Humoral Response to BNT162b2 mRNA SARS-CoV-2 Vaccine in Patients with Nondialysis Chronic Kidney Disease

Patients with severe CKD have been excluded from major vaccines trials (1). So far, immune response to coronavirus disease 2019 vaccination in nontransplanted, nondialyzed patients with CKD has not been determined and raises questions given their known under-responsiveness to vaccination.

We assessed the serologic response of patients with CKD from our center 1 month after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination (BNT162b2 Pfizer/BioNTech Comirnaty, two doses, 3 to 6 weeks apart). Kidney transplant recipients and patients undergoing maintenance dialysis were excluded. Patients with CKD stage 3b, 4, or 5 (eGFR below 45 ml/min per 1.73 m²) with a negative prevaccinal antiprotein N serology and a monitoring of anti-Spike receptor-binding domain (RBD) IgGs (Electrochemiluminescence Immunoassay; Roche Elecsys) 1 month after the second dose were included. Patients were classified as “responders” (anti-Spike RBD IgGs above 30 binding antibody units [BAU]/ml) and “nonresponders.”

We retrospectively collected serology results and biologic and clinical data from patients vaccinated between January and May 2021, including the use of immunosuppressive therapy at the time of vaccination and rituximab therapy within 6 months before vaccination. The Wilcoxon test (quantitative variables, P≤0.05 considered as significant) and the Fisher exact test (qualitative variables, P≤0.05 considered as significant) were performed using “R studio version 1.3.1056.”

Seventy-five patients were included in the study. Median time between the two BNT162b2 injections was 28 days (interquartile range [IQR], 26–28), whereas median time between the second injection and anti-Spike RBD IgGs measurement was 31 days (IQR, 31–37). Anti-Spike RBD IgGs were detectable in 69 patients (92%), six patients had a negative postvaccinal serology (8% of the cohort), and six (8%) had a low immune response (anti-Spike RBD IgGs below 30 BAU/ml). Thus, nonresponders represent 16% of our cohort (12 patients). All nonresponders had significantly lower lymphocyte counts than responders, despite similar white blood cell count (Table 1) (P=0.003). There was a strong association between chronic immunosuppressive treatment and nonresponse (P<0.001). All nonresponders had lymphopenia, even in patients without chronic immunosuppressive therapy (median lymphocytes count in these five patients was 1.27 G/L; IQR, 0.99–1.45).

Table 1.

Characteristics of the two groups of patients: “responders” (anti-Spike receptor-binding domain IgGs equal or above 30 binding antibody units/ml) and “nonresponders” (anti-Spike receptor-binding domain IgGs below 30 binding antibody units/ml)

Parameter	Anti-Spike Protein Humoral Response
	Total	Responders, ≥30 U/ml		Nonresponders, <30 U/ml		P Value
		Parameter	Missing Values, n/%	Parameter	Missing Values, n/%
N, %	75 (100)	63 (84)	0	12 (16)	0
Age, yr	75 (65–81)	75 (66–82)	0	70 (62–80)	0	NS
Men, %	44 (59)	37 (59)	0	7 (58)	0	NS
Mean eGFR, ml/min per 1.73 m2	20 (15–26)	20 (15–26)	0	19 (15–28)	0	NS
Time between first and second mRNA vaccine injections, d	28 (26–28)	28 (26–28)	0	28 (24–28)	0	NS
Time between second mRNA vaccine injection and serology, d	31 (31–37)	31 (29–34)	0	31 (28–35)	0	NS
Anti-Spike RBD IgGs 1 mo after second vaccine dose, BAU/ml	243 (243–243)	243 (243–243)	0	0.8 (0–6)	0	<0.001a
CKD etiology, n (%)			0	NS	0
Vasculitis/SLE	9 (12)	5 (8)		4 (33)
Vascular disease: HN, diabetes	26 (35)	25 (40)		1 (8)
Genetic disorder, including ADPKD and Alport syndrome	9 (12)	8 (13)		1 (8)
Urinary tract disorders	11 (15)	9 (14)		2 (17)
Others: glomerulopathies, toxic, interstitial nephritis	20 (27)	16 (25)		4 (33)
Biologic data
Leukocytes count-serology, d	25 (22–32)	25 (12–40)	2 (3)	19 (1–47)	1 (8)	NS
Leucocytes/mm3	6030 (5085–7790)	6030 (5250–7790)	2 (3)	6140 (4527–7513)	1 (8)	NS
Lymphocytes/mm3	1480 (1229–1980)	1570 (1310–2025)	2 (3)	1100 (770–1390)	1 (8)	0.003a
Hemoglobin, g/dl	11.7 (11.3–12.0)	11.7 (10.9–12.6)	2 (3)	11.0 (10.5–12.2)	1 (8)	NS
Platelets/mm3	228,000 (182,000–270,000)	228,000 (183,000–270,000)	2 (3)	245,000 (174,000–272,500)	1 (8)	NS
Albumin, g/dl	4.1 (3.7–4.3)	4.1 (3.7–4.3)	22 (35)	4.2 (3.8–4.4)	0	NS
PTH, pg/ml	121 (84–197)	124 (83–177)	10 (16)	114 (93–271)	1 (8)	NS
Chronic immunosuppressive therapy
Immunosuppressive therapy	10 (13)	3 (5)	0	7 (58)	0	<0.001a
Steroids		3 (5)		3 (25)
Calcineurin inhibitor		0 (0)		4 (33)
Mycophenolate mofetil		2 (3)		3 (25)
Rituximab within past 6 mo		0 (0)		3 (25)

