Disease In Kidney Transplant Recipients Research Articles

Progression of Kidney Disease in Kidney Transplant Recipients With a Failing Graft: A Matched Cohort Study.

Few studies have assessed outcomes in transplant recipients with failing grafts as most studies have focused on outcomes after graft loss. To determine whether renal function declines faster in kidney transplant recipients with a failing graft than in people with chronic kidney disease of their native kidneys. Retrospective cohort study. Alberta, Canada (2002-2019). We identified kidney transplant recipients with a failing graft (2 estimated glomerular filtration rate [eGFR] measurements 15-30 mL/min/1.73 m2 ≥90 days apart). We compared the change in eGFR over time (eGFR with 95% confidence limits, LCLeGFRUCL) and the competing risks of kidney failure and death (cause-specific hazard ratios [HRs], LCLHRUCL). Recipients (n = 575) were compared with propensity-score-matched, nontransplant controls (n = 575) with a similar degree of kidney dysfunction. The median potential follow-up time was 7.8 years (interquartile range, 3.6-12.1). The hazards for kidney failure (HR1.101.331.60) and death (HR1.211.592.07) were significantly higher for recipients, while the eGFR decline over time was similar (recipients vs controls: -2.60-2.27-1.94 vs -2.52-2.21-1.90 mL/min/1.73 m2 per year). The rate of eGFR decline was associated with kidney failure but not death. This was a retrospective, observational study, and there is a risk of bias due to residual confounding. Although eGFR declines at a similar rate in transplant recipients as in nontransplant controls, recipients have a higher risk of kidney failure and death. Studies are needed to identify preventive measures to improve outcomes in transplant recipients with a failing graft.

LB2307. Safety and Efficacy of Letermovir (LET) versus Valganciclovir (VGCV) for Prevention of Cytomegalovirus (CMV) Disease in Kidney Transplant Recipients (KTRs): A Phase 3 Randomized Study

