De Novo Malignancies After Kidney Transplant: Where Do We Stand and Does the Head and Neck Region Require More Caution?

OBJECTIVES: The aim of this study was to investigate the characteristics of de novo malignancies arising in kidney transplant recipients followed in a tertiary hospital in Turkey and to examine the tumors in the head and neck region as a subgroup. MATERIALS AND METHODS: Data from kidney transplant recipients treated at our institution between January 2010 and July 2022 were retrospectively analyzed in this single-center study. Data regarding malignancies were noted according to the pathologists' reports. In situ malignancies and those arising after graft loss were not evaluated. RESULTS: The study population comprised 231 patients (165 men; 71.4%) with a median follow-up of 11 years (2853 patient-years). The recipients had a higher cancer risk than the general population (standardized incidence rate = 3.04; 95% CI, 1.82-4.26). Thirty de novo malignant tumors were detected in 24 patients (10.4%). The mean age at diagnosis of cancer was 54.88 ± 11.44 years. The median time from transplant to cancer diagnosis was 11.5 years (range, 7-18.8 y). Nonmelanoma skin cancers (56.7% of all tumors) were the most common malignancies. Twenty-two lesions (73.3%) that developed in 17 patients (7.4%) were localized to the head and neck region: 15 (68.2%) were cutaneous and 7 (31.8%) were noncutaneous. The median time from transplant to head and neck cancer diagnosis was 12 years (range, 7.5-17.5 y). Mortality rate was higher in cancer patients (10 [41.7%] vs 17 [8.2%]; P < 0.01). CONCLUSIONS: The incidence of de novo malignancy in kidney transplant recipients was relatively higher compared with previous data. Nonmelanoma skin cancers were the most common type. Three-quarters of all lesions were in the head and neck region, and two-thirds were of cutaneous origin.

The impact of arteriovenous fistulas and tunneled cuffed venous catheters on morbidity and mortality in hemodialysis patients: A single center experience.

BACKGROUND/AIM: Hemodialysis is the most used renal replacement therapy option for patients with end-stage renal disease. Arteriovenous fistulas (AVFs) and tunnel-cuffed venous catheters (tCVC) are commonly used vascular access routes and have advantages and disadvantages compared to each other. This study focuses on the effects of AVFs and tCVCs on morbidity and mortality in hemodialysis patients. METHODS: The records (between January 2015 and January 2017) of 110 patients (55 patients with AVF and 55 patients with tCVC) under hemodialysis therapy for at least 6 months were evaluated retrospectively. The data about blood tests, hospitalizations, and mortality were compared between patients with AVF and tCVC. FINDINGS: Fifty-five patients (25 male, 58 ± 14 years old) were undergoing hemodialysis via AVF. Fifty-five patients (17 male, 63 ± 14 years old) were undergoing hemodialysis via tunneled CVCs. Thirty (54.5%) of the hospitalization patients had AVF and 46 (83.6%) had CVCs (p < 0.01). The only independent predictor of hospitalization was the use of tCVC as vascular access, according to multivariate regression analysis (p = 0.01). Seven (30%) of the dead patients had AVF and 16 (69.6%) had CVCs (p = 0.035). Use of tCVC appeared to be a mortality predictor in univariate regression analysis (p = 0.039). But the significance did not continue in multivariate model (p = 0.578) in which the duration of hemodialysis appeared as the only significant factor (p = 0.002). CONCLUSION: Patients undergoing hemodialysis via AVF had fewer all-cause hospitalizations and mortality rate than those using tunneled CVCs.

Comparison Between RIFLE, AKIN, and KDIGO: Acute Kidney Injury Definition Criteria for Prediction of In-hospital Mortality in Critically Ill Patients.

INTRODUCTION: Acute kidney injury (AKI) is an important lifethreatening complication in patients hospitalized in intensive care units (ICU). This study was conducted to determine the incidence of AKI in the medical intensive care unit of a tertiary university hospital and to compare the predictive performance of three different AKI criteria (RIFLE, AKIN, and KDIGO) for in-hospital mortality. METHODS: The data of all consecutive patients were evaluated from their hospitalization to ICU until discharge or death, retrospectively. Patients with end-stage renal disease, history of kidney transplantation, those who stayed in the ICU for less than 72 hours, who underwent dialysis before admission to the ICU, and those with incomplete medical records were excluded. AKI was defined using serum creatinine criteria of RIFLE, AKIN, and KDIGO. RESULTS: 303 patients were included in this study. According to RIFLE, AKIN, and KDIGO criteria the incidence of AKI were 47.9 %, 44.6%, and 50.2%; respectively. In-hospital mortality rates were higher in AKI patients (P < .05 according to all three criteria). Regression analysis revealed that AKI was a predictor of in-hospital mortality (P < .05, for all). The ROC analyses showed that each of these criteria had similar abilities to predict in-hospital mortality (area under (Au) ROC for RIFLE = 0.76, AuROC for AKIN = 0.72, and AuROC for KDIGO = 0.76). CONCLUSION: The incidence of AKI was higher with KDIGO criteria. In-hospital mortality rates were higher in patients with AKI. Each criteria had similar abilities to predict in-hospital mortality.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

