Median follow-up after infection was 14.5 months. sCr and GFR were 1.87 mg/dl and 47 at three to six months and 1.89 mg/dl and 48 at nine to 12 months post-infection. New-onset proteinuria occurred in five of 14 patients (36%), with complete resolution in all at three- to six-month follow-up. Of the AKI patients, 78% had a complete recovery at three to six month follow-up. Mean baseline sCr and GFR of patients with incomplete recovery were 2.35 and 31.5 with pre-existing proteinuria. Of our entire cohort, there was only one patient who experienced graft loss. This patient had baseline sCr and GFR of 3.8 mg/dl and 22, preexisting proteinuria on urinalysis, and a history of biopsy-proven rejection. Conclusion: AKI is common among KTR hospitalized with COVID-19 infection. Most of them recovered, although we observed that patients with lower renal function and existing proteinuria had a lower recovery rate.

Introduction

The Municipal Health Commission in Wuhan, China reported the first cases of viral pneumonia later attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 [1]. At the time of manuscript preparation, the World Health Organization has reported over 356 million reported cases and 5.6 million deaths attributable to the 2019 coronavirus disease (COVID-19). [2]. Kidney transplant recipients (KTRs) are at increased risk of severe disease and death caused by infection with COVID-19. There is a paucity of information on the evolution of graft function among hospitalized recipients who overcome infection. This article was previously presented as a meeting abstract at the American Society of Nephrology (ASN) Kidney Week, November 4-7, 2021.

Materials & Methods

This was an institutional review board (IRB)-approved (reference number: 2020-732), single-center, retrospective cohort study of adult KTRs with reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 hospitalized at a Single Transplant Center in New Orleans, Louisiana between March 15, 2020 and January 15, 2021. The institutional IRB granted a waiver of informed consent. Inclusion criteria included kidney transplant patients with a functioning allograft aged over 18 years. KTRs who succumbed to the COVID-19 virus were excluded from the study. We performed an electronic medical record chart review to collect and analyze patient demographics, comorbid factors, maintenance of immunosuppression, patient presentation, immunosuppression modifications, patient clinical course, and transplant outcomes. Renal function was analyzed before infection, during initial hospitalization and up to 12 months after infection. We used serum creatinine (sCr), glomerular filtration rate (GFR) and proteinuria as surrogate markers for renal function. A standardized form using a Microsoft Excel sheet (Microsoft Corporation, Redmond, WA) was used to extract relevant information. Descriptive statistics were used to examine the cohorts. Categorical values ​​were reported as frequencies, represented as n (%) and examined by chi-square analysis. Continuous variables were reported as medians (interquartile range (IQR): 25–75) and examined with the Mann–Whitney U test.