Abstract Background VGCV is approved for prophylaxis in adult KTRs at high risk for CMV disease (donor CMV-seropositive/recipient CMV-seronegative [D+/R-]); however, its use is limited by myelosuppression. LET is non-myelotoxic, does not require dose modification in renal impairment, and is approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. This randomized, double-blind, Phase 3 non-inferiority study (NCT03443869; MK-8228-002) evaluated CMV prophylaxis with LET vs. VGCV in adult CMV D+/R- KTRs. Methods Adult CMV D+/R- KTRs were randomized 1:1 within 7 days post-kidney transplant (KT) to receive either LET 480 mg QD (PO/IV) with acyclovir (400 mg PO BID, adjusted for renal function), or VGCV (900 mg PO QD, adjusted for renal function), through Week 28 post-KT and followed up through Week 52 post-KT. Randomization was stratified by use of lymphocyte-depleting induction immunosuppression. The primary endpoint was the proportion of participants (pts) with CMV disease adjudicated by blinded committee through Week 52 post-KT (non-inferiority margin,10%). Results A total of 601 pts were randomized; 589 received ≥ 1 dose of study medication (median age [range], 51 [18–82] years; male, 72%; Black/African American, 9%; deceased donor, 60%; received lymphocyte-depleting induction immunosuppression, 46%), of whom two had detectable CMV viral DNA on Day 1 and one was CMV R+ (full analysis set, 586 pts). The proportion of pts with CMV disease through Week 52 post-KT was 10.4% with LET vs. 11.8% with VGCV (stratum-adjusted treatment difference, -1.4% [95% CI -6.5, 3.8]; Table 1). Drug-related adverse events (AEs) were reported in 19.9% of pts with LET and 35.0% of pts with VGCV through Week 28 post-KT. The rate of discontinuations due to an AE was 4.1% in the LET arm and 13.5% in the VGCV arm (Table 2). The incidence of neutropenia (absolute neutrophil count < 1000/µL) during the treatment phase was lower with LET than with VGCV (4.1% vs. 19.5%; difference, -15.4% [95% CI -20.7, -10.5]). Conclusion The study met its primary endpoint: LET was non-inferior to VGCV in preventing CMV disease in high-risk (CMV D+/R-) KTRs through Week 52 post-KT, and led to a lower rate of myelotoxicity than VGCV. Disclosures Ajit P. Limaye, MD, AiCuris: Advisor/Consultant|MedPace: Data Safety Monitoring Boards|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Novartis: Data Safety Monitoring Boards|Sana: Advisor/Consultant Klemens Budde, MD, Abbvie: Grant/Research Support|Abbvie: Honoraria|Alexion: Grant/Research Support|Alexion: Honoraria|Astellas: Grant/Research Support|Astellas: Honoraria|Bristol Myers Squibb: Grant/Research Support|Bristol Myers Squibb: Honoraria|Chiesi: Grant/Research Support|Chiesi: Honoraria|CSL Behring: Grant/Research Support|CSL Behring: Honoraria|Fresenius: Grant/Research Support|Fresenius: Honoraria|Hansa: Grant/Research Support|Hansa: Honoraria|Hexal: Grant/Research Support|Hexal: Honoraria|Hookipa Biotech: Grant/Research Support|Hookipa Biotech: Honoraria|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Novartis: Grant/Research Support|Novartis: Honoraria|Otsuka: Grant/Research Support|Otsuka: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Grant/Research Support|Roche: Honoraria|Sandoz: Grant/Research Support|Sandoz: Honoraria|Shire: Grant/Research Support|Shire: Honoraria|Siemens: Grant/Research Support|Siemens: Honoraria|Takeda: Grant/Research Support|Takeda: Honoraria|Veloxis: Grant/Research Support|Veloxis: Honoraria|Vitaeris: Grant/Research Support|Vitaeris: Honoraria Atul Humar, MD, MSc, FRCPC, Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support|Takeda: Advisor/Consultant Julia Garcia-Diaz, MD, Astellas Pharma US, Inc.: Advisor/Consultant|Astellas Pharma US, Inc.: Speaker's Bureau Robert P. Carroll, BM BCh (Oxon), FRACP, DM (Oxon), Bristol Myers Squibb: Grant/Research Support|HANSA Biopharma: Advisor/Consultant Yoshihiko Murata, MD, PhD, Former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Valerie L. Teal, MS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Current Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Christopher L. Gilbert, n/a, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Barbara A. Haber, MD, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co.,: Stocks/Bonds.

Host and viral RNA dysregulation during BK polyomavirus infection in kidney transplant recipients.

Early detection of BK polyomavirus (BKPyV) infection in kidney transplant recipients (KTRs) would enhance their quality of life and save the allograft. Still, many patients lose their grafted kidneys because of this infection. BKPyV microRNAs (miRNAs) have been detected in KTRs during viral infection. BKPyV produces two mature miRNAs that are named BKV-miR-B1-5p and BKV-miR-B1-3p. Additionally, BKPyV associated nephropathy (BKVAN) in kidney transplanted patients cause changes in the expression level of host genes and miRNAs such as IFN-ɣ, BCLA2A1, has-miR-10, and has-miR-30a. BKVAN can alter viral genes and miRNAs expression level, too, like viral miRNAs and T-Ag. However, their potential value as viral infection markers and the regulatory network produced by their expression during viral-host interactions needs more consideration since there are no approved medications for treating BKPyV-related diseases in KTRs. Hence, it is vital to recognize complicated facts regarding the impact of BKPyV infection on the distribution of miRNAs and mRNAs within the host cell and the virus. This article is categorized under: Translation > Regulation RNA Processing > Processing of Small RNAs RNA in Disease and Development > RNA in Disease.

Seasonal variation of cytomegalovirus disease in kidney transplant recipients.

