Post-renal Transplant Recipients Research Articles

Evaluation of new-onset BK viruria in post-renal transplant recipients by quantitative PCR

BackgroundThe BK polyomavirus infection poses a substantial challenge for organ transplant recipients due to immunosuppression, resulting in BK virus-associated nephropathy (BKVAN) and a considerable risk of graft loss. Screening and prompt decrease of immunosuppression are essential for averting these consequences. We examined the frequency of BK viruria (viral load in urine) among post-renal transplant recipients, along with its association with age, viral load, and the timing of viral reactivation. MethodsThe prospective cohort study was conducted at the Tertiary Care Hospital in Rawalpindi over a 12-month period, from January 1 to December 31, 2023. Urine specimens from 108 renal transplant recipients were collected and analysed for BK viruria every three months during the follow-up assessments. DNA extraction was performed using TANbead extractor, and amplification was carried out with Bio-Rad CFX-96 thermal cycler using Sacace TM amplification kit. Data was analysed using SPSS version 27. ResultsIn the cohort of 108 renal transplant recipients, BK viruria was detected in 16.7 % of cases. There was a higher prevalence of BK viruria in females (20 %) than males (16 %). The majority of positive cases were within the 41–60 years age group (61.1 %). Most of the patients (66.6 %) had viral loads below 1 million copies/ml. BK viruria was predominantly detected during the third quarter (between 7 and 9 months) post-transplant. The Chi-square test was applied between age and viral load, showing a significant association (p = 0.01). Similarly, gender and viral load also showed a significant relationship (p = 0.019). ConclusionThe study showed the frequency of 16.7 % of BK viruria in our small cohort after renal transplantation during the initial 12 months post-transplant. Age of recipients correlated with viral load and time of viral reactivation: middle-aged recipients had higher viral loads. BK viruria increased progressively over the initial nine months, with peak incidence in the third quarter post-transplant.

Thrombotic Microangiopathy in Renal Transplant Recipients

Background and Aim: Thrombotic microangiopathy (TMA) is a disease of microvasculature, triggered by numerous immunological and nonimmunological factors. The aim of this study is to identify the incidence, etiology, and clinical characteristics of posttransplant TMA in renal allografts and its impact on graft outcome. Patients and Methods: In this retrospective study, the records of patients who underwent renal transplantation between January 2013 and December 2017 were reviewed, and those recipients who had allograft biopsy-proven TMA were analyzed. Based on the clinical characteristics and investigations, the recipients were divided into two groups: those with systemic features of TMA and those with allograft-limited TMA. The clinical course and graft outcome of both the groups were compared and analyzed. Results: The number of patients who underwent renal transplantation during the study period was 212. Out of them, 16 patients had biopsy-proven TMA. Five patients had TMA with systemic features and the remaining 11 patients had allograft-limited TMA. In this study, the incidence of TMA among postrenal transplant recipients was 7.5%. The most common cause for TMA was acute antibody-mediated rejection (ABMR), followed by TMA due to tacrolimus toxicity. In one patient, TMA was secondary to disseminated tuberculosis (TB). TB as a cause of TMA is rarely reported. One-year graft survival in patients with allograft-limited TMA was 72.7% when compared to 50% in patients with systemic TMA, but this difference was statistically insignificant (P = 0.2). The graft loss was high in patients with TMA secondary to ABMR in both the groups. Conclusion: One-year graft survival is better in patients with allograft-limited TMA. Diligent search for an etiology for TMA should be made in all patients with TMA, as the treatment differs between each category.

Point-of-care-ultrasound for the assessment of post-renal transplant recipients.

Postoperative imaging for deceased donor renal transplants is often delayed, as these surgeries occur after-hours. These delays can be critical in identifying immediate complications. To our knowledge, there are no formal training programs for point-of-care ultrasound (POCUS) in this setting; therefore, we aimed to develop and evaluate a feasible and practical POCUS curriculum for the assessment of a renal transplant graft. Urology and nephrology transplant physicians completed a three-hour online course, followed by a five-hour hands-on seminar for sonographic scanning. Simulated patients with transplanted kidneys were used. Course material was developed with licensed ultrasound technologists based on Sonography Canada national competency profiles. Pre- and post-course surveys focused on user confidence, while pre- and post-course multiple-choice questionnaires assessed theoretical knowledge. Twelve participants were included, six of whom were urologists. Theoretical knowledge in POCUS improved significantly (p<0.001). Confidence in manipulation of ultrasound controls, Doppler imaging, and POCUS of the transplant kidney also improved (all p<0.001, d>2.0). Participants indicated an increased likelihood of POCUS use in clinical practice and that training should be integrated into a transplant fellowship. We introduced a novel and guideline-based POCUS curriculum that leveraged local ultrasound educators and found improved theoretical knowledge and skill confidence in our cohort of transplant physicians. This course will serve as the first step toward a validated competency-based training system for POCUS use in the immediate post-renal transplant setting, and likely will be incorporated into the training of the modern transplant physician.

