Disease In Kidney Transplant Recipients Research Articles

Successful Cost-Effective Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients Using Low-Dose Valganciclovir.

Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures. Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients. In this prospective trial, 201 kidney transplant patients were randomized (1:1) to receive 450 mg/d (group 1, n = 100) or 900 mg/d (group 2, n = 101) valganciclovir prophylaxis for the first 6 months after transplant. Patients were studied for incidence of cytomegalovirus disease, leucopenia episodes, rejection episodes, and graft outcomes along with associated costs over 1 year. Costs (in US dollars) of treatment of rejection were also analyzed. Demographic features of the studied groups were comparable. We found that the cost of cytomegalovirus care in group 1 patients was significantly lower (by 50% at 6 months; P < .001), with less leukopenia episodes (P = .04), lower doses of granulocyte colony-stimulating factor (by 30% at 6 months; P = .03), higher doses of mycophenolate mofetil (P = .04), and less rejection episodes (P = .01) compared with group 2. In group 2, there were more episodes of cytomegalovirus infection (P = .052) and BK virus nephropathy (P = .04). Graft and patient outcomes were satisfactory in both groups. Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer, effective and without breakthrough infection, and less costly than using the usual dose.

Low level of MAp44, an inhibitor of the lectin complement pathway, and long-term graft and patient survival; a cohort study of 382 kidney recipients.

BackgroundHigher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient’s native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation.MethodsTwo mannan-binding lectin (MBL) associated proteases, MASP-2 and MASP-3 (activators of the lectin pathway) and two MBL-associated proteins, MAp44 and MAp19 (inhibitors of the lectin pathway) were measured at the time of transplantation in 382 patients (≥17 years old) transplanted in 2000–2001. The cohort was followed until December 31, 2014. Data on patient and graft survival were obtained from the Norwegian Renal Registry. Cox proportional hazard regression models were performed for survival analyses.ResultsLow MAp44 level (1st versus 2–4 quartile) was significantly associated with overall mortality; HR 1.52, 95 % CI 1.08–2.14, p = 0.017. In the sub analyses in groups below and above median age (51.7 years), low MAp44 as a predictor of overall mortality was statistically significant only in recipients of ≤51.7 years; HR 2.57, 95 % CI 1.42–4.66, p = 0.002. Furthermore, low MAp44 was associated with mortality due to infectious diseases; HR 2.22, 95 % CI 1.11–4.41, p = 0.023. There was no association between MASP-2, MASP-3 or MAp19 levels and patient mortality. No association between any measured biomarkers and death censored graft loss was found.ConclusionsLow MAp44 level at the time of transplantation was associated with increased overall mortality in kidney recipients of median age of 51.7 years or below and with mortality due to infectious diseases in the whole patient cohort after nearly 14-years of follow up after transplantation. No associations between other effector molecules; MASP-2, MASP-3 or MAp19 and recipient mortality were found, as well as no association of any biomarker with death censored graft loss.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0373-9) contains supplementary material, which is available to authorized users.

Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients

Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34–51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12–55] and 40 [21–53] mL/min/1.73 m2, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

Monitoring of intracellular adenosine triphosphate in CD4(+) T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients.

The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.

Bisphosphonates for preventing bone disease in kidney transplant recipients: a meta-analysis of randomized controlled trials.

An estimated 60% of kidney transplant recipients have mineral bone disease and about 0.5% break their hip within the first year after transplantation. We conducted a systematic review of benefits and harms of bisphosphonates in kidney transplant recipients. We searched CENTRAL (Issue 5, 2015) for randomized controlled trials in all languages and screened the reference list of an earlier Cochrane review. One reviewer identified the trials, extracted all data, and assessed risk of bias. Meta-analysis used a random effects model, with results expressed as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Bisphosphonates have uncertain effects on death (RR 0.45, CI 0.04-4.69) and vertebral fractures (RR 0.58, CI 0.24-1.43, I(2) 0%). Bisphosphonates moderately to importantly reduce the loss of vertebral bone mineral density (MD 5.98%, CI 3.77-8.18% change from baseline in g calcium/cm² at 12months, I(2) 91%) and femoral bone mineral density (MD 5.57%, 3.12-8.01% change from baseline in g calcium/cm² at 12months, I(2) 69%). At this stage, insufficient evidence exists to support routine use of bisphosphonates to reduce fracture risk after kidney transplantation. Data on important health outcomes are lacking, surrogate outcomes poorly reflect bone quality in kidney transplant recipients, and serious adverse events are not studied and reported systematically.

