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1.
Clin Transplant ; 38(5): e15329, 2024 May.
Article in English | MEDLINE | ID: mdl-38722085

ABSTRACT

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.


Subject(s)
BK Virus , Graft Rejection , Graft Survival , Kidney Function Tests , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Viremia , Humans , Kidney Transplantation/adverse effects , BK Virus/immunology , BK Virus/isolation & purification , Female , Male , Polyomavirus Infections/immunology , Polyomavirus Infections/virology , Polyomavirus Infections/complications , Middle Aged , Graft Rejection/etiology , Graft Rejection/immunology , Follow-Up Studies , Tumor Virus Infections/immunology , Tumor Virus Infections/virology , Viremia/immunology , Viremia/virology , Prognosis , Risk Factors , Glomerular Filtration Rate , Adult , Postoperative Complications , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Retrospective Studies , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/immunology , Kidney Diseases/virology , Kidney Diseases/immunology , Kidney Diseases/surgery , Transplant Recipients
2.
Transplantation ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38685195

ABSTRACT

BACKGROUND: The current landscape of organ donation and transplantation (ODT) registries is not well established. This narrative review sought to identify and characterize the coverage, structure, and data capture of ODT registries globally. METHODS: We conducted a literature search using Ovid Medline and web searches to identify ODT registries from 2000 to 2023. A list of ODT registries was compiled based on publications of registry design, studies, and reports. Extracted data elements included operational features of registries and the types of donor and recipient data captured. RESULTS: We identified 129 registries encompassing patients from all continents except Antarctica. Most registries were active, received funding from government or professional societies, were national in scope, included both adult and pediatric patients, and reported patient-level data. Registries included kidney (n = 99), pancreas (n = 32), liver (n = 44), heart (n = 35), lung (n = 30), intestine (n = 15), and islet cell (n = 5) transplants. Most registries captured donor data (including living versus deceased) and recipient features (including demographics, cause of organ failure, and posttransplant outcomes) but there was underreporting of other domains (eg, donor comorbidities, deceased donor referral rates, waitlist statistics). CONCLUSIONS: This review highlights existing ODT registries globally and serves as a call for increased visibility and transparency in data management and reporting practices. We propose that standards for ODT registries, a common data model, and technical platforms for collaboration, will enable a high-functioning global ODT system responsive to the needs of transplant candidates, recipients, and donors.

3.
Transplant Rev (Orlando) ; 38(3): 100854, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38608414

ABSTRACT

BACKGROUND: Impact of donor smoking history on kidney transplant recipient outcomes is undefined. METHODS: We systematically searched, critically appraised, and summarized associations between donor smoking and primary outcomes of death-censored and all-cause graft failure (DCGF, ACGF), and secondary outcomes of allograft histology, delayed graft function, serum creatinine, estimated glomerular filtration rate, and mortality. We searched MEDLINE, Embase, and Cochrane Databases from 2000 to 2023. Risk of bias was assessed using Risk of Bias in Non-randomized Studies - of Exposure tool. Quality of evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation Working Group recommendations. We pooled results using inverse variance, random-effects model and reported hazard ratios for time-to-event outcomes or binomial proportions. Statistical heterogeneity was assessed with I2 statistic. RESULTS: From 1785 citations, we included 17 studies. Donor smoking was associated with modestly increased DCGF (HR 1.05 (95% CI: 1.01, 1.09); I2 = 0%; low quality of evidence), predominantly in deceased donors, and ACGF in adjusted analyses (HR 1.12 (95% CI: 1.06, 1.19); I2 = 20%; very low quality of evidence). Other outcomes could not be pooled meaningfully. CONCLUSIONS: Kidney donor smoking history was associated with modestly increased risk of death-censored graft failure and all-cause graft failure. This review emphasizes the need for further research, standardized reporting, and thoughtful consideration of donor factors like smoking in clinical decision-making on kidney utilization and allocation.