Studies conducted in the northern United States found cytomegalovirus (CMV) disease after liver transplantation follows a seasonal pattern, with increased incidence in fall and winter. This has not been evaluated in kidney transplant recipients. Improved understanding of CMV seasonality may help guide use of preventative therapies. We evaluated adult patients receiving a kidney transplant at our center in Wisconsin from January 1, 1995 to December 31, 2018. CMV event was defined as quantifiable viral replication with clinical signs or symptoms suspicious for CMV per current consensus recommendations. Seasons were divided as follows: winter (December-February), spring (March-May), summer (June-August), and fall (September-November). The primary objective was to evaluate the annual distribution of CMV disease and determine whether this differed by season. There were 6151 kidney transplants in the study period. A total of 913 patients had 1492 episodes of CMV. Median time from transplant to first detection was 5.51 months (interquartile range [IQR] 2.87-11.7). The observed overall incidence exceeded the expected incidence in winter (+.7%), spring (+5.5%), and fall (+3.4%) and was less than expected in summer (-9.5%) (p=.18). The incidence of CMV during summer, however, was 21% less than expected (p=.001) in recipients who were CMV positive (R+) at the time of transplantation. No such difference was observed in CMV negative recipients (R-; p=.58). CMV after kidney transplant appears to be less common during the summer season in patients who were R+ at transplant but does not follow seasonal variation in R-. Reasons for this are unclear but are likely related to CMV-specific cell-mediated immunity. These findings may have clinical implications, particularly the use of non-pharmacologic strategies to improve response to antiviral therapy.

Prevalence of cardiovascular diseases in kidney transplant recipients and its relationship with asymmetric dimethylarginine, fibroblast growth factor-23 and multiple inflammatory markers.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, a marker of endothelial damage and progression of atherosclerosis. Research confirms the association of ADMA with an increased risk of cardiac complications and an increased risk of death, graft loss among kidney transplant recipients (KTRs). The aim of our study was to establish the significance of ADMA and FGF-23 as biomarkers of cardiovascular risk as well as predictors of graft failure and progression of chronic transplant kidney disease in comparison to CKD subjects. In addition, an analysis of the relationship between ADMA, FGF23 and cardiovascular diseases in CKD subjects and KTRs was performed. The study group included 132 KTRs. The control group consisted of age- and sex-adjusted 40 individuals with clinically stable CKD. ADMA, FGF-23, hs-CRP and IL-6 were measured by the enzyme-linked immunoassay method (ELISA). Parameters of body mass composition such as fat mass, FTI, lean tissue mass, LTI, body water and overhydration were assessed by multi-frequency bioimpedance analysis (BIA). Cardiovascular diseases (CVDs) were present in 31.8% of KTRs. Independent variables related to nutritional status (SGA, s-albumin), according to multivariate regression, may have an impact on the prevalence of CVD in the kidney transplant recipients' group. Our study findings suggested a correlation between ADMA and serum albumin (r=-0.41, p<0.05), oxLDL (r=-0.42, p<0.05) and overhydration (OH%, r=0.28, p<0.05). Moreover, administration of statins and/or angiotensin-converting-enzyme inhibitors was significantly related to a reduction of ADMA in KTRs. We have also identified a significant positive correlation between FGF-23 levels and inflammatory markers (hs-CRP, IL-6) and negative with overall index of renal function (eGFR-CKD EPI, eGFR-MDRD). Nutritional status, inflammation and endothelial dysfunction markers (ADMA, FGF-23) are considerably altered even in stable kidney transplant recipients.

Progression of Kidney Disease in Kidney Transplant Recipients With a Failing Graft: A Matched Cohort Study

Progression of Kidney Disease in Kidney Transplant Recipients With a Failing Graft: A Matched Cohort Study

Recurrence of Glomerular Disease in Kidney Transplant Recipients in a National Cohort

Recurrence of Glomerular Disease in Kidney Transplant Recipients in a National Cohort

The Potential Protective Effect and Underlying Mechanisms of Physiological Unconjugated Hyperbilirubinemia Mediated by UGT1A1 Antisense Oligonucleotide Therapy in a Mouse Model of Cyclosporine A-Induced Chronic Kidney Disease.

