Antibody response to non-mRNA SARS-CoV-2 vaccine in kidney transplant recipients.

BACKGROUND: Kidney transplant recipients (KTRs) show poor antibody response to the SARS-CoV-2 vaccine. There is limited data on immune response to non-mRNA vaccines in KTRs. We studied the antibody response to the SARS-CoV-2 non-mRNA vaccine in a cohort of kidney transplant recipients. METHODS: We included KTRs following up in the tertiary care transplant outpatient clinic from February to April 2022. SARS-CoV-2 spike protein IgG antibody titers were measured using chemiluminescence immunoassay. Data on demographic, clinical, and laboratory characteristics were collected, and patients were characterized by the history of Coronavirus disease 2019 (COVID-19) infection in the past and the number of vaccine doses received. Predictors of antibody response were obtained using multivariate regression analysis. RESULTS: S1/S2 IgG anti-SARS-CoV-2 antibodies were detected in 197 (87.94%) of 224 KTRs with a median [IQR] titers of 307.5 AU/ml [91 AU/ml - 400 AU/ml]. Neutralizing range antibody titers were found in 170/224 (75.9%) KTRs. Diabetes at the time of vaccination was associated with poorer antibody response (aOR 0.31, 95% confidence interval [CI] - 0.10, 0.90; p = 0.032) and vaccination with Covishield™ (ChAdOx1 nCoV- 19 Recombinant CoronaVirus Vaccine) showed higher antibody response as compared to Covaxin™ (BBV152) (aOR 5.04, 95% CI - 1.56, 16.22; p = 0.007). Graft dysfunction at baseline was associated with poorer antibody response. CONCLUSIONS: KTRs showed good antibody response after SARS-CoV-2 vaccination with non-mRNA vaccines. Diabetes and graft dysfunction were associated with poor seroconversion rates.

Acute oxalate nephropathy: exploring the role of excess dietary oxalate intake.

Acute oxalate nephropathy is a rare but important cause of severe acute kidney injury. We report here two cases presenting as unexplained AKI which were confirmed histologically to be due to acute oxalate nephropathy. Dietary oxalate or its precursor vitamin C was the cause of oxalate exposure in both of these cases. While one patient recovered, another continued to need dialysis and succumbed to underlying metastatic cancer. This cause should be suspected in all patients presenting with unexplained AKI, and detailed history about dietary intake of oxalate or vitamin C should be inquired.

Overnight 1-mg DST Serum Cortisol in Various Stages of Chronic Kidney Disease-Normative Data and Underlying Mechanisms.

Context: Data on the overnight 1 mg-dexamethasone suppression test (ONDST) in renal dysfunction are limited. Objective: We aim to determine the normative range of ONDST cortisol across chronic kidney disease (CKD) stages and reasons for its alteration. Methods: Prospectively, 180 CKD (30 each in G2-G5/5D) patients and 30 healthy controls underwent ONDST 8 Am serum cortisol (chemiluminescent immunoassay [CLIA]). In an exploratory cohort, 45 (15 each: G3b/G4, G5/G5D, and healthy controls) individuals' blood biochemistry for basal (8 Am) cortisol and adrenocorticotropin (ACTH), post-ONDST 8 Am dexamethasone, ACTH, cortisol (CLIA and liquid chromatography-tandem mass spectrometry), and 4 Pm cortisol was collected. Results: Post-ONDST cortisol (µg/dL) correlated inversely (r = 0.47; P < .005) with estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2), with 95th percentile being 1.2 in controls, 3.0 in G2, 3.2 in G3a, 4.3 in G3b, 4.7 in G4, 5.7 in G5, and 7.1 in G5D. In the exploratory cohort, basal 8 Am cortisol and ACTH, and post-ONDST dexamethasone were similar among controls and CKD subgroups. ONDST ACTH (for evaluating the hypothalamo-pituitary-adrenal axis) was slightly higher in G5/5D vs controls (8.9 vs 6.1 pg/mL), while it was similar in G3b/G4 vs controls. Median 8 Am ONDST cortisol was similar on CLIA and LC-MS/MS in controls and higher on CLIA in G3b/4 (1.7 vs 1.1 µg/dL; P = .012) and G5/5D (2.4 vs 1.7 µg/dL; P = .002) than LC-MS/MS. Post-ONDST serum cortisol drop from 8 Am to 4 Pm was significant in controls (0.5-<0.2 µg/dL) and G3b/4 (1.7-1.2 µg/dL), but not in G5/5D (2.4-2.2 µg/dL). Conclusion: The normative data of ONDST serum cortisol with eGFR-based cutoffs are useful in evaluating Cushing syndrome in CKD. Prolonged cortisol half-life and immunoassay-related assay cross-reaction are likely contributors to higher ONDST cortisol.

Clinical Course and Outcomes of COVID-19 in Kidney Transplant Recipients.

