Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on ...long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions.
We conducted a single-centre, observational cohort study examining adult patients (≥ 18 years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31
, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT.
The cumulative probability of SC within 30 days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 95% CI: 1.11, 2.86), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 95% CI: 1.37, 2.77).
Early SC following KT are common and have a significant influence on long-term patient outcomes.
Context:
Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The ...epidemiology of leukopenia in patients on valganciclovir remains poorly understood.
Objective:
To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation.
Methods:
In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models.
Results:
A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio HR 2.34 95% confidence interval CI, 1.37-4.00) and high baseline body mass index (HR 1.05 95% CI, 1.02-1.09) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 95% CI, 0.78-0.97) was significantly associated with a decreased risk of leukopenia.
Conclusions:
These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.
Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize ...exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R2=26.2%, right kidney R2=26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J‐test: P=.02, Cox–Pesaran test: P=.01) and Mayo formulas (J‐test: P=.004, Cox–Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology.
While there is increasing reliance on a negative virtual crossmatch to proceed with deceased donor kidney transplantation, a flow cytometry crossmatch (FCXM) is still usually performed after the ...transplant has already occurred. Our center has eliminated pretransplant physical crossmatches for most patients, and since 2018, we have eliminated the systematic performance of posttransplant FCXMs.
We studied all deceased donor kidney transplants in our program between June 1, 2018, and March 31, 2021, to evaluate the impact of eliminating retrospective FCXMs on resource utilization and graft outcomes (ie, the occurrence of antibody-mediated rejection AMR in the first 3-mo posttransplant).
A total of 358 kidney transplants occurred during the study period, and approximately 70% of these transplants proceeded without the performance of any FCXM. Incidence rates of AMR were low (9.63 per 1000 person-months), which compared favorably with the incidence rate of AMR during the 3-y period preceding the policy (4.82 per 1000 person-months,
= 0.21).
Our results suggest that moving away from retrospective FCXM and relying exclusively on the virtual crossmatch is safe and efficient for kidney allocation.
Background:
Functional disability is defined as the need for assistance with self-care tasks.
Objective:
To document changes in functional status over time among older prevalent renal transplant ...recipients.
Design:
Single center, prospective, follow-up study.
Setting:
Single center, tertiary care transplant center.
Patients:
Patients, with a functioning kidney transplant, aged 65 years or older who underwent assessment of functional status approximately 12 months previously.
Measurements:
Validated tools used included Barthel Index, the Lawton-Brody Scale of Instrumental Activities of Daily Living, the Timed Up and Go test, the Veterans Specific Activity Questionnaire, the Mini-Cog, and dynamometer handgrip strength.
Methods:
Outpatient assessment by a trained observer.
Results:
Of the 82 patients previously studied, 64 (78%) patients participated in the follow-up study (mean age 70.5 ± 4.4 years, 58% male, 55% diabetic). Among those completing functional status measures, 32 (50%) had functional disability at baseline. Over the 1-year period, 11 (17%) of these patients experienced progressive functional decline, 6 (9%) exhibited no change, and 15 (23%) had functional recovery. Eleven patients (17%) initially independent, developed new-onset disability. One of the strongest predictors of progressive functional decline was having 1 or more falls in the previous year.
Limitations:
Assessments were performed only on 2 occasions separated by approximately 1 year.
Conclusions:
Fluctuations in disability states are common among older adults living with renal transplants. Episodes of functional disability may place individuals at higher risk of persistent and/or progressive disability.
Despite comprehensive multidisciplinary candidacy assessments to determine appropriateness for solid organ transplantation, limitations persist in identifying candidates at risk of adverse outcomes. ...Frailty measures may help inform candidacy evaluation. Our main objective was to create a solid organ transplant frailty index (FI), using the cumulative deficits model, from data routinely collected during candidacy assessments. Secondary objectives included creating a social vulnerability index (SVI) from assessment data and evaluating associations between the FI and assessment, waitlist, and posttransplant outcomes.
In this retrospective cohort study of solid organ transplant candidates from Toronto General Hospital, cumulative deficits FI and SVI were created from data collected during candidacy evaluations for consecutive kidney, heart, liver, and lung transplant candidates. Regression modeling measured associations between the FI and transplant listing, death or removal from the transplant waitlist, and survival after waitlist placement.
