Long-term CD4 lymphopenia is associated with accelerated decline of kidney allograft function

Persistent CD4 T-cell lymphopenia after kidney transplantation has been associated with an increased occurrence of opportunistic infections, malignancies and even mortality, but studies have focussed only on the first few years after kidney transplantation. In this study, we investigated the risk factors and clinical significance of long-term profound CD4 lymphopenia detected ≥10 years after renal transplantation.

Between 2007 and 2010, 6206 CD4 T-cell counts, including 1507 counts <300/mm(3), were identified in an active cohort of 1876 kidney transplant patients. We identified 27 HIV-negative lymphopenic kidney transplant recipients out of 513 patients with graft survival over 10 years. We compared this cohort to 54 non-lymphopenic controls matched for the date of kidney transplantation.

The prevalence of CD4 lymphopenia 10 years after transplantation was 5.3%. CD4 T-cell lymphopenia was associated with significantly lower thymic output and with B-cell lymphopenia (P < 0.05). The duration of pre-transplant dialysis, but not the use of lymphopenic induction or recipient age, was significantly associated with a persistent CD4 lymphopenia (6.1 versus 3.0 years, P = 0.008). CD4 lymphopenia was associated with a higher frequency of cancer (50 versus 29.6%, P = 0.047). Most strikingly, long-term lymphopenia was significantly and independently associated with an accelerated decline in renal allograft function (P = 0.005), despite a similar rate of biopsy-proven acute rejection and comparable immunosuppression.

Our study shows an association between long-term CD4 T-cell lymphopenia in kidney recipients and malignancy and an accelerated decline of kidney allograft function.