Abstract 126: Effect of Immunosuppressive Therapy, Clinical, and Demographic Parameters on Kidney Function After Cadaveric Renal Transplant

Author(s):  
Justin Muste ◽  
Eugene Pashkovetsky ◽  
Stephani Wang ◽  
Monika Misak ◽  
Nikolaos Chandolias ◽  
...  

Background: We compared effects of immunosuppression and co-morbidities on kidney function following renal transplant. Methods: We perfomed retrospective chart review in 211 consecutive renal transplant recipients, treated at a single medical center between 2004 to 2014, who also underwent a post-transplant echocardiogram. Patients were stratified into ESRD/CKD-4 group and CKD1-3 according to standard GFR criteria. The study was approved by IRB. Results: Average age was 52.4 +/- 11.8 years old, 41% were females, 95% with history HTN, 81% with dislipidemia, 20% with CAD, 42% with diabetes mellitus, 26% past smokers, 16% on thyroid replacement therapy, 8% with history of congestive heart failure. The average hemoglobin was 11.9 +/- 2.2 mg/dL. Sixty percent of patients were on triple immunosuppressive therapy. In our study cohort, with an average time post-kidney transplant of 41.7+/-34.8 months, 26.5% patients had ESRD/CKD-4. Female gender (OR 2.26, 95% CI 1.21-4.20; p=0.01), diabetes mellitus (OR 0.502, 95% CI 0.26-0.96; p=0.03), triple immunosuppressive therapy (OR 0.279, CI 0.15-0.23; p<0.0001), and hemoglobin (OR 0.632, 95% CI 0.53-0.76; p<0.0001) were significant independent predictors of post-kidney transplant GFR. In multivariable regression analysis, post-transplant hemoglobin (OR 0.641, 95% CI 0.53-0.77; p<0.0001) and triple immunosuppressive therapy (OR 0.282, CI 0.15-0.53; p=0.0004) were significant predictors of preserved GFR and lower CKD category. Conclusions: Higher Hgb levels and triple immune-suppressive therapy are associated with improved kidney function post-renal transplant. Additional studies are needed to identify causes of decreased hemoglobin in this patient population and to develop treatment strategies aimed at preserving GFR.

2020 ◽  
Author(s):  
Bethany Dale ◽  
Subhassih Bose ◽  
Sheng Kuo ◽  
Alana Burns ◽  
Pierre Daou ◽  
...  

BACKGROUND End Stage Kidney Disease (ESKD) patients require complex and expensive medical management. Kidney transplantation remains the treatment of choice for ESKD and is considered superior to all other modalities of renal replacement therapy (RRT) or dialysis. However, access to kidney transplant is limited by critical supply-demand making it extremely important to ensure longevity of transplanted kidneys. This is prevented through life-long immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury is undertaken through an armamentarium of screening modalities. Post-transplant surveillance for kidney function and injury remained key to follow up care. While kidney function, quantified by estimated glomerular filtration rate (eGFR) and serum creatinine (SCr), and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection post-transplant, they have recently been demonstrated to be inferior in performance to that of AlloSure® (CareDx, Inc. Brisbane, CA), circulating donor-derived cell-free DNA (dd-cfDNA). OBJECTIVE The outcomes and methods of monitoring renal transplant recipients (RTR) post-transplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure® dd-cfDNA in an actively managed protocol assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology. METHODS The study protocol will acquire data from a phase IV observational trial to assess a cohort of 2500 RTR patients managed using AlloSure® dd-cfDNA and patient care managers versus 1000 propensity matched historic controls using UNOS SRTR data. Data will be managed in a centralized electronic data server. RESULTS The primary outcome will be superior allograft survival, as a composite of return to dialysis, re-transplant, death due to allograft failure and death with a functional graft DWFG (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in eGFR and immune activity through development of donor specific antibody (DSA). CONCLUSIONS Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior.


Nephron ◽  
2021 ◽  
pp. 1-13
Author(s):  
Ana Elena Rodríguez-Rodríguez ◽  
Esteban Porrini ◽  
Mads Hornum ◽  
Javier Donate-Correa ◽  
Raúl Morales-Febles ◽  
...  

Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20–30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.


