Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-21) is considered to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to assess urinary miR-21 expression levels in the kidney transplant recipients and determine their application in the evaluation of IFTA and kidney allograft function. The expression levels of miR-21 were quantified in the urine of 31 kidney transplant recipients with biopsy-assessed IFTA (IFTA 0 + I: n = 17; IFTA II + III: n = 14) by real-time quantitative PCR. Urine samples were collected at the time of protocolar biopsies performed 1 or 2 years after kidney transplantation. MicroRNA-191-5p was used as reference gene. MiR-21 was significantly up-regulated in IFTA II + III group compared to IFTA 0 + I group (p = 0.003). MiR-21 correlated significantly with serum concentration of creatinine (r = 0.52, p = 0.003) and eGFR (r = −0.45; p = 0.01). ROC analysis determined the diagnostic value of miR-21 with an area under curve (AUC) of 0.80 (p = 0.0002), sensitivity of 0.86 and specificity of 0.71. miR-21 is associated with renal allograft dysfunction and IFTA. Therefore, it could be considered as a potential diagnostic, non-invasive biomarker for monitoring renal graft function.
INTRODUCTION Early prognostic markers that identify high-risk kidney transplant recipients may lead to optimization of immunosuppressive therapy and improved long-term outcomes. OBJECTIVES The aim of this study was to assess whether the measurement of urinary concentrations of CCL2 and CXCL10 chemokines can be a valuable noninvasive tool for identifying ongoing pathological processes in a kidney allograft. PATIENTS AND METHODS The study included 40 patients who underwent a protocol biopsy within 1-year post kidney transplant. The urinary concentrations of CCL2 and CXCL10 with reference to creatinine in urine were assayed in all patients. On the basis of biopsy results, a study group was selected (n = 25), including patients with a diagnosis of interstitial fibrosis and tubular atrophy grades II to III (n = 16), BK virus (BKV) nephropathy (n = 4), or mild inflammatory lesions fulfilling the criteria for mild rejection processes or borderline lesions (n = 11). Patients with normal biopsy results were included in a control group (n = 15). RESULTS The ratio of CCL2 to creatinine (CCL2:Cr) was a significant independent predictor of BKV nephropathy (odds ratio, 1.1; 95% CI, 1.0-1.2; P = 0.04). The CXCL10:Cr ratio was not found to be an independent predictor of BKV nephropathy (odds ratio, 1.3; 95% CI, 0.99-1.71; P = 0.06). CONCLUSIONS The CCL2:Cr and CXCL10:Cr ratios may predict BKV nephropathy. The diagnostic value of CCL2 and CXCL10 in BKV infection should be further evaluated.
BACKGROUND: Mini Chromosome Maintenance 5 (MCM5) is considered as a urinary biomarker of bladder cancer. ADXBLADDER is a commercially available test to detect MCM5 antibodies. OBJECTIVE: External validation of ADXBLADDER test as a urinary biomarker of histopathologically confirmed non-muscle invasive bladder cancer (NMIBC) recurrence. METHODS: The study enrolled 119 consecutive patients with a history of NMIBC and 37 healthy volunteers matched as controls. Single, full-void urine samples were collected from patients before cystoscopy ± TUR. To measure MCM5 expression, Arquer Diagnostics ADXBLADDER test was used. The study protocol was registered within the clinical trials database (NCT03796299). RESULTS: Among patients with NMIBC history, recurrence was diagnosed in 83 patients (69.7%). ADXBLADDER demonstrated sensitivity of 73.5% (95% confidence interval (CI) 62.7%–82.6%), specificity of 33.3% (95% CI 18.6% to 51%), overall negative predictive value (NPV) of 35.3% (95% CI 23.3% to 49.5%) and overall positive predictive value of 71.8% (95% CI 66.1% to 76.8%) for detecting recurrence. In a control group, false positive ADXBLADDER results were noticed in 18 patients (48.6%). The sensitivity and NPV were the highest in invasive tumors (100% and 100%, respectively) and in high-grade recurrences (81.8% and 94.1%, respectively). CONCLUSIONS: ADXBLADDER has a moderate sensitivity and poor specificity in detecting NMIBC recurrence. However, it properly diagnoses patients with T1+ stage recurrence or high-grade tumors.
SummaryBackgroundTrichobezoar is an uncommon entity observed mostly in young women. Symptoms in presenting patients are usually due to the large mass of the bezoar or malabsorption of nutrients. Trichobezoar is almost always associated with trichotillomania and trichophagia.Case ReportThree teenage girls, aged 13, 15, and 16, were diagnosed due to palpable epigastric masses. Additionally the oldest patient presented with symptoms of ileus while the other two patients had weight loss and anaemia. Besides the 15-year-old patient complained of paroxysmal abdominal pains. Patients were subjected to plain radiographic examinations of abdomen which revealed large epigastric tumours, with additional calcifications observed in the youngest girl. Subsequent gastroscopy (the 15-year-old patient) or ultrasonographic examination and computed tomography scans (13- and 16-year-old patients) allowed to establish the diagnosis of giant bezoars: trichobezoars in two older patients and tricho-plaster bezoar in the youngest one. All the tumours were surgically resected and psychiatric treatment was undertaken.Conclusions1. Trichobezoar should be taken into consideration in differential diagnosis of epigastric tumours in children, especially teenage girls. 2. The conventional ultrasonographic and radiographic examinations of the abdomen are insufficient for determination of the nature of the mass. A thorough medical history interview and clinical examination may give directions regarding the further diagnosis.3. Trichotillomania and trichophagia are obsessive-compulsive disorders, and therefore patients with trichobezoars should be under psychiatric care to prevent recurrence of the disease.
(1) Background: Only unbound tacrolimus particles are considered to be active and capable of crossing cellular membranes. Thus, the free-drug concentration might be better associated with clinical effects than the total drug concentration used for dosage adjustment. We propose a new, fully validated online liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unbound tacrolimus concentration measurement. (2) Methods: The determination of the unbound tacrolimus concentration in plasma ultrafiltrate was performed with the Nexera LC system with LCMS-8050 triple quadrupole MS using ascomycin as an internal standard. Chromatographic separation was made using a HypurityC18 analytical column. MS/MS with electrospray ionization and positive-ion multiple-reaction monitoring was used. The unbound tacrolimus level was determined in 36 patients after solid organ transplantation (n = 140). (3) Results: A lower limit of quantification 0.1 pg/mL was achieved, and the assay was linear between 0.1 and 20 pg/mL (R2 = 0.991). No carry-over was detected. The within-run and between-run accuracies ranged between 97.8–109.7% and 98.3–107.1%, while the greatest imprecision was 10.6% and 10.7%, respectively. Free tacrolimus in patients’ plasma ultrafiltrate varied between 0.06 and 18.25 pg/mL (median: 0.98 pg/mL). (4) Conclusions: The proposed method can be easily implemented. The significance of the unbound tacrolimus concentration needs to be investigated. This may facilitate the individualization and optimization of immunosuppressive treatment.
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