Risk Factors of Cytomegalovirus Disease in Kidney Transplant Recipients: A Single-Center Study in Thailand

BackgroundCytomegalovirus (CMV) infection significantly causes morbidity in kidney transplant (KT) recipients. This study aims to investigate the incidence, timing, and risk factors of CMV infection in KT recipients. MethodsThis is a single-center retrospective study at a tertiary referral hospital. Patients who underwent KT from January 2012 to September 2014 were included. CMV infection was defined as the presence of CMV measured by polymerase chain reaction. Logistic regression analysis was performed to assess independent risk factors of CMV infection after KT. ResultsOf 121 KT patients enrolled, 120 patients had CMV D+/R+ serostatus, and 1 had D-/R+. CMV infection occurred in 33 (27.2%) of patients with a median follow-up time of 16 (IQR 4–25) months. Of those, 25 had CMV viremia and 8 had CMV disease mainly involving the gastrointestinal system. In total, 86% of CMV cases occurred within 3 months. All recipients received anti–IL-2 receptor antibody (IL-2 RA), low-dose rabbit antithymocyte globulin (rATG; total of 1.5 mg/kg), or standard-dose rATG (1.5 mg/kg/day for 3–5 days) for induction. Of those, the incidences of CMV infection were 19.6%, 50%, and 67%, respectively. Preemptive strategy was used in all but 1 patient in the IL-2 RA and low-dose rATG group, whereas universal prophylaxis was given in 67% of patients in the standard-dose rATG group. Independent risk factors of CMV infection were older recipient age (per 10-year increase, OR 1.5; 95% CI 1.04–2.23), and induction with standard (OR 8.19; 95% CI 2.29–34) and low-dose rATG (OR 3.87; 95% CI 1.06–12.23). ConclusionsMore than 25% of KT recipients developed CMV infection within 6 months after KT. The risk is increased in older recipients and induction with rATG. The level of CMV risk in low-dose rATG is 52% lower than in standard-dose rATG. In a limited-resource setting such as Thailand, deferred or preemptive strategy may be acceptable in patients who received IL-2 RA and low-dose rATG, while prophylactic therapy should be given to patients who received standard-dose rATG.

High-Grade Proteinuria as a Cardiovascular Risk Factor in Renal Transplant Recipients

BackgroundProteinuria is a marker of graft damage and is closely associated with a higher risk of morbidity, mortality, and cardiovascular disease in kidney transplant recipients (KTRs). Arterial stiffness is a well-known predictor of vascular calcification and systemic arteriosclerosis. In our study, we aimed to investigate the association between proteinuria and graft/patient survival and to determine whether proteinuria may be a predictor for cardiovascular disease in our KTR population. MethodsNinety KTRs (31 women; age, 38.7 ± 11 years, with 45.9 ± 9.6 months post-transplantation period) with normal graft functions in the 3 to 5 years of the post-transplantation period were enrolled. All patients were evaluated for their standard clinical (age, sex, and duration of hemodialysis) parameters. High-grade proteinuria was defined as proteinuria >500 mg/day in the 24-hour urine collection. All patients were evaluated by means of pulse-wave velocity (PWV) measurement at the initiation of the study. ResultsPatients were divided into 2 groups: group 1 (high-grade proteinuria) patients with ≥500 mg/24 hours (n = 30) and group 2 (low-grade proteinuria) patients with <500 mg/24 hours (n = 60). High-grade proteinuria was correlated with higher PWV measurements and lower estimated glomerular filtration levels. Proteinuria appears to precede the elevation of serum creatinine and thus may be a useful marker of renal injury and may also be a contributing factor on deterioration of the graft. ConclusionsHigh-grade (>500 mg/day) proteinuria in KTRs is strongly associated with poor graft survival and increased risk of cardiovascular events. In our study, we proved the significant difference between high-grade and low-grade proteinuric patients, and we suggest 500 mg/day as the threshold of proteinuria in KTR population.