Cytomegalovirus Reactivation in Postrenal Transplant Patients Immediately in Association with Coronavirus Disease 2019 (COVID-19) Infection: A Case Report of 2 Patients and a Brief Review of the Literature

Introduction: The coronavirus disease 2019 (COVID-19) infection has been associated with multiple opportunistic infections, including secondary cytomegalovirus (CMV) reactivation. Several cases of CMV syndrome and invasive CMV infection have been reported following severe COVID-19 infection worldwide during the COVID-19 pandemic in both immunocompetent and immunosuppressed patients. A case-control study conducted in India showed that during the first and second waves, CMV was the most common co-infection among fatal cases of severe COVID-19 lung infection in Indian renal transplant recipients. Case Presentation: We present 2 cases of CMV disease in postrenal transplant patients who developed clinical manifestations of CMV co-infection after mild COVID-19 infection during the fourth wave of COVID-19 infection in India. In both cases, CMV infection was treated by discontinuing mycophenolate mofetil and administering ganciclovir injections. However, the treatment resulted in 2 contrasting clinical outcomes: Cure and death. Conclusions: We reviewed the recent literature on the increased incidence of CMV reactivation after both COVID-19 infection and vaccination in immunocompetent and immunocompromised populations. Subsequently, we discussed some clinical questions relevant to the population of postrenal transplant recipients after the detection of mild COVID-19 infection.

#6846 CHRONIC CMV DIARRHOEA IN RENAL TRANPLANT RECIPIENTS - AN UNDERRECOGNISED SPECTRUM OF COMPARTMENTALISED GUT INVASIVE CMV DISEASE

Abstract Background and Aims Chronic diarrhoea in post-renal transplant recipients due to Cytomegalovirus (CMV) presents as Blood CMV PCR (polymerised chain reaction) positive chronic diarrhoea and Gut-invasive (rectal tissue PCR positive, blood PCR-negative) compartmentalised CMV. The available literature on compartmentalised gut CMV is scarce. The aim is to study the clinical presentation and outcome of patients with compartmentalized gut invasive CMV when compared with Blood CMV positive chronic diarrhea in renal transplant recipients. Method This is a retrospective single-centre follow-up study of patients with CMV disease who were transplanted between 2000 and 2020. Diagnostic variables like blood CMV PCR (polymerised chain reaction) positivity with constitutional symptoms, presence or absence of chronic diarrhoea, tissue PCR positivity and site of tissue biopsy were given harmony codes and 6 syndromes were identified – CMV diarrhoea (Blood PCR positive, presence of diarrhoea), compartmentalized gut invasive CMV (Blood PCR negative, presence of diarrhoea, rectal tissue quantitative CMV PCR positive), Acute CMV syndrome, CMV Esophagitis, CMV nephropathy, CMV cystitis. Out of which patients presenting with diarrhoea (first two groups) were included for analysis. The baseline descriptive statistical measures were carried out using analysis of variance. The time to CMV disease from transplant was computed by identifying the pattern of distribution at 10%, 50% and 90% between groups using reliability models. The time to death from diagnosis was analyzed by identifying the pattern by parametric log-logistic distribution. Survival analysis was done by a parametric reliability model identifying location, scale and threshold parameters, from which month-wise prediction of probabilities was found for survival. The proportion of adverse outcomes (relapse, death and graft loss) between the two groups were analyzed by one-way ANOVA and Tukey pairwise comparison. All the patients were followed up till death or last follow-up. Results Out of 2208 renal transplants done between 2000 and 2020, 118 (5.3%), patients developed CMV disease. Chronic diarrhoea was the presentation in 88 (57%), of which 47 had manifestations of CMV diarrhoea, and 41 had compartmentalized gut CMV. Induction agents used (CMV diarrhoea Vs compartmentalized gut CMV) were basiliximab (51% Vs 56%), ATG (27% Vs 17%), Grafalon (0% Vs,2.4%) and no induction (21%,24%). Only 31.9% and 26.8% received Valganciclovir prophylaxis for pre-specified indications respectively. The time to CMV diagnosis from transplant for 10%, 50% and 90% of patients (in months) was 12,63,154 for CMV diarrhoea;12,52 and 139 months for compartmentalized gut CMV. The mean duration (weeks) of diarrhoea was similar in both groups (7 Vs 7.3). Associated opportunistic infections causing diarrhoea were higher in compartmentalized gut CMV (28% Vs 46% p = 0.08); the commonest being cryptosporidium. Quantitative PCR in the blood ranged from 1245 to 2511345 copies/ml; whereas in gut tissue, it ranged from 1325 to 3517920/25 mg. The major histopathological finding in compartmentalized gut CMV was active inflammatory pathology in 34 (83%) patients. The probability of survival was significantly lower (72.6%; CI 60% to 83%) in CMV diarrhoea when compared with compartmentalized Gut CMV (87.2%; CI 76% to 94%) for initial 12 months (p&amp;lt;0.05); however at 5 years (56.2%, Vs 58.5%) and 10 years (48.5% Vs 42.7%) the survival was similar. Compartmentalized gut CMV was associated with a higher relapse rate (19.5%) when compared with CMV diarrhoea (6.4%) on follow-up (p = 0.06). The mortality (36% Vs 29%; p = 0.490) and graft loss (25% Vs 22%; p = 0.692) were similar between both the group. Conclusion Compartmentalized gut invasive CMV represents a larger proportion of chronic diarrhoeal illness with a higher relapse rate, which needs invasive gut tissue PCR analysis, despite negative blood PCR, for early diagnosis and management.

