Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Early Effect of the Circular Model of Kidney Allocation in the United States.

BACKGROUND: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. METHODS: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after the onset of COVID-19 and the implementation of KAS250 were evaluated using an interrupted time-series model. Changes in allocation practices (biopsy, machine perfusion, and virtual cross-match) were also evaluated. RESULTS: Post-KAS250 saw a two-fold increase in kidneys imported from nonlocal organ procurement organizations (OPO) and a higher proportion of recipients with calculated panel reactive antibody (cPRA) 81%-98% (12% versus 8%; P <0.001) and those with >5 years of pretransplant dialysis (35% versus 33%; P <0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards after KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased, whereas reliance on virtual cross-match increased, which was associated with shorter CIT. CONCLUSIONS: Early trends after KAS250 show an increase in transplant access to patients with cPRA>80% and those with longer dialysis duration, but this was accompanied by an increase in CIT and a suggestion of worsening kidney discards.

Transitional B cell cytokines risk stratify early borderline rejection after renal transplantation.

Borderline rejection (BL) in renal transplantation is associated with decreased allograft survival, yet many patients with BL maintain stable graft function. Identifying patients with early BL at risk for shortened allograft survival would allow for timely targeted therapeutic intervention aimed at improving outcomes. 851/1187 patients transplanted between 2013-18 underwent early biopsy (0-4 mos). 217/851 (25%) had BL and were compared to 387/851 without significant inflammation (NI). Serial surveillance and for-cause biopsies and seven-year follow-up were used to evaluate histological and clinical progression. To identify high-risk patients, we examined clinical/histological parameters using regression and non-linear dimensionality reduction (tSNE) and a biomarker based on peripheral blood transitional-1 B cell (T1B) IL-10/TNFα ratio. Compared to NI, early BL was associated with increased progression to late acute rejection (AR; 5-12 mos), premature interstitial fibrosis and tubular atrophy (IFTA) and decreased seven-year graft survival. However, decreased graft survival was limited to BL patients who progressed to late AR or IFTA, and was not influenced by treatment. Although tSNE clustered patients into groups based on clinical factors, the ability of these factors to risk stratify BL patients was modest. In contrast, a low T1B IL-10/TNFα ratio at 3 months identified BL patients at high risk for progression to AR (ROC AUC 0.87) and poor 7-yr graft survival (52% vs. 92%, p=0.003), while BL patients with a high ratio had similar graft survival to patients with NI (91%, p=NS). Thus, progressive early allograft inflammation manifested as BL that progresses to late AR in the first post-transplant year represents a high-risk clinical state for poor allograft outcomes. Such high-risk status can be predicted by the T1B IL-10/TNFα ratio before irreversible scarring sets in, thus allowing timely risk stratification.

Long-term immunological outcomes of early subclinical inflammation on surveillance kidney allograft biopsies.

The long-term impact of early subclinical inflammation (SCI) through surveillance biopsy has not been well studied. To do this, we recruited a prospective observational cohort that included 1000 sequential patients who received a kidney transplant from 2013-2017 at our center. A total of 586 patients who underwent a surveillance biopsy in their first year post-transplant were included after excluding those with clinical rejections, and those who were unable to undergo a surveillance biopsy. Patients were classified based on their biopsy findings: 282 with NSI (No Significant Inflammation) and 304 with SCI-T (SCI and Tubulitis) which was further subdivided into 182 with SC-BLR (Subclinical Borderline Changes) and 122 with SC-TCMR (Subclinical T Cell Mediated Rejection, Banff 2019 classification of 1A or more). We followed the clinical and immunological events including Clinical Biopsy Proven Acute Rejection [C-BPAR], long-term kidney function and death-censored graft loss over a median follow-up of five years. Episodes of C-BPAR were noted at a median of two years post-transplant. Adjusted odds of having a subsequent C-BPAR was significantly higher in the SCI-T group [SC-BLR and SC-TCMR] compared to NSI 3.8 (2.1-7.5). The adjusted hazard for death-censored graft loss was significantly higher with SCI-T compared to NSI [1.99 (1.04-3.84)]. Overall, SCI detected through surveillance biopsy within the first year post-transplant is a harbinger for subsequent immunological events and is associated with a significantly greater hazard for subsequent C-BPAR and death-censored graft loss. Thus, our study highlights the need for identifying patients with SCI through surveillance biopsy and develop strategies to prevent further alloimmune injuries.

