Disease In Kidney Transplant Recipients Research Articles

Barriers and enablers to exercise in kidney transplant recipients: Systematic review of qualitative studies.

Exercise has the potential to reduce the susceptibility to comorbidity and cardiovascular disease in kidney transplant recipients. However, kidney transplant recipients report lower levels of exercise compared to the general population, prompting an investigation into the barriers and enablers to exercise in this transplant cohort. This systematic review aimed to explore and map the barriers and enablers to exercise in kidney transplant recipients. Seven electronic databases were systematically searched. Themes were synthesised and then deductively categorised using the Theoretical Domains Framework. Eleven studies were included in the review. Commonly reported barriers to exercise were lack of exercise guidance (n = 9 studies), physical limitations (n = 5 studies) and a fear of harming the kidney (n = 7 studies). Enablers were a desire to return to normality (n = 5 studies), physical and mental benefits (n = 3 studies), goal setting and tracking improvements (n = 3 studies). At the local level, barriers identified by kidney transplant recipients were a lack of knowledge, fear of injuring the kidney, bad weather and physical limitations. Perceived enablers were already living an active lifestyle, mental benefits, exercise preferences and social support. Key findings of this research were an increased demand for specific/explicit exercise information regarding type and intensity, and personalised guidance and support for kidney transplant recipients after transplantation. These findings can be used to inform the development of exercise resources and interventions for kidney transplant recipients and their health care professionals within the local community and at a greater level.

Cardioprotective effect of SGLT2 inhibitor in diabetic kidney transplant recipients: A multicenter propensity score matched study

BackgroundKidney transplantation improves the cardiovascular outcomes of patients with end-stage kidney disease. However, cardiovascular disease remains the leading cause of premature death and graft loss in kidney transplant recipients (KTRs) with diabetes. We evaluated the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in KTRs with diabetes. MethodsA total of 750 KTRs with diabetes were enrolled from six tertiary hospitals. Among them, 129 (17.2%) patients were prescribed SGLT2i. The primary outcome was the incidence of major adverse cardiovascular events (MACE), which comprised of myocardial infarction (MI), death from cardiovascular causes, hospitalization for heart failure, and stroke. Multivariable Cox regression analysis and propensity score matching were used to investigate the effect of SGLT2i on clinical outcomes. ResultsIn the matched cohort, MACE occurred in 5 (3.9%) patients in the SGLT2i group and 15 (11.8%) patients in the non-SGLT2i group, out of 127 patients in each group over 55.3 months. The incidence of MACE and MI was lower in the SGLT2i group than in the non-SGLT2i group (P=0.036 and 0.008, respectively). In multivariate analysis, the SGLT2i group had a lower risk of MACE and MI than the non-SGLT2i group (adjusted hazard ratio, 0.30 and 0.04; 95% confidence interval, 0.10–0.88 and 0.004–0.40; P=0.028 and 0.006, respectively). There was no difference in the incidence of urinary tract infection between the two groups. ConclusionsSGLT2i significantly decreased the risk of cardiovascular events in KTRs with diabetes, particularly lowering the incidence of MI and death from cardiovascular causes. Therefore, SGLT2i can be used to reduce the burden of cardiovascular disease in KTRs with diabetes.

Post-Transplant Bone Disease in Kidney Transplant Recipients: Diagnosis and Management.

Kidney transplantation is the preferred gold standard modality of treatment for kidney failure. Bone disease after kidney transplantation is highly prevalent in patients living with a kidney transplant and is associated with high rates of hip fractures. Fractures are associated with increased healthcare costs, morbidity and mortality. Post-transplant bone disease (PTBD) includes renal osteodystrophy, osteoporosis, osteonecrosis and bone fractures. PTBD is complex as it encompasses pre-existing chronic kidney disease-mineral bone disease and compounding factors after transplantation, including the use of immunosuppression and the development of de novo bone disease. After transplantation, the persistence of secondary and tertiary hyperparathyroidism, renal osteodystrophy, relative vitamin D deficiency and high levels of fibroblast growth factor-23 contribute to post-transplant bone disease. Risk assessment includes identifying both general risk factors and kidney-specific risk factors. Diagnosis is complex as the gold standard bone biopsy with double-tetracycline labelling to diagnose the PTBD subtype is not always readily available. Therefore, alternative diagnostic tools may be used to aid its diagnosis. Both non-pharmacological and pharmacological therapy can be employed to treat PTBD. In this review, we will discuss pathophysiology, risk assessment, diagnosis and management strategies to manage PTBD after kidney transplantation.

De novo Inflammatory Bowel Disease in Kidney Transplant Recipients: A Single-Center Case Series Study.