Dietary quality indices and recurrent chronic kidney disease in Taiwanese post-renal transplant recipients.

This study investigated the association between dietary quality indices and recurrent chronic kidney disease (rCKD) in Taiwanese post-renal transplant recipients (RTRs). This prospective study recruited RTRs aged >18 years with a functioning allograft and without any acute rejection in the past 3 months from September 2016 to June 2018. Dietary quality indices included the Alternative Healthy Eating Index (AHEI) and AHEI-2010, and the Taiwanese version of the AHEI (AHEI-Taiwan) was calculated using 3-day dietary records, and calculated scores were divided into quartiles. Laboratory data were collected from medical records. rCKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the associations. This study included 102 RTRs. The RTRs with higher AHEI, AHEI-Taiwan, and AHEI-2010 scores were older and had higher eGFRs and lower odds of rCKD. As compared with the lowest quartile, patients with the highest quartiles of the AHEI [odds ratio (OR), 0.10; 95% confidence interval (95% CI): 0.02, 0.49; p-trend = 0.004), AHEI-2010 (OR, 0.17; 95% CI: 0.04, 0.72; p-trend = 0.016], and AHEI-Taiwan (OR, 0.13; 95% CI: 0.03-0.59; p-trend = 0.008) had lower odds of rCKD, respectively. As compared with the lowest quartile, patients who consumed the highest quartiles of red and processed meat had 11.43 times higher odds of rCKD (OR, 11.43; 95% CI: 2.30-56.85; p for trend <0.01). Higher dietary quality indices are associated with lower odds of rCKD in Taiwanese RTRs. Particularly, a positive association between a higher intake of red meat and processed meat and higher odds of rCKD remained exists after transplantation in Taiwanese RTRs. Further dietary guidelines and individualized dietary education were necessary for RTRs to prevent graft function deterioration.

1259. Bictegravir or Dolutegravir-Containing Antiretroviral Regimens in Solid Organ Transplantation: Single-Center Experience