The combination of exposure to Tacrolimus, mycophenolic acid, Inosine 5'-Monophosphate Dehydrogenase activity and inhibition in the first week define early histological outcomes in renal transplant recipients.

Therapeutic drug monitoring is routine for Tacrolimus, while levels are not routinely monitored for mycophenolic acid (MPA). This study investigated the effect of early post-transplant pharmacokinetics (PK) of MPA and Tacrolimus along with the pharmacodynamics (PD) of MPA on biopsy-proven acute rejection (BPAR) after renal transplantation. A prospective PK/PD study with limited sampling (three blood samples) was conducted in renal transplant recipients on week 1, around Day 6 (n = 42) and at the 3rd-month biopsy on Day 90 (n = 23). The partial exposures (area under curve [AUC]0-3.5 h ) of both MPA and Tacrolimus obtained during the first week were more predictive of rejection (combined clinical and subclinical rejection) by Day 90 than their trough concentrations or Day 90 exposures. Patients with rejection had significantly worse renal function (eGFR) and a comparatively lower exposure to MPA during the first post-transplant week. The lower MPA exposure was also associated with sub-optimal inosine monophosphate dehydrogenase (IMPDH) inhibition in patients with rejection, and the probability of rejection was higher in the presence of an increased pre-transplant IMPDH activity. A composite of parameters, including MPA exposure and IMPDH activity was found to predict acute rejection and may be beneficial along with tacrolimus monitoring early after renal transplantation.

Rabbit antithymocyte globulin dose and early subclinical and clinical rejections in kidney transplantation.

Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5-6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R-) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group (n = 56) received <5 mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG (P < .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12-3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.

Function and longevity of renal grafts from high-KDPI donors.

BACKGROUND: High kidney-donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. METHODS: We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I-KDPI ≤ 25% (n = 151), Group II-KDPI 26-50% (n = 182), Group III-KDPI 51-75% (n = 176), and Group IV-KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5-years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group. FINDINGS: High-KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups (P = .06). Although patient survival was signigicantly lower for recipients of high-KDPI grafts, death-censored graft survival was similar among the four KDPI groups (P = .33). CONCLUSIONS: The shorter functional survival of high-KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.

The Clinical Impact of Anti-HLA Donor Specific Antibody Detection Through First Year Screening on Stable Kidney Transplant Recipients.

Anti-HLA Donor Specific Antibody (DSA) detection post kidney transplant has been associated with adverse outcomes, though the impact of early DSA screening on stable patients remain unclear. We analyzed impact of DSA detection through screening in 1st year stable patients (n = 736) on subsequent estimated glomerular filtration rate (eGFR), death censored graft survival (DCGS), and graft failure (graft loss including return to dialysis or re-transplant, patient death, or eGFR < 20 ml/min at last follow up). Patients were grouped using 1st year screening into DSA+ (Class I, II; n = 131) or DSA- (n = 605). DSA+ group were more DR mismatched (p = 0.02), more sensitized (cPRA ≥90%, p = 0.002), less Caucasian (p = 0.04), and had less pre-emptive (p = 0.04) and more deceased donor transplants (p = 0.03). DSA+ patients had similar eGFR (54.8 vs. 53.8 ml/min/1.73 m2, p = 0.56), DCGS (91% vs. 94%, p = 0.30), and graft failure free survival (76% vs. 82%, p = 0.11). DSA timing and type did not impact survival. Among those with a protocol biopsy (n = 515), DSA detected on 1st year screening was a predictor for graft failure on multivariate analysis (1.91, 95% CI 1.03-3.55, p = 0.04). Overall, early DSA detection in stable patients was an independent risk factor for graft failure, though only among those who underwent a protocol biopsy.

Economic analysis of screening for subclinical rejection in kidney transplantation using protocol biopsies and noninvasive biomarkers.