Cyclosporine A (CSA) is an immunosuppressive drug that has improved transplant survival rates. However, its use is often limited because it is thought to be linked to the development of chronic kidney disease after kidney transplants. This study aimed to investigate the protective effects and underlying mechanisms of physiological unconjugated (UC) hyperbilirubinemia mediated by UGT1A1 antisense oligonucleotide in a mouse model of CsA-induced chronic kidney disease, and match these with that of chitosan (CH) as a natural chelator against kidney injury. In the current study, CsA-treated mice were given an intravenous injection of UGT1A1 antisense morpholino oligonucleotide (16 µg/kg) every third day for 14 days. In serum samples, bilirubin, creatinine, and urea were determined. Markers of oxidative stress, antioxidant activities, and mRNA expression of target genes PPAR-α, cFn, eNOS, NF-B, AT1-R, ETA-R, Kim-1, and NGAL were measured in the kidney tissues. Moreover, histopathological examinations were carried out on the kidney tissue. Physiological UC hyperbilirubinemia could be a promising protective strategy against CsA-induced kidney disease in transplant recipients. UGT1A1 antisense oligonucleotide-induced physiological UC hyperbilirubinemia serum significantly protected against CsA-induced kidney dysfunction. UCB acts as a signaling molecule that protects against kidney disease through different mechanisms, including antioxidant, anti-inflammatory, and hormonal action, by activating nuclear hormone receptors (PPAR-α). Moreover, it significantly downregulated mRNA expression of NF-kB, ETA-R, iNOS, AT1-R, cFn, Kim-1, and NGAL in the kidney tissue and alleviated CsA-induced kidney histological changes in CsA-treated mice.

COVID-19 Disease in Kidney Transplantation Recipients: A Single-Center Study (Experience of Dr. Shariati Hospital)

Background: Coronavirus disease 2019 (COVID-19 disease) is caused by SARS-CoV-2. In December 2019, several outbreaks of severe and life-threatening pneumonia with unknown organism were reported in Wuhan, China and the disease spread rapidly all over the world and caused the biggest pandemic. There was no clear information regarding incidence, morbidity, and mortality rate of COVID-19 disease in kidney transplant recipients or other solid organ transplant recipients. Therefore, we designed a study to evaluate the factors that can have any impact on kidney transplant recipients infected with SARS-Cov2.&#x0D; Methods: Our research was a retrospective cross-sectional study. The study population was all adult kidney transplant recipients (&gt; 18 years old) who were hospitalized due to COVID-19 disease according to national guidelines from 1st March, 2020 to 20th April, 2020 in Shariati Hospital, Tehran, Iran. Demographic data, common clinical complaints, vital signs, types and dose of immunosuppressive drugs, comorbidity diseases, and basic laboratory tests were extracted from the medical records using a data collection form.&#x0D; Results: According to the results of our investigation, mortality rate was 69.2% in kidney transplant recipients who were admitted in our hospital. No one died under the age of 47 years, while no one survived over the age of 58 years. As a result, age can be a reliable predictor of survival rate in kidney transplant recipients with COVID-19 pneumonia. All patients in non- survivors’ group were elderly and needed intubation, mechanical ventilation, and renal replacement.&#x0D; Conclusion: In addition to early referral and early start of appropriate and specific treatments of COVID-19 in patients with kidney transplantation, our general advice, is discontinuation of antimetabolite drugs at admission time, dose reduction of calcineurin inhibitors, and even withdrawal of all immunosuppressive drugs except steroids in critical cases.

MO987: Risk Predictors and Impact of Post-Transplant Cardiovascular Disease in A 20-Year Cohort of Kidney Transplant Recipients