Abstract Background Solid organ transplantation (SOT) is the definitive treatment for end-organ failure in HIV-positive recipients. Bictegravir (BIC) or dolutegravir (DTG) based antiretroviral therapy (ART) is the preferred ART due to high efficacy, excellent tolerability and minimal drug interactions, yet there is a paucity of data on these second generation integrase inhibitors (INSTIs) in SOT. We report the Memorial Transplant Institute’s experience using second generation INSTI-containing ART with or without emtricitabine/tenofovir alafenamide (FTC/TAF) in persons with HIV. Table 1.Demographics and clinical features of 16 patients with HIV undergoing solid organ transplantation (SOT).3TC: lamivudine; AA: African American; BIC: bictegravir; DTG: dolutegravir; F: female; FTC: emtricitabine; H: Hispanic/Latino/a/x; IN: integrase; M: male; NH: Non-Hispanic/Latino/a/x; PR: protease; RPV: rilpivirine; RT: reverse transcriptase; SOT: solid organ transplantation; TAF: tenofovir alafenamide; W: whiteTable 2.Clinical course of 8 patients with HIV after solid organ transplantation (SOT).3TC: lamivudine; ABC: abacavir; ART: antiretroviral therapy; ATV: atazanavir; BIC: bictegravir; c: cobicistat; DTG: dolutegravir; DRV: darunavir; eFGR: estimated glomerular filtration rate; ETR: etravirine; FTC: emtricitabine; r: ritonavir; RAL: raltegravir; RPV: rilpivirine; RTV: ritonavir; SOT: solid organ transplantation; TAF: tenofovir alafenamide Methods This single-center observational study compiles data from medical records of all persons with HIV undergoing SOT seen by the Division of Infectious Disease from January 2017 through April 2022. We report clinical information and ART management of SOT candidates and recipients in our center. Results Sixteen patients met inclusion criteria: 8 SOT candidates (7 kidney, 1 heart) and 8 SOT recipients (all kidney). Demographics are presented in Table 1. Patients were 63% male with a mean age of 55 years, CD4 323 cells/mm3, and living with HIV for 16 years. ART regimens were BIC/FTC/TAF (50%), DTG/rilpivirine (RPV) (19%), DTG + FTC/TAF (19%) and RPV/FTC/TAF + DTG (6%), and DTG/lamivudine (6%). All pharmacokinetic enhancers were discontinued to avoid drug interactions with anti-rejection medications. Last on-treatment HIV RNA was &amp;lt; 200 copies/mL for 100% of patients. The clinical course of 8 post-renal transplant recipients is presented in Table 2. The most common post-SOT regimen was BIC/FTC/TAF. Post-SOT patients maintained HIV RNA &amp;lt; 200 copies/mL. No ART-related adverse effects were documented. Two allograft- or life-threatening infections and one episode of acute antibody rejection was reported. Expectedly, serum creatinine decreased and estimated glomerular filtration rate increased post-renal transplant. Conclusion We provide additional insight into the use of BIC- and DTG-containing ART with or without FTC/TAF in the peri-SOT period. Our growing experience suggests second generation INSTI-containing ART regimens with or without FTC/TAF are effective and well tolerated following kidney transplantation. Additional research on the use of second generation INSTIs in the SOT patient population is needed. Disclosures All Authors: No reported disclosures.

P393 Clinical spectrum and molecular characterization of Rhytidhysteron spp. (now Gloniopsis) from India

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective Rhytidhysteron spp. are emerging dematiaceous fungi implicated in subcutaneous infections in immunocompromised as well as immunocompetent individuals. Diagnosis of Rhytidhysteron spp is delayed owing to non-sporulation and misidentification. The present study was conducted to characterize Rhytidhysteron spp. isolated from India by molecular techniques.MethodWe retrieved a total of eight isolates of Rhytidhysteron spp from our National Culture Collection for Pathogenic Fungi (NCCPF) that were received from various centers across India. Colony morphology on Sabouraud's dextrose agar (SDA) and potato dextrose agar (PDA) was recorded. Molecular identification was performed by sequencing internal transcribed spacer (ITS) and 28 s region of rDNA. Phylogenetic tree was constructed using the Neighbor-Joining method along with sequences of standard strains retrieved from the NCBI database.Results Rhytidhysteron spp was confirmed by sequencing from cutaneous specimens of eight cases. Six patients were immunocompetent while two were post-renal transplant recipients. Phenotypic features on SDA and PDA revealed growth of greyish-black mycelia on the obverse with black pigmentation on reverse after 7 days of incubation. On microscopic examination of lactophenol cotton blue mount, only dematiaceous septate hyphae without any spores were noted. On phylogenetic analysis of 28 s region, four of our isolates were closely clustered with Gloniopsis calami (Fig.1b), whereas two isolates with G. pneumonia and one each with G. percutanea, and Gloniopsis spp. (Fig.1b). On ITS phylogeny, the same four isolates closely clustered with G. calami (Fig.1a) as in 28 s region, one each isolate clustered with G. pneumonia, and G. percutanea while two isolates formed a separate clade with Rhytidhysteron rufulum (Fig.1a).ConclusionThis fungus is often difficult to identify due to lack of sporulation making morphological identification challenging. Therefore, molecular sequencing is a must for its identification. However, identification using the sequence of ITS and 28 s rDNA does not clearly correlate. Hence to confirm the identity additional genes needs to be sequenced and analyzed.