Successful Treatment of Posttransplant Recurrent Complement C3 Glomerulopathy with Eculizumab.

Two-thirds of complement C3 glomerulopathy (C3G) recur after transplantation and commonly cause graft loss. There is not a standard treatment protocol for these cases. We present a kidney transplant patient with recurrent C3G who was successfully treated with eculizumab. Nephrotic proteinuria and hematuria occurred and creatinine levels increased after transplantation. A graft biopsy revealed recurrent C3G. The patient was administered 250 mg pulse methylprednisolone for 3 days and had 9 sessions of plasmapheresis. Since elevated creatinine levels and proteinuria persisted, eculizumab was instituted. A complete remission was observed after 9-month maintenance eculizumab treatment. Eculizumab may be a potentially effective option in kidney transplant patients with recurrent C3G unresponsive to other treatment modalities.

Increased serum renalase in peritoneal dialysis patients: Is it related to cardiovascular disease risk?

BACKGROUND: Renalase, with possible monoamine oxidase activity, is implicated in degradation of catecholamines; which suggests novel mechanisms of cardiovascular complications in patients with chronic kidney diseases. Epicardial adipose tissue (EAT) has been found to correlate with cardiovascular diseases (CVD) in dialysis patients. The present study aimed to evaluate the association of serum renalase levels with EAT thickness and other CVD risk factors in peritoneal dialysis (PD) patients. METHODS: The study included 40 PD patients and 40 healthy controls. All subjects underwent blood pressure and anthropometric measurements. Serum renalase was assessed by using a commercially available assay. Transthoracic echocardiography was used to measure EAT thickness and left ventricular mass index (LVMI) in all subjects. RESULTS: The median serum renalase level was significantly higher in the PD patients than in the control group [176.5 (100-278.3) vs 122 (53.3-170.0)ng/ml] (p=0.001). Renalase was positively correlated with C-reactive protein (r=0.705, p<0.001) and negatively correlated with RRF (r=-0.511, p=0.021). No correlation was observed between renalase and EAT thickness or LVMI. There was a strong correlation between EAT thickness and LVMI in both the PD patients and the controls (r=0.848, p<0.001 and r=0.640, p<0.001 respectively). CONCLUSIONS: This study indicates that renalase is associated with CRP and residual renal function but not with EAT thickness as CVD risk factors in PD patients.

The impact of calcineurin inhibitors and mammalian target of rapamycininhibitors on anxiety and depression scores in kidney transplant patients.

BACKGROUND/AIM: Depression and anxiety are prevalent symptoms in kidney transplant patients. We aimed to evaluate the frequency and the severity of depression and anxiety symptoms in kidney transplant recipients using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). The data were compared between the patients on CNI-based and mTORi-based maintenance immunosuppressive regimens. MATERIALS AND METHODS: A total of 94 kidney transplant patients were enrolled in the study after exclusion of the patients already taking neuropsychiatric medications or unwilling to participate in the study. Participants were asked to self-report the inventories. RESULTS: Analysis of data showed that 62 (66%) recipients had BDI scores that indicated depression. The patients on CNI-based regimens (n = 74) had increased total BDI scores compared those on mTORi-based regimens [18 (8.75-28) vs. 6 (5.25-14.25), respectively, P < 0.001]. Regarding BAI scores, 79 patients (84%) had prominent anxiety symptoms. The patients on CNI-based regimens had significantly increased total BAI scores compared to those on mTORi-based regimens [21 (13-30.50) vs. 10.50 (8.25-14.75), respectively, P < 0.001]. CONCLUSION: Our results identified fewer side effects of mTORi-based maintenance immunosuppressive regimens regarding depression and anxiety symptoms compared to CNI-based regimens in kidney transplant patients.

