Infection In Kidney Transplant Recipients Research Articles

Measurement of Humoral Immune Competence and the Risk of Sinopulmonary Infection in a Cohort of Kidney Transplant Recipients

PurposeThe aim of this study was to determine if measurement of B cell protective immunity was associated with susceptibility to sinopulmonary infection in kidney transplant recipients. Methods and MaterialsA prospective cohort of 168 patients with stable graft function (median 4.1 years) underwent assessment of B-lymphocyte antigen CD19 (CD19+) cell number, immunoglobulin G concentration, and seroresponses to influenza vaccination upon study entry. Patients received a single dose of a trivalent, seasonal influenza vaccine. ResultsAfter 2 years follow-up, 31 patients (18%) developed sinopulmonary infection. CD19+ cell number was strongly associated with future sinopulmonary infection. A higher proportion of patients with CD19+ cell counts below the fifth percentile for controls developed sinopulmonary infections than those above the fifth percentile, 30% (23 of 77 patients) compared with 9% (7 of 79 patients; P = .001). There was a trend toward a higher proportion of patients with reduced immunoglobulin G concentrations developing infections than in the normal range for controls, 29% (14 of 48 patients) compared with 15% (16 of 108 patients; P = .060). Influenza vaccination seroresponses were poor in patients and controls such that they could not be used to identify a subgroup of patients at high risk for the development of severe pulmonary infection. ConclusionsMonitoring B-cell numbers represents a simple, inexpensive means of stratifying transplant recipients' risk of sinopulmonary infection.

Hepatitis C viremia as a risk factor for opportunistic infections in kidney transplant recipients.

The aim of the present study was to determine the clinical characteristics, frequency of opportunistic infections (OI) in HCV-positive kidney recipients, and to evaluate HCV replication as a risk factor for developing an OI. We conducted a retrospective study of all kidney recipients from 2003 to 2014. A total of 1203 kidney transplants were performed during the study period. Opportunistic infections were recorded in 251 patients (21%) and nucleic acid amplification testing (NAAT) positivity in 75 (6%). Patients who are HCV NAAT positive were more likely to present an OI than those who are HCV NAAT negative (45% vs 20%, P<0.001). Multivariate analysis showed the factors that were independently associated with the development of OI to be acute rejection, graft loss, post-transplantation hemodialysis, and HCV replication. Liver cirrhosis after transplantation could not be considered a risk factor to develop OI. To conclude, a high index of suspicion of OI must be maintained in the case of kidney recipients with HCV replication. Active surveillance of cytomegalovirus infection and other prophylactic strategies against OI should be considered after 6month post-transplantation. Prompt initiation of DAA therapies may be a useful option aiming to decrease the incidence of OI after transplantation.

Impact of Urinary Tract Infections in Kidney Transplant Recipients: A 4-Year Single-Center Experience

BackgroundUrinary tract infection (UTI) is the most frequent bacterial infection in kidney transplant recipients (KTRs), yet little is known about the impact of severe UTIs. We aimed to explore the burden of severe UTIs post renal transplant on both graft function and health care resources. MethodsWe conducted a retrospective review of KTRs with severe UTI warranting hospital admission at our center between January 1, 2012, and December 31, 2015. ResultsWe identified 198 UTI-related hospital admissions in 83 KTRs representing 7.4% of transplant admissions; 44.6% were men and 45 (54.2%) had recurrent admissions. The most commonly isolated pathogens were E coli (47.5%) and Klebsiella (16.2%): extended-spectrum β-lactamase–producing organisms were detected in 31.3% of Klebsiella and in 25.5% of E coli. During UTI, the median serum creatinine increased from 126 to 196.5 μmol/L, then decreased to 149 and 161 μmol/L 3 months and 1 year after UTI, respectively. Acute kidney injury complicated 40.9% of UTIs (23.7% stage 1, 12.1% stage 2, 5.1% stage 3), with no significant difference between single and recurrent admission groups (χ2 = 0.36, P = .5). The 1-year mortality and death-censored graft loss were 1.2% and 3.6%, respectively. The median length of hospital stay was 4 days (286 days per annum) and the estimated annual cost was £87,665 ($117,347). ConclusionsUTI post renal transplant represents a substantial burden on health care resources and patient morbidity in terms of acute kidney injury and deterioration in graft function. Thus, applying proper preventative and management strategies is paramount.