A Cross-sectional Prospective Study of Pleural Effusion Among Cases of Chronic Kidney Disease

Pleural effusions of diverse aetiologies are encountered in patients with chronic kidney disease (CKD). The objectives of the present study were to examine the frequency of occurrence, causes, clinical features and management strategies of pleural effusion in patients with CKD including renal transplant recipients. A prospective cross-sectional observational analysis of pleural effusion in adult patients with CKD (stages 3 to 5) attending the Departments of Nephrology and Respiratory Medicine of a tertiary care institution in Eastern India was performed over a period of one year (February 2010 to January 2011). Pleural effusion was found in 29 out of 430 patients with CKD (6.7%) and in two out of 34 post-renal transplant recipients (5.9%) evaluated during the study period. The mean age was 37.35 +/- 1.8 (mean +/- SEM [standard error of mean]) with a male to female ratio of 2:1. Exudates and transudates were found in equal frequencies. Heart failure was the single most common cause (41.9%, 13 of 31). Tuberculosis (TB) (n = 8, 25.8%) and uraemic effusions (n = 6, 19.4%) were responsible for the majority of exudates. Unilateral effusion with a normal heart size had a positive predictive value of 83.3% for non-heart failure aetiology. Symptomatic pleural effusion was present in a small proportion of 6.7%; (n = 29) patients with CKD including post-renal transplant recipients. Heart failure, TB and uraemic effusions accounted for most of the cases. Differentiating TB from uraemic effusion requires a combined clinico-pathological approach and this differentiation is absolutely necessary for proper management.

Content Validity of a Self-Management Behavior Assessment Tool for Adult Post-Renal Transplant Recipients Using a Modified Delphi Method

Background: Self-management is important for post-renal transplant recipients to resolve renal dysfunction, heart failure, and post-transplant psychosocial issues, and to maintain transplant kidney function, etc. However, because recipients may be unable to adequately self-manage, healthcare providers need to provide self-management support for recipients to improve their skills and confidence in managing their disease. However, it is difficult to comprehensively assess the self-management behaviors in a busy outpatient support setting. Furthermore, since there are no uniform standards for assessment, it is based on the experience and abilities of medical personnel. Therefore, self-management behavior of post-renal transplant recipients is not sufficiently evaluated. Objective: This study aimed to evaluate content validity of a tool that can assess self-management behaviors of adult post-renal transplant recipients, consisting of consensus components from experts familiar with the follow-up of adult post-renal transplant recipients. Methods: A three-round modified Delphi method was used to assess the self-management behaviors of adult post-renal transplant recipients by a panel of experts consisting of certified transplant recipient coordinators, physicians, outpatient nurses, and researchers familiar with the follow-up of post-renal transplant recipients. Regarding management behaviors of adult post-renal transplant recipients, the experts rated the appropriateness and validity of each item using a Likert scale. Consensus ratings from the experts were made by calculating the median, interquartile range, and interquartile range percentage. In the third round, an item-level content validity index was calculated to assess content validity. Conclusions: The 41-item self-management behavior scale for kidney transplant recipients assessed self-management behaviors in five domains: medication, exercise, fluids and diet, disease and symptom prevention and management, and psychosocial adjustment. The content validity of this tool was confirmed, and it can be used to more easily assess the recipients’ self-management behaviors in the post-renal transplant follow-up. This tool can potentially contribute to the maintenance of transplant kidney function and high QOL in recipients.

Echocardiographic manifestations in patients on renal replacement therapy and renal transplant recipients

