Leucine-Rich Alpha-2-Glycoprotein (LRG-1) as a Potential Kidney Injury Marker in Kidney Transplant Recipients.

BACKGROUND Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. To improve patient and transplant survival, non-invasive diagnostic methods for different pathologies are important. Leucine-rich alpha-2-glycoprotein (LRG-1) is an innovative biomarker that is elevated in cases of angiogenesis, inflammation, and kidney injury. However, there are limited data about the diagnostic role of LRG-1 in kidney transplant recipients. The aim of this study was to evaluate the association between serum LRG-1, urine LRG-1, and kidney transplant function and injury. MATERIAL AND METHODS We enrolled 35 kidney transplant recipients in the study. LRG-1 in the serum and urine was detected using ELISA. We evaluated the correlation of serum and urine LRG-1 with traditional serum and urine kidney injury markers. RESULTS A higher level of serum LRG-1 correlates with a higher level of urine LRG-1. Serum LRG-1 has a positive correlation with transplant age, serum urea, serum creatinine, serum cystatin C, proteinuria, and fractional excretion of sodium (FENa) and a negative correlation with hemoglobin and estimated glomerular filtration rate (eGFR). Urine LRG-1 has a positive correlation with serum cystatin C, proteinuria, and urine neutrophil gelatinase-associated lipocalin (NGAL). CONCLUSIONS Higher levels of serum and urine LRG-1 are associated with kidney transplant injury and functional deterioration. Thus, LRG-1 might be also as a biomarker for tubular dysfunction in patients after kidney transplantation.

Clinicopathological Significance of Exosomal Proteins CD9 and CD63 and DNA Mismatch Repair Proteins in Prostate Adenocarcinoma and Benign Hyperplasia.

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.

Achievement of treatment targets predicts progression of vascular complications in type 1 diabetes.

BACKGROUND AND AIM: To study the association between achievement of guideline-defined treatment targets on HbA1c, low-density lipoproteins (LDL-C), and blood pressure with the progression of diabetic complications in patients with type 1 diabetes (T1D). METHODS: The study included 355 patients at baseline and 114 patients with follow-up data after 3-5 years. Outcome variables were the progression of diabetic kidney disease, retinopathy, or cardiovascular disease (CVD). We used logistic regression and other machine learning algorithms (MLA) to model the association of achievement of treatment targets and probability of progression of complications. RESULTS: Achievement of the target blood pressure was associated with 96% lower odds of a new CVD event (0.04 (95% CI 0.00, 0.53), p = 0.016), and 72% lower odds of progression of any complication (0.28 (95% CI 0.09, 0.89), p = 0.027. Achievement of HbA1c target was associated with lower odds of composite complication progression by 82% (0.18 (95% CI 0.04, 0.88), p = 0.034.) None of the patients who achieved HbA1c target progressed in CVD. MLA demonstrated good accuracy for the prediction of progression of CVD (AUC 0.824), and lower accuracy for other complications. CONCLUSION: The achievement of blood pressure and HbA1c treatment targets is associated with lower odds of vascular complication of T1D in a real life study.

Impact of interval walking training managed through smart mobile devices on albuminuria and leptin/adiponectin ratio in patients with type 2 diabetes.

BACKGROUND: Interval walking training has demonstrated more pronounced positive effects on physical fitness and metabolism in type 2 diabetes (T2D), compared to continuous walking. One of the pathogenic mechanisms of T2D is associated with derangements in leptin/adiponectin axis, which might predispose affected individuals to vascular inflammation and albuminuria. The aim of this study was to investigate the effects of interval walking training delivered through smart mobile devices upon albuminuria and leptin/adiponectin ratio in patients with T2D. METHODS: Patients with T2D aged 35-75 were randomized into control (n = 26) and interval training (IT, n = 14) groups. Patients in IT group had to perform three 60-min interval walking sessions (3 min intervals of slow and fast walking with the intensity of 40% and 70% of the peak energy expenditure) per week delivered by smartphone application for four months. The adherence to training was monitored remotely. Outcome measures were albuminuria, leptin/adiponectin ratio, obesity indicators, and glycaemic control. Leptin and adiponectin concentration was measured in serum samples by Luminex technology. RESULTS: In the IT group compared to control group, we observed a statistically significant decrease in albuminuria (p = .002) and leptin/adiponectin ratio (p = .01), as well as a decrease in HbA1c close to statistical significance (p = .09). In IT group, changes in leptin/adiponectin ratio correlated significantly with changes in hip circumference (p = .024). CONCLUSION: Interval walking training is beneficial for vascular health in T2D via impact on albuminuria and leptin/adiponectin ratio.