The Role of Secondary Cytomegalovirus Prophylaxis for Kidney and Liver Transplant Recipients

The role of secondary cytomegalovirus (CMV) prophylaxis, defined as the continuation of valganciclovir to prevent relapse after the successful treatment of CMV disease, is not well understood. Cases of CMV disease in patients who underwent kidney or liver transplantation from January 2001 to January 2010 were reviewed to determine if the use of secondary prophylaxis was associated with fewer relapses or other favorable outcomes. Secondary prophylaxis was used at the discretion of each treating clinician, without an institutional protocol. Twenty-two cases of CMV disease in kidney transplant recipients and 20 cases in liver transplant recipients were included. Relapsed CMV disease was significantly more common among kidney transplant recipients (5/22 vs. 0/20, P = 0.049). Of 22 kidney transplant recipients, 16 received secondary prophylaxis. After a mean of 3.7 years, relapsed CMV disease occurred in three of 16 patients who received secondary prophylaxis and in two of six who did not. Among liver transplant recipients, only two of 20 patients received secondary prophylaxis. After a mean of 3.2 years, no relapsed CMV disease occurred. The use of secondary prophylaxis was not significantly associated with fewer episodes of CMV relapse, graft loss, or death. Time to clearance of CMV viremia during treatment was significantly longer in those who relapsed (mean, 30 days vs. 20 days; P = 0.037). These findings suggest that secondary CMV prophylaxis may not provide additional benefit after the successful treatment of CMV disease, particularly among liver transplant recipients.

Liver disease in kidney transplant recipients.

Kidney transplant recipients can develop acute and chronic liver disease from a variety of conditions. Chronic viral hepatitis from hepatitis C is seen in increased frequency in hemodialysis patients. Genetic conditions, such as polycystic kidney disease, which lead to the need for kidney transplantation are also associated with liver diseases including congenital hepatic fibrosis and polycystic liver disease. Other conditions that can induce liver disease in this immune-suppressed population include a multitude of viral infections, as well as other systemic infections that can involve the liver. Drug induced liver injury is also seen in increased rates due to the use of poly-pharmacy, the effect of immune-suppression on drug metabolizing pathways in the liver and the potential of drug to drug interactions. Post transplant metabolic syndrome is also increased in kidney transplant recipients and this can lead to development of non-alcoholic fatty liver disease. A knowledge of the presentation of these liver diseases is essential in diagnosing the cause of liver disease as well as informing the diagnostic workup. Specific therapies for the various conditions will also be discussed in this review.

Hepatitis C Increases Risk of CMV Disease in Kidney Transplant Recipients: The National Experience in Taiwan.

Objective: This national prospective cohort study aimed to evaluate risk factors for cytomegalovirus (CMV) disease in kidney transplant recipients (KTRs). Methods:From January 1, 1997, through December 31, 2009, we selected all de novo kidney transplant recipients from Taiwan National Health Insurance Research Database. The Cox proportional hazards regression model was used to determine which variables were related significantly to the development of CMV disease. Results: Of 4501 KTRs, the mean age was 45.2±12.3 and 52.5% were male. In a mean follow up of 5.4 years, 341 (7.6%) have episodes of CMV disease. The overall prevalence of CMV disease was 14.8 per 1000 patient-years. The cumulative incidences of CMV disease in KTR were 2.6% in 3 months, 3.9% in 6 months, 4.8% in 1 year, 6.9% in 5 years and 7.6% in 10 years. The repeated CMV disease occurred in 80 (23.5%) of KTRs. Hepatitis C infection was associated with the development of CMV disease in KTRs (hazard ratio, 1.87 [95% CI, 1.25˜2.81], P<0.01) and the incidence rate was 27.9 per 1000 patient-year.Figure: No Caption available.Moreover, the other independent risk factors for CMV disease identified in multivariate analysis were treatment with mycophenolate mofetil or mycophenolic acid and children less than 18 years (hazard ratios, 1.67 [95% CI, 1.23˜2.27, P<0.01], 1.94 [95% CI, 1.45˜2.58, P<0.01] and 3.32 [95% CI, 2.06˜5.34, P<0.0001], respectively).Table: No Caption available.Conclusions:Hepatitis C infection, children and the use of mycophenolate mofetil or mycophenolic sodium increase the risk of CMV disease in Taiwanese KTRs. Our results contribute to develop the preventive strategy of CMV infection in KTRs.