Incidence, Risk Factors, and Outcomes of Clostridium difficile Infections in Kidney Transplant Recipients.

Kidney transplant recipients (KTR) may be at increased risk for Clostridium difficile infections (CDI) but risk factors and outcomes in this population have not been well studied. An observational cohort study was conducted to determine the incidence, risk factors, and outcomes of CDI in KTR. A total of 1816 KTR transplanted between 2000 and 2013 at the Toronto General Hospital were included. Sixty-eight patients developed CDI. Controls were selected at a 4:1 ratio using risk-set sampling, and risk factors were explored using conditional logistic regression models. The impact of CDI on graft outcomes was evaluated using Cox proportional hazards models. The incidence rate of CDI was 0.64 cases/100 person-years. Independent predictors of CDI included antibiotic use (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.35-6.15), increased duration of hospitalization posttransplant (OR, 1.04; 95% CI, 1.02-1.06]), receiving a deceased donor kidney (OR, 2.98; 95% CI, 1.47-6.05), and a history of biopsy-proven acute rejection (OR, 5.82; 95% CI, 2.22-15.26). In the Cox proportional hazards model, CDI was found to be an independent risk factor for the subsequent development of biopsy-proven acute rejection (hazard ratio, 2.18; 95% CI, 1.34-3.55). Our results confirm that transplant-specific factors place KTR at a higher risk for CDI. Clostridium difficile infections may increase the risk of adverse outcomes, such as biopsy-proven acute rejection. These findings emphasize the importance of preventive strategies to reduce the morbidity associated with CDI in KTR.

Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients.

Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+ ) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.

Effect of Interferon-Gamma Gene Polymorphism +874 A/T on Cytomegalovirus Infection in Kidney Transplant Recipients With and Without Prophylactic Treatment with Valganciclovir

Introduction The specific mechanism that can explain the linking of Citomegalovirus (CMV) infection with diminished graft function is not totally clear due to there are numerous issues involved. Some cytokines with antiviral proprieties such as interferon gamma (IFN-γ) have been studied. In fact, the SNP +874 A/T of IFN-γ gene, which is linked to their levels, has been associated with increased risk of CMV infection in both lung and kidney transplant recipients. Our purpose was to replicate the association of this SNPin an independent population of kidney transplant patients. Materials and Methods A retrospective analysis was performed in 600 consecutive transplanted kidney recipients. The SNP+874 A/T (rs2430561) was genotyped by TaqMan chemistry under conditions recommended by manufacturer and analyzed in a 7900HT Fast Real-Time PCR System (Applied Biosystem, Foster City, CA, USA). CMV viral load was determined by quantitative nucleic acid amplification testing (QNAT). Results and Discussion Patients with CMV infection were 205 (34.2%) and the median time after transplant to the onset of CMV infection was 2.7 months (range 1.2-5.3 months).We found no association of IFN-γ+874 A/T polymorphism in either univariate or multivariate analyses and regardless of prophylactic treatment with valganciclovir (Tables 1 and 2). Due to antiviral properties of this cytokine and the implication of the aforementioned polymorphism in their level, it would seem the most appropriate approach to assess the risk of CMV infection; however, this association could not be stablished in our well powered cohort. The previously reported association of IFN-γ +874 A/T polymorphism with CMV infection in kidney transplant and lung transplant recipients showed 52 and 42 CMV positives patients respectively. In the adjusted model we found interactions between prophylaxis with status CMV D+ / R- (P-interaction = 0.010), with thymoglobulin induction therapy (P-interaction = 0.034) and with thymoglobulin anti-rejection therapy (P-interaction = 0.002). Data showed that CMV seropositive recipients and no thymoglobulin therapy, the prophylaxis with valganciclovir is not an advantage (Table 2); however if thymoglobulin is used for induction and/or rejection, valganciclovir profilaxis is a protective key for CMV infection (Table 2). Related to well-known associated factors, increased infection risk was observed for recipient age, delayed graft function and (initial immunosuppressive treatment with mammalian target of rapamycin inhibitors (mTORi), (Table 2).Conclusion Our data suggest that IFN-γ +874 A/T polymorphism is not a predictive marker of CMV infection in a Spanish cohort of kidney transplant patients, the thymoglobulin therapy is not a risk factor for CMV infection when it is associated with prophylaxis with valganciclovir and the protective effect of imTORis not improved with prophylactic treatment.