Subclinical rejection (SCR) screening in kidney transplantation (KT) using protocol biopsies and noninvasive biomarkers has not been evaluated from an economic perspective. We assessed cost-effectiveness from the health sector perspective of SCR screening in the first year after KT using a Markov model that compared no screening with screening using protocol biopsy or biomarker at 3 months, 12 months, 3 and 12 months, or 3, 6, and 12 months. We used 12% subclinical cellular rejection and 3% subclinical antibody-mediated rejection (SC-ABMR) for the base-case cohort. Results favored 1-time screening at peak SCR incidence rather than repeated screening. Screening 2 or 3 times was favored only with age <35 years and with high SC-ABMR incidence. Compared to biomarkers, protocol biopsy yielded more quality-adjusted life years (QALYs) at lower cost. A 12-month biopsy cost $13 318/QALY for the base-case cohort. Screening for cellular rejection in the absence of SC-ABMR was less cost effective with 12-month biopsy costing $46 370/QALY. Screening was less cost effective in patients >60 years. Using biomarker twice or thrice was cost effective only if biomarker cost was <$700. In conclusion, in KT, screening for SCR more than once during the first year is not economically reasonable. Screening with protocol biopsy was favored over biomarkers.

Kidney allograft rejection: Diagnosis and treatment practices in USA- A UNOS survey.

We studied diverse rejection management strategies across centers by conducting a UNOS survey of kidney transplant program directors in 2017. There were 104 total responses from 235 kidney transplant programs representing 88 unique transplant programs (response rate 37%). Information was collected on center-specific management practices. Pertinent center-specific data were obtained from the OPTN database. Of the respondents, 33% were considered large centers (>100 transplants/year). Thymoglobulin was the most commonly used induction agent at 84%, 72% responders do rapid steroid withdrawal, and mycophenolic acid (MPA) is the major antimetabolite (100%). For diagnosing TCMR, 100% used indication biopsy, 28% used protocol biopsy, 2% used serum biomarkers, and none used urine cytokines. For ABMR, 99% used indication biopsy, 34% used protocol biopsy, 72% used DSA, 21% used C1q positive DSA, and none used gene profiling (ENDATS). The treatment of subclinical and clinical TCMR included iv/PO steroids. PP/IVIG were the commonest treatments for ABMR. The use of rituximab, bortezomib, and eculizumab increased from C4D-ABMR to recurrent ABMR. There are diverse management practices for diagnosing and treating rejection. An effort to harmonize these diverse practices for management of TCMR and ABMR will give an opportunity to pool data for evaluating clinical outcomes.

Donation after circulatory death is associated with increased fibrosis on 1-year post-transplant kidney allograft surveillance biopsy.

AIM: The use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here, we investigated the effect of DCD on fibrotic changes on 1 1-year post 1-transplant surveillance kidney allograft biopsy. METHODS: Recipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]). Banff scores for interstitial fibrosis and tubular atrophy were summed as IFTA and compared between the groups. RESULTS: DCD and DBD groups were comparable for baseline characteristics. Delayed graft function was 39% in DCD versus 19% in DBD, P = .0002. Patient and graft survival were comparable for DCD and DBD cohorts. IFTA scores were higher in DCD compared to DBD (2.43±..13 vs. 2.01±..08, P = .0054). On multivariate analysis, the odds of IFTA > 2 in the DCD group was 2.5× higher (95%CI: 1.354.63) than in the DBD group. Within the DCD group, kidneys with IFTA > 2 had inferior 5-year graft survival (P = .037). CONCLUSION: Compared to DBD kidneys, DCD kidneys developed a greater degree of fibrotic changes on 1-year post-transplant surveillance biopsy, which affected graft longevity within the DCD cohort.

Early subclinical tubulitis and interstitial inflammation in kidney transplantation have adverse clinical implications.