Abstract BACKGROUND AND AIMS Although improvement in histocompatibility matching, immunosuppressive therapy and antimicrobial treatment have led to improved long-term allograft survival, cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in kidney transplant recipients (KTR). In addition to the accumulated risks due to chronic kidney disease and dialysis, kidney transplantation conveys its own unique risk factors for CVD. These include the metabolic effects of immunosuppressive treatments such as post-transplant hyperglycaemia, dyslipidaemia and hypertension as well as the effects of suboptimal kidney function including volume overload, anaemia, mineral bone disease and left ventricular hypertrophy. The predictors of cardiovascular diseases in KTR, however, have not been clearly defined. This study aimed to first ascertain the incidence of post-transplant CVD in those KTR without a prior confirmed history of CVD, then identify the predictors of CVD transplant associated CVD risk factors and finally evaluate the impact of CVD on graft and patient survival in this era of modern immunosuppressive medications. METHOD We evaluated 962 KTR transplanted between 2000 and 2020 and followed in a single centre. About 328 KTR with a history of pre transplant CVD were excluded. CVD was defined as a composite of Ischaemic heart disease, myocardial infarction, heart failure, stroke or peripheral vascular disease. Logistic regression analyses were performed to identify the risk predictors of post-transplant CVD. Kaplan–Meier plots and multivariate Cox proportional hazards regression analysis were used to identify and characterize predictors of dialysis free survival. RESULTS Among 634 KTR included in the analysis (mean age: 45 ± 15 years), CVD was reported in 101 KTR (16%) during a median follow-up of 95.9 months. About 274(43%) were females, 531(84%) were Caucasians. KTR with post-transplant CVD were likely to be older (50 ± 13 versus 44 ± 15 years; P &amp;lt; 0.001), had spent more time on dialysis [median (IQR) 21 (1–51) versus 11 (0–3) months; P = 0.004] and received cyclosporin maintenance (18% versus 7%; P = 0.01). Incidence of post-transplant CVD was independently predicted by older age [OR: 1.40 (1.15–1.70: P = 0.001)], tacrolimus therapy [OR: 0.81 (0.71–0.93), P = 0.002], mean haemoglobin concentration [OR: 0.86 (0.75–1.00), P = 0.049] and average C-reactive protein (CRP) level [OR: 1.13 (1.02–1.25), P = 0.02] (Figure 1). The median dialysis free survival was significantly lower in KTR who developed post-transplant CVD (14.7 versus 20 years, P = 0.009). In the multivariate Cox regression analysis, the factors associated with worse dialysis free survival in our cohort (survival with a functioning graft) were older age at transplantation [hazard ratio (HR): 1.03; P &amp;lt; 0.001), a history of post-transplant CVD (HR: 1.68; P = 0.006), higher post-transplant parathormone levels (HR: 1.02; P &amp;lt; 0.001), higher mean urine protein creatinine ratio (uPCR) (HR: 1.003: P &amp;lt; 0.001), a greater annual rise in uPCR (HR: 1.002; P &amp;lt; 0.001) and a history of acute rejection (HR: 1.56; P = 0.03). Statin treatment was associated with better dialysis free survival outcome (HR: 0.60; P = 0.01). CONCLUSION The incidence of post-transplant CVD in KTR with no history of pre-transplant CVD was 16%. Age at transplantation and average CRP were independent predictors of post-transplant CVD whereas treatment with Tacrolimus was associated with a lower risk of CVD. Statin therapy was associated with better dialysis free survival whereas a higher PTH was linked to poor survival. It was interesting to note that diabetes was not independently associated with the risk and outcome of post-transplant CVD in our cohort.

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients.

Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients. Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients. Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R2 37.8%, p = 0.027). As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

Outcomes of Interventional Management of Coronary Artery Disease in Kidney Transplant Recipients

Cardiovascular disease is the most common cause of death among kidney transplant (KT) recipients. Trials routinely exclude patients with end-stage renal disease when assessing the effect of coronary artery revascularization. We looked to compare long-term outcomes in patients who underwent percutaneous coronary intervention (PCI) before KT with those managed medically. We identified all patients who underwent coronary artery catheterization before KT from January 2008 to November 2019 at the Cleveland Clinic. The primary endpoint was all-cause mortality. A total of 272 patients were included, of whom 52 (19.11%) underwent PCI, and the remaining 220 patients were managed medically. The median age in the PCI group was 57.4 years (interquartile range [IQR], 46.9-61.2 years), whereas it was 53.9 years (IQR, 44.6-61 years) in the group medically managed. Baseline characteristics including sex, race, hypertension, diabetes, smoking, and hyperlipidemia were comparable in both groups. The median time to KT was 2.4 years (IQR, 1-5 years) in the PCI group vs 1.2 years (IQR, 0.6-3.3 years) in the medically managed group (P=.001). Among patients who underwent PCI, 40.4% had single vessel disease and 59.6% had multivessel disease compared with 16.8% and 28.6%, respectively, in the medically managed group (P < .001). Overall, there was no difference in mortality in the PCI group compared with the medically managed group after 10 years of follow-up (P=.416). Patients with coronary artery disease can be safely treated with PCI before KT and have comparable outcomes to those who are managed medically.