Cryptococcal Infections in Kidney Transplant Recipients. A Single Center Experience

Introduction Cryptococcal infections are reported to be an infrequent but important cause of morbidity and mortality in solid organ transplant recipients. Best treatment and the need for secondary prophylaxis are still debated. The aim of this research was to describe incidence, clinical presentation, treatment and outcomes of kidney transplant recipients with cryptococcal infections observed at our institution. Materials and Methods Retrospective analysis of cryptococcal infections observed in patients (Pts) transplanted from January 1st 2008 to October 1st 2017. Data on demography, immunosuppression, clinical presentation, treatment and outcome was recollected. Results and Discussion 1413 transplants were performed in the period 2008-2017. A total of 12 cases of cryptococcal infection was observed (incidence:0.85%). Pts were 3 males/9 females. Age: Median 53.87 (range 20-72) years. Donors were: Deceased: 7 (58.3%); Living related 3 (25 %) Living non-related 2(16.7%.%). Immunosuppression: 10 received induction with timoglobulin. Maintenance immunosuppression: Tacrolimus (FK)- mycophenolic acid (MPA)- prednisone (P): 8 (67%), MPA-P/FK-MPA-P- belatacept/Belatacept MPA-P/and;, sirolimus-FK-MPA-P: 1 each.Four Pts suffered rejections previous to cryptococcal infection (Median time before cryptococcosis: 344.5 (Range: 83-1022) days). Time to infection after transplantation: Median 27.37 (range 3.2-84.3) months. Clinical forms: Meningeal: 6 (50%); Disseminated: 4 (33.3%); Pulmonary: 1 (8.3%); Pleural: 1 (8.3%). Median CD4 count at diagnosis: 88/mm3 (range 47-172). One Pt had a post-mortem diagnosis. Treatment: (Induction): Liposomal Amphotericin B (L-AmB) 9 Pts; L-AmB+Fluconazole: 2 pt. Immunosuppression was temporarily minimized on all Pts until infection was controlled. Consolidation: Fluconazole 11 Pts. (2 pt. still on treatment), 9 pt. completed treatment (median: 12 (range 8,5-20) months,). Outcomes All treated Pts (11/11) cured. 9 Pts maintained a functioning graft. Of these, 7 completed treatment (with no secondary prophylaxis) with no relapse of follow-up (FU). Median FU: 13,17 (range 3,44-72,33) months. 2 Pts lost the graft on FU (unrelated to cryptococcosis), and 1 Pt died of unrelated cause. Conclusion Treatment with induction with L-AmB (with or without fluconazole), combined with appropriate immunosuppression management was successful in all clinical forms of cryptococcal infection. No relapses were observed in Pts with treatment completed and no secondary prophylaxis.

Efficacy and Tolerability of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in Kidney Transplant Recipients

Efficacy and Tolerability of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in Kidney Transplant Recipients

Role of the Early Association of a mTOR Inhibitor and Tacrolimus in BK Polyomavirus Infection in Kidney Transplant Recipients

Role of the Early Association of a mTOR Inhibitor and Tacrolimus in BK Polyomavirus Infection in Kidney Transplant Recipients

Causes and Consequences of Poliomavirus BK Infection in Kidney Transplant Recipients