This prospective observational cohort study compared the impact of subclinical tubulitis with or without interstitial inflammation to interstitial inflammation alone and to no inflammation in early post kidney transplant biopsies. A study cohort of 415 patients (living and deceased donor recipients) was divided into three groups on the basis of their three-month biopsy: 149 patients with No Inflammation (NI), 83 patients with Isolated Interstitial Inflammation (IIF), and 183 patients with Tubulitis [(with or without interstitial inflammation) (TIF) but not meeting criteria for Banff IA]. TIF was further divided into 56 patients with tubulitis without interstitial inflammation (TIF0) and 127 patients with tubulitis alongside interstitial inflammation (TIF1). TIF was significantly associated with higher incidence of subsequent T-cell mediated rejection (clinical or subclinical) at one year compared to IIF (31% vs 15%) and NI (31% vs 17%). Chronicity on one-year biopsy was significantly higher in TIF compared to IIF (22% vs 11%) and NI (22% vs 7%). De novo donor-specific antibody development was significantly higher in TIF compared to NI (6% vs 0.7%). Tubulitis subgroups (TIF0 and TIF1) revealed comparable effects on de novo donor-specific antibody and interstitial fibrosis/tubular atrophy development. However, tubulitis with interstitial inflammation had a significantly higher incidence of subsequent rejection and posed an increased hazard for the composite end point (subsequent acute rejection and death censored graft loss) compared to other groups [adjusted hazard 2.1 (95% confidence interval 1.2-3.5)]. Thus, subclinical tubulitis is a marker of adverse immunological events, but tubulitis with interstitial inflammation has a worse prognosis. Hence, the Banff 1997 (TIF1) and Banff 2005 classifications (TIF) for borderline change may have different implications.

Donor acute kidney injury and its effect on 1-year post-transplant kidney allograft fibrosis.

Transplantation of kidneys from deceased donors with acute kidney injury (AKI) can expand the donor pool. We investigated the effect of donor AKI on renal function and chronic changes on protocol biopsies at 1-year post-transplant. Donor AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. Between 2013 and 2017, 333 kidneys were transplanted and subsequently biopsied after 1 year. Fifty-three kidneys from AKI donors (AKIN stage I n = 42, stage II n = 8, stage III n = 3) were compared to 280 kidneys from non-AKI donors. At 1-year follow-up, patient and graft survival were comparable. Donor AKI was not predictive of IFTA (Banff interstitial fibrosis plus tubular atrophy scores) at 1-year post-transplant biopsy (2.10 ± 1.28 in AKI, 2.09 ± 1.22 in non-AKI, P = .95). Donor AKI was also not associated with progression of IFTA from 3 to 12 months (P = .69), or inferior glomerular filtration rate (eGFR, P = .94). In a multivariate analysis, the odds of IFTA >2 were comparable between AKI and non-AKI groups. In conclusion, the transplantation of kidneys from donors with predominantly stage I AKI results in comparable function and degree of fibrosis on protocol biopsies 1-year post-transplant. Selected grafts from donors with AKI are a valuable tool for expanding the donor pool for kidney transplantation.

Post-transplant donor specific antibody is associated with poor kidney transplant outcomes only when combined with both T-cell-mediated rejection and non-adherence.

Post-transplant donor specific antibody (DSA) is associated with poor renal allograft outcomes. However, variable timing of DSA assessment and inclusion of patients who undergo desensitization treatments have hindered our understanding of its consequences and limited its predictive value. Here we prospectively studied non-desensitized patients to determine factors associated with poor four-year outcomes in patients who developed post-transplant DSA. Using serial monitoring, 67 of 294 patients were found to develop DSA by one year. Compared to patients who do not develop DSA, those with DSA exhibit an increased incidence of both clinical and subclinical T-cell-mediated rejection (TCMR). The combination of TCMR plus DSA led to an almost three-fold increase in graft loss compared to either DSA or TCMR alone. Moreover, DSA was associated with higher Banff grade TCMR and chronic changes at one year. Antibody-mediated rejection was uncommon and always associated with TCMR. Amongst factors independently associated with DSA plus TCMR; non-adherence is potentially modifiable. Non-adherence, measured as intra-patient variability of calcineurin trough levels during the first post-transplant year, further risk-stratified patients with DSA plus TCMR such that about 75% of these patients had impending graft loss by four years, whereas adherent patients with DSA plus TCMR had outcomes comparable to other patient groups. Thus, early post-transplant DSA, especially in non-adherent patients, is associated with increased incidence of TCMR and represents a high-risk group of patients who might benefit from targeted therapeutic interventions.

Short-term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol.

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24-months and allograft histology score at 12-month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24-months posttransplant, and at last follow-up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12-months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor-specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long-term implications for kidney allograft function.

