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Background Cardiorenal syndromes (CRSs) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown. Methods The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5 123 193 patients who were admitted in a French hospital in 2012). Results Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence), while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%). The incidence of major outcomes was 57.3%, 53.0%, 79.2% for death; 18.8%, 10.9%, 27.5% for cardiovascular death; 52.6%, 34.7%, 64.3% for HF; 6.2%, 5.5%, 5.6% for myocardial infarction (MI); 6.1%, 5.8%, 5.3% for ischaemic stroke; and 23.1%, 4.8%, 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively. As compared with isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischaemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared with isolated CKD, the risk of ESKD was similar for cardiorenal CRS only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5 123 193 patients). Conclusions The additional impact of CRS versus isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated.

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 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 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.

BACKGROUND AND AIMS Post-transplantation patient care requires development and validation of noninvasive biomarkers to improve allograft monitoring and prevention from unnecessary biopsies. Preliminary reports have suggested the association of donor derived cell-free DNA (dd-cfDNA) with allograft rejection. However, there is no proof of its added value beyond standard of care patient management in large and deep phenotyped cohorts. METHOD A total of 1210 concomitant evaluations of allograft histology, anti-HLA DSA and functional parameters between 2013 and 2018 were included corresponding to 637 evaluations in the derivation cohort and 573 in the validation cohort. dd-cfDNA was measured in plasma at the time of the evaluation. Diagnoses were assessed using Banff 2019 criteria. Parameters associated with kidney allograft rejection were assessed using uni- and multivariable logistic regression. We developed a risk model using the variables that were independently associated with rejection. RESULTS Higher levels of dd-cfDNA were observed for AMR and TCMR or both compared to other diagnoses (Figure 1A). We found incremental dd-cfDNA levels with increasing Banff lesion scores for g, ptc, i, t, cg and C4d (Figure 1B). There was no association of dd-cfDNA levels with allograft inactive lesions. In multivariable analysis, dd-cfDNA (P CONCLUSION We demonstrate the independent and added value of dd-cfDNA in addition to conventional features to predict rejection. This first integrative system shows improved performance for patient monitoring and could help physicians in decision-making process.