Humoral and cellular response after BNT162b2 vaccine booster in hemodialysis patients and kidney transplant recipients.

BACKGROUND: Vulnerable populations, such as hemodialysis (HD) patients and kidney transplant (RTx) recipients, have priority for anti-COVID-19 vaccination, because of their impaired immune status. Here, we investigated the immune response after vaccination with BNT162b2 (two doses plus booster) in HD and RTx patients. METHODS: A prospective, observational study was started in two homogeneous groups of 55 HD and 51 RTx patients previously matched from a cohort of 336 patients. Anti-RBD IgG levels, assayed after the second dose with BNT162b2 mRNA, were used to stratify subjects into quintiles. After the second dose and after booster, anti-RBD and IGRA test were evaluated in RTx and HD, belonging to the first and fifth quintiles. RESULTS: After the second dose of vaccine, the median circulating levels of anti-RBD IgG were significantly higher in HD (1456 AU/mL) compared to RTx (27.30 AU/mL). IGRA test showed significantly higher values in the HD (382 mIU/mL) compared with the RTx (73 mIU/mL). After the booster, humoral response increased significantly in both HD (p = 0.0002) and RTx groups (p = 0.009), whereas the T-cellular immunity remained essentially stable in most patients. In RTx patients with a low humoral response after the second dose, the third dose did not significantly strengthen either humoral or cellular immunity. CONCLUSIONS: For HD and RTx, there is great variability in the humoral response to anti-COVID-19 vaccination, with a stronger response in the HD group. The booster dose was ineffective at reinforcing the humoral and cellular immune response in most RTx patients hyporesponsive to the second dose.

[Development of mesangial immunoglobulin IgA glomerulonephritis and p-ANCA positivity in a patient with psoriatic arthritis]. / Insorgenza di glomerulonefrite a depositi mesangiali di IgA e positività di p-ANCA in un paziente affetto da artrite psoriasica in trattamento con etanercept.

Tumor necrosis factor (TNF) inhibitors are widely used for the treatment of various rheumatic diseases. These agents may lead to development of systemic autoimmune diseases and renal complications. We report a patient with psoriatic arthritis and renal failure treated with two TNF inhibitors (Etanercept and then Adalimumab). After this treatment he developed proteinuria with nephrotic syndrome. A renal biopsy was performed highlighting GN with mesangial IgA deposits. Then he developed p-ANCA positivity. Following that, etanercept and adalimumab were stopped and a treatment by corticosteroids was initiated, but renal function decreased. Currently the patient is treated by haemodialysis. In our patient, the pathogenic role for anti-TNF therapy is suggested by the close temporal relationship with development of glomerular disease and by the improvement in proteinuria after drug withdrawal. However, the patient was treated once more with TNF agents, so he developed end stage renal disease.

Predictors of serum creatinine in haemodialysis patients: a cross-sectional analysis.

BACKGROUND: C-reactive protein (CRP) levels, an acute phase response index, predict cardiovascular outcome and are inversely related to visceral proteins, including albuminaemia in haemodialysis patients. Less definite is the relationship between inflammation and markers of somatic proteins such as serum creatinine in such patients. To explore these questions, a cross-sectional analysis of potential predictors of serum creatinine was performed. METHODS: One hundred and seventy-nine prevalent haemodialysis patients as of June 2001 were included in the cohort. Midweek pre-dialysis blood samples were collected during the months of June, September through to December 2001 inclusive, and determinations of serum urea (urease method), creatinine (alkaline picrate method) and CRP levels by means of a high sensitivity immunonephelometric method were performed. Furthermore, pre- and post-dialysis body weights were recorded and 2 min post-dialysis serum urea levels were determined three times. They were utilized for the calculation of single pool Kt/V and of normalized protein catabolic rate (nPCR). Each of the data represents the mean of three determinations made every 3 months in the study period. RESULTS: The analysis of multivariate linear regression was able to validate our model characterized by a dependent variable, serum creatinine and four independent variables (age, CRP, Kt/V and nPCR) (R(2)=0.60; F=24.10; P<0.00001; SE=1.94). Age (-0.08 mg/dl decrease in serum creatinine per 1-year increase in age), Kt/V (-0.25 mg/dl decrease in serum creatinine per 0.1 increase in Kt/V) and nPCR (0.10 mg/dl increase in serum creatinine per 0.1 g protein/kg/day increase in nPCR) were independently predictive of serum creatinine (P<0.00001). CRP and dialysis vintage did not predict serum creatinine. Stratifying the patients for the effects of CRP, only CRP values 4 mg/l were not. A further insight was given by the stratification of the patients for the effects of the interquartile ranges of CRP: it showed a progressive and statistically significant reduction of beta-coefficient inversely related to the increasing CRP values (P=0.003). Thus, the nature of the correlation between CRP and serum creatinine changes with increasing CRP values: from being a direct one, it shows a trend towards a transformation into an indirect one with beta=0 at a CRP value of approximately 9 mg/l. However, this indirect relationship does not reach statistical significance. CONCLUSIONS: The present cross-sectional study suggests that the activation of acute phase response does not influence creatinine metabolism in haemodialysis patients; in contrast, age, Kt/V and nPCR predict serum creatinine levels. Larger prospective trials are needed to achieve a definitive answer about the relationship between somatic proteins, acute phase response activation and nutrition in dialysis patients.