Early allograft inflammation and scarring associate with graft dysfunction and poor outcomes in renal transplant recipients with delayed graft function: a prospective single center cohort study.

Early histological progression that associates with delayed graft function (DGF) and its relationship to graft outcomes is less well-understood. We systematically evaluated early acute and chronic histological changes associated with DGF through serial biopsies (protocol: 3 and 12 months; for-cause) and related them to graft outcomes. 56/294 (19.04%) of our patients had DGF. DGF was associated with a progressive increase in both Banff 't' and 'i' scores from 2 weeks to 3 and 12 months with a resultant increase in T cell mediated rejection (TCMR) that was significantly greater than those with primary graft function (PGF). This increase in TCMR was predominantly sub-clinical TCMR diagnosed on protocol biopsy. Furthermore, TCMR in patients with DGF was recurrent/persistent at 12 months. Importantly, the combination of DGF and TCMR was associated with significantly worse interstitial fibrosis and tubular atrophy (IFTA) and interstitial fibrosis with inflammation (IF + 'i') as early as 3 months and worse renal function. Finally, DGF with TCMR was associated with significantly worse graft loss. In this regard, DGF without TCMR had comparable chronic histology and outcomes to PGF. Thus, DGF with TCMR (predominantly sub-clinical), represents a high-risk patient group who may benefit from early novel immunosuppression augmentation strategies to improve graft outcomes.

Kidney allograft surveillance biopsy practices across US transplant centers: A UNOS survey.

BACKGROUND: The approach to the diagnosis and management of subclinical rejection (SCR) in kidney transplant recipients remains controversial. METHODS: We conducted a survey through UNOS across US transplant centers regarding their approach to surveillance biopsies and reasons for the nonperformance of surveillance biopsies. RESULTS: Responses were obtained from 106/238 centers (45%), and only 18 (17%) of the centers performed surveillance biopsies on all patients and 22 (21%) performed biopsy for select cases. The most common time points for surveillance biopsies were 3 and 12  months post-transplant. The common reasons for not performing biopsies were low yield (n = 44, 65%) and the belief that it will not change outcome (n = 24, 36%). The incidence of SC-TCMR was ≥ 10% among 39% of centers. The mean serum creatinine was slightly worse by 0.06 mg/dL at 1 year and 0.07 mg/dL at 3 years among centers performing biopsy, P < .0001. The. 1-and 3-year Observed-Expected (O-E) graft survival was similar among centers performing biopsies vs. those not performing biopsy (P = .07, .88). CONCLUSION: Only 17% of US centers perform surveillance biopsies, with another 21% performing surveillance biopsies in select cases (among centers that responded to the survey). Greater uniformity in the approach and management of this condition is of paramount importance.

Cytomegalovirus infection in high-risk kidney transplant recipients receiving thymoglobulin induction-a single-center experience.

BACKGROUND: The burden of cytomegalovirus infection in CMV high-risk (donor positive to recipient negative) kidney transplant recipients getting thymoglobulin induction and six months of valganciclovir is not well characterized. Additionally, the role of post-prophylaxis surveillance remains unclear. METHODS: One-year observational study of forty-eight high-risk CMV kidney transplant recipients transplanted under thymoglobulin between January 2013 and July 2014. All received valganciclovir for six months, followed by monthly CMV PCR for three months. RESULTS: CMV infection defined as viremia with or without symptoms occurred in 40% (19/48). Of these, 47% (9/19) occurred during prophylaxis, 32% (6/19) during surveillance and 21% (4/19) during post-surveillance period (9-12 months). Among breakthrough infections, suboptimal valganciclovir dosing was present in 55% (5/9). With routine surveillance, there was a trend toward lower CMV-related hospitalization (17% vs 56% and 75% during prophylaxis and post-surveillance, respectively [P=.23]) and lower mean peak viral loads (19 432 copies/mL vs 97 925 copies/mL and 536 021 copies/mL during prophylaxis and post-surveillance, respectively [P=.07]). CONCLUSION: CMV infection remains a significant problem with thymoglobulin induction despite six months of valganciclovir. Suboptimal valganciclovir dosing was common among breakthrough infections. Monthly surveillance post-prophylaxis appears to detect early CMV infection with lower degree of viremias requiring fewer hospitalizations.