4.
Clin Transplant ; 38(4): e15292, 2024 04.
Article in English | MEDLINE | ID: mdl-38545888

ABSTRACT

BACKGROUND: There is variability in recommended viral monitoring protocols after kidney transplant. In response to increased demand for laboratory testing during the COVID-19 pandemic, the Transplant Manitoba Adult Kidney Program updated its monitoring protocols for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) to a reduced frequency. METHODS: This single-center nested case-control study evaluated 252 adult kidney transplant recipients transplanted from 2015 to 2021, with the updated protocols effective on March 19th 2020. Cases included recipients transplanted after the protocol update who developed CMV, EBV, and BKV DNAemia and were matched to controls with DNAemia transplanted prior to the protocol update. The primary outcome was the difference in maximum DNA load titers between cases and matched controls. Secondary outcomes included time to initial DNAemia detection and DNAemia clearance. Safety outcomes of tissue-invasive viral disease were described. RESULTS: There were 216 recipients transplanted preupdate and 36 recipients postupdate. There was no difference between cases and controls in maximum or first DNA load titers for EBV, CMV, or BKV. Cases experienced earlier EBV DNAemia detection (26 (IQR 8, 32) vs. 434 (IQR 96, 1184) days, p = .005). Median follow-up was significantly longer for recipients transplanted preupdate (4.3 vs. 1.3 years, p < .0001). After adjusting for follow-up time, there was no difference in DNAemia clearance or tissue-invasive viral disease. CONCLUSION: Our findings suggest that reduced frequency viral monitoring protocols may be safe and cost-effective. This quality assurance initiative should be extended to detect longer-term and tissue-invasive disease outcomes.


Subject(s)
BK Virus , Cytomegalovirus Infections , Epstein-Barr Virus Infections , Kidney Transplantation , Adult , Humans , Herpesvirus 4, Human/genetics , Cytomegalovirus/genetics , Kidney Transplantation/adverse effects , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/etiology , BK Virus/genetics , Case-Control Studies , Pandemics , Cytomegalovirus Infections/diagnosis , DNA , DNA, Viral/genetics , Transplant Recipients
5.
Am J Transplant ; 22(3): 761-771, 2022 03.
Article in English | MEDLINE | ID: mdl-34717048

ABSTRACT

The prevalence and long-term impact of T cell-mediated rejection (TCMR) is poorly defined in the modern era of tacrolimus/mycophenolate-based maintenance therapy. This observational study evaluated 775 kidney transplant recipients with serial histology and correlated TCMR events with the risk of graft loss. After a ~30% incidence of a first Banff Borderline or greater TCMR detected on for-cause (17%) or surveillance (13%) biopsies, persistent (37.4%) or subsequent (26.3%) TCMR occurred in 64% of recipients on follow-up biopsies. Alloimmune risk categories based on the HLA-DR/DQ single molecule eplet molecular mismatch correlated with the number of TCMR events (p = .002) and Banff TCMR grade (p = .007). Both a first and second TCMR event correlated with death-censored and all-cause graft loss when adjusted for baseline covariates and other significant time-dependent covariates such as DGF and ABMR. Therefore, a substantial portion of kidney transplant recipients, especially those with intermediate and high HLA-DR/DQ molecular mismatch scores, remain under-immunosuppressed, which in turn identifies the need for novel agents that can more effectively prevent or treat TCMR.


Subject(s)
Kidney Transplantation , Allografts , Graft Rejection , Graft Survival , HLA Antigens , HLA-DR Antigens , Kidney Transplantation/adverse effects , T-Lymphocytes
6.
Am J Transplant ; 22(3): 772-785, 2022 03.
Article in English | MEDLINE | ID: mdl-34860468

ABSTRACT

The effectiveness of T cell-mediated rejection (TCMR) therapy for achieving histological remission remains undefined in patients on modern immunosuppression. We systematically identified, critically appraised, and summarized the incidence and histological outcomes after TCMR treatment in patients on tacrolimus (Tac) and mycophenolic acid (MPA). English-language publications were searched in MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Ovid), CINAHL (EBSCO), and Clinicaltrials.gov (NLM) up to January 2021. Study quality was assessed with the National Institutes of Health Study Quality Tool. We pooled results using an inverse variance, random-effects model and report the binomial proportions with associated 95% confidence intervals (95% CI). Statistical heterogeneity was explored using the I2  statistic. From 2875 screened citations, we included 12 studies (1255 participants). Fifty-eight percent were good/high quality while the rest were moderate quality. Thirty-nine percent of patients (95% CI 0.26-0.53, I2 77%) had persistent ≥Banff Borderline TCMR 2-9 months after anti-rejection therapy. Pulse steroids and augmented maintenance immunosuppression were mainstays of therapy, but considerable practice heterogeneity was present. A high proportion of biopsy-proven rejection exists after treatment emphasizing the importance of histology to characterize remission. Anti-rejection therapy is foundational to transplant management but well-designed clinical trials in patients on Tac/MPA immunosuppression are lacking to define the optimal therapeutic approach.


