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.

These results suggest that glomerular hyperfiltration may lead to increased proximal tubular sodium reabsorption in the obese.

<b><i>Background:</i></b> Glomerular hyperfiltration (GH) is a hallmark of renal dysfunction in diabetes and obesity. Recent clinical trials demonstrated that SGLT2 inhibitors are renoprotective, possibly by abating hyperfiltration. The present review considers the current evidence for a cause-to-effect relationship between hyperfiltration-related physical forces and the development of chronic kidney disease (CKD). <b><i>Summary:</i></b> Glomerular hyperfiltration is associated with glomerular and tubular hypertrophy. Hyperfiltration is mainly due to an increase in glomerular capillary pressure, which increases tensile stress applied to the capillary wall structures. In addition, the increased ultrafiltrate flow into Bowman’s space heightens shear stress on the podocyte foot processes and body surface. These mechanical stresses lead to an increase in glomerular basement membrane (GBM) length and to podocyte hypertrophy. The ability of the podocyte to grow being limited, a mismatch develops between the GBM area and the GBM area covered by foot processes, leading to podocyte injury, detachment of viable podocytes, adherence of capillaries to parietal epithelium, synechia formation and segmental sclerosis. Mechanical stress is also applied to post-filtration structures, resulting in dilation of glomerular and tubular urinary spaces, increased proximal tubular sodium reabsorption by hypertrophied epithelial cells and activation of mediators leading to tubulointerstitial inflammation, hypoxia and fibrosis <b><i>Key Messages:</i></b> GH-related mechanical stress leads to both adaptive and maladaptive glomerular and tubular changes. These flow-related effects play a central role in the pathogenesis of glomerular disease. Attenuation of hyperfiltration is thus an important therapeutic target in diabetes and obesity-induced CKD.