For 794 patients, 40 variable FI and 10 variable SVI were created (258 lung, 222 kidney, 201 liver, and 113 heart transplant candidates). The FI correlated with assessment outcomes; patients with medical contraindications (mean FI 0.35 ± 0.10) had higher FI scores than those listed (0.29 ± 0.09),
< 0.001. For listed patients, adjusted for age, sex, transplant type, and SVI, higher FI was associated with an increased risk of death (pretransplant or posttransplant) or delisting (hazard ratio 1.03 per 0.01 FI score, 95% confidence interval, 1.01-1.05,
= 0.01).
A cumulative deficits FI can be derived from routine organ transplant candidacy evaluations and may identify candidates at higher risk of adverse outcomes.
Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens ...are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR.
We analyzed non-HLA antibodies in sera from 80 kidney transplant patients with AMR, mixed rejection, acute cellular rejection (ACR), or acute tubular necrosis. IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pretransplant or at the time of diagnosis.
Fifteen non-HLA antibodies were significantly increased (
< 0.05) in AMR and mixed rejection compared with ACR or acute tubular necrosis pretransplant, and 7 at diagnosis. AMR and mixed cases showed significantly increased pretransplant levels of IgG anti-Ro/Sjögren syndrome-antigen A (SS-A) and anti-major centromere autoantigen (CENP)-B, compared with ACR. Together with IgM anti-CENP-B and anti-La/SS-B, these antibodies were significantly increased in AMR/mixed rejection at diagnosis. Increased IgG anti-Ro/SS-A, IgG anti-CENP-B, and IgM anti-La/SS-B were associated with the presence of microvascular lesions and class-II donor-specific antibodies (
< 0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared with ACR were reproduced in an external cohort of 60 kidney transplant patients.
This is the first study implicating autoantibodies anti-Ro/SS-A and anti-CENP-B in AMR. These antibodies may participate in the crosstalk between autoimmunity and alloimmunity in kidney AMR.
Delayed graft function (DGF) is commonly considered a risk factor for acute rejection, although this finding has not been uniformly observed across all studies. The link between DGF and acute ...rejection may have changed over time due to advances in immunosuppression and medical management. Here we conducted a cohort study of 645 patients over 12 years to evaluate the association of DGF and biopsy-proven acute rejection (BPAR) in a modern cohort of kidney transplant recipients. DGF was defined as the need for at least one dialysis session in the first week after kidney transplantation. The 1-, 3-, and 5-year cumulative probabilities of BPAR were 16.0, 21.8, and 22.6% in the DGF group, significantly different from the 10.1, 12.4, and 15.7% in the non-DGF group. In multivariable Cox proportional hazards model, the adjusted relative hazard for BPAR in DGF (vs. no DGF) was 1.55 (95% confidence interval (CI): 1.03, 2.32). This association was generally robust to different definitions of DGF. The relative hazard was also similarly elevated for T-cell- or antibody-mediated BPAR (1.52 (0.92, 2.51) and 1.54 (0.85, 2.77), respectively). Finally, the association was consistent across clinically relevant subgroups. Thus DGF remains an important risk factor for BPAR in a contemporary cohort of kidney transplant recipients. Interventions to reduce the risk of DGF and/or its aftereffects remain of paramount importance to improve kidney transplant outcomes.
Wide variations in tacrolimus levels have been identified as a risk factor for inferior kidney allograft survival but past studies have not properly accounted for the dynamic nature of drug exposure ...over time. Here we evaluated whether time-varying exposure to tacrolimus increases the risk of long-term adverse outcomes in a retrospective cohort study in adult kidney transplant recipients on tacrolimus-based immunosuppression. Time-dependent Cox proportional hazards models were used to examine the association between the standard deviation of tacrolimus levels (TacSD) starting at 1-year post-transplant and the composite end point of late allograft rejection, transplant glomerulopathy, or total graft loss (including death). Among 356 patients, there was a significant 27% increase in the adjusted hazard of the composite end point for every 1-unit increase in TacSD (hazard ratio 1.27 (95% confidence interval 1.03, 1.56)). There was also a graded increase in the relative hazard for the composite end point by TacSD threshold (hazard ratios 1.33, 1.50, 1.84, and 2.56 for TacSD 1.5, 2, 2.5, and 3, respectively). The results were similar for total graft loss and the composite end point excluding death. Thus, increased time-dependent TacSD may be an independent risk factor for adverse kidney transplant outcomes. TacSD may serve as a monitoring tool to identify high-risk patients. Whether interventions to decrease TacSD will improve outcomes requires further study.
Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective ...cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio HR, 1.24 per 0.1 mmol/L decrease; 95% confidence interval 95% CI, 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.
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