Subject(s)
Graft Rejection , Kidney Transplantation , Graft Rejection/drug therapy , Graft Rejection/etiology , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Mycophenolic Acid/therapeutic use , T-Lymphocytes , Tacrolimus/therapeutic use
7.
Clin J Am Soc Nephrol ; 16(12): 1805-1812, 2021 12.
Article in English | MEDLINE | ID: mdl-34697092

ABSTRACT

BACKGROUND AND OBJECTIVES: Although progressive decline in physical activity and function are common in individuals with worsening CKD, little is known about the effect of dialysis initiation on physical activity. We assessed for any association of progression to dialysis in people with advanced CKD with temporal rates of change in physical activity and function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Canadian Frailty Observation and Interventions Trial (CanFIT) participants with an eGFR of <30 ml/min per 1.73 m2 were included. Outcomes included change in physical activity level, measured using the Physical Activity Scale for the Elderly, and physical function, measured using the chair stand, 4-m gait speed, and grip strength tests. Generalized linear regression models were conducted to determine whether dialysis initiation was associated with greater decline in physical activity or function. RESULTS: Of 386 individuals, 162 progressed to dialysis. Both assessments were completed by 98% of individuals for the Physical Activity Scale for the Elderly, 86% for the chair stand test, 84% for the gait speed test, and 91% for the grip strength test. Median (interquartile range) interassessment follow-up was 427 (357-578) days for the "stable advanced CKD" group and 606 (428-1000) days for the "progressed to dialysis" group. Self-reported physical activity and gait speed significantly declined in both groups. Mean (SD) chair stand time increased from 20.8 (17.1) to 24.0 (21.0) seconds among patients with stable advanced CKD, and from 18.5 (15.4) to 27.4 (22.2) seconds among those who progressed to dialysis (adjusted difference in change, 5.2 seconds; 95% confidence interval, 0.8 to 9.7 seconds; P=0.02). CONCLUSIONS: Patients with advanced CKD experience progressive declines in physical activity and function. Transition to dialysis is associated with accelerated decline in physical function, as measured by the chair stand test.


Subject(s)
Exercise , Renal Insufficiency, Chronic , Humans , Aged , Canada , Gait , Renal Dialysis , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/complications
8.
Can J Kidney Health Dis ; 8: 20543581211033405, 2021.
Article in English | MEDLINE | ID: mdl-34497716

ABSTRACT

BACKGROUND: Women scientists are less likely to obtain Assistant Professorship and achieve promotion, and obtain less grant funding than men. Scientist/clinician-scientist training programs which provide salary awards as well as training and mentorship are a potential intervention to improve outcomes among women scientists. We hypothesized whether a programmatic approach to scientist/clinician-scientist training is associated with improved outcomes for women scientists in Canada when compared with salary awards alone. Trainees within the Kidney Research Scientist Core Education and National Training Program (KRESCENT), Canadian Child Health Clinician Scientist Program (CCHCSP), and the Canadian Institutes of Health Research (CIHR) salary award programs were evaluated. OBJECTIVE: To examine whether the structured KRESCENT training program with salary support improves academic success for women scientists relative to salary awards alone. DESIGN: Retrospective cohort study. SETTING: Canadian national research scientist and clinician-scientist training programs and salary awards. PARTICIPANTS: KRESCENT cohort (n = 59, 2005-2017), CCHCSP cohort (n = 58, 2002-2015), and CIHR (n = 571, 2005-2015) Salary Awardees for postdoctoral fellows (PDF) and new investigators (NI). MEASUREMENTS: National operating grant funding success, achieving an academic position as an Assistant Professor for PDF, or achieving promotion to Associate Professor for NI. METHODS: The gender distribution of each cohort was determined using first name and NamepediA and was examined for PDF and NI, followed by a description of trainee outcomes by gender and training level. RESULTS: KRESCENT and CIHR PDF were balanced (12/27, 44% men and 55/116, 47% women) while CCHCSP had a higher proportion of women (13/20, 65%). KRESCENT and CCHCSP NI retained women scientists (19/32, 59% and 22/38, 58% women), whereas CIHR NI had fewer women (165/455, 36% women vs 290/455, 64% men, P = 0.01). There was a high rate of NI operating grant success (91%-95%) with no gender differences in each cohort. There was a high proportion of CCHCSP PDF who achieved an Assistant Professorship (18/20, 90%) that may be due in part to a longer follow-up period (9.3 ± 3 years) compared with KRESCENT PDF (7/27, 26%, 0.88 ± 4.5 years), and these data were not available for CIHR PDF. Women KRESCENT NI showed increased promotion to Associate Professor (P = 0.02, 0.25 ± 3.2 years follow-up) and CCHCSP NI had high promotion rates (37/38, 97%, 6.9 ± 3.6 years follow-up) irrespective of gender. There was an overall trend toward more men pursuing biomedical research. LIMITATIONS: KRESCENT and CCHCSP training program cohort size and heterogeneity; assigning gender by first name may result in misclassification; lack of data on the respective applicant pools; and inability to examine intersectionality with gender, ethnicity, and sexual orientation. CONCLUSION: Overall trainee performance across programs is remarkable by community standards regardless of gender. KRESCENT and CCHCSP training programs demonstrated balanced success in their PDF and NI, whereas the CIHR awardees had reduced representation of women scientists from PDF to NI. This exploratory study highlights the utility of programmatic training approaches like the KRESCENT program as potential tools to support and retain women scientists in the academic pipeline during the challenging PDF to NI transition period.