Serum apelin is associated with affective disorders in peritoneal dialysis patients.

OBJECTIVE: Depression and anxiety are prevalent affective disorders in peritoneal dialysis (PD) patients. Recent research has proposed a potential role of apelinergic system in pathogenesis of depression. The present study aimed to evaluate the frequency of depression and anxiety and their potential relation with serum apelin levels among PD patients. METHODS: A total of 40 PD patients were enrolled into the study. Depressive symptoms and anxiety were assessed with the Beck's Depression Inventory and the Beck's Anxiety Inventory. Serum apelin-12 levels were measured by immunoenzymatic assays using commercially available ELISA kit for standard human apelin. RESULTS: Of the patients, 16 (40%) had depression, 20 (50%) had anxiety. The patients with depression and anxiety had a significantly longer time on dialysis (p < 0.001 for both), significantly higher serum apelin (p < 0.001 for both) and C-reactive protein levels (p < 0.001 for both) than those without depression and anxiety. In multivariate analysis, serum apelin was the only parameter associated independently with depression and anxiety scores. CONCLUSIONS: A substantial number of PD patients had depression and anxiety. Increased levels of serum apelin may constitute a significant independent predictor of development of depression and anxiety in PD patients.

Efficacy of Combined Plasmapheresis and Intravenous Immunoglobulin Therapy in Kidney Transplant Patients With Chronic Antibody-mediated Rejection.

INTRODUCTION: Antibody-mediated rejections (AMRs) are critical clinical issues encountered in short- and long-term follow-up of kidney transplant patients. Whereas plasmapheresis is a mainstay treatment option in acute AMR cases, there is a paucity of data regarding its efficacy in management of chronic AMR. This report describes our experience addressing this issue. MATERIALS AND METHODS: We retrospectively investigated the data of 7 kidney transplant patients diagnosed with chronic AMR who were on 5 sessions of plasmapheresis (1 to 2 volume exchanges with fresh frozen plasma) on alternate days and 200 mg/kg of intravenous immunoglobulin after each session of plasmapheresis. RESULTS: At 6 months after the initiation of treatment, 6 patients experienced partially improved kidney function. One patient had no response and her kidney function progressively deteriorated. CONCLUSIONS: Our preliminary results are encouraging for the combination of plasmapheresis and intravenous immunoglobulin as an adjunctive therapy for kidney transplant patients suffering from chronic AMR.

Echocardiographic epicardial adipose tissue measurements provide information about cardiovascular risk in hemodialysis patients.

Epicardial adipose tissue (EAT) is a cardiovascular risk predictor in general population. However, its value has not been well validated in maintainance hemodialysis (MHD) patients. We aimed to assess associations of EAT with cardiovascular risk predictors in nondiabetic MHD patients. In this cross-sectional study, we measured EAT thickness by transthoracic echocardiography in 50 MHD patients (45.8 ± 14.6 years of age, 37 male). Antropometric measurements, bioimpedance analysis, left ventricular (LV) mass, carotis intima media thickness, blood tests, homeostasis model assessment for insulin resistance (HOMA-IR) and hemodialysis dose by single-pool urea clearence index (spKt/V) were determined. The mean EAT thickness was 3.28 ± 1.04 mm. There were significant associations of EAT with body mass index (ß = 0.590, P < 0.001), waist circumference (ß = 0.572, P < 0.001), body fat mass (ß = 0.562, P < 0.001), percentage of body fat mass (ß = 0.408, P = 0.003), percentage of lean tissue mass (ß = -0.421, P = 0.002), LV mass (ß = 0.426, P = 0.002), carotis intima media thickness (ß = 0.289, P = 0.042), triglyceride/high-density lipoprotein cholesterol ratio (ß = 0.529, P < 0.001), 1/HOMA-IR (ß = -0.386, P = 0.006), and spKt/V (ß = -0.311, P = 0.028). No association was exhibited with visfatin C, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha (for all, P > 0.05). Body mass index, waist circumference, body fat mass, percentage of lean tissue mass, LV mass, triglyceride/high-density lipoprotein cholesterol ratio, HOMA-IR, and spKt/V appeared as independent predictors of EAT. EAT was significantly associated with body fat measures, cardiovascular risk predictors, and dialysis dose in MHD patients.

The effect of dietary salt restriction on hypertension in peritoneal dialysis patients.