Objectives 1) To investigate the risk factors for the development of polyomavirus BK infection (BKI). 2) Evaluate the impact of the same on graft survival and renal function at one year. Methods We included 692 consecutive patients who received a kidney transplant in our unit during 2005-2015. Demographic data, pretransplant comorbidity, IC (leukocytes, lymphocytes, CD4, CD8 and CD4 / CD8 ratio), renal function [creatinine, glomerular filtration rate (GFR) by Cockroft-Gault and proteinuria], dose and type of immunosuppression a 1 were collected. 3, 6 and 12 months post-transplant and incidence of infections during the first year. Results The prevalence of BKI in our unit has gone from 5 to 13% in recent years. It appears at 3.7 (2.7-8.2) months post-transplant, with a viral load of 90000 (2000-4450000) copies. We performed conversion to imTOR in 84% of the cases, with serum negativization in 90%. The risk factors related to viral replication in the univariate analysis were: severe UTI [RR = 4.19 (1.93-9.10), p = 0.020], treatment with thymoglobulin [RR = 2.45 (1.25-4.78), p = 0.007], time on dialysis>2 years [RR = 1.45 (1.16-1.80), p = 0.004], pretransplant DM [RR = 1.77 (0.99-3.54), p = 0.076], retransplantation [RR = 1.25 (0.94-1.29), p = 0.109], TCD4 lymphocytes <200/mcl in 3 months (RR = 2.02 (0.96-3.86), p = 0.060], TCD8 lymphocytes <200/mcl in 3 months [RR = 2.46 (1.09-5.54), p = 0.026]. In the multivariable analysis, only persists TCD8 lymphocytes <200/mcl in the third month [RR = 2.58 (1.10-6.04), p = 0.028] and treatment with thymoglobulin [RR = 2.09 (0.93-4.71), p = 0.074]. There were no differences in graft survival (92 vs 90%) or in renal function at one year (FG: 58 ± 16 vs 56 ± 18 ml / min, p = 0.419, proteinuria / creat 0.3 ± 0.5 vs 0.2 ± 0.2 mg / mg). Conclusions The prevalence of BKI has increased in recent years in the kidney transplant population, but with an adequate management of immunosuppression and early conversion to imTOR may not negatively influence the results. The main risk factors for the development of active viral replication in our unit were the presence of CD8 + count <200/mcl.

Natural killer cell function predicts severe infection in kidney transplant recipients.

The aim of this study was to determine if natural killer cell number (CD3- /CD16± /CD56± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P=.018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P<.0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P=.051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.

Risk factors associated with Clostridium difficile infection in kidney transplant recipients.

Solid organ transplant recipients are especially vulnerable to Clostridium difficile infection (CDI) due to cumulative risk factors including increased exposure to healthcare settings, persistent immunosuppression, and higher rates of antimicrobial exposure. We aimed to identify risk factors associated with CDI development in kidney transplant recipients including implications of immunosuppressive therapies and acid-suppressing agents. This was a single-center, non-interventional, retrospective case-control study of adult subjects between June 1, 2009 and June 30, 2013. During this time, 728 patients underwent kidney transplantation. Overall, 22 developed CDI (cases) and were matched 1:3 with 66 controls. Cases and controls were also matched for induction agent, kidney allograft type (living or deceased), and time from transplant to CDI result (±60days). The majority of subjects received a deceased donor kidney (77.3%) and basiliximab induction therapy (86.4%). The overall CDI incidence was 3%. Factors independently associated with CDI were average tacrolimus trough (AOR=1.25, 95% CI=1.00-1.56, P=.048) and antibiotic exposure for urinary tract infections (UTI) (AOR=4.17, 95% CI=1.12-15.54, P=.034). Proton pump inhibitor use was not associated with CDI (OR=0.81, 95% CI=0.29-2.29, P=.691). Maintaining a clinically appropriate tacrolimus trough and judicious antibiotic use and selection for UTI treatment could potentially reduce CDI in the kidney transplant population.