CONTEXTE: Les chercheuses sont moins susceptibles que les hommes d'obtenir une promotion ou un poste de professeur adjoint, en plus d'obtenir moins de subventions. Des programmes de formation pour les chercheurs et chercheurs cliniciens offrant des bourses salariales ainsi que de la formation et du mentorat pourraient s'avérer pertinents pour améliorer la situation des femmes en sciences. Nous avons émis l'hypothèse qu'une approche programmatique de la formation des chercheurs et chercheurs cliniciens pourrait améliorer les résultats pour les chercheuses canadiennes comparativement aux bourses salariales seules. Pour ce faire, les stagiaires du Programme national de formation scientifique et d'encadrement des chercheurs spécialisés dans le domaine rénal (KRESCENT), du Programme canadien des cliniciens-chercheurs en santé de l'enfant (PCCCSE) et des programmes de bourses salariales des Instituts de recherche en santé du Canada (IRSC) ont été évalués. OBJECTIFS: Vérifier si le programme de formation structuré KRESCENT avec soutien salarial favorise le succès académique des scientifiques féminines par rapport aux bourses salariales uniquement. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Programmes nationaux de formation et de bourses salariales pour les chercheurs et les chercheurs cliniciens du Canada. SUJETS: La cohorte KRESCENT (n = 59; 2005-2017), la cohorte PCCCSE (n = 58; 2002-2015) et les récipiendaires d'une bourse salariale des IRSC (n = 571; 2005-2015) destinées aux boursiers postdoctoraux (BPD) et aux nouveaux chercheurs (NC). MESURES: Le succès du financement des subventions de fonctionnement nationales, l'obtention d'un poste de professeur adjoint à l'université pour les BPD ou l'obtention d'une promotion au poste de professeur agrégé pour les NC. MÉTHODOLOGIE: La répartition des genres dans chaque cohorte a été déterminée à l'aide du prénom et de Namepedia, et a été examinée en fonction du statut (BPD ou NC). Les résultats des stagiaires ont été décrits selon le genre et le niveau de formation. RÉSULTATS: Dans le cas des BPD, les cohortes KRESCENT et IRSC étaient plutôt équilibrées (44 % d'hommes [12/27] pour KRESCENT et 47 % [55/116] de femmes pour IRSC). Les femmes BPD étaient plus nombreuses dans la cohorte PCCCSE (13/20 [65 %]). Du côté des NC, les femmes étaient majoritaires dans les cohortes KRESCENT et PCCCSE (respectivement 59 % [19/32] et 58 % [22/38] de femmes) et les hommes étaient plus nombreux dans la cohorte IRSC (64 % d'hommes [290/455]; 36 % de femmes [165/455] [p = 0,01]). Nous avons observé un taux élevé de réussite des subventions de fonctionnement chez les NC (91 à 95 %) dans toutes les cohortes, sans égard au genre. Une forte proportion de BPD du PCCCSE avaient obtenu un poste de professeur adjoint (18/20 [90 %]); ceci pourrait s'expliquer en partie par le plus long suivi (9,3 ± 3 ans) comparativement aux BPD du KRESCENT (7/27 [26 %]; 0,88 ± 4,5 ans). Ces données n'étaient pas disponibles pour les BPD des IRSC. On a vu une augmentation des promotions à des postes de professeurs agrégés pour les nouvelles chercheuses de la cohorte KRESCENT (p = 0,02, pour 0,25 ± 3,2 ans de suivi). Les NC du PCCCSE présentaient un taux élevé de promotions (37/38 [97 %]; 6,9 ± 3,6 ans de suivi), indépendamment du genre. Une tendance globale pour un plus grand nombre d'hommes poursuivant des recherches biomédicales a été observée. LIMITES: Parmi les limites, on compte la taille et l'hétérogénéité des cohortes KRESCENT et PCCCSE; de possibles erreurs de classification dues à l'attribution du genre par le prénom; le manque de données sur les bassins respectifs de candidats; l'incapacité d'examiner l'intersectionnalité avec le genre, l'origine ethnique et l'orientation sexuelle. CONCLUSION: Le rendement global des stagiaires dans l'ensemble des programmes est remarquable, quel que soit leur genre, par rapport aux normes communautaires. Les programmes de formation de KRESCENT et PCCCSE ont démontré un succès équilibré chez leurs BPD et NC, tandis que les récipiendaires d'une bourse des IRSC ont montré une plus faible représentation de chercheuses tant chez les BPD et les NC. Cette étude exploratoire met en lumière la pertinence d'approches de formation programmatique comme le KRESCENT pour soutenir et retenir les scientifiques féminines dans le domaine académique pendant la difficile période de transition entre le statut de boursière postdoctorale et celui de nouvelle chercheuse.