Does the cytomegalovirus infection cause kidney transplant rejection in Erbil city patients, Kurdistan region of Iraq?

Does the cytomegalovirus infection cause kidney transplant rejection in Erbil city patients, Kurdistan region of Iraq?

Racial Differences in Medication Utilization for Secondary Prevention of Cardiovascular Disease in Kidney Transplant Recipients: A Post Hoc Analysis of the FAVORIT Trial Cohort

Rationale & ObjectiveBlack kidney transplant recipients have higher prevalences of cardiovascular disease (CVD) risk factors and less intensive risk factor control than White kidney transplant recipients. Our objective was to evaluate racial disparities in receipt of statins and aspirin for secondary CVD prevention among kidney transplant recipients in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial.Study DesignCohort study.Setting & ParticipantsFAVORIT participants of White, Black, and Other races from the United States and Canada with a history of CVD at study entry or who experienced a nonfatal CVD event during follow-up.PredictorRace.OutcomeReceipt of statins and aspirin for secondary CVD prevention.Analytical ApproachWe used parametric (Weibull), proportional-hazards, interval-censored survival models to evaluate the independent association of race with receipt of statins and aspirin for secondary CVD prevention.ResultsOf the 4,110 kidney transplant recipients enrolled in FAVORIT trial, 978 met the inclusion criteria (78% White, 17% Black, and 6% Other race). Compared with the White race, Black and Other races were associated with lower hazards of receiving statins (Black race: adjusted HR, 0.76 [95% CI, 0.60-0.97]; Other race: adjusted HR, 0.87 [95% CI, 0.60-1.27]) and aspirin (Black race: adjusted HR, 0.85 [95% CI, 0.67-1.08]; Other race: adjusted HR, 0.63 [95% CI, 0.43-0.94]).LimitationsLack of granular information on potential indications or contraindications for aspirin or statin use for secondary CVD prevention.ConclusionsPost hoc findings from the FAVORIT trial demonstrated that Black race was associated with a lower likelihood of receiving statins and Other race was associated with a lower likelihood of receiving aspirin for secondary CVD prevention. This represents a potential target to improve CVD care in non-White kidney transplant recipients.

Bone and Mineral Disease in Kidney Transplant Recipients.

After kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.

Relevance of the perioperative edema index measured by bioelectrical impedance analysis for prediction of cardiovascular disease in living‐donor kidney transplantation

ObjectivesPerioperative management of fluid status during kidney transplantation is important, because volume overload can increase the risk of cardiovascular disease in recipients. The edema index calculated by bioelectrical impedance analysis is commonly used to correctly evaluate fluid status. We evaluated the relevance of the edema index for cardiovascular disease in kidney transplant recipients, and searched for predictors of high edema index in the perioperative period during kidney transplantation.MethodsA total of 88 recipients were included in this study. The group in which the edema index at discharge was &gt;0.40 was termed as the “high edema index group”, and that with ≤0.40 was termed as the “low edema index group”. We assessed cardiovascular disease‐free survival and cardiovascular disease‐specific survival in the two groups by using Cox proportional regression analyses adjusted by inverse probability of treatment weighting analysis. The patients’ background and conventional cardiovascular disease risk factors were assessed to estimate predictors for a high edema index.ResultsA high edema index was significantly associated with short cardiovascular disease‐free survival after kidney transplantation (hazard ratio 10.01; P &lt; 0.05) in the inverse probability of treatment weighting model. There were no significant differences in the cardiovascular disease‐specific survival. In multivariate logistic regression analyses, non‐pre‐emptive kidney transplantation and dyslipidemia were significant independent predictors of a high edema index (odds ratio 3.59, P &lt; 0.05 and odds ratio 4.05, P &lt; 0.01, respectively).ConclusionsA high edema index is associated with the incidence of cardiovascular disease. Overhydration should be especially avoided in recipients with these factors, and their fluid volume should be carefully managed.

