Background and objectives: In kidney transplant recipients (KTR), hyperuricemia (HU) is a commonly-observed phenomenon, due to calcineurin inhibitors and reduced kidney graft function. Factors predicting HU, and its association with graft function, remains equivocal. Materials and Methods: We conducted a retrospective longitudinal study to assess factors associated with HU in KTR, and to determine risk factors associated with graft function, measured as glomerular filtration rate (GFR). Moreover, GFR > 60 mL/min/1.73 m² was considered normal. HU was defined as a serum uric acid level of > 416 μmol/L (4.70 mg/dL) in men and >357 μmol/L (4.04 mg/dL) in women, or xanthine-oxidase inhibitor use. We built multiple logistic regression models to assess predictors of HU in KTR, as well as the association of demographic, clinical, and biochemical parameters of patients with normal GFR after a three-year follow-up. We investigated the effect modification of this association with HU. Results: There were 144 patients (mean age 46.6 ± 13.9), with 42.4% of them having HU. Predictors of HU in KTR were the presence of cystic diseases (OR = 9.68 (3.13; 29.9)), the use of diuretics (OR = 4.23 (1.51; 11.9)), and the male gender (OR = 2.45 (1.07; 5.56)). Being a younger age, of female gender, with a normal BMI, and the absence of diuretic medications increased the possibility of normal GFR. HU was the effect modifier of the association between demographic, clinical, and biochemical factors and a normal GFR. Conclusions: Factors associated with HU in KTR: Presence of cystic diseases, diuretic use, and male gender. HU was the effect modifier of the association of demographic, clinical, and biochemical factors to GFR.

Introduction. Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. Methods. The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. Results. Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. Conclusions. CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.

BACKGROUND Major adverse cardiovascular (CV) events (MACEs) are the primary cause of morbidity and mortality in kidney transplantation (KT) recipients. The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors. AIM To investigate the association between potential CV risk factors related to KT and MACEs, and their potential modification by hyperuricemia (HU). METHODS The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019. The mean age of patients at KT was 55.0 years ± 14.2 years (range 15.0–89.0 years). Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs. To explore the potential effect modification by uric acid (UA), patients were categorized into groups based on UA levels: (1) Low (< 356 μmol/L); (2) Normal (356–416 μmol/L); (3) High (416–475 μmol/L); and (4) Very high (> 475 μmol/L). RESULTS MACEs occurred in 145 of 545 (26.6%) KT recipients. The most prevalent comorbidities were hypertension (87%), dyslipidemia (78%), secondary hyperparathyroidism (68%), HU (63%) and anemia (33%). In the multivariate logistic regression model, the most significant factors associated with MACEs were previous CV events [odds ratio (OR) = 70.6, 95%CI: 24.9–200.1], left ventricular hypertrophy (LVH) (OR = 12.6, 95%CI: 2.7– 58.3), HU treatment (OR = 4.3, 95%CI: 2.4–7.6), and anemia (OR = 5.3, 95%CI: 2.9–9.8). Effect modification by the presence of HU revealed that independent factors associated with MACEs were age (OR = 1.03, 95%CI: 1.0–1.1), previous CV events (OR = 41.7, 95%CI: 13.6–127.6), LVH (OR = 15.3, 95%CI: 2.0–116.6), HU treatment (OR = 2.5, 95%CI: 1.3–4.6) and anemia (OR = 5.4, 95%CI: 2.8–10.5). Effect modification by UA levels dichotomized at 475 μmol/L (very high level of UA) revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels. CONCLUSION A very high level of UA was observed to act as an effect-modifying factor for MACEs, especially when combined with other risk factors such as age, previous CV events, LVH, and anemia.