Introduction: Kidney transplant recipients (KTR) are at increased risk of morbidity and mortality due to coronavirus disease 2019 (COVID-19). This study aimed to explore the clinical characteristics and outcomes of COVID-19 in KTR. Methods: We reviewed the clinical profile, outcomes, and immunological responses of recipients admitted with COVID-19. We determined the risk factors for mortality and severe COVID-19. Results: Out of 452 recipients on follow-up, 60 were admitted with COVID-19. Prevalent comorbidities were hypertension (71%), diabetes (40%), lung disease (17%). About 27% had tuberculosis. The median Sequential Organ Failure Assessment score at presentation was 3 (interquartile range [IQR] 1-5). There was a high incidence of diarrhea (52%) and anemia (82%). Treatment strategies included antimetabolite withdrawal (85%), calcineurin inhibitor decrease or withdrawal (64%), increased steroids (53%), hydroxychloroquine (21%), remdesivir (28.3%), and tocilizumab (3.3%). Severe COVID-19 occurred in 34 (56.4%) patients. During a median follow-up of 42.5 days (IQR 21-81 days), 83% developed acute kidney injury (AKI) and eight (13%) died. Mortality was associated with the baseline graft dysfunction, hypoxia at admission, lower hemoglobin and platelets, higher transaminases, higher C reactive protein, diffuse radiological lung involvement, hypotension requiring inotropes, and Kidney Diseases Improving Global Outcomes (KDIGO) stage 3 AKI (univariate analysis). Around 57% of patients remained RT-PCR positive at the time of discharge. By the last follow-up, 66.6% of patients developed IgM (immunoglobulin M) antibodies and 82.3% of patients developed IgG antibodies. Conclusion: COVID-19 in kidney transplant recipients is associated with a high risk of AKI and significant mortality.

Cardiovascular Complications in Kidney Transplant Recipients with COVID-19: A Case Series.

Kidney transplant recipients (KTRs) are at a higher risk for developing severe COVID-19 which can be associated with cardiovascular complications. We studied five KTRs recipients infected with COVID-19 who developed severe cardiovascular complications. Two patients presented with ST segment myocardial infarction and two with clinically suspected myocarditis. One patient presented with atrial fibrillation. Two of these patients developed cardiogenic shock. Inflammatory markers were at peak during the event in four of these who had presented with severe COVID-19. Coronary angiography done in two patients with STEMI did not reveal any evidence of atherosclerotic coronary artery disease. Also, based on the cardiovascular (CV) risk estimation by Framingham score, four patients had low CV risk and one patient had intermediate CV risk. All five patients survived. Even with low CV risk, KTRs can develop myocardial injury and arrhythmias solely because of severe COVID-19.

High dependency renal unit for the management of COVID-19 in patients with severe acute or chronic kidney disease.

Coronavirus disease 2019 (COVID-19) in patients with severe impairment of kidney function is associated with high mortality. We evaluated the effect of high dependency renal unit (HDRU), with nephrologists as primary care physicians, as a quality improvement initiative for the management of these patients. This was a quasi-experimental observational study conducted at a tertiary care hospital in western India. Patients hospitalized for COVID-19 with pre-existing end-stage-renal-disease and those with severe AKI requiring dialysis (AKI-D) were included. For the first 2 months, these patients were cared for in medical wards designated for COVID-19, after which HDRU was set up for their management. With nephrologists as primary care providers, the 4 key components of care in HDRU included: care bundles focusing on key nephrology and COVID-19 related issues, checklist-based clinical monitoring, integration of multi-specialty care, and training of nurses and doctors. Primary outcome of the study was in-hospital mortality before and after institution of the HDRU care. Secondary outcomes were dialysis dependence in AKI-D and predictors of death. A total of 238 out of 4254 (5.59%) patients with COVID-19, admitted from 28th March to 30th September 2020, had severe renal impairment (116 AKI-D and 122 end-stage-renal-disease). 145 (62%) had severe COVID-19. From 28th May to 31st August 2020, these patients were managed in HDRU. Kaplan-Meier analysis showed significant improvement in survival during HDRU care [19 of 52 (36.5%) in pre-HDRU versus 35 of 160 (21.9%) in HDRU died, P ≤ .01]. 44 (67.7%) AKI-D survivors were dialysis dependent at discharge. Breathlessness and altered mental status at presentation, development of shock during hospital stay, and leukocytosis predicted mortality. HDRU managed by nephrologists is a feasible and potentially effective approach to improve the outcomes of patients with COVID-19 and severe renal impairment.

Recovery of kidney function after AKI because of COVID-19 in kidney transplant recipients.

Evidence on the evolution of graft function in kidney transplant recipients recovering from coronavirus disease-2019 (COVID-19) is lacking. This multicenter observational study evaluated the short-term clinical outcomes in recipients with acute kidney injury (AKI) secondary to COVID-19. Out of 452 recipients following up at five centers, 50 had AKI secondary to COVID-19. 42 recipients with at least 3-month follow-up were included. Median follow-up was 5.23 months [IQR 4.09-6.99]. Severe COVID-19 was seen in 21 (50%), and 12 (28.6%) had KDIGO stage 3 AKI. Complete recovery of graft function at 3 months was seen in 17 (40.5%) patients. Worsening of proteinuria was seen in 15 (37.5%) patients, and 4 (9.5%) patients had new onset proteinuria. Graft failure was seen in 6 (14.3%) patients. Kidney biopsy revealed acute tubular injury (9/11 patients), thrombotic microangiopathy (2/11), acute cellular rejection (2/11), and chronic active antibody-mediated rejection (3/11). Patients with incomplete recovery were likely to have lower eGFR and proteinuria at baseline, historical allograft rejection, higher admission SOFA score, orthostatic hypotension, and KDIGO stage 3 AKI. Baseline proteinuria and the presence of orthostatic hypotension independently predicted incomplete graft recovery. This shows that graft recovery may remain incomplete after AKI secondary to COVID-19.