Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

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Preventing Coronavirus Disease 2019 in Kidney Transplant Recipients: Where Should We Begin?

Nephron ◽

10.1159/000515165 ◽

2021 ◽

pp. 1-5

Author(s):

Leonardo V. Riella ◽

Jamil R. Azzi ◽

Paolo Cravedi

Keyword(s):

Risk Factors ◽

General Population ◽

Kidney Transplant ◽

Opportunistic Infections ◽

Population Data ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Viral Spread ◽

Increased Risk ◽

The Uk

Context: Chronic immunosuppression is associated with an increased risk of opportunistic infections. Although kidney transplant recipients with coronavirus disease 2019 (COVID-19) have higher mortality than the general population, data on their risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are unknown. Subject of Review: A recent single-center screening study from the UK (Transplantation. 2021 Jan 1;105(1):151–7) showed that 89 (10.4%) of 855 consecutive kidney transplant recipients tested positive for SARS-CoV-2 antibodies. Risk factors for infection included a nonwhite background, diabetes, and a history of allograft rejection. Risk factors for mortality in individuals who developed COVID-19 were older age and receiving steroids. Second Opinion: This study shows that the rate of SARS-CoV-2 infection in kidney transplant recipients is similar to the one observed in the general population in the same area (13%), indicating that transplant recipients are not at increased risk of COVID-19. However, the investigators raise the interesting point that since transplant individuals were advised to shelter earlier than the general population, they may be in fact more susceptible. This statement is hard to substantiate, but the identification of specific risk factors for infection and poor outcomes is crucial to tailor strategies to prevent spread of the infection. This is particularly important, considering that kidney transplant recipients may be at increased risk of prolonged viral spread and in-host viral mutations, making them not just a particularly fragile population for COVID-19 but also a potentially major source of further contagions.

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Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors

Anais Brasileiros de Dermatologia ◽

10.1590/abd1806-4841.20164891 ◽

2016 ◽

Vol 91 (4) ◽

pp. 455-462 ◽

Cited By ~ 5

Author(s):

André Pinho ◽

Miguel Gouveia ◽

José Carlos Cardoso ◽

Maria Manuel Xavier ◽

Ricardo Vieira ◽

...

Keyword(s):

Risk Factors ◽

Skin Cancer ◽

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Non Melanoma Skin Cancer ◽

Melanoma Skin

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Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10122586 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2586

Author(s):

Stephan Kemmner ◽

Christopher Holzmann-Littig ◽

Helene Sandberger ◽

Quirin Bachmann ◽

Flora Haberfellner ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Graft Function ◽

Delayed Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Operating Characteristics ◽

Lower Odds ◽

Increased Risk

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.

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Risk Factors and Outcomes of Early Hospital Readmission in Canadian Kidney Transplant Recipients: A Population-Based Multi-Center Cohort Study

Canadian Journal of Kidney Health and Disease ◽

10.1177/20543581211060926 ◽

2021 ◽

Vol 8 ◽

pp. 205435812110609

Author(s):

Kyla L. Naylor ◽

Gregory A. Knoll ◽

Justin Slater ◽

Eric McArthur ◽

Amit X. Garg ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Kidney Transplant ◽

Hospital Readmission ◽

Graft Failure ◽

Population Based ◽

Income Quintile ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk

Background: Early hospital readmissions (EHRs) occur commonly in kidney transplant recipients. Conflicting evidence exists regarding risk factors and outcomes of EHRs. Objective: To determine risk factors and outcomes associated with EHRs (ie, hospitalization within 30 days of discharge from transplant hospitalization) in kidney transplant recipients. Design: Population-based cohort study using linked, administrative health care databases. Setting: Ontario, Canada. Patients: We included 5437 kidney transplant recipients from 2002 to 2015. Measurements: Risk factors and outcomes associated with EHRs. We assessed donor, recipient, and transplant risk factors. We also assessed the following outcomes: total graft failure, death-censored graft failure, death with a functioning graft, mortality, and late hospital readmission. Methods: We used multivariable logistic regression to examine the association of each risk factor and the odds of EHR. To examine the relationship between EHR status (yes vs no [reference]) and the outcomes associated with EHR (eg, total graft failure), we used a multivariable Cox proportional hazards model. Results: In all, 1128 kidney transplant recipients (20.7%) experienced an EHR. We found the following risk factors were associated with an increased risk of EHR: older recipient age, lower income quintile, several comorbidities, longer hospitalization for initial kidney transplant, and older donor age. After adjusting for clinical characteristics, compared to recipients without an EHR, recipients with an EHR had an increased risk of total graft failure (adjusted hazard ratio [aHR]: 1.46, 95% CI: 1.29, 1.65), death-censored graft failure (aHR: 1.62, 95% CI: 1.36, 1.94), death with graft function (aHR: 1.34, 95% CI: 1.13, 1.59), mortality (aHR: 1.41, 95% CI: 1.22, 1.63), and late hospital readmission in the first 0.5 years of follow-up (eg, 0 to <0.25 years: aHR: 2.11, 95% CI: 1.85, 2.40). Limitations: We were not able to identify which readmissions could have been preventable and there is a potential for residual confounding. Conclusions: Results can be used to identify kidney transplant recipients at risk of EHR and emphasize the need for interventions to reduce the risk of EHRs. Trial registration: This is not applicable as this is a population-based cohort study and not a clinical trial.

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428 Increased incidence of non-melanoma skin cancers among rural kidney transplant recipients

Journal of Investigative Dermatology ◽

10.1016/j.jid.2020.03.436 ◽

2020 ◽

Vol 140 (7) ◽

pp. S56

Author(s):

H. Maredia ◽

J. Motter ◽

A. Massie ◽

D. Segev ◽

M. Loss

Keyword(s):

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Skin Cancers ◽

Melanoma Skin

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Delayed Kinetics of IgG, but not IgA, Anti-spike Antibodies in Transplant Recipients following SARS-CoV-2 Infection

Journal of the American Society of Nephrology ◽

10.1681/asn.2021040573 ◽

2021 ◽

pp. ASN.2021040573

Author(s):

Paolo Cravedi ◽

Patrick Ahearn ◽

Lin Wang ◽

Tanuja Yalamarti ◽

Susan Hartzell ◽

...

Keyword(s):

Kidney Transplant ◽

Organ Transplant ◽

Late Time ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cross Sectional ◽

Time Points ◽

Increased Risk ◽

Significant Difference ◽

Kinetics Of

Background: Kidney organ transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies directed against the virus are thought to offer protection, but a thorough characterization of anti-SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods: We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semi-quantitative Luminex-based multiplex assay, we determined IgM, IgG, IgG1-4 and IgA antibodies against 5 distinct viral epitopes. Results: Kidney transplant recipients showed lower levels of total IgG anti-trimeric spike (S), S1, S2, and receptor-binding domain (RBD), but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG anti-spike protein epitopes were also lower than in immunocompetent controls. Anti-SARS-CoV-2 antibodies were predominantly IgG1 and IgG3 with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG anti-Spike, S1, S2, RBD and NC were not significantly different between cohorts. There was no significant difference in the kinetics of either IgM or IgA anti-Spike, S1, RBD or S2 based on timing after diagnosis or transplant status. Conclusions: Kidney transplant recipients mount early anti-SARS-CoV-2 IgA and IgM responses while IgG responses are delayed compared to immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19.

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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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