Short Course of Low Dose Valgancicolvir Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients.

Background: Valganciclovir (VGCV) prophylaxis at 900mg once daily for 200 days appears both toxic and often un-affordably costly for renal allograft recipients of developing countries. We aim to study the efficacy and cost benefit of low dose valganciclovir prophylaxis (450 mg once daily for first 3 months) among kidney transplant recipients. Methods: We studied a cohort of KTRs between Jan 2005 to Dec 2011. VGCV prophylaxis was offered at 450 mg once daily for 3 months to all KTRs from 2007. CMV disease pattern, severity, other associated infections and survival were noted. Analysis was performed using standard statistical methods. Results:Of the 531 KTRs were studied (mean age =38±12.1 years; M:F = 3.5:1), 9% were deceased donor grafts recipients. Basiliximab induction was used in 58% with prednisolone + Tacrolimus + Mycophenolate in 80% and low dose VGCV prophylaxis was used in 60.5%. The overall incidence of CMV disease was 16 %. VGCV prophylaxis at 450mg once daily for a period of 3 months effectively reduced CMV disease (11% vs. 23%; p<0.01;), delayed its onset (median time of 12 months vs 3 months), and reduced the degree of viremia, associated infections such as post transplant TB, varicella zoster virus and Hepatitis C virus infections and mortality, while improving graft survival significantly.Figure: No Caption available.There were no increased incidence of clinically resistant CMV disease among low dose VGCV prophylaxis patients during the follow up period of 36.3 (6.0-86.5) months. The cost of this regime is four times lower than the standard dose (900mg) VGCV recommended for 200 days as per guidelines. Conclusions: In our study, low dose VGCV prophylaxis significantly reduced the incidence of CMV disease, delayed its onset, degree of viremia and reduced the attendant complications while improving survival. In resource limited countries, with an added advantage of 4x less cost, a 3month course of low dose VGCV is effective and did not result in an increased incidence of clinically resistant CMV disease within first 36 months.

Increased Graft Failure and Mortality Following Cytomegalovirus Disease in Kidney Transplant Recipients Undergoing Contemporary Immunosuppression and CMV Prophylaxis.

The relationship between CMV disease and outcome in cohorts undergoing contemporary immunosuppression and CMV prophylaxis is unclear. There also remains clinical equipoise regarding whether (and to what extent) immunosuppression should be increased following an initial reduction at the time of CMV disease. We studied 624 adult patients transplanted between 2007 and 2012, all of whom received a standardised immunosuppression protocol of tacrolimus, mycophenolate and maintenance corticosteroid; valganciclovir prophylaxis (100 days) was administered to CMV seronegative recipients from seropositive donors. CMV disease was treated with valganciclovir until viral DNA was absent for 2 weeks. Immunosuppression was reduced in the event of CMV disease, and not then augmented in the absence of a defined clinical indication (i.e. rejection). End measures of interest were mortality (including death after graft failure), graft failure (return to dialysis or retransplantation) with death modelled as a competing risk (Fine and Grey), and overall graft failure. Over a median follow up of 48 months (range 24-78 months), 84 patients developed CMV disease of whom 9 patients (10.7%) died. Causes of death in those patients experiencing CMV disease were tissue invasive CMV disease (n=2), bacterial sepsis (n=3), and cardiovascular disease (n=4). The independent risk factors for mortality were CMV disease (HR: 2.41; 95% CI: 1.10-5.24; p=0.03) and recipient age (HR: 2.24; 95% CI: 1.54-3.35; p<0.001). Increased rates of overall graft failure (graft loss or death) was seen in 16/84 (19.0%) of patients experiencing CMV disease, and in 63/540 (11.6%) of those free from CMV disease (p=0.07). A significant increase in risk of overall graft failure was evident in the adjusted model (HR: 1.98; 95%CI: 1.21-3.24; p=0.02). In the context of a standardised prophylaxis strategy and contemporary immunosuppression, CMV disease represents an on-going risk to patients and grafts, and supports further strategies to minimise this infective complication. The observation of increased mortality and overall graft failure (in the absence of an effect on death-censored graft failure) supports the policy of avoiding excessive immunosuppression escalation following an episode of CMV disease.

