Mineralocorticoid receptor blockade with spironolactone has no direct effect on plasma IL-17A and injury markers in urine from kidney transplant patients

Kidney transplantation is associated with increased risk of cardiovascular morbidity. Interleukin-17A (IL-17A) mediates kidney injury. Aldosterone promotes T-helper-17 (Th-17) lymphocyte differentiation and IL-17A production through the mineralocorticoid receptor (MR). In this exploratory, post-hoc substudy, it was hypothesized that 1-year intervention with the MR antagonist spironolactone lowers IL-17A and related cytokines and reduces epithelial injury in kidney transplant recipients. Plasma and urine samples were obtained from kidney transplant recipients from a double-blind randomized clinical trial testing spironolactone (n=39) versus placebo (n=41). Plasma concentrations of cytokines IFN-γ, IL-17A, TNF-α, IL-6, IL-1β, and IL-10 were determined before and after 1-year treatment. Urine calbindin, clusterin, KIM-1, osteoactivin, TFF3, and VEGF/creatinine ratios were analyzed. Blood pressure and plasma aldosterone concentration at inclusion did not relate to plasma cytokines and injury markers. None of the cytokines changed in plasma after spironolactone intervention. Plasma IL-17A increased in the placebo group. Spironolactone induced an increase in plasma K+ (0.4 ± 0.4 mmol/L). This increase did not correlate with plasma IL-17A or urine calbindin and TFF3 changes. Ongoing treatment at inclusion with angiotensin-converting-enzyme inhibitor and/or angiotensin II receptor blockers was not associated with changed levels of IL-17A and injury markers and had no effect on the response to spironolactone. Urinary calbindin and TFF3 decreased in the spironolactone group with no difference in between-group analyses. In conclusion, irrespective of ongoing ANGII inhibition, spironolactone has no effect on plasma IL-17A and related cytokines or urinary injury markers in kidney transplant recipients.

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Local Angiotensin-Converting Enzyme 2 Gene Expression in Kidney Allografts Is Not Affected by Renin-Angiotensin-Aldosterone Inhibitors

Kidney & Blood Pressure Research ◽

10.1159/000513710 ◽

2021 ◽

Vol 46 (2) ◽

pp. 245-249

Author(s):

Monika Cahova ◽

Martin Kveton ◽

Vojtech Petr ◽

David Funda ◽

Helena Dankova ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Kidney Transplant ◽

Converting Enzyme ◽

Transplant Recipients ◽

Angiotensin Ii Receptor ◽

Kidney Transplant Recipients ◽

Angiotensin Converting Enzyme 2 ◽

Renin Angiotensin ◽

Receptor Blockers

Background: Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (ACE2) expression. Methods: In this study, we evaluated the effect of ACEi or ARB treatment on expression of ACE2, ACE, and AGTR1 in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (n = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. Results: The therapy with RAAS blockers was not associated with increased ACE2, ACE, or ATGR1 expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. Conclusions: ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.

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Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽

10.3390/antiox10071102 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1102

Author(s):

Angelica Rodriguez-Niño ◽

Diego O. Pastene ◽

Adrian Post ◽

M. Yusof Said ◽

Antonio W. Gomes-Neto ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Cox Regression ◽

Carbonyl Stress ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

High Concentrations ◽

Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

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Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients

Journal of Clinical Medicine ◽

10.3390/jcm10132854 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2854

Author(s):

Fernanda Rodrigues ◽

J. Swarte ◽

Rianne Douwes ◽

Tim Knobbe ◽

Camilo Sotomayor ◽

...

Keyword(s):

Small Bowel ◽

Kidney Transplant ◽

Surrogate Marker ◽

Bacterial Overgrowth ◽

Dietary Factors ◽

Multivariable Logistic Regression Analysis ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

The Relationship

Background: Diarrhea is common among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate marker of small bowel dysbiosis, which may drive diarrhea. We studied the relationship between exhaled H2 and diarrhea in KTR, and explored potential clinical and dietary determinants. Methods: Clinical, laboratory, and dietary data were analyzed from 424 KTR participating in the TransplantLines Biobank and Cohort Study (NCT03272841). Fasting exhaled H2 concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was defined as fast transit time (types 6 and 7 according to the Bristol Stool Form Scale, BSFS) of 3 or more episodes per day. We studied the association between exhaled H2 and diarrhea with multivariable logistic regression analysis, and explored potential determinants using linear regression. Results: KTR (55.4 ± 13.2 years, 60.8% male, mean eGFR 49.8 ± 19.1 mL/min/1.73 m2) had a median exhaled H2 of 11 (5.0–25.0) ppm. Signs of small intestinal bacterial overgrowth (exhaled H2 ≥ 20 ppm) were present in 31.6% of the KTR, and 33.0% had diarrhea. Exhaled H2 was associated with an increased risk of diarrhea (odds ratio 1.51, 95% confidence interval 1.07–2.14 per log2 ppm, p = 0.02). Polysaccharide intake was independently associated with higher H2 (std. β 0.24, p = 0.01), and a trend for an association with proton-pump inhibitor use was observed (std. β 0.16 p = 0.05). Conclusion: Higher exhaled H2 is associated with an increased risk of diarrhea in KTR. Our findings set the stage for further studies investigating the relationship between dietary factors, small bowel dysbiosis, and diarrhea after kidney transplantation.