Biologic assessment was collected at the closest time to the monitoring of the anti-Spike protein humoral response, with a cutoff of 90 days except for albumin and PTH assessment, which was collected during the past year before severe acute respiratory syndrome coronavirus 2 serology. Results of quantitative variables are expressed as medians (interquartile ranges). Comparability between groups was evaluated by the nonparametric Wilcoxon test. Results of qualitative variables are expressed with the number of patients/percentage. Comparability between groups was evaluated by Fisher exact test. NS, nonsignificant; RBD, receptor-binding domain; BAU, binding antibody units; HN, hypertensive nephrosclerosis; ADPKD, autosomal dominant polycystic kidney disease; PTH, serum parathormone.

^a P≤0.05 was considered significant.

All six patients with a negative postvaccinal serology had significant comorbidities: two were solid organ transplant recipients (liver and heart-lung), one suffered from a neuroendocrine tumor, and three were treated with rituximab (two for ANCA-associated vasculitis and one for lymphoma). Two patients treated with rituximab therapy received the treatment in the month preceding vaccination, and one received it 6 months before. There were no responders with a history of solid organ transplantation or treatment with rituximab within the past 6 months.

On the basis of our data, lymphocyte count below 1.3 G/L associated with chronic immunosuppressive therapy was highly predictive of a poor immune response in patients with CKD (receiver operating characteristic curve analysis to set the lymphocytes count threshold; sensitivity, 45%; specificity, 100%; positive predictive value, 100%; negative predictive value, 91%).

In this first description of SARS-CoV-2 mRNA vaccine serologic response in nondialyzed, nontransplanted patients with CKD, we report a high rate of immunization following two doses of BNT162b2. Although we cannot conclude yet on vaccine efficacy in this population (lack of postvaccination SARS-CoV-2 infection rate in patients with CKD), these data are encouraging. They are consistent with those reported in patients on dialysis, showing an overall good serologic response to two BNT162b2 injections (2). Efficiency of SARS-CoV-2 mRNA vaccination needs to be studied in larger cohorts of patients with CKD (3). Moreover, ongoing studies are trying to define protective thresholds for anti-Spike RBD IgGs by correlating serology results with neutralizing antibodies (4). The emergence of variants may, however, change those thresholds. Postvaccinal serology may help to point out high-risk patients with CKD and immunity system impairment due to their comorbidities or treatment who may need the same management as transplanted patients (three to four vaccine injections).

Disclosures

G. Blancho reports consultancy agreements with Astellas and Novartis, receiving honoraria from Astellas and Novartis, and serving as a scientific advisor or member of Novartis. M. Hourmant reports ownership interest in Sanofi. All remaining authors have nothing to disclose.

Funding

None.