Risk Factors for Late-Onset Cytomegalovirus Infection or Disease in Kidney Transplant Recipients

CMV-D+/R- serostatus is the only well-established risk factor for late-onset cytomegalovirus (CMV) infection/disease (i.e., incident CMV infection/disease after cessation of prophylactic antiviral therapy). This study aimed to explore other potential risk factors for late-onset CMV infection/disease in kidney transplant recipients. We conducted a retrospective cohort study of 641 kidney transplant recipients in Toronto, Canada, from January 1, 2003, to December 31, 2010. The cumulative incidence of late-onset CMV infection/disease was assessed using the Kaplan-Meier product-limit method. Potential risk factors for late-onset CMV infection/disease were examined using Cox proportional hazards regression models. Cumulative incidence estimates for CMV infection/disease after prophylaxis cessation in D+/R- versus D+/R+ versus D-/R+ patients were 26.2% versus 7.4% versus 3.1% at 6 months and 30.0% versus 7.7% versus 3.7% at 1 year, respectively. D+/R- serostatus (vs. R+ serostatus) and an estimated glomerular filtration rate of less than 45 mL/min (vs. ≥ 60 mL/min) at prophylaxis cessation were independently associated with late-onset CMV infection/disease (hazard ratio, 4.04 [95% confidence interval, 2.39-6.83]; and hazard ratio, 2.03 [95% confidence interval, 1.07-3.88], respectively). Patients with lower estimated glomerular filtration rate at prophylaxis cessation may be at an increased risk of late-onset CMV infection/disease and should be considered for more intensive CMV viral load monitoring, particularly within the first year after prophylaxis cessation.

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.

Two cases of invasive pneumococcal disease in kidney transplant recipients

Two cases of invasive pneumococcal disease in kidney transplant recipients

54-P: NO ASSOCIATION BETWEEN THE NUMBER OF ACTIVATING KIR GENES AND THE INCIDENCE OF CMV DISEASE IN LIVER TRANSPLANT RECIPIENTS

Aim Late onset CMV disease is an important complication in CMV seronegative transplant recipients (R-) receiving livers from CMV positive donors (D+) after discontinuation of antiviral prophylaxis. Predicting the risk of developing CMV disease will allow for better targeted therapy. Natural Killer (NK) cells may play a role in modulating CMV disease. Increased number of NK activating killer cell immunoglobulin-like receptors (KIR) genes has previously been associated with a lower rate of CMV disease in kidney transplant recipients. Methods We assessed the relationship between recipient, or donor, KIR genotype and the incidence of CMV disease in a cohort of consecutive CMV D+R- liver transplant recipients (n = 170). All recipients received 3 months of standard anti-viral prophylaxis and were followed for 1 year post transplant or until death. Fifty six patients (33%) developed CMV disease post transplant. HLA and KIR genotyping of recipients and donors was performed by SSP and SSO methods respectively. Results We observed no association between the number or type of recipient, or donor, activating KIR genes and the incidence of CMV disease. There was a trend towards a lower incidence of CMV disease in patients who had 1) 3 recipient inhibitory KIR genes (2DL1, 2DL2, 2DL3) compared to patients with only 1 or 2 genes (27.8% vs. 35.7%), 2) licensed donor NK cells with cognate recipient HLA-C ligands (28.8% vs. 39.3%), p > 0.05 for all comparisons. Conclusions Our results do not support a role for activating KIR in the control of CMV disease in the current setting. Inhibitory KIR may play a role in controlling CMV disease in liver transplant recipients and should be further explored in a larger study.

West Nile virus and kidney disease

West Nile virus (WNV), the causative agent of West Nile fever and West Nile neuroinvasive disease in humans, has become endemic in many countries in all continents. Concerns on long-term mobility from WNV have arisen from recent studies that reported chronic kidney disease in patients who recovered from WNV infection, supported by data from animal models that showed prolonged excretion of the virus with urine. The purpose of this review is to summarize and discuss the results of studies in the literature that investigated WNV infection of the kidney in humans and in animal models and WNV excretion with urine, the potential damage to the kidney caused by WNV infection, the risk of WNV disease in kidney transplant recipients, the significance of detecting WNV in urine and its use in the diagnosis of WNV infection, and kidney involvement by other mosquito-borne flaviviruses.