Predictors of Hyperuricemia after Kidney Transplantation: Association with Graft Function.

BACKGROUND: 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. 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.

Effects of systemically transplanted allogeneic bone marrow multipotent mesenchymal stromal cells on rats' recovery after experimental polytrauma.

BACKGROUND: The aim of this study was to evaluate impact of transplantation of bone marrow mesenchymal stromal cells (BM MMSCs) on recovery after polytrauma and bone fracture repair. METHODS: A total 27 Wistar-Kyoto rats were divided into three groups (n = 9): normal control (A), polytrauma (B), and polytrauma treated with BM MMSC transplantation (C). The experimental polytrauma model was made on male rats by causing multiple fractures and hemorrhagic shock. At 36 hours 9 days after surgery, nine rats received allogeneic BM MMSCs (1 × 10(6) cells per kilogram) intravenously. The day before operation and at Days 3 and 10 after surgery as well as at the end of the experiment, blood analysis was carried out. At 10, 20, and 30 days after surgery the rats' locomotor activity was assessed in an open-field test. At Day 30, rats were euthanized, and macroscopic and histologic observations of rats' lower extremities was performed. RESULTS: The treated animals gained weight faster regained their physical activity earlier. These outcomes were associated with locomotor activity test results, blood glucose and lactate ratios, as well as less marked muscle atrophy.Rat treatment with BM MMSC transplantation stimulated bone fracture healing-bone edge consolidation and enhanced callus formation, as well as the size and maturity of newly formed trabeculae.Red blood cell analysis results showed delayed recovery after hemorrhage in the rats receiving allogeneic BM MMSCs: restoration of red blood cell counts, hematocrit level, and hemoglobin level was slower in the untreated animals. CONCLUSION: Allogeneic BM MMSC transplantation improved rats rehabilitation scores after experimental polytrauma.

Anemia as a complication of parvovirus b19 infection in renal transplant recipients.

BACKGROUND: The frequency of B19 infection in renal transplant donors and recipients was studied to determine the significance of active viral infection in the development of anemia. MATERIAL AND METHODS: Serum, plasma, and peripheral blood leukocyte samples of 47 renal transplant donors, 38 recipients with anemia (Group 1), and 25 without anemia (Group 2) after renal transplantation were evaluated for the presence of anti-B19 specific antibodies (ELISA) and B19 DNA (nPCR). RESULTS: Active persistent B19 infection after renal transplantation was detected in 12 of the 38 in the Group 1 (10 had reactivation and 2 primary infection), and none of the recipients in the Group 2 had it. Of the 12 recipients in the Group 1, 10 were seropositive and 2 seronegative before renal transplantation; 10 received the transplants from the seropositive and 2 from seronegative donors. rHuEPO therapy-resistant severe anemia was detected only in the recipients with active B19 infection after renal transplantation in the Group 1 (7/12). The logistic regression analysis revealed a significant relationship between active B19 infection and severe anemia (OR, 0.039; 95% CI, 0.006-0.257; P=0.001). CONCLUSIONS: Active B19 infection was documented only in the anemic recipients and could be associated with the development of severe anemia after renal transplantation. This allows us to recommend concurrent screening for viral DNA in plasma and detection of anti-B19 IgM class antibodies. To find the association between B19 infection and the development of anemia, further investigations are necessary.

Hepatitis B and C virus variants in long-term immunosuppressed renal transplant patients in Latvia.

The incidence of genome variants of hepatitis B and hepatitis C viruses among 38 long-term (2-15 years) immunosuppressed patients after renal transplantation and 10 patients undergoing dialysis was investigated. Twelve patients had only HBV infection, 9 had only HCV infection and 14 were co-infected. Regions corresponding to the HBV X/EnII/BCP, preC/C, preS/S and to the HCV core were sequenced for molecular characterization of the HBV and HCV genomes. Fifty-seven percent of HBV DNA isolates belonged to genotype D and 42% to genotype A, whereas 77% of HCV RNA isolates belonged to genotype 1b and only 17% to genotype 3a. One sample (6%) was of genotype 2c. Detailed analysis of the above-mentioned HBV genome regions revealed the presence of nucleotide point mutations, which, in some cases, resulted in amino acid substitutions. The clinical significance of such mutations is discussed.