Successful Treatment of Strongyloides stercoralis Hyperinfection in a Kidney Transplant Recipient: Case Report

Strongyloides stercoralis (SS) can cause hyperinfection and disseminated infection in immunosuppressed individuals, with risk of mortality. We report the case of a cadaveric kidney transplant recipient who developed gastrointestinal symptoms and eosinophilia, approximately 3 months after transplantation. Stool examination and esophagogastroduodenoscopy with biopsies were positive for SS larvae. The patient was started on oral ivermectin and immunosuppression was reduced, but still the clinical picture got worse with metabolic ileus and respiratory symptoms, with the need for administration of subcutaneous ivermectin and combined therapy with albendazol. The patient survived and graft function was preserved. The patient was unlikely to be the source of infection. We also present a review of cases of SS infection in kidney transplant recipients.

Cytomegalovirus Status of Kidney Transplant Recipients and Cardiovascular Risk

BackgroundCytomegalovirus (CMV) infection is associated with an increased risk of cardiac complications in kidney transplant recipients (KTRs). Some data suggest that CMV may be involved in atherogenesis. The aim of the study was the analysis of CMV medical history in KTRs and its influence on cardiovascular (CV) incidents. Materials and MethodsThe study observed 254 patients (165 male/89 female) with mean age of 47.2 (range, 15–81) years and duration of dialysis before transplantation 29.2 months who received transplants in 1 university unit (2007–2013). Thirty-six patients were transplanted preemptively. The mean time of observation lasted 7 years. KTRs suffered from diabetes, hypertension, and hyperlipidemia (17.3%, 88.5%, and 61%, respectively). Coronary artery disease was diagnosed in 19.6% patients, 3.5% underwent elective coronary surgery operation, and 9.05% had CV incidents before transplantation. The following CMV donor/recipient (D/R) viral statuses were noticed in the study group: D+/R+ (68.9%), D+/R− (16.9%), D−/R+ (10.2%), and D−/B− (3.9%). D+/R− received universal CMV prophylaxis; the rest were under preemptive CMV prophylaxis. CMV infection affected 87 (34.25%) patients; there were 24 primary infections and 85 secondary infections (some patients had more than 1 CMV). Mean time of diagnosis of the primary and secondary CMV infection was 190.7 and 160.5 days, respectively. ResultsDuring observation 22 patients experienced 26 CV incidents: 15 were D+/R+, 6 were D+/R−, and 1 was D−/R+. CMV infections occurred in 40.9% of patients with CV incidents after kidney transplantation. In comparison, 33.6% patients without CV incidents after kidney transplantation suffered from CMV infection. ConclusionsCMV infection in KTRs was not a crucial risk factor for CV incidents.

Clinical Significance of Gastrointestinal Carriage of Klebsiella Pneumoniae-Producing Extended-Spectrum Beta-Lactamases in Kidney Graft Recipients

The burden of Klebsiella pneumoniae (KP) producing extended-spectrum beta-lactamases (ESBL+) urinary tract infections (UTIs) is a growing problem after kidney transplantation (KTX). The study was aimed at evaluating the incidence of KP ESBL+ gut colonization in KTX recipients and its correlation with clinical outcomes with special regard to UTIs.The study included all KTX patients hospitalized in our department between January 2014 and December 2016. During this period 2018 KTX patients were admitted: 605 in 2014, 750 in 2015, and 663 in 2016, respectively. Screening for drug-multiresistant Enterobacteriaceae gut carriage was performed in 104 patients (2014), 122 (2015), and 166 (2016).In 2014, 2015, and 2016, 18 (17.3%), 26 (21.3%), and 30 (18.1%) patients had positive test results, and 44 (42.3%), 36 (29.5%), and 45 (27.4%) KTX patients were diagnosed with KP ESBL+ UTI. In 2014, KP ESBL+ UTI was diagnosed in 30 (34.9%) cases with negative anal swab and in 14 patients (77.8%) with positive test result (P = .0008). In 2015, KP ESBL+ UTI was diagnosed in 21 patients (21.9%) with negative anal swab and in 15 (57.7%) with positive test result (P = .0004). In 2016, KP ESBL+ UTI was diagnosed in 24 patients (17.8%) with negative anal swab and in 21 (72.4%) with positive test result (P = .000001).In conclusion, we have revealed a strong association between gut K. pneumoniae colonization, female sex, and MPA intake and KP ESBL+ urinary tract infections in kidney transplant recipients. Our results indicate the very important role of KP ESBL+ screening, while strategies of identified carriers require further research.

