Deficiência de vitamina B12 em receptores de transplante renal: frequência e associação com resistência à insulina, biomarcadores inflamatórios e função microvascular

Abstract

Vitamin B12 (B12) deficiency is associated with the development of hyperhomocysteinemia (Hhcys), a risk factor for cardiovascular disease (CVD). There is evidence that B12 may help prevent atherosclerosis due to antioxidant and anti-inflammatory effects. CVD is an important cause of death in kidney transplant recipients (KTR). Longitudinal investigations indicate a relationship between elevated homocysteine levels (hcys) and risk of CVD in KTR. However, the frequency of B12 deficiency and its association with cardiovascular risk markers in these patients is not yet known. The aim of the present study was to evaluate serum levels of B12, determining the frequency of deficiency, and its association with serum levels of hcys, insulin resistance, inflammatory markers, cutaneous microvascular reactivity and retinal vascular diameters in KTR. Observational, cross-sectional and longitudinal study conducted with adult KTR (18-65 years) at least 6 months after kidney transplantation (KTx). Were exluded patients with AIDS, cancer and autoimmune diseases, amputees, under dialysis therapy and using B12 supplements. Laboratory tests performed at baseline: glucose, insulin, B12, hcys, adiponectin, tumor necrosis factor-α, interleukin-8 and C-reactive protein (CRP). After 2 years the KTRs were submitted to the evaluation of laboratory parameters: glucose, insulin, B12, hcys, leptin and CRP; cutaneous microvascular reactivity by Laser Speckle Contrast Imaging; and the diameter of the retinal vessels by nonmidriatic retinography. Glomerular filtration rate was estimated (eGFR; ml/min) by the CKD-EPI equation. Serum B12 concentration at baseline was used to assess the association with all other variables, and deficiency was defined as < 200pg / mL. At baseline, 218 RTR (121 men), 49 (41–55) years, TxR time 115 (26–171) months and eGFR 52 ± 1.4 ml/min were evaluated. The frequency of B12 deficiency was 14% (n=31). At baseline serum B12: (1) was negatively associated with hcys, even after adjusting for age, sex and time from KTx in patients with eGFR ≥60 (r=-0.54; p=0.01), but after additional adjustment for eGFR the association was no longer significant; (2) was significantly lower in the Hhcys group (428 vs. 246pg / mL, p <0.05); (3) was not associated with insulin resistance and inflammatory markers. After 2 years, 171 patients were reevaluated. The analysis of the association betwenn serum levels of B12 obtained at baseline with the variables obtained after 2 years revealed: (1) negative association with insulin (r=-0.40; p=0.01) and HOMA-IR (r=-0.38; p=0.02) in patients with eGFR < 60 after adjustments for age, sex, time of RTx and eGFR, but after additional adjustment for body mass index the association was no longer significant; (2) negative association, after adjustments for confounders, with CRP in KTR with eGFR ≥ 60 (r=-0.43; p=0.04) and with leptin in the total group (r=-0.26; p=0.04) and in those with eGFR < 60 (r=-0.36; p=0.03); (4) absence of association with serum hcys, cutaneous microvascular reactivity and retinal vascular diameters. The present study suggests that in KTR the frequency of B12 deficiency is high and serum levels of B12 are inversely associated with inflammatory markers in longitudinal analysis