9.
Am J Kidney Dis ; 78(3): 391-398, 2021 09.
Article in English | MEDLINE | ID: mdl-33581165

ABSTRACT

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is associated with declining physical function and activity. In the general population, lower physical activity is associated with poorer quality of life and greater all-cause mortality. The aim of this study was to assess if lower physical activity levels are associated with adverse health outcomes in patients with advanced CKD. STUDY DESIGN: A multicenter prospective cohort study. SETTING & PARTICIPANTS: 579 adult patients with CKD glomerular filtration rate categories 4 and 5 (G4-G5) treated at 4 Canadian multidisciplinary kidney health clinics between 2012 and 2018. EXPOSURE: Patient-reported measures of physical activity using the Physical Activity Scale for the Elderly (PASE) questionnaire and subsequently stratified PASE scores into tertiles. OUTCOME: All-cause mortality, progression to kidney failure, and future falls. ANALYTICAL APPROACH: Outcomes were analyzed using time-dependent proportional hazards models and logistic regression models. RESULTS: In 1,193 days of follow-up observation, 118 patients died, 204 progressed to dialysis, and 129 reported a fall. When compared with low physical activity, higher levels of physical activity were associated with a 52% lower all-cause mortality (adjusted HR, 0.48; 95% CI, 0.27-0.85) in models adjusted for age, sex, and comorbidity. No associations were detected between higher levels of physical activity and either slower progression to kidney failure or a lower rate of future falls. LIMITATIONS: Physical activity and falls were self-reported. Our population was of limited racial/ethnic diversity, which may affect generalizability. Findings were observational and do not indicate whether interventions targeting physical activity may affect adverse health outcomes. CONCLUSIONS: Higher levels of physical activity were associated with about 50% lower all-cause mortality in the advanced CKD population. These findings are consistent with a potential benefit from maintained physical activity as patients approach kidney failure.