Background: Chronic kidney disease (CKD) patients have 20–30 times greater risk of cardiovascular morbidity and mortality. Echocardiography is quintessential in cardiovascular evaluation and monitoring in CKD patients. This study was designed to determine the echocardiographic manifestations in patients on renal replacement therapy (RRT) and recipients of renal transplantation. Materials and Methods: An observational cross-sectional study was undertaken in a tertiary care hospital. All CKD patients on RRT or post renal transplant were included. Patients with known cardiac disease, malignancy were excluded. Demographic details, thorough history, physical examination and 2D echocardiography were performed for the patients. Results: Of the 51 patients, 60% were on dialysis and remaining were post renal transplant recipients. The mean age of study population was 44.16±13.66 years, with 64.7% males. 47% of patients were of age group of 41 years to 60 years. The most common etiology of CKD was hypertension in 16 (31.4%) followed by diabetes in 11 (21.6%). Only 8 patients (15.7%) had normal echocardiograms. LVH (80.4%) was most common abnormality, followed by diastolic dysfunction (74.5%), systolic dysfunction (13.7%), mitral regurgitation (13.7%) and pericardial effusion (5.8%). Around 95.2% had concentric hypertrophy. Diastolic dysfunction was observed in 90.2% and 80.9% of cases with LVH and hypertension respectively and was significantly associated with both (p=0.001, p=0.003 respectively). Conclusions: Left ventricular hypertrophy was the most common abnormality in CKD patients and renal transplant recipients. Diastolic function was affected in majority of patients. Early identification of cardiac abnormalities by echocardiography prior to manifestation of cardiac complications may result in better prognosis for this patient population.

Endovascular management of vascular complications in renal allograft - An observational study

Context: Role of endovascular management of vascular complications in renal transplant recipients. Aims: To present our experience in endovascular management of vascular complications in renal transplant recipients with a literature review. Settings and Design: A retrospective observational study. Materials and Methods: This is a retrospective analysis of postrenal transplant recipients referred to our department for the evaluation and endovascular management of vascular complications from January 2010 to December 2014. Cases of transplant renal artery stenosis (TRAS) and common iliac artery (CIA) stenosis were treated with percutaneous transluminal balloon angioplasty with or without stenting. Intraparenchymal pseudoaneurysms, arteriovenous fistula (AVF), and active contrast extravasation cases were managed with coil and/or glue embolization. Treated patients were followed up with serial blood pressure measurements, serum creatinine estimation, and Doppler evaluation in the postprocedure period and at 3-month and 6-month intervals. Results: Among a total of ten patients, there were five TRAS, two intraparenchymal pseudoaneurysms with active contrast extravasation, one AVF, one active renal bleed with peri-graft hematoma, and one right CIA stenosis. Intraparenchymal pseudoaneurysms, AVF, and active extravasations were postbiopsy. All treated patients showed improved renal function, increased hematocrit, improved blood pressure control in the postprocedure period, and follow-up. Conclusions: Vascular complications in renal transplant patients may lead to graft dysfunction, increased morbidity, and even graft loss if left untreated. Endovascular interventions are first-line treatments with excellent short- and long-term outcomes.

Dietary Nutrients and Cardiovascular Risk Factors among Renal Transplant Recipients.

Cardiovascular disease (CVD) is the leading cause of mortality in post-renal transplant recipients (RTRs). Adequate nutrient intake is a protective factor for CVD. We examined the associations of macronutrients and micronutrients with traditional and nontraditional CVD risk factors. Conducted from September 2016 to June 2018, this cross-sectional study included 106 RTRs aged ≥18 years with a functioning allograft. Dietary intake data from 3-day dietary records were collected. Nutrient intake adequacy was defined using various instruments, including the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. CVD risk factors were defined according to the K/DOQI guidelines. Bivariate and multivariate logistic regression models were used to analyze the associations. CVD risk was present in all patients; the lowest proportions of adequate intake were 2.8% for dietary fiber and 0.9% for calcium. Adequate nutrient intake was associated with a lower likelihood of the occurrence of traditional CVD risk factors (specifically, 1.9–31.3% for hyperlipidemia and 94.6% for diabetes mellitus). It was also associated with a lower likelihood of the occurrence of nontraditional CVD risk by 0.8% for hypophosphatemia and 34% for hyperuricemia. Adherence to dietary guidelines should be promoted among RTRs to decrease CVD risk.

The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients.

The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C0/D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients. Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C0/D at 5, 10, 15, and 30days after transplantation. Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C0/D than those with the TC/CC genotype (p < 0.05). Additionally, the TAC C0/D values of recipients with the capacity for low IL-10 activity (-819 TT) engrafted with CYP3A5 non-expressers were higher compared to the intermediate/high activity of IL-10 -819C > T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p < 0.05). Genetic polymorphisms of IL-10 -819C > T and CYP3A5 6986A > G influence the TAC C0/D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period.