Nucleic Acid Tests for BK Polyomavirus Is Critical in Renal Transplant Recipients

This study evaluates the incidence of BK polyomavirus (BKV) and prognosis of BKV infection in kidney transplant recipients (KTRs) who received transplantation in our hospital before and after regular BKV nucleic acid test (NAT) was implemented. MethodsThe study included 74 KTRs who received a single kidney either from standard- or expanded-criteria deceased donor between March 2011 and March 2017. BKV NATs were regularly checked in 26 patients (group 1) in the first posttransplant year in accordance with current guidelines since NAT was implemented in our laboratory in 2014. We retrospectively compared 48 KTRs (group 2) who either received NAT when necessary in another laboratory or were not checked before 2014. ResultsThere was no significant difference in patient characteristics between groups. BKV viruria were confirmed in 8 of 26 (30.8%) group 1 patients, whereas only 2 of 48 (4.2%) BKV infections were confirmed in group 2. None of the BKV(+) KTRs in group 1 developed BK polyomavirus-associated nephropathy (BKVAN), whereas 2 BKV(+) patients (100%) of group 2 developed BKVAN, which indicates renal function deterioration and biopsy-validated nephropathy. There was no significant difference in graft survival and renal function between the 2 groups. ConclusionsThe risk of BKV infection is considerably higher in KTRs using NAT. Because there is no approval treatment, early diagnosis of BKV infection and early reduction of immunosuppression agents is critical for KTRs. Implementation of regular BKV NAT is mandatory before BKVAN and malignant neoplasms develop.

Valganciclovir Pharmacokinetics in Patients Receiving Oral Prophylaxis Following Kidney Transplantation and Model-Based Predictions of Optimal Dosing Regimens.

Valganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide dosing in this patient group. This study aimed to describe the population pharmacokinetics of valganciclovir in a large sample of kidney transplant recipients and predict optimal dosing based on Monte Carlo simulations. Therapeutic drug monitoring (TDM) data from adult kidney transplant recipients who received valganciclovir prophylaxis during a 10-year study period were collected retrospectively. A non-parametric pharmacokinetic analysis and Monte Carlo simulations to determine the probabilities of reaching an area under the drug concentration-time curve (AUC) target of 40-50mg·h/L with various dosing regimens at different levels of renal function were conducted using the Pmetrics™ package for R. This study included 792 ganciclovir concentration measurements derived from 97 patients. A one-compartment oral absorption model best described the data. The final covariate model was as follows: CL(ganciclovir)=TVCL×(CLCR/51)0.75, where CL is the clearance, TVCL is the typical value of ganciclovir clearance, creatinine clearance (CLCR) according to the Cockcroft-Gaultt equation and 51 is the mean CLCR determined in the study. In the simulations, the probability of reaching the targeted AUC was insufficient when using the recommended dosing regimens for prophylaxis, especially in patients with impaired renal function at CLCR<50mL/min. Higher doses of valganciclovir corrected to renal function are suggested for use as oral prophylaxis for CMV infection in kidney transplant recipients. Further study is required to establish TDM targets to ensure adequate drug concentrations while avoiding potentially toxic drug exposures.

Unexpected donor-derived infectious transmissions by kidney transplantation: A systematic review.