Urinary Tract Infection and Kidney Transplantation: A Review of Diagnosis, Causes, and Current Clinical Approach

Urinary tract infection (UTI), including bacteriuria, cystitis, and pyelonephritis, is the most common infectious complication after kidney transplantation (KTx). Over the past few years, many medical groups assumed this pathological process to be a “benign” disease in kidney transplant recipients (KTxR). However, increased medical and scientific advances in knowledge and management of KTx complications have raised questions about UTI as a pathological process that decreases and worsens kidney allograft function and survival. This review sought to clarify diagnostic criteria, as well as to describe factors associated with UTI in KTxR that expose its effects on the allograft. We sought to show the uncertainty of important topics within the field of UTI among kidney allograft recipients and to propose a practical clinical approach to KTxRs with UTI.

Cytomegalovirus Exposure and Cardiovascular Disease in Kidney Transplant Recipients

Some data suggest that cytomegalovirus (CMV) may be involved in atherogenesis. However, there are few data suggesting that CMV may contribute to posttransplantation atherosclerosis. We studied a cohort of 570 consecutive renal transplant recipients. The impact of CMV on atherosclerotic events was analyzed with respect to other known main cardiovascular risk factors. The mean follow-up duration (± SD) was 87 ± 31 months. A total of 357 patients were considered to be CMV exposed, and 213 were considered to be CMV naive. Cox regression analysis revealed that CMV exposure (hazard ratio [HR], 1.80 [95% confidence interval {CI}, 1.06-3.05]; P = .030) was an independent risk factor for atherosclerotic events. A total of 213 patients remained CMV negative during follow-up, 225 CMV-positive patients had no replication after transplantation, and 132 CMV-positive patients experienced CMV replication after transplantation. Atherosclerotic event rates were 8.5%, 13.3%, and 18.2%, respectively (P = .034). Cox regression analysis revealed that patients with posttransplantation CMV replication had an increased risk of atherosclerotic events (HR, 2.06 [95% CI, 1.03-4.15]; P = .042) and death (HR, 1.76 [95% CI, 1.08-2.89]; P = .024). There was also a trend toward an increased risk of atherosclerotic events in CMV-positive patients without posttransplantation replication (HR, 1.62 [95% CI, .91-3.05]; P = .098). Both pretransplantation CMV exposure and posttransplantation CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients.

The Effects of Preemptive Therapy Using a Very Low Threshold of pp65 Antigenemia to Prevent Cytomegalovirus Disease in Kidney Transplant Recipients: A Single-Center Experience

BackgroundPreemptive therapy is a valid option for cytomegalovirus (CMV) disease prevention in kidney transplant recipients. However, there are controversies regarding the appropriate threshold value to be reached before starting antiviral drugs. The aim of this study was to evaluate the benefit of a low threshold of the CMV pp65 antigenemia test as a guide to initiate the therapy. MethodsWe performed a prospective study on 47 consecutive kidney recipients. The CMV pp65 antigenemia test was performed over 6 months posttransplantation; patients who displayed ≥2/200,000 CMV antigen-positive leukocytes were treated for 2 months with valgancyclovir (450 mg twice a day). ResultsTwenty-five patients developed CMV infections, which were initially diagnosed at 55 ± 25 days posttransplantation. The number of CMV antigen-positive cells/200,000 leukocytes on the first positive test was 17 ± 22. The test first became negative at 17 ± 8 days after the diagnosis. A positive correlation was observed between the number of CMV antigen-positive cells and the time to obtain the first negative test (P = .01). At the end of follow-up (35.3 ± 16.4 months), none of the patients had developed CMV syndrome. Among the CMV-positive recipients, the creatinine levels showed no differences from the values before the CMV infection. No difference in creatinine levels was noted between CMV infection positive versus negative patients. ConclusionOur data suggested that a CMV antigenemia titer ≥ 2/200.000 leucocytes can be considered to be an appropriate threshold to start anti-CMV preemptive therapy.