Incidentally detected isolated Aspergillus fumigates infection of the renal allograft

Fungal infection represents 5% of the infections of post renal transplant recipients. The frequency of invasive Aspergillus ranges from 0.5% to 2.2% with a mortality rate of 88%. In renal transplantation, Aspergillus infection usually affects primarily the lungs with occasional dissemination and the central nervous system. Involvement of a renal allograft in the isolated form is rare. A-35-year-old male post-renal transplant patient presented in our institute for routine follow up examination. Ultrasound and computed tomography (CT) were conducted in our radiology department, suggestive of abscess formation in mid pole of transplanted kidney. The patient did not have any clinical symptoms. His serum creatinine level was also within normal limit. Diagnosis of Aspergillus fumigates was made by aspiration of pus. Treatment started according to culture and sensitivity report. Ultimately graft nephrectomy was performed to control infection. Aspergillus infection of a renal allograft remains a key issue for nephrologists and infection specialists. For diagnosis of fungal infection, a high index of suspicious is necessary. In the present case, the infected allograft nephrectomy and the elimination of immune-compromised state and the prompt administration of antifungal therapy, made recovery possible. However, early diagnosis remains difficult.

Preemptive HLA Antibody Screening Prior to Episodic Transplant Renal Biopsy Enables Early Diagnosis and Therapeutic Response in Asymptomatic Chronically Active Antibody-Related Rejection: A Case Report

Common management of renal transplant recipients includes episodic renal biopsy based on clinical findings such as an increase in proteinuria or serum creatinine. When antibody-related rejection is suspected from the renal biopsy, subsequent testing for donor-specific antibodies (DSAs) is performed. We instead performed preemptive screening of asymptomatic post–renal transplant recipients for DSAs prior to renal biopsy. In this case, a 30-year-old woman with a secondary transplant was positive for 61 anti-HLA antibodies of class I and class II, among which DQ2 was a DSA with a mean fluorescence index of 2039. The patient had a living kidney transplant 9 years earlier. She had never been diagnosed with rejection, her serum creatinine was around 1.0 mg/dL, and her proteinuria was negative. Following the positive DSA result, a renal biopsy was performed, and she was diagnosed as C4d-negative chronic-active antibody-mediated rejection (CAABMR) with a Banff score of cg1b, (g + ptc) ≥ 2, and C4d 0. Intravenous steroid pulse, deoxyspagarin, antithymocyte globulin, rituximab, and oral everolimus were administrated. The treatment resulted in a gradual decrease in the DSA, which became negative 1 year later. The patient’s serum creatinine remains around 1.0 mg/dL, and proteinuria remains negative. Treatments for advanced CAABMR are often expensive and ineffective. Our present case suggests that early detection and treatment through preemptive HLA antibody screening could improve the prognosis of renal transplants.

Cytomegalovirus Infection in Postrenal Transplant Recipients: 18 Years’ Experience From a Tertiary Referral Center

BackgroundCytomegalovirus (CMV) reactivation or infection is one of the most important infectious complications in transplant recipient leading to significant morbidity and mortality. Its early detection and prompt treatment is imperative to improve transplant outcome. The present study estimated the frequency of CMV in renal transplant recipients (RTR). Various aspects of pp65Ag assay and quantitative real-time polymerase chain reaction (qRT-PCR) were evaluated in relation to the recent guidelines for CMV detection and treatment. MethodsRetrospectively, data of clinically suspected cases of CMV (1610 out of total 2681 renal transplants) were analyzed along with a comparison of pp65Ag assay and qRT-PCR. ResultsThe overall incidence of CMV syndrome was 14.25%; however, the incidence of CMV viremia in the clinically suspected group was 23.73%. The proportion of positive cases with pp65Ag assay and qRT-PCR were 13.6% (95% CI; 7.9-22.3) and 19.3% (95% CI; 12.4-28.8) with a substantial agreement (Cohen’s kappa = 0.632) between the 2 techniques. CMV positive recipients were treated with ganciclovir until their viral count was negative or up to 3 weeks, followed by 3 months of prophylaxis with valganciclovir. No graft failure or mortality was reported secondary to CMV infection until 3 to 5 years of follow-up. ResultsCMV infection is quite prevalent in RTR, and early detection and immediate treatment or prophylaxis is of utmost importance. qRT-PCR is the gold standard and preferred over other methods; however pp65Ag assay still holds its importance in low-economic countries and populations where CMV infection is more prevalent and financial constraints are a major limitation.