Results

Cohort demographics and baseline characteristics

During the study period, we identified 48 patients diagnosed with RT-PCR-confirmed COVID-19 between March 15, 2020, and January 15, 2021. Of these patients, 18 required hospitalization (37.5%). Four of the patients (22.2%) succumbed to COVID-19 and were excluded from the study. The median age of patients was 47 years (IQR: 43.25-51.5) and the majority of patients (71.4%) were male. The vast majority of patients in the study were Black (85.7%). The median transplant harvest (time since transplant surgery) was nearly four years (IQR: 2.5–14 years). Only one patient was in the first year of transplantation. Of the comorbidities, hypertension was the most prevalent among our patient cohort (85.7%), followed by obesity (35.7%) and diabetes mellitus (25%). One patient had a history of active or previous malignancy. None of our patients reported a history of underlying asthma or chronic obstructive pulmonary disease (COPD). Four patients (28.6%) received a living donor kidney transplant and the remaining 10 (71.4%) received a deceased donor kidney transplant. Most patients (9/14) received the combination of a calcineurin inhibitor (CNI), mycophenolate mofetil or mycophenolic acid (MMF/MPA) and prednisone. Among our cohort, 42.9% had a history of previous opportunistic infection and 28.6% had a history of allograft rejection. The mean baseline sCr, a measurement obtained from laboratory results within three months before the diagnosis of COVID-19, was 2 ± 0.70 mg/dl. Baseline GFR was 44 ± 15 and six patients had proteinuria on routine urinalysis. Table 1 reports further cohort demographics. Number Percentage Total patients admitted 14 Median age (years) 47 (IQR: 43.25-51.5) Male 10 71.4% Race Black 12 85.7% White 2 14.3% Median time to transplant (months) 47 .5 (IQR: 2811t <2.50). μηνών 1 7,1% 12-24 μηνών 2 ​​14,3% >24 months 11 78.6% Comorbidities Hypertension 12 85.7% Obesity, BMI > 30 5 35.7% Diabetes Mellitus 3 21.4% History 1% Renal hypertension 1% Renal malignancy. 8 57.1% Hypertension and diabetes mellitus 2 14.3% Hypertension and human immunodeficiency virus (HIV) 1 7.1% Lupus nephropathy 1 7.1% Polycystic kidney disease 1 7.1% Neurogenic cyst 1 7.1% Chronic chronic kidney disease (CKD) 2 2 14.3% Stage 3 5 35.7% Stage 4 3 21.4% Stage 5 4 28.6% Donor kidney type Deceased 10 71.4% Alive 4 28.6% Maintenance immunosuppression. 85.7% History of opportunistic infection 6 42.9% History of rejection 4 28.6% Table 1: Cohort demographics All continuous variables are reported as median (IQR: 25–75). Categorical values ​​are frequencies reported as n (%). IQR = interquartile range.

Hospital course and clinical outcomes

Admission data and clinical outcomes are presented in Table 2. Of the 14 patients who were admitted and survived, the median duration of symptoms before admission was 6.5 days (IQR: 4.25–7). The most common presenting symptoms were cough (42.9%) and fever (35.7%), followed by dyspnea (21.4%). Of the patients, 21.4% reported nausea or vomiting, myalgia, and fatigue at presentation and 14.3% reported diarrhea. Patients were hospitalized for a median of three days (IQR: 2–6). The most common adjustment of the immunosuppressive regimen was to change or withdraw MMF/MPA (64.3%), while only 28.6% had the CNI dose adjusted or withdrawn. Number Percentage Total patients admitted 14 Duration of symptoms before admission (days) 6.5 (IQR: 4.25-7) Symptom presentation Fever 5 35.7% Cough 6 42.9% Nausea/vomiting 3 21.4% Myalgia 3 21.4% 2.3 2114 Diarrhea % Fatigue 3 21.4% Length of Hospitalization (days) 3 (IQR: 2-6) Immunosuppressant Modulation Maintained/Adjusted Calcineurin Inhibitor (CNI) 4 28.6% Maintained/Adjusted Mycophenolic acid (MPA) 9 64.3% Heldsteroids3 Results Urinalysis (U/A) with proteinuria 11 78.6% Nasal cannula 2 14.3% Mechanical ventilation 0 0% Acute kidney injury (AKI) 9 64.3% Dialysis required in patient 1 7.1% Graft loss 1 7.1% Table 2: clinical results All continuous variables are reported as median (IQR: 25–75). Categorical values ​​are frequencies reported as n (%). IQR = interquartile range. On admission, acute phase reagents specific for COVID-19 were measured. Mean C-reactive protein (CRP), ferritin, procalcitonin, lactate dehydrogenase (LDH), and D-dimer were reported at 6.6 mg/L, 1716.5 ng/mL, 0.45 ng/mL, 277 U/L, and 3,4, respectively (Table 3). Induction 3-6 months follow-up 9-12 months follow-up Number of patients 14 14 11 C-reactive protein (CRP) (mean ± SD, mg/L) 6.6 ± 9.8 Ferritin (mean ± SD, ng/mL ) 1716.5 ± 1156.9 Procalcitonin (mean ± SD, ng/mL) 0.45 ± 0.44 lactate dehydrogenase (LDH) (mean ± SD, U/L) 277 ± 82 White blood count (WBC) (mean ± SD, k/ul) 2.5 7.06 ±1.92 7.24 ± 1.88 Hemoglobin (mean ± SD, gm/dl) 12.0 ± 2.8 11.2 ± 1 .56 12.2 ±…