Evolution of care and outcomes of kidney transplantation in plasma cell dyscrasias: A single center experience

Abstract Background: Historically, managing kidney failure from Plasma Cell Dyscrasias (PCDs) was limited to dialysis, as kidney transplantation (KT) was rarely considered due to poor prognoses and relapse concerns. However, recent therapeutic advancements have significantly improved patient survival and hematological response rates. Despite these improvements, current trends in KT referrals, listing, and outcomes for this population remain poorly characterized. This study aims to address this gap by examining our center's referral patterns, evaluating progression through the KT process, and identifying factors associated with successful KT and patient outcomes. Methods: We conducted a single-center, retrospective study of adults with kidney failure secondary to Multiple Myeloma (MM), Smoldering Myeloma (SMM), Light Chain (AL) Amyloidosis, or Monoclonal Gammopathy of Renal Significance (MGRS). This cohort included all patients formally evaluated for KT or seen at our institution from 2011 to 2024. We excluded individuals with Monoclonal Gammopathy of Undetermined Significance (MGUS) alone or those referred for other organ transplants. Patients were divided into KT and Non-KT groups. Clinical, demographic, and laboratory data were extracted from electronic health records using Redcap. PCD diagnoses and hematologic responses followed International Myeloma Working Group (IMWG) criteria; a deep response was defined as a Complete Response (CR) or Very Good Partial Response (VGPR). Post-KT outcomes such as biopsy-proven acute rejection (BPAR) were assessed using standard definitions. Statistical analyses were performed in R (v4.4.0). We compared continuous and categorical variables between groups using Wilcoxon rank-sum and Fisher's exact tests, respectively. A LASSO logistic regression model—including age, type 2 diabetes (T2DM), coronary artery disease (CAD), smoking status, and hematologic response at referral—was used to identify predictors of KT. Finally, a competing risks analysis assessed cause-specific mortality in the non-KT cohort. Results: Of 345 patients screened, 33 met the inclusion criteria. The cohort included patients with MM (n=20, 60.6%), AL Amyloidosis (n=8, 24.2%), MGRS (n=6, 18.1%), and SMM (n=7, 21.2%), with some having overlapping diagnoses. Referrals surged after 2020, accounting for over half of the cohort (17/33). 13 patients (39.4%) received a KT—10 of whom were transplanted after 2020—while 20 (60.6%) did not. Attrition primarily occurred before KT approval, with patients being denied (24.2%), withdrawing (9.1%), or remaining under evaluation at data censure (9.1%). Denials were most commonly due to comorbidities (62%), nonadherence (50%), or active/untreated PCD (25%). T2DM was significantly more prevalent in the non-KT group (35% vs. 0%, p=0.027). Our LASSO regression model confirmed this, identifying the absence of T2DM as a strong positive predictor for KT (log-odds coefficient = +0.99), while CAD was a weak negative predictor (log-odds coefficient = -0.004). Notably, a deep hematologic response (CR/VGPR) at referral did not predict receipt of a KT (present in 62% of KT vs. 50% of non-KT patients). Post-KT outcomes were excellent. At a median follow-up of 39 months, death-censored graft survival was 100% with no PCD recurrence; these outcomes were achieved while a minority of patients (4/13, 30.8%) received post-KT maintenance therapy. Organs were sourced from living (46.2%) and deceased (53.8%) donors, with an efficient median time from approval to KT of 2.0 months. Overall patient survival was 85% (11/13); these two deaths occurred with functioning grafts at 10- and 11-years post-KT. BPAR occurred in 23% of recipients. In contrast, for the non-KT cohort, the 10-year cumulative incidence of mortality from non-PCD causes was 59.1%, with no deaths attributed to PCD progression, as the primary driver of mortality. Conclusions: Referrals of patients with PCD for KT have increased since 2020, with most approved candidates achieving excellent post-KT outcomes. Cardiovascular comorbidities, particularly T2DM and CAD, were the primary barriers to KT and key drivers of mortality. While graft survival was excellent, BPAR remains a notable concern post-KT. Although these single-center findings are promising, the small sample size limits their generalizability. Therefore, a multicenter study is planned to validate these results and identify broader, systemic barriers to care.