BK polyomavirus genotypes and progression of BKV disease in renal transplant recipients

Background. BK virus (BKV) reactivation is a significant cause of BK Polyomavirus associated nephropathy (BKPyVN) resulting in acute graft rejection in 1-10% of post-renal transplant recipients. However, the association of BKV genotypes with development of BKPyVN is poorly understood. Here we aimed to determine the prevalence of BKV genotypes in post-renal transplant recipients, and its association with BKPyVN disease progression. Method. Two methods were utilised to genotype BKV. A 800bp fragment of virus VP1 antigen region was amplified using nested (PCR) followed by sequencing. The genotypes were determined according to a previously developed algorithm based on analysing 100bp region of the VP1 gene. Furthermore, the logarithm results were validated with the constructed phylogenetic tree. The results were correlated with patient viral loads and development of BKPyVN. Results. BK virus DNA was detected in 32 (69%) of 46 post-renal transplant recipients with BK viremia, while BKPyVN was only reported in two (4.3%)patients. 30 out of 32 samples were successfully genotyped (93.7%) with 23 (76.6%) belonging to the BKV Ib-2 subtype and seven (23.3%) belonging to the BKV Ib-1 subtype and with no cases representing genotype II, III and IV. All cases with confirmed BKPyVN matched to the BKV Ib-2 genotype. Additionally, no significance differences were observed between BKV genotypes in regards to viral loads, development of viremia, HLA mismatch, age or sex. Conclusion. The results indicate no correlations between BKV genotypes and the development of BKPyVN. Furthermore,a high distribution of BKV genotype Ib-2 was found among BKV infected patients within this cohort.

Urolithiasis in post renal transplant recipients: Case series

Renal transplantation represents the optimal management option for end-stage renal disease. it is associated with favourable outcome. Urolithiasis after renal transplant is an extremely rare condition, with an incidence less than 1% after renal transplantation.We reported six post renal transplant patients who had renal stones. The stones located in the transplanted kidney, its ureter or both. Transplanted kidney and ureteric stones had been reported 2 – 3 years after transplantation, while the urinary bladder calculi reported 8 – 10 years after transplantation, at the site of ureteral implantation to the bladder over the site of sutures and in the absence of any post-transplant complications. A written consent has been signed by the patient to release information for this study. The treatment was individualized for each patient. Interestingly, one patient with asymptomatic post-transplant renal stone needs no intervention “we watched and see” and he passed the stone within shortest follow up period that confirmed by ultrasound examination. Others, underwent extracorporeal wave lithotripsy or percutaneous nephrostomy and antegrade double-J stent insertion.

Association Between Polymorphisms in Cytokine Gene and Viral Infections in Renal and Liver Transplant Recipients: A Systematic Review.

Although transplantations are associated with an increased risk of post-transplantation infections, they greatly improve life expectancy and patients' quality of life. Cytokine genes play an important role in the success of transplants due to their immunological functions. A systematic review was conducted to evaluate cytokine gene polymorphisms and risk of cytomegalovirus (CMV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in kidney and liver transplant recipients. A systematic search was conducted using PubMed, EMBASE, Medline and Google Scholar from their inception until January 28, 2019 using appropriate key words. Review articles, case reports or series, studies conducted on non-human subjects and published in languages other than English were excluded. Data were abstracted using a standardized form. The quality of the studies included was assessed using "Risk of Bias Assessment tool for Non-randomized Studies (RoBANS)". Thirty-one studies met our inclusion criteria; populations studied were diverse with a sample ranging from 20 to 1,671. Nineteen studies evaluated Interleukin (IL)-28B polymorphism, while six studies evaluated interferon lambda (IFN-λ) gene polymorphisms and their impact on CMV, HCV, and HBV progression. Polymorphisms in IL-10 gene were investigated in six studies. Polymorphisms in IL-12B and IL-1B gene were associated with a higher risk of developing CMV infections while polymorphisms in IL-28B were associated with a lower incidence of CMV infection in renal transplant recipients. Similarly, polymorphisms in IL-28B were associated with higher liver dysfunction from HBV infection in liver transplant recipients. Studies included had low risk of bias. Cytokine gene polymorphisms IL-12B and IL-1B were found to be associated with an increased risk of infection in kidney transplants and IL-28B in liver transplant recipients. However, the small number and heterogeneity of studies limits the generalization of our results. Further research may lead to finding these associations in larger studies which perhaps improve the use of genetic testing and targeted antiviral therapy. This will further reduce the risk of viral infections associated with cytokine gene polymorphisms in post renal and liver transplant recipients.