Subject(s)
Exercise/physiology , Glomerular Filtration Rate/physiology , Outcome Assessment, Health Care , Renal Insufficiency, Chronic/therapy , Renal Replacement Therapy/methods , Aged , Aged, 80 and over , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/physiopathology , Risk Factors
10.
Am J Kidney Dis ; 76(4): 471-479.e1, 2020 10.
Article in English | MEDLINE | ID: mdl-32464161

ABSTRACT

RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease and prevent heart failure events. However, SGLT2 inhibitors may increase the risk for acute kidney injury (AKI). Our objective was to assess whether SGLT2 inhibitor use, compared with all other glucose-lowering drugs (oGLDs), is associated with increased rates of AKI. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba, Canada, with type 2 diabetes mellitus followed up from June 2014 until March 2017. EXPOSURES: Initial SGLT2 inhibitor or oGLD use ascertained through a province-wide outpatient prescription database. OUTCOME: The primary outcome was incident AKI, identified either by an increase in serum creatinine level and/or hospital discharge codes for AKI while taking glucose-lowering drugs (on-treatment approach). ANALYTICAL APPROACH: A propensity score analysis was used to assemble groups of incident users of SGLT2 inhibitors and a 1:1 matched set of oGLD users. The rate of AKI was compared across matched groups using cause-specific hazards models. Sensitivity analyses considered exposure to be constant throughout follow-up after initiation of the drug treatment (intention-to-treat approach) or incorporated recurrent exposures (new user design). RESULTS: Comparing 4,778 incident users of SGLT2 inhibitors with 4,778 incident users of oGLDs, there were no differences observed in the primary outcome (HR, 0.64; 95% CI, 0.40-1.03; P = 0.06) using an on-treatment approach. In neither set of sensitivity analyses were SGLT2 inhibitors associated with increased risk for AKI. LIMITATIONS: Drug choice may have been related to AKI risk, laboratory data were obtained from clinical care, and changes in adverse event reporting may have followed the US Food and Drug Administration warning. There were insufficient data to compare individual SGLT2 inhibitors. CONCLUSIONS: Compared with oGLDs, SGLT2 inhibitors were not observed to be associated with increased risk for AKI in a clinical population-based cohort.


Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Diabetes Complications/chemically induced , Diabetes Complications/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Adult , Aged , Cohort Studies , Diabetes Mellitus, Type 2/complications , Female , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
11.
Am J Kidney Dis ; 75(1): 138-143, 2020 01.
Article in English | MEDLINE | ID: mdl-31515140

ABSTRACT

Improving precision in predicting alloreactivity is an important unmet need and may require individualized consideration of non-HLA antibodies. We report a 21-year-old man with kidney failure from immunoglobulin A nephropathy who met all traditional criteria for a "low-risk" transplant for immune memory. He was unsensitized and received a haplotype-matched living donor kidney transplant from his mother. There were no anti-HLA donor-specific antibodies and flow cross-match was negative. After immediate function, he developed delayed graft function on postoperative day 2. The transplant biopsy specimen was suggestive of antibody-mediated rejection and acute tubular injury with increased vimentin proximal tubular expression compared to the implantation biopsy specimen. He had a history of juvenile idiopathic arthritis, and non-HLA antibody screening demonstrated preformed anti-vimentin antibody. He was successfully treated with plasmapheresis, intravenous immunoglobulin, antithymocyte globulin, and methylprednisolone, with renal recovery. The follow-up biopsy specimen demonstrated decreased vimentin expression with decreased alloinflammation, and graft function remains stable at 1 year posttransplantation (estimated glomerular filtration rate, 62mL/min/1.73m2). We postulate that preformed anti-vimentin autoantibodies bound to vimentin expressed on apoptotic tubular epithelial cells induced by ischemia-reperfusion injury and to constitutively expressed vimentin on peritubular capillaries and podocytes. Our case is suggestive of the involvement of anti-vimentin antibody, for which the pathogenic epitopes may be exposed during ischemia-reperfusion injury.


Subject(s)
Antibodies/immunology , Glomerulonephritis, IGA/surgery , Graft Rejection/immunology , Kidney Failure, Chronic/surgery , Kidney Transplantation , Vimentin/immunology , Antilymphocyte Serum/therapeutic use , Delayed Graft Function/immunology , Delayed Graft Function/therapy , Glomerulonephritis, IGA/complications , Glucocorticoids/therapeutic use , Graft Rejection/therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Kidney Failure, Chronic/etiology , Male , Methylprednisolone/therapeutic use , Plasmapheresis , Young Adult
12.
Curr Opin Nephrol Hypertens ; 28(3): 233-237, 2019 05.
Article in English | MEDLINE | ID: mdl-30844883

