FC 114: Monoclonal Gammopathy in Kidney Transplanted Patients: Novel Insights into Long-Term Outcomes
Authors: Meuleman Marie-Sophie , Mouyabi Steven , Gueguen Juliette , Vicca Stéphanie , Aubert Olivier , Bienaimé Frank , Arnulf Bertrand , Anglicheau Dany , Bridoux Franck , Cohen Camille 
Published: May 2022

Abstract

BACKGROUND AND AIMS
As in the general population the prevalence of monoclonal gammopathies (MG) in kidney transplant (KT) candidates increases with age. Little is known about the epidemiology and long-term consequences of MG on overall survival, graft outcomes and infectious and neoplastic complications in patients undergoing KT.

METHOD
We retrospectively identified patients with MG at the time of transplant (KTMG) or appearing de novo after the KT (DNMG) in 3059 patients who underwent a KT from January 2007 to June 2019 at Necker Hospital Paris (N = 1978) and from January 1998 to December 2017 at CHU Poitiers, France (N = 1081). Using a propensity score, we established a control cohort of KTMG from Necker Hospital, matched on the main covariates influencing post KT outcomes.

RESULTS
We identified 70 (2.3%) KTMG and 114 (3.7%) DNMG patients, presenting with identical demographic characteristics except for an older age in KTMG (62 versus 57 years; P = 0.03). MG isotypes among the 184 KT recipients with MGUS were IgG (n = 117, 64%), IgA (n = 16, 9%) or IgM (n = 16, 9%). Interestingly, DNMG patients presented more frequently with bi- or triclonal MG than KTMG patients (n = 28, 25% versus n = 7, 10%, respectively; P = 0.02). At the time of KT, among 62 patients with available sFLC measurement in KTMG, 11 (17%) had an abnormal kappa/lambda ratio. Because of systematic evaluation of SPEP during follow-up, we observed that MG disappeared during follow up more frequently in DNMG compared to KTMG (n = 51, 45% versus n = 17, 24%, respectively; P = 0.007). Figure 1 represents the results of SPEP during follow-up.
FIGURE 1: Monoclonal gammopathy timescale. Serum protein electrophoresis follow-up from KT;each patient is represented by one line. Blueand green lines represent negative SPEP, performed before and after the detection of MG, and red lines represent positive SPEP with MG identification. Clinical last follow-up is represented by dots: red dot for death, blue dot for graft loss and green dot for last follow-up alive with functional graft.
Overall survival was poorer in KTMG than in DNMG (87 versus 176 months; P &lt; 0.001). Cox model including age, sex, rank of transplantation and KTMG or DNMG revealed that age, rank of transplantation and KTMG were independent risk factors for death. Graft survival, occurrence of rejection and haematological complications were comparable between the two groups.
To better evaluate the effect of MGUS at the time of KT, KTMG patients from Necker Hospital were compared with matched KT recipients. There was no difference between KTMG and controls regarding the main baseline predictors of post-KT outcomes except for lower level of residual gammaglobulins [7.5 g/L (IQR 6–9.9)] in KTMG versus 10.7 g/l (IQR 8.9–13.1) in controls (P &lt; 0.0001). KTMG patients developed more frequently solid cancers (15% versus 5%; P = 0.04) and bacterial infections (63% versus 48%; P = 0.08). There was no significant difference regarding survival, frequency of rejection or haematological complications. However, KTMG patients with an abnormal kappa/lambda ratio at the time of KT tended to have poorer overall survival than those with normal kappa/lambda ratio and controls (respective medians 72, 87 and 103 months; P = 0.08) (Figure 2).

CONCLUSION
We report here the largest cohort of KT recipients who underwent systematic SPEP screening at the time of KT and yearly during post-transplant follow-up. We observed that MGUS prevalence in KT candidates is close to that reported in the general population. We confirm that outcomes of patients harboring MGUS at the time of KT are similar to those of matched controls without MGUS, supporting that MGUS should not be a contraindication for KT. Nevertheless, we observed that KTMG patients developed more frequently and earlier solid cancers and infections, suggesting that MGUS is associated with a relative immunodeficiency in these patients. We also showed that patients with abnormal sFLC kappa/lambda ratio experienced poor outcomes, claiming for systematic measurement of sFLC in the pre-KT workup.
Clinical last follow-up is represented by dots: red dot for death, blue dot for graft loss and green dot for last follow-up alive with functional graft.