Gastrointestinal complications are common after solid organ transplantation. New-onset inflammatory bowel disease (IBD) after transplantation (de novo) is a major differential diagnosis of diarrhea after liver transplantation (LT) because of its high incidence in the field. However, the incidence of IBD after kidney transplantation (KT) remains unknown. This case series comprised six de novo IBD patients who had undergone KT at our hospital from April 1998 to December 2020. In this period, 232 KT recipients were identified. Participants were analyzed based on their colonoscopy diagnoses. Detailed clinical information regarding both KT- and IBD-related symptoms or outcomes was obtained, and we calculated the incidence of de novo IBD from the date of KT. Of the 232 recipients in the median observation period of 6.1 (interquartile range: 2.6, 10.8) years, six recipients (one with Crohn's disease and five with ulcerative colitis) were diagnosed with de novo IBD. The incidence of de novo IBD after KT was 355.8/100,000 person-years (95% confidence interval, 159.8-791.9 per 100,000 person-years). Bloody stools and diarrhea did not always occur, with bloody stools occurring in three and diarrhea in 2 patients at the time of diagnosis. No recipient developed graft failure or extraintestinal complications (e.g., IBD-related nephritis or arthritis). Despite a small sample size, this study's results indicate that the incidence of de novo IBD after KT may be similar to that after LT and higher than that in the general population. Larger studies are required to validate these preliminary findings.

Characteristics of COVID-19 Disease in Renal Transplant Recipients.

Background and Objectives: Kidney transplant recipients are at risk of developing more severe forms of COVID-19 infection. The aim of this study was to compare the clinical course of COVID-19 infection among kidney transplant patients and a control group. Materials and Methods: We examined 150 patients hospitalized with COVID-19 infection. Patients were divided into study (kidney transplant recipients, n = 53) and control (without a history of kidney transplantation, n = 97) groups. Demographics, clinical characteristics, treatment data, and clinical outcomes were assessed. Results: The median patient age was 56.0 (46.0-64.0) years, and seventy-seven patients (51.3%) were men. The median Charlson comorbidity index was higher in the study group (3.0 vs. 2.0, p < 0.001). There was a higher incidence of hypoxemia in the control group upon arrival (52.6% vs. 22.6%, p = 0.001) and a higher NEWS index median (2.0 vs. 1.0 points, p = 0.009) and incidence of pneumonia during hospitalization (88.7% vs. 73.6%, p = 0.023). In the study group, there were more cases of mild (26.4% vs. 11.3%, p = 0.023) and critically severe forms of COVID-19 infection (26.4% vs. 3.1%, p < 0.001), kidney failure was more prevalent (34.0% vs. 1.0%, p < 0.001), and a greater number of patients were transferred to the intensive care unit (22.6% vs. 3.1%, p < 0.001) and died (18.9% vs. 1.0%, p < 0.001). Multivariable analysis revealed that treatment in the intensive care unit correlated with a higher mortality rate than transplantation itself (HR = 20.71, 95% CI 2.01-213.33, p = 0.011). Conclusions: The course of the COVID-19 disease in kidney transplant recipients is heterogeneous and can be more severe than in the general population. Even though patients may be hospitalized with fewer symptoms, complications and death are more likely to occur.

Causes of Original Kidney Disease among Libyan Kidney Transplant Recipients

Abstract Introduction End-stage renal disease (ESRD) has become a significant problem in the North African region. There are few references about the primary causes of ESRD in kidney transplant (KT) recipients. The aim of this study was to determine the causes of the original kidney disease in KT recipients in Tripoli Central Hospital, Tripoli, Libya. Methods This is a hospital-based, retrospective descriptive study. It includes all KT recipients who were followed up in the outpatient clinic, at the Libyan National General Authority for Organ, Tissue, and Cell Transplantation and nephrology clinic in Tripoli Central Hospital during 2021, Tripoli, Libya. Results Data on 360 KT recipients were retrieved. Sixty-eight percent of the of the patients were males: 31.1% of all enrolled individuals were between 31 and 40 years. Patient mean age was 36.66 ± 11.86 years. The most common validated cause for ESRD was unknown (55.3%), followed by chronic glomerulonephritis (CGN; 15%), diabetes mellitus and systemic hypertension each equally (10.3%), congenital abnormalities (3.6%), polycystic kidney disease (3.3%), and nephrolithiasis (1.9%). Conclusion Original cause of kidney disease in most recipients was undetermined, possibly due to limited diagnostic tools or delayed presentation. However, CGN is a main known cause.

Tubulo-interstitial inflammation increases the risk of graft loss after the recurrence of IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN. We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL). A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3years 18.0% vs 45.3%, log-rank 7.588, P=.006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119-4.910, P=.024) independently of other histologic and clinical variables. In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies.