ABSTRACT

PURPOSE OF REVIEW: Lifetime risk of outcomes is emerging as a highly relevant health indicator, even in the context of low absolute risk of disease progression in short time frames. Evidence to support this concept for kidney failure is increasing, with growing emphasis on the long-term impact of risk factors occurring early in life. RECENT FINDINGS: Proteinuria and stage of chronic kidney disease (CKD) are now established predictors of CKD progression in children, and youth with type 2 diabetes are emerging as a group at significant risk. Recent population-based studies have also examined the lifetime risk of end-stage renal disease in individuals with any childhood CKD. A recent study found that even in the absence of biomarkers of renal injury, childhood CKD can increase the lifetime risk of end-stage renal disease four-fold, and up to 10-fold in adults less than 40 years of age. SUMMARY: Children with CKD are at high lifetime risk of kidney failure and require follow-up. Identifying children at highest lifetime risk through the use of biomarkers and risk equations, and determining the optimal duration and intensity of follow-up requires further research.


Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Kidney Failure, Chronic/etiology , Adolescent , Adult , Biomarkers , Child , Disease Progression , Female , Humans , Male , Renal Insufficiency, Chronic/complications
13.
Can Urol Assoc J ; 10(9-10): 301-305, 2016.
Article in English | MEDLINE | ID: mdl-27800047

ABSTRACT

INTRODUCTION: Renal transplantation remains the gold standard treatment for end-stage renal disease, with living donor kidneys providing the best outcomes in terms of allograft survival. As the number of patients on the waitlist continues to grow, solutions to expand the donor pool are ongoing. A paradigm shift in the eligibility of donors with renal anomalies has been looked at as a potential source to expand the living donor pool. We sought to determine how many patients presented with anatomic renal anomalies at our transplant centre and describe the ex-vivo surgical techniques used to render these kidneys suitable for transplantation. METHODS: A retrospective review was performed of all patients referred for surgical suitability to undergo laparoscopic donor nephrectomy between January 2011 and January 2015. Patient charts were analyzed for demographic information, perioperative variables, urological histories, and postoperative outcomes. RESULTS: 96 referrals were identified, of which 81 patients underwent laparoscopic donor nephrectomy. Of these patients, 11 (13.6%) were identified as having a renal anomaly that could potentially exclude them from the donation process. These anomalies included five patients with unilateral nephrolithiasis, four patients with large renal cysts (>4 cm diameter), one patient with an angiomyolipoma (AML) and one patient with a calyceal diverticulum filled with stones. A description of the ex-vivo surgical techniques used to correct these renal anomalies is provided. CONCLUSIONS: We have shown here that ex-vivo surgical techniques can safely and effectively help correct some of these renal anomalies to render these kidneys transplantable, helping to expand the living donor pool.

14.
Can Urol Assoc J ; 10(7-8): 253-257, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27878046

ABSTRACT

INTRODUCTION: Laparoscopic living donor nephrectomy is the standard of care at high-volume renal transplant centres, with benefits over the open approach well-documented in the literature. Herein, we present a retrospective analysis of our single-institution donor nephrectomy series comparing the mini-open donor nephrectomy (mini-ODN) to the laparoscopic donor nephrectomy (LDN) with regards to operative, donor, and recipient outcomes. METHODS: From 2007-2011, there were 89 cases of mini-ODN, at which point our centre transitioned to LDN; 94 cases were performed from 2011-2014. In total, 366 patients were reviewed, including donor and recipient pairs. Donor and recipient demographics, intraoperative data, postoperative donor recovery, recipient graft outcomes, and financial cost were assessed comparing the surgical approaches. RESULTS: We demonstrate a reduced estimated blood loss (347.83 vs. 90.3 cc), lower intraoperative complication rate (4 vs. 11) and shorter length of hospital stay (2.4 vs. 3.3 days) for patients in the LDN group. Operative time was significantly longer for the LDN group (108.4 vs. 165.9 minutes), although this did not translate to a longer warm ischemia time (mean 2.0 minutes for each group). The rate of delayed graft function and recipient 12-month creatinine were comparable for ODN and LND. Overall cost of LDN was $684 higher for an uncomplicated admission. CONCLUSIONS: Despite a longer surgical time and higher upfront cost, our study supports that LDN yields several advantages over the mini-ODN, with a lower estimated blood loss, fewer intraoperative complications, and shorter length of hospital stay, all while maintaining excellent renal allograft outcomes.

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