2020 ◽  
Vol 9 (2) ◽  
pp. 511 ◽  
Author(s):  
Maryse C. J. Osté ◽  
Jose L. Flores-Guerrero ◽  
Eke G. Gruppen ◽  
Lyanne M. Kieneker ◽  
Margery A. Connelly ◽  
...  

Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (≥18 y) with a functioning graft for ≥1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 ± 13.6 y (53.6% men) and plasma BCAA was 377.6 ± 82.5 µM. During median follow-up of 5.3 (IQR, 4.2–6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08–1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c < 5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM.


2018 ◽  
Vol 33 (5) ◽  
pp. 897-910 ◽  
Author(s):  
Britta Höcker ◽  
Martin Aguilar ◽  
Paul Schnitzler ◽  
Lars Pape ◽  
Martin Bald ◽  
...  

Biomedicine ◽  
2021 ◽  
Vol 41 (2) ◽  
pp. 482-488
Author(s):  
Krithika Muralidhara ◽  
Subramanian Kannan ◽  
Ishthiaque Ahamed ◽  
Krishna Kishore ◽  
Llyod Vincent ◽  
...  

Introduction and Aim: Post Transplant Diabetes Mellitus (PTDM) constitutes a major co-morbidity that has significant impact on the patient and renal allograft outcome. Various traditional risk factors like dialysis vintage, immunosuppressive medication, viral infections have known to be associated with PTDM. Novel risk factors and its causative role in PTDM remains unexplored. The study looked at the incidence of PTDM at 6 months post renal transplantation and correlation of PTDM with known traditional and novel risk factors like pre-transplant C-reactive protein (CRP) level and Trace element deficiency.   Material and Methods: 30 consecutive renal transplant recipients more than 18 years of age were inducted into the study. Demographic data, known pre-transplant and post-transplant risk factors associated with development of PTDM were collected. Pre-transplant CRP and serum Trace element (Aluminum, Copper, Selenium and Zinc) levels were estimated. PTDM was diagnosed by home based glucometer monitoring and confirmed by Oral glucose tolerance test (OGTT).   Results: The incidence of PTDM was 36.6% at six months post renal transplant. Among the pre-transplant risk factors, higher age and positive family history of diabetes mellitus had a strong association with the occurrence of PTDM. Pre-transplant Zinc deficiency emerged as a significant novel risk factor for the development of PTDM.   Conclusion: Apart from known traditional risk factors, novel risk factors are associated with development of PTDM.


2020 ◽  
Vol 9 (2) ◽  
pp. 415 ◽  
Author(s):  
Oyuntugs Byambasukh ◽  
Maryse C. J. Osté ◽  
António W. Gomes-Neto ◽  
Else van den Berg ◽  
Gerjan Navis ◽  
...  

(1) Background: Little is currently known about the health impacts of daily-life moderate-to-vigorous physical activity (MVPA) in relation to the development of post-transplant diabetes mellitus (PTDM) and the long-term survival of renal transplant recipients (RTRs). (2) Methods: We analyzed self-reported data on MVPA within non-occupational and occupational domains, estimated with the SQUASH questionnaire, from a prospective cohort study of RTRs (n = 650) with a functioning graft exceeding 1 year. PTDM diagnoses were based on plasma glucose levels (≥126 mg/dL), HbA1c (≥6.5%), and the use of antidiabetic medication. Mortality data were retrieved from patient files up to the end of September 2015. (3) Results: During a median follow-up period of 5.3 years, 50 patients (10%) developed PTDM and 129 (19.8%) died. Of these deaths, 53 (8.9%) were caused by cardiovascular disease. Cox regression analyses showed that higher MVPA levels among patients were associated with a lower risk of PTDM (hazard ratio (HR); 95% confidence interval (95%CI) = 0.49; 0.25–0.96, p = 0.04), cardiovascular- (0.34; 0.15–0.77, p = 0.01), and all-cause mortality (0.37; 0.24–0.58, p < 0.001) compared with No-MVPA patients, independently of age, sex, and kidney function parameters. Associations of MVPA with cardiovascular and all-cause mortality remained significant and materially unchanged following further adjustments made for transplant characteristics, lifestyle factors, metabolic parameters, medication use, and creatinine excretion (muscle mass). However, the association between MVPA and PTDM was no longer significant after we adjusted for metabolic confounders and glucose levels. (4) Conclusion: Higher MVPA levels are associated with long-term health outcomes in RTRs.


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