COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes.

BACKGROUND: COVID-19 has been associated with high morbidity and mortality in kidney transplant recipients. However, risk factors for COVID-19 disease in patients with kidney transplants remain poorly defined. METHODS: We enrolled patients who underwent kidney transplantation and were actively followed up in two hospitals in Paris on March 1st, 2020. Patients were screened for baseline and transplant characteristics, functional parameters, comorbidities, and immunosuppressive therapies. COVID-19 disease was assessed. Patients were followed up during the pandemic until April 30th, 2020 by the COVID-19 SLS KT survey program, including teleconsulting, at-home monitoring for patients with COVID-19, and a dedicated phone hotline platform. RESULTS: Among 1216 patients with kidney transplants enrolled, 66 (5%) patients were identified with COVID-19 disease, which is higher than the incidence observed in the general population in France (0.3%). Their mean age was 56.4±12.5 years, and 37 (56%) patients were men. The following factors were independently associated with COVID-19 disease: non-White ethnicity (adjusted odds ratio [OR], 2.17; 95% confidence interval [95% CI], 1.23 to 3.78; P=0.007), obesity (OR, 2.19; 95% CI, 1.19 to 4.05; P=0.01), asthma and chronic pulmonary disease (OR, 3.09; 95% CI, 1.49 to 6.41; P=0.002), and diabetes (OR, 3.33; 95% CI, 1.92 to 5.77; P<0.001). The mortality rate related to COVID-19 disease was 1% in the overall study population and 24% in COVID-19-positive patients. CONCLUSIONS: Patients with kidney transplants display a high risk of mortality. Non-White ethnicity and comorbidities such as obesity, diabetes, asthma, and chronic pulmonary disease were associated with higher risk of developing COVID-19 disease. It is imperative that policy makers urgently ensure the integration of such risk factors on response operations against COVID-19.

Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients.

Anti-angiotensin II type 1 receptor (AT1R) antibodies have been associated with allograft rejection. We hypothesized that circulating AT1R antibodies might identify kidney transplant recipients at increased risk of allograft rejection and loss who are not identified by the HLA system. We prospectively enrolled 1845 kidney transplant recipients from two centers. Donor-specific HLA antibodies (DSAs) and AT1R antibodies were measured at the time of the first acute rejection episode or at 1 year post-transplant. Allograft biopsy was performed to evaluate the rejection phenotype and to assess for endothelial activation. Overall, 371 (20.1%) participants had AT1R antibodies, 334 (18.1%) had DSAs, and 133 (7.2%) had both. AT1R antibodies were associated with an increased risk of allograft loss (adjusted HR 1.49, 95% CI 1.07-2.06 for AT1R antibodies alone and 2.26, 95% CI 1.52-3.36 for AT1R antibodies and DSAs). Participants with AT1R antibodies had a higher incidence of antibody-mediated rejection (AMR) compared with participants without AT1R antibodies (25.0% vs. 12.9%). Among 77 participants with histological features of AMR but without DSAs, 51 (66.2%) had AT1R antibodies. Compared to participants with prototypical DSA-mediated rejection, those with AT1R antibody-associated rejection had a higher prevalence of hypertension, more vascular rejection with arterial inflammation, higher levels of endothelial-associated transcripts, and lack of complement deposition in allograft capillaries. Thus, AT1R antibodies may identify kidney transplant recipients at high risk of allograft rejection and loss, independent of the HLA system. Recognition of complement-independent AT1R antibody-mediated vascular rejection could lead to the development of new treatment strategies to improve allograft survival.

Response to treatment and long-term outcomes in kidney transplant recipients with acute T cell-mediated rejection.

The recent recognition of complex and chronic phenotypes of T cell-mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR-a condition previously considered to lack relevant consequences for allograft survival-to the standard of care. In a prospective cohort of kidney recipients (n = 256) with biopsy-proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3 months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR = 0.94; 95% CI = 0.92-0.96; P < .001), proteinuria (HR = 1.40; 95% CI = 1.10-1.79; P = .007), time since transplantation (HR = 1.02; 95% CI = 1.00-1.03; P = .016), peritubular capillaritis (HR = 2.27; 95% CI = 1.13-4.55; P = .022), interstitial inflammation in sclerotic cortical parenchyma (i-IF/TA) (HR = 1.87; 95% CI = 1.08-3.25; P = .025), and donor-specific anti-HLA antibodies (DSAs) (HR = 2.67; 95% CI = 1.46-4.88; P = .001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI = 0.68; 95% CI = 0.41-0.95; P < .001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i-IF/TA, and anti-HLA DSAs (cross-validated accuracy = 0.80). Compared with responders (n = 155, 60.5%), nonresponders (n = 101, 39.5%) had a higher incidence of de novo DSAs, antibody-mediated rejection, and allograft loss at 10 years (P < .001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes.