Objectives We aimed to evaluate rates of antibody response to mRNA SARS-CoV-2 vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. Methods A prospective cohort study including consecutive kidney transplant recipients in a single referral transplant center. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks following second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. Results Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titer was 15.5 AU/mL (interquartile range [IQR] 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio [OR] 1.025 per ml/min/1.73m 2 , 95% confidence interval [CI] 1.014 - 1.037, p<0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95% CI 1.782 - 3.089, p<0.001), younger age (OR 1.032 per year decrease, 95% CI 1.015 - 1.05, p<0.001) and lower calcineurin inhibitors (CNI) blood level (OR 1.987, 95% CI 1.146 - 3.443, p=0.014). No serious adverse events to the vaccine were reported. Conclusions Kidney transplant recipients demonstrated inadequate antibody response to mRNA SARS-CoV-2 vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.

Secondary hyperparathyroidism is characterized by an increase in parathyroid (PT) cell number, and parathyroid hormone (PTH) synthesis and secretion. It is still unknown as to what stimuli regulate PT cell proliferation and how they do this. We have studied rats with dietary-induced secondary hyper-and hypoparathyroidism, rats given 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and rats after 5/6 nephrectomy for the presence of PT cell proliferation and apoptosis. PT cell proliferation has been measured by staining for proliferating cell nuclear antigen (PCNA) and apoptosis by in situ detection of nuclear DNA fragmentation and correlated with serum biochemistry and PTH mRNA levels. A low calcium diet led to increased levels of PTH mRNA and a 10-fold increase in PT cell proliferation. A low phosphate diet led to decreased levels of PTH mRNA and the complete absence of PT cell proliferation. 1,25(OH)2D3 (25 pmol/d x 3) led to a decrease in PTH mRNA levels and unlike the hypophosphatemic rats there was no decrease in cell proliferation. There were no cells undergoing apoptosis in any of the experimental conditions. The secondary hyperparathyroidism of 5/6 nephrectomized rats was characterized by an increase in PTH mRNA levels and PT cell proliferation which were both markedly decreased by a low phosphate diet. The number of PCNA positive cells was increased by a high phosphate diet. Therefore hypocalcemia, hyperphosphatemia and uremia lead to PT cell proliferation, and hypophosphatemia completely abolishes this effect. Injected 1,25(OH)2D3 had no effect.These findings emphasize the importance of a normal phosphate and calcium in the prevention of PT cell hyperplasia. (J. Clin. Invest. 1995. 96:1786-1793.) Key words: parathyroid hormone * apoptosis* hyperplasia * 1,25(OH)2D3 chronic renal failure.

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The combination of high TWCV and exposure to low drug levels might identify high-risk patients in the early post-transplantation period.