Unexpected donor-derived transmission of infections is rare, but is associated with significant morbidity and mortality. We aimed to provide an overview of published cases on unexpected infectious transmissions. We systematically reviewed all published evidence describing any unexpected donor-derived viral, bacterial, fungal, and parasitic infections in kidney transplant recipients. In all, 119 studies (case reports [n=36], case series [n=78], cohort studies [n=2], and case-control studies [n=3]) involving 139 donors and 207 kidney recipients were included. Donor-derived viral (n=116, 56.0%) infections were most prevalent, followed by bacterial (32, 15.5%), fungal (32, 15.5%), and parasitic (27, 13.0%) infections. The most commonly reported viral infections were human immunodeficiency virus (HIV) (n=20, 9.7%), human T-cell lymphotrophic virus (HTLV) (n=20, 9.7%), and West Nile virus (WNV) (n=13, 6.3%). The most frequent bacterial infections were caused by Mycobacterium tuberculosis (10, 4.8%) and Pseudomonas aeruginosa (9, 4.3%). Candida species were the most frequent causes of fungal donor-derived infections (8, 3.9%). Toxoplasma gondii accounted for seven (3.4%) cases of transmitted parasitic infections. Patients with rabies experienced the highest probability of recipient death from virus-related complications at 90.0%, within a median time of 2.8months after transplantation. The frequency of donor-derived infectious transmission appears low in kidney transplantation, with viral transmissions being most commonly reported overall.

Cytomegalovirus Infection Monitoring Based on Interferon Gamma Release Assay in Kidney Transplantation

BackgroundCytomegalovirus (CMV) is the most common viral infection after kidney transplantation and is associated with significant morbidity and mortality. Recent studies showed that CMV-specific CD8+ T cells play the crucial role in protection against CMV. The Quantiferon-CMV (QF-CMV) is an interferon gamma (IFN-γ) release assay (IGRA test) that measures the IFN-γ response to a range of T-cell epitopes of CMV. In the present study, we analyzed the clinical utility of QF-CMV assay to predict CMV infection in kidney transplant recipients and evaluated if reactive result in QF-CMV test could be predictor of the duration of treatment. MethodsWe studied 75 renal transplant recipients who had IGRA testing just before transplantation. The donor and recipient variables were reported from the clinical history. The variables related to transplantation were collected from transplantation process data and included CMV infection or disease, CMV treatment, and immunosuppressive treatment. Laboratory variables were C3-C4 complement fractions and DNA quantification of CMV. ResultsFifty percent of patients had CMV infection, and 35.9% had CMV disease. The time of negativization of CMV DNA was 56.61 ± 23.5 days. Univariate analysis related to CMV infection only showed a statistically significant relation with thymoglobulin treatment (P = .001). Statistically significant variables in relation with CMV infection incidence were donor serology (P = .044) and thymoglobulin treatment (P = .004). The probability of CMV infection was lower with positive IGRA assay (P = .025). ConclusionWe found that IFN-γ response measured by QF-MV is a protective factor against CMV infection in post-transplantation kidney recipients.

Prediction of Early BK Virus Infection in Kidney Transplant Recipients by the Number of Cells With Intranuclear Inclusion Bodies (Decoy Cells).

BackgroundBK virus (BKV) is the cause of nephropathy. Because BKV nephropathy can progress to graft loss, early diagnosis of BKV infection is very important. In this study, we aimed to investigate the utility of quantifying cells with intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening and monitoring of BKV infection in renal transplant recipients at our hospital.MethodsThis was a retrospective single-center study. Urine sediment examination was performed at each outpatient visit, and the number of decoy cells was measured in the whole microscopic field. Patients (n = 41) were divided into the BK viremia group (blood positive for BKV DNA by polymerase chain reaction [PCR]) and non-BK viremia group (blood negative for BKV DNA by PCR), and the decoy cell count in urinary sediments was examined.ResultsThe maximum decoy cell count was significantly higher (P = 0.04) in the BK viremia group than in the non-BK viremia group. In the receiver operating characteristic curve for the maximum decoy cells, the cutoff value was 507 cells. The area under the receiver operating characteristic curve was 0.8774 (95% confidence interval, 0.7739-0.9810). The number of decoy cells at the time of appearance in the BK viremia group was not significantly different from that in the non-BK viremia group. However, the BK viremia group showed an increasing trend, whereas the non-BK viremia group showed a decreasing trend, in the number of decoy cells. There was a positive correlation between the number of decoy cells and the data from the urine BKV-DNA PCR quantification (correlation coefficient [r] = 0.74).ConclusionsMeasurement of decoy cells in urinary sediments may predict early BKV infection, and if performed quickly, it may be useful for screening and continuous monitoring of BKV infection in renal transplant recipients.