Preemptive reduction of immunosuppression upon high urinary polyomavirus loads improves patient survival without affecting kidney graft function.

BACKGROUND: Polyomavirus (PV) is a major cause of kidney graft disease. Monitoring by polymerase chain reaction (PCR) on blood is currently recommended. In order to avoid irreversible lesions, we investigated the clinical impact of preemptive reduction of immunosuppression (IS) in kidney transplant recipients (KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC virus. MATERIAL AND METHODS: From 2000 to 2011, in our single center, 789 consecutive KTR were distributed into 4 groups, according to the maximal Upv levels (by PCR) during the first year and the therapeutic option: (A) Upv <104 copies (cp)/mL (n=573), (B) ≥104 Upv <107 cp/mL (n=100), and (C) Upv ≥107 cp/mL (n=116); in group C, the IS drug doses were reduced in subgroup Ca (n=102) only, as 14 patients (subgroup Cb) were at risk for graft rejection. RESULTS: The preemptive reduction of IS (group Ca) increased patient survival as compared with all other groups (P<.05), did not modify graft function, and increased graft survival vs group A (risk ratio: 5.7, confidence interval: 1.8-18.1, P=.003). Differences for risk factors are as follows (groups Ca vs A): incidence of human leukocyte antigen (HLA) immunization (>5% panel reactive antibodies): 3% vs 8% (P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute rejection: 9.8% vs 24.2% (P=.005). PV-associated nephropathy occurred only in group Ca (2% of total grafts) without effect on patient or graft outcome. CONCLUSION: The reduction of IS in patients with high Upv loads is beneficial for patient survival and does not affect graft survival or graft function.

Large decrease of anti-tetanus anatoxin and anti-pneumococcal antibodies at one year after renal transplantation.

AIMS: In kidney transplant recipients (KTR), antibody (Ab) synthesis is hampered by AZA and CsA. We here report in a prospective cohort study, the effects of mycophenolate mofetil (MMF) associated to a calcineurin inhibitor on plasma levels of anti-tetanus anatoxin Ab (TAnAb) and anti-pneumococcal Ab (PnPsAb). METHODS: Serum titers of the TAnAb and the PnPsAb against serotypes 14, 19F and 23F were measured in 94 KTR on Day 0 (T0) and 1 year (T12) after renal transplantation and in 49 healthy controls. RESULTS: 1) At T0, TAnAb were detected in only 71% of patients vs. 98% of controls (p < 0.0001) and the titers were significantly lower in KTR (1.46 UI/ml vs. 2.74 in controls, p = 0.01); they further decreased between T0 and T12 (1.46 UI/ml to 0.31, p < 0.0001). The calculated half-life (t1/2) of TAnAb was 7.7 months, as compared to more than 10 years in a normal population. 2) In KTR, PnPsAb titers decreased significantly between T0 and T12 (p < 0.005); the t1/2 of the different PnPsAb ranged from 9.2 to 11.9 months. CONCLUSIONS: In KTR treated by MMF and CNI, the TAnAbs and PnPsAbs titers decrease significantly and profoundly during the first year. Immunization pre-transplantation should be encouraged to maintain adequate post-transplant Abs levels.

Evolution of immunoglobulin and mannose binding protein levels after renal transplantation: association with infectious complications.

Hypogammaglobulinemia (hypo-Ig) and low mannose binding protein (MBP) levels might be involved in the infectious risk in renal transplantation. In 152 kidney transplant recipients treated with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF), during the first year, we prospectively recorded the incidence of hypogammaglobulinemia, and low MBP levels. Their influence on infectious complications was evaluated in 92 patients at 3 and 12 months (T3 and T12). The proportion of deficiency increased significantly: hypo-IgG: 6% (T0), 45% (T3), and 30% (T12) (P < 0.001); hypo-MBP: 5%, 11%, and 12% (P = 0.035). Hypo-IgG at T3 was not associated with an increased incidence of first-year infections. A significantly higher proportion of patients with combined hypogammaglobulinemia [IgG+ (IgA and/or IgM)] at T3 and with isolated hypo-IgG at T0 developed infections until T3 compared with patients free of these deficits (P < 0.05). Low MBP levels at T3 were associated with more sepsis and viral infections. Hypogammaglobulinemia is frequent during the first year after renal transplantation in patients treated with a CNI and MMF. Hypo-IgG at T0 and combined Igs deficts at T3 were associated with more infections. MBP deficiency might emerge as an important determinant of the post-transplant infectious risk.