Kidney transplant recipients after nonrenal solid organ transplantation show low alloreactivity but an increased risk of infection

Abstract Background Cryptococcosis is the third most common invasive fungal infection in solid organ transplant (SOT) recipients. There are no nationally representative data describing the incidence, risk factors, and outcomes of cryptococcosis after SOT. Methods We assembled a large cohort of adult SOT recipients using Classification of Diseases, Ninth Revision, Clinical Modification billing data from Healthcare Cost and Utilization Project State Inpatient Databases of Florida (2006–2012), New York (2006–2011), and California (2004–2010). Demographics, comorbidities, death, and cryptococcal infections coded during hospitalization were identified. Results A total of 42634 adults with SOT were identified during the study period. Cryptococcal disease was identified in 0.37% (n = 158), 44% of which had meningitis (n = 69). Median time to diagnosis of cryptococcosis was 464 days (range, 4–2393). The median time to onset of cryptococcosis was earlier for lung (191 days; range, 7.5–1816), heart (195 days; range, 4–1061), and liver (200 days; range, 4–1581) compared with kidney transplant recipients (616 days; range, 12–2393; P < .001, log rank test). Very early-onset disease (<30 days after transplantation) more frequently occurred in liver and lung transplant recipients. Lung transplant recipients had the highest risk of cryptococcosis (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.21–3.60). Cryptococcosis was associated with death (HR, 2.29; 95% CI, 1.68–3.11), after adjusting for age, type of SOT, and other comorbidities. Conclusions Cryptococcosis is rare after SOT, but it is associated with significantly increased risk of death. Lung transplant recipients are at highest risk for cryptococcosis among SOTs. Nonkidney transplants have earlier onset of cryptococcosis and higher risk of death compared with kidney transplant recipients.

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Do Liver Transplant Recipients Have a Higher Risk for Cryptococcosis Than Non-liver Transplant Recipients?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.041 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S87-S87

Author(s):

Hsin-Yun Sun ◽

Aristine Cheng ◽

Cheng-Maw Ho ◽

Rey-Heng Hu ◽

Nai-Kuan Chou ◽

...

Keyword(s):

Liver Transplant ◽

Organ Transplantation ◽

Solid Organ Transplantation ◽

Tertiary Hospital ◽

Solid Organ ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

European Organization ◽

Increased Risk ◽

Liver Transplant Recipients

Abstract Background Patients with liver cirrhosis have an increased risk for cryptococcosis. However, it is unknown whether they remain at a higher risk for cryptococcosis after liver transplantation. Methods Patients undergoing solid organ transplantation at a tertiary hospital in Taiwan were included for analysis. Cryptococcosis was defined based on criteria proposed by the European Organization for Research and Treatment in Cancer and the Mycoses Study Group. Only Nystatin oral suspension but no systemic anti-fungal agents was prescribed routinely post-transplant. Results From 2001 to 2016, in total, 1576 patients underwent solid organ transplantation, including 756 kidney, 411 liver, 336 heart, 61 lung, and 12 multi-organ transplantation. Cryptococcosis developed in 20 patients (1.3%), including cryptococcemia in 9, pulmonary/urine in 6, meningitis in 3, and surgical site infection in 2. Its incidence was 3.2% (13/411) in liver, 1.5% (5/336) in heart, and 0.3% (2/756) in kidney transplant recipients. Compared with 1165 non-liver transplant recipients, 441 liver transplant recipients had a significant higher incidence of cryptococcosis (3.1% vs. 0.6%, P < 0.01) and developed the disease with a shorter median duration after transplantation (75 vs. 213 days). Cryptococcosis with very-early onset (<30 days after transplantation) developed in 38.5% (5/13) of liver transplant recipients with cryptococcosis, but only 14.3% (1/7) in non-liver transplant recipients. Six patients (30%) died after a median follow-up duration of 399 days, and only two deaths were related to cryptococcosis. Conclusion Our findings showed that liver transplant recipients still had a higher risk for cryptococcosis, and the disease developed earlier after transplantation than non-liver transplant recipients. Disclosures All authors: No reported disclosures.

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Solid organ transplantation and pregnancy

Russian Journal of Woman and Child Health ◽

10.32364/2618-8430-2021-4-4-333-338 ◽

2021 ◽

Vol 4 (4) ◽

pp. 333-338

Author(s):

M.A. Lysenko ◽

◽

P.V. Kozlov ◽

V.M. Grabovskiy ◽

I.Yu. Kokaya ◽

...

Keyword(s):

Immunosuppressive Therapy ◽

Organ Transplantation ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Postnatal Period ◽

Current Data ◽

Solid Organ ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Liver And Kidney

This paper highlights the management of pregnancy, delivery, and the postpartum period after solid organ transplantation. First, statistical data on the prevalence and pattern of organ transplantation are addressed. The most relevant issues of pregnancy management in organ transplant recipients include identifying optimal criteria of transplant function monitoring, assessment of pregnancy and medication effects on the fetus, and pregnancy complication development. Next, the authors review major pharmacological classes of immunosuppressive therapy, pregnancy risks, complications, and outcomes associated with these medications, relevant pregnancy planning and management issues, and delivery in liver and kidney transplant recipients. Finally, the effect of breastfeeding (in the context of regular immunosuppressive therapy) on the postnatal period is discussed. Current data demonstrate that favorable pregnancy outcome after organ transplantation is most likely at least one year after transplantation in case of stable organ functioning, careful monitoring of recipient and transplant, adequate immunosuppressive therapy, diagnostic monitoring of fetus throughout pregnancy, and timely delivery. KEYWORDS: pregnancy, transplantation, liver, kidney, immunosuppressive therapy, complications, breastfeeding. FOR CITATION: Lysenko M.A., Kozlov P.V., Grabovskiy V.M. et al. Solid organ transplantation and pregnancy. Russian Journal of Woman and Child Health. 2021;4(4):333–338 (in Russ.). DOI: 10.32364/2618-8430-2021-4-4-333-338.

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Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

Current Pharmaceutical Design ◽

10.2174/1381612826666200531152901 ◽

2020 ◽

Vol 26 (28) ◽

pp. 3497-3506

Author(s):

Raymund R. Razonable

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Cmv Infection ◽

Future Directions ◽

Prevention And Treatment ◽

Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

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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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Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽

10.1136/bmjopen-2020-043731 ◽

2021 ◽

Vol 11 (4) ◽

pp. e043731

Author(s):

Adnan Sharif ◽

Javeria Peracha ◽

David Winter ◽

Raoul Reulen ◽

Mike Hawkins

Keyword(s):

Organ Transplantation ◽

Record Linkage ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Study Cohort ◽

Solid Organ ◽

Post Transplantation ◽

Increased Risk ◽

Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

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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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Viral Enteritis in Solid-Organ Transplantation

Viruses ◽

10.3390/v13102019 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2019

Author(s):

Anum Abbas ◽

Andrea J. Zimmer ◽

Diana Florescu

Keyword(s):

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Post Transplantation ◽

Organ Transplant Recipients ◽

Increased Risk ◽

Viral Enteritis ◽

Solid Organ Transplant Recipients

Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.

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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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