Inflammatory Bowel Diseases and Kidney Transplantation: A Narrative Review of Clinical Management Approaches.

Inflammatory bowel disease is not uncommon among kidney transplant recipients. In transplant patients with chronic diarrhea and abdominal pain, de novo inflammatory bowel disease can be considered among differential diagnoses, after exclusion of infectious causes and drug-induced diarrhea. Inflammatory bowel disease, in the cnnnontext of organ transplant, is associated with a higherrisk of morbidity, increased rate of hospitalization, and higher mortality.Therefore, a multidisciplinary approach, before and after transplant, among a gastroenterologist specialized in inflammatory bowel disease, a gastrointestinal surgeon, and a transplant clinician is essential, given the higher clinical complexity for this subgroup of patients. Limited data are available on management of inflammatory bowel disease in kidney transplant recipients, although the concurrent use of immunosuppressive therapy can mitigate flare-ups but with increased infection risks. Colorectal cancer can be a serious complication of inflammatory bowel disease; hence, patient compliance with regular colonoscopy surveillance programs is crucial. Patients with inflammatory bowel disease who are undergoing kidney transplant have a shorter overall survival rate compared with matched control groups. However, inferences based on studies involving inflammatory bowel disease in kidney transplant recipients are blighted by small sample sizes,thus making it difficult to draw accurate conclusions. Our review was undertaken to comprehensively report the clinical approaches to kidney transplant recipients with inflammatory bowel disease, describing their clinical course, outcomes, and management plan.

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis.

Letermovir has changed the game of primary prophylaxis against cytomegalovirus (CMV) for hematopoietic stem cell transplant (HSCT) and more recently, solid organ transplant recipients. This is largely due to letermovir's similar efficacy in protecting against CMV reactivation and disease, along with its superior safety profile, notably reduced myelotoxicity, and lack of renal dose adjustment compared to standard agents like valganciclovir. This review will describe the potential benefits and clinical considerations of letermovir as prophylaxis among transplant recipients, with a focus on recent evidence describing nonviral outcomes of CMV. Recent evidence has demonstrated improved safety (e.g., less myelosuppression) and tolerability with no difference in rates of CMV infection or disease in kidney transplant recipients given letermovir compared to valganciclovir. Real-world studies and meta-analyses in HSCT populations have explored various nonviral outcomes with letermovir use. Letermovir prophylaxis was associated with reduced mortality, lower rates of graft versus host disease, delayed CMV immune reconstitution, improved tolerability with extended durations, and decreased healthcare utilization. Letermovir is an effective antiviral agent for CMV prevention and has demonstrated enhanced safety, which may allow for extended durations of primary prophylaxis among transplant recipients along with other improved clinical outcomes by mitigating the indirect effects of CMV.

Does Monocyte Chemoattractant Protein-1 Levels Determine the Prognosis of Covid-19 Disease in Kidney Transplant Recipients?

In the normal population, a high monocyte chemoattractant protein (MCP-1) level is an important biomarker for the progression of COVID-19. This study investigated whether MCP-1 level can determine the disease prognosis in kidney transplant (KT) patients with COVID-19. A total of 89 patients, including 49 KT patients (group 1) diagnosed with COVID-19 who required hospitalization, and 40 KT patients who did not have COVID-19 disease (group 2), were included. Demographic characteristics and laboratory results of the patients were recorded. The serum reserved for MCP-1 was stored at -80°C and studied blindly by a single microbiologist at the end of the study. While the mean age of the patients was 51.0 years (40.0-59.50) in group 1, it was 48.0 years (40.75-54.75) in group 2 (P > .05). In terms of the female sex, it was 36 (73.5%) and 27 (67.5%) in group 1 and group 2, respectively (P > .05). Similarly, there was no significant difference between the 2 groups regarding primary disease and basal graft function (P > .05). There was a statistically significant difference in inflammation indicators in group 1 compared with group 2 (P < .05). A correlation was found between inflammation indicators and COVID-19 (P < .05). However, no significant correlation was detected between COVID-19 disease and MCP-1 levels in both groups (P > .05). Also, according to basal MCP-1 levels, we did not find a significant difference between survival and nonsurvival patients (164.0 pg/mL [146.0-202.0] vs 156.0 pg/mL [143.0-173.0], respectively (P > .05). Monocyte chemoattractant protein, an indicator of inflammation, was not found to predict the prognosis of COVID-19 disease in kidney recipients.

Can Fetuin-A Deficiency Predict the Severity of COVID-19 Disease in Kidney Transplant Recipients?