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Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05253-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aziza Ajlan ◽

Hassan Aleid ◽

Tariq Zulfiquar Ali ◽

Hala Joharji ◽

Khalid Almeshari ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Double Blind ◽

Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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Correlation of Prolonged Total Ischemic Time with Body Mass Index in Kidney Transplant: A Single Center Report

BioScientia Medicina ◽

10.32539/bsm.v5i11.367 ◽

2021 ◽

Vol 5 (11) ◽

pp. 1009-1013

Author(s):

Eriawan Agung Nugroho ◽

Erwin Wibowo ◽

Prathita Amanda Aryani

Keyword(s):

Body Mass Index ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Body Mass ◽

The Body ◽

Health Concern ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Ischemic Time ◽

Increased Risk

Background: Chronic kidney disease (CKD) is a rising health concern worldwide, especially in Indonesia. The treatment of choice for end-stage renal disease is Kidney Transplantation.1 Numerous studies showed that prolonged total ischemic ischemic time may cause hypoxia of the graft tissue and increased risk of ischemia and reperfusion injury (IRI) and delayed graft function (DGF).2 Body mass index of kidney transplant recipients may cause prolonged duration of the procedure, as well as prolonged total ischemic time. This study aimed to determine the correlation between prolonged total ischemic time with body mass index. Method: This was an observational and cross-sectional analysis at Kariadi General Hospital Semarang involving patients who underwent kidney transplantation from January 2016 to December 2019. The total ischemic time was recorded intraoperatively. The Body Mass Index data were provided by medical records. The program used to statistically analyze the data was SPSS 23.0, and Spearman was used for hypothesis testing. Result: This study included 25 kidney transplant recipients. The mean total ischemic time was 43,27 ± 6,63 minutes. There was a significant positive correlation between prolonged ischemic time and body mass index (r= 0,506 ; p= 0,010). Conclusion: Prolonged total ischemic time was positively correlated with increased body mass index and these results are statistically significant.

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Venous Thromboembolism and the Risk of Death and Graft Loss in Kidney Transplant Recipients

American Journal of Nephrology ◽

10.1159/000480304 ◽

2017 ◽

Vol 46 (4) ◽

pp. 343-354 ◽

Cited By ~ 6

Author(s):

Ngan N. Lam ◽

Amit X. Garg ◽

Greg A. Knoll ◽

S. Joseph Kim ◽

Krista L. Lentine ◽

...

Keyword(s):

Retrospective Study ◽

Venous Thromboembolism ◽

General Population ◽

Kidney Transplant ◽

Graft Loss ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Risk Of Death ◽

Increased Risk

Background: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described. Methods: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant. Results: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE. Conclusions: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss.

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Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York

Journal of the American Society of Nephrology ◽

10.1681/asn.2020030375 ◽

2020 ◽

Vol 31 (6) ◽

pp. 1150-1156 ◽

Cited By ~ 80

Author(s):

Keyword(s):

New York ◽

Kidney Transplant ◽

Severe Disease ◽

Treatment Protocol ◽

Current Treatment ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Radiographic Findings ◽

Increased Risk

BackgroundThe novel SARS-CoV-2 virus has caused a global pandemic of coronavirus disease 2019 (COVID-19). Although immunosuppressed individuals are thought to be at an increased risk of severe disease, little is known about their clinical presentation, disease course, or outcomes.MethodsWe report 15 kidney transplant recipients from the Columbia University kidney transplant program who required hospitalization for confirmed COVID-19, and describe their management, clinical course, and outcomes.ResultsPatients presented most often with a fever (87%) and/or cough (67%). Initial chest x-ray most commonly showed bilateral infiltrates, but 33% had no acute radiographic findings. Patients were managed with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin. Although 27% of our patients needed mechanical ventilation, over half were discharged home by the end of follow-up.ConclusionsKidney transplant recipients with COVID-19 have presentations that are similar to that of the general population. Our current treatment protocol appears to be associated with favorable outcomes, but longer follow-up of a larger cohort of patients is needed.

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Herpes Zoster in Kidney Transplant Recipients: A Series of Three Cases

Case Reports in Nephrology and Dialysis ◽

10.1159/000508807 ◽

2020 ◽

Vol 10 (3) ◽

pp. 139-146 ◽

Cited By ~ 1

Author(s):

Ramy M. Hanna ◽

Farid Abd-El-Malak ◽

Ammar Alnaser ◽

Rumi Cader ◽

Julie M. Yabu

Keyword(s):

Herpes Zoster ◽

Kidney Transplant ◽

Clinical Course ◽

Clinical Manifestations ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Varicella Zoster ◽

Organ Rejection ◽

Increased Risk ◽

Disseminated Disease

Kidney transplant recipients require lifelong immunosuppression to prevent organ rejection. The need for this intervention, however, leads to decreased cellular immunity and, in turn, increased risk of developing herpes zoster (HZ) from reactivation of latent varicella zoster virus. HZ commonly presents as a painful rash in a dermatome presentation followed by post-herpetic neuralgia. In immunosuppressed individuals, the presentation can be atypical and vary in severity depending on degree of immunosuppression and host immune response. We present the clinical course of 3 kidney transplant recipients who developed HZ after transplantation at different times post-transplant with varying clinical manifestations. The balance between maintaining immunosuppression and preventing or subsequently treating disseminated disease is discussed.

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