Novel coronavirus disease in kidney-transplant recipients: Correspondence

Novel coronavirus disease in kidney-transplant recipients: Correspondence

Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients.

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

Denosumab-Induced Hypocalcemia and Hyperparathyroidism in de novo Kidney Transplant Recipients

Introduction: Denosumab represents a realistic treatment option to increase bone mineral density in kidney transplant recipients (KTRs). It is still unknown how and at what extent posttransplantation bone disease and graft function influence the effects of denosumab on mineral metabolism indexes. In this study, we analyze risk factors of hypocalcemia and parathyroid hormone (PTH) increase after denosumab administration in eighteen de novo KTRs and its management before and after this treatment. Methods: We conducted a monocentric, observational, prospective study on de novo KTRs. All KTRs enrolled received a single 60 mg subcutaneous dose of denosumab every 6 months. Before kidney transplantation, no patients were treated with calcio-mimetic. After kidney transplantation and before antiresorptive therapy, no patients were treated with calcio-mimetic drugs and/or vitamin D receptor agonists, while all patients received nutritional vitamin D supplementation (from 1,000 IU to 1,500 IU daily). Results: Hypocalcemia was related to the degree of lumbar osteoporosis (p = 0.047); the increase in the PTH level was correlated to baseline bone turnover markers (bone alkaline phosphatase, serum osteocalcin, and β-C-terminal telopeptide), the 25 OH status, and eGFR. The introduction of calcitriol, after the PTH increase, in addition to cholecalciferol was necessary to ensure an adequate control of serum calcium and PTH during a follow-up of 15 months. Following the treatment with denosumab, it was observed an improvement of areal bone mineral density both at lumbar and femoral sites with a mean percentual increase of 1.74% and 0.25%, respectively. Conclusions: Denosumab is an effective treatment for bone disease in KTRs. In our study, the increase in PTH is not a transient event but prolonged throughout the follow-up period and requires continuous supplementation therapy with calcitriol.

Risks and Benefits of Kidney Transplantation during the COVID-19 Pandemic: Transplant or Not Transplant?

COVID-19 has significantly affected the transplant community, by leading to decreased transplant activity and increased waiting list time. As expected, COVID-19 causes substantial mortality in both ESKD and kidney transplant populations. This is due to underlying CKD and a high prevalence of comorbid conditions, such as diabetes mellitus, hypertension, and cardiovascular disease in this group. Transplant programs have faced the difficult decision of weighing the risks and benefits of transplantation during the pandemic. On one hand, there is a risk of COVID-19 exposure leading to infection while patients are on maximum immunosuppression. Alternatively, there are risks of delaying transplantation, which will increase waitlist times and may lead to waitlist-associated morbidity and mortality. Cautious and thoughtful selection of both the recipient's and donor's post-transplant management has been required during the pandemic, to mitigate the risk of morbidity and mortality associated with COVID-19. In this review article, we aimed to discuss previous publications related to clinical outcomes of COVID-19 disease in kidney transplant recipients, patients with ESKD on dialysis, or on the transplant waiting list, and the precautions transplant centers should take in decision making for recipient and donor selection and immunosuppressive management during the pandemic. Nevertheless, transplantation in this milieu does seem to be the correct decision, with careful patient and donor selection and safeguard protocols for infection prevention. Each center should conduct risk assessment on the basis of the patient's age and medical comorbidities, waitlist time, degree of sensitization, cold ischemia time, status of vaccination, and severity of pandemic in their region.