BackgroundThis study aims to investigate whether fetuin A deficiency predicts the prognosis of COVID-19 disease in kidney transplant recipients (KTRs). MethodThe study was conducted on 35 hospitalized KTRs with COVID-19 pneumonia between November 2020 and June 2021. Serums were collected for fetuin-A measurement at admission and after six months of follow-up. The demographic and laboratory data of the patients were recorded and analyzed with the appropriate statistical method. ResultsA total of 35 KTRs, 23 of which (65.7%) were men, were included in the study. The mean age of the patients was 51.6 ± 14.0 years. Seventeen (48.6%) patients had severe disease criteria and required intensive care (ICU) support. Biopsy-proven acute rejection developed in 6 (17.1%) patients in the follow-up. At admission, the median fetuin-A value was 173.5 mcg/mL (143.5-199.25) in the moderate disease group and 126.0 mcg/mL (89.4-165.5) in the severe patient group (p = 0.005). While the Median fetuin-A value at the time of diagnosis was 173.5 mcg/mL (143.5-199.25), and in the 6th month was 208 mcg/mL [184-229] (p<0.001). By ROC analysis, the effect of serum fetuin-A level in predicting the severity of COVID-19 disease was significant (AUC: 0.771, p = 0.006, 95% CI: 0.615-0.927). When serum fetuin-A cut-off value was taken as 138 mcg/mL to determine disease severity, it was shown to have 83.3% sensitivity and 64.7% specificity. ConclusionsSerum fetuin-A level can predict disease severity in kidney transplant recipients in the presence of active COVID-19 disease.

The Outcome of COVID-19 Infection on Kidney Transplantation Recipients in Southern Saudi Arabia: Single-Center Experience

To report the incidence, risk factors, and outcome of severe COVID-19 disease in kidney transplant recipients attending a Saudi hospital at a single center in the Kingdom of Saudi Arabia. A retrospective chart-based cohort study involving all kidney transplant recipients tested for COVID-19 in the Armed Forces Hospital Southern Region, KSA. Of 532 kidney transplant recipients who reported to the center, from March 2020 to June 2022, 180 were tested for COVID-19. Of these recipients, 31 (17%) tested positive. Among the 31 positive recipients, 11 were treated at home, 15 were admitted to the noncritical isolation ward, and 5 were admitted to the intensive care unit (ICU). Older age (P=.0001), higher body mass index (P=.0001), and history of hypertension (P=.0023) were more frequent in the COVID-19-positive recipients. Admission to the ICU was more frequent in older recipients (P=.0322) with a history of ischemic heart disease (P=.06) and higher creatinine baseline (P=.08) presenting with dyspnea (P=.0174), and acute allograft dysfunction (P=.002). In the ICU group, 4 (80%) patients required hemodialysis, and 4 (80%) died. Kidney transplant recipients with COVID-19 could have a higher risk for developing acute kidney injury, dialysis, and mortality than the general population. ICU admission and renal replacement therapy were more evident in older recipients with a history of ischemic heart disease, presenting with shortness of breath (P=.017) and a higher serum creatinine baseline. Acute allograft dysfunction was the independent predictor of mortality among patients admitted to the ICU.

Prevalence of metabolic dysfunction-associated fatty liver disease in kidney transplant recipients: A cross-sectional study using FibroScan.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is expected to be prevalent among kidney transplant recipients (KTRs). In this study, we evaluated the prevalence of MAFLD among KTRs, data that have not been investigated by any clinical study to date. We included a total of 52 KTRs and 53 age-, sex-, and BMI-matched individuals as the control group through prospective consecutive recruitment. We detected the presence of hepatic steatosis and liver fibrosis using the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) defined by FibroScan. Among the KTRs, 18 (34.6%) had metabolic syndrome. The prevalence of MAFLD among the KTRs and controls was 42.3% and 51.9%, respectively (p=0.375). The CAP and LSM values did not differ significantly between the KTRs and controls (p=0.222 and p=0.119). Among the KTRs, patients with MAFLD had significantly higher age, BMI, waist circumference, LDL, and total cholesterol levels (p<0.001, p=0.011, p=0.033, p=0.022, and p=0.029, respectively). In multivariable analysis, age was the only independent factor for MAFLD among the KTRs (OR: 1.120, 95% confidence interval (CI): 1.039-1.208). MAFLD among KTRs did not show a significantly higher prevalence compared to the normal population. Further clinical studies with larger populations are needed.

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 &amp;lt; 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 &amp; Dohme: Grant/Research Support|Merck Sharp &amp; 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 &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc.,: Stocks/Bonds Valerie L. Teal, MS, Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc.,: Current Employee|Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc.,: Stocks/Bonds Christopher L. Gilbert, n/a, Current employee of Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc.,: Stocks/Bonds Barbara A. Haber, MD, Current employee of Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; 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