BACKGROUND/AIM: To investigate the effect of dietary salt restriction on blood pressure levels, total sodium removal, and hydration status of peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Thirty-one stable PD patients who consulted a renal dietitian monthly for dietary recommendations, including restricted salt intake <5 g/day, and education about hypertension and hypervolemia were included in this study. Baseline and third month clinical and laboratory findings, bioelectrical impedance analysis results, and urinary and peritoneal sodium removal values were recorded. RESULTS: The mean age of the patients was 47.6 years and the mean time on PD was 39.6 months. The mean total sodium removal decreased slightly from 139.4 ± 69.1 to 136.2 ± 64.8 mmol/day (P > 0.05) for the whole sample, and from 164.3 ± 70.9 to 154.2 ± 72.3 mmol/day (P > 0.05) for the hypertensive subgroup (n: 17). Systolic blood pressure (from 134.3 ± 20.1 to 127.2 ± 19.5 mmHg, P: 0.01), diastolic blood pressure (from 83.2 ± 12.0 to 77.4 ± 10.5 mmHg, P: 0.01) and total body water (from 39.2 ± 10.9 to 38.3 ± 9.3 L, P: 0.04) decreased significantly. CONCLUSION: We demonstrated that even a little reduction in daily dietary sodium intake caused significant decreases in blood pressure levels and fluid overload.

Protective effect of adrenomedullin on contrast induced nephropathy in rats / Efecto protector de la adrenomedulina en la nefropatía inducida por contraste en ratas

Background and aims: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. Methods: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. Results: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. Conclusion: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue

Antecedentes y objetivos: La incidencia de la nefropatía inducida por contraste (NIC) está aumentando y la vasoconstricción renal y la hipoxia medular son mecanismos importantes. Los enfoques terapéuticos son muy limitados y existe un gran interés en avanzar en las estrategias preventivas. La adrenomedulina es un péptido relativamente nuevo con propiedades antioxidantes, vasoactivas y vasodilatadoras. Nuestro objetivo es investigar si la adrenomedulina puede jugar un papel preventivo frente al desarrollo de la NIC experimental. Métodos: Se distribuyeron ratas Wistar albinas (n = 24) de forma aleatoria en cuatro grupos de 6: control (C), adrenomedulina (A), medio de contraste (MC) y adrenomedulina más medio de contraste (AMC). Las ratas no ingirieron agua desde el día 1 al día 4 (durante 72 horas). Posteriormente, se les administraron las sustancias de forma intravenosa. Los grupos A y AMC recibieron una dosis de adrenomedulina de 12 µg/kg. Los grupos MC y AMC recibieron una única dosis de medio de contraste de alta osmolaridad: 10 ml/kg de diatrizoato (Urografin 76 %, Schering AG, Alemania). Los días 1 y 6 se tomaron muestras de sangre para realizar análisis de función renal y de marcadores inflamatorios, incluidos el TNF-α, IL-1β, IL-6 e IL-18. Tras el sacrificio, se examinaron las histologías renales con tinción hematoxilina-eosina. Resultados: En comparación con el grupo MC, los niveles de cistatina C sérica fueron significativamente inferiores en el grupo AMC (P < 0,05). Además, la tasa de excreción diaria de proteínas, los cambios absolutos en el gasto urinario diario y los valores de aclaramiento de la creatinina fueron significativamente inferiores en el grupo AMC que en el grupo MC (P < 0,05). En la evaluación histopatológica, en lo que respecta al grado de daño tubular y los valores de congestión medular, el grupo AMC presentaba niveles ligeramente mejores en comparación con el grupo MC. Sin embargo, según los marcadores inflamatorios, las diferencias no presentaron significación estadística. Conclusión: El estudio ha demostrado que la adrenomedulina resulta beneficiosa en los análisis de función renal deteriorada en un modelo experimental de NIC. Por lo tanto, la adrenomedulina puede ser un candidato para la profilaxis de la NIC. No obstante, se necesitan más estudios que arrojen luz sobre este tema

Protective effect of adrenomedullin on contrast induced nephropathy in rats.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. METHODS: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. RESULTS: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. CONCLUSION: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue.

Life threatening chylothorax in a patient with congenital thrombophilia: case report.

We reported here a case of bilateral chylothorax as a result of widespread thrombi formation in a patient who was heterozygote for factor V leiden gene mutation and who had antithrombin III deficiency. We performed bilateral chest tubes, thrombolytic and oral anticoagulant therapy. The patient responded to the therapy. She has been in follow up without symptoms for 18 months.