Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Redox Metabolism and Vascular Calcification in Chronic Kidney Disease.

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the H2O2-scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.

[Usefulness of cold ureteral biopsy during radical cystectomy as a predictor of recurrence risk: Review of our series.] / Utilidad de la biopsia fría ureteral durante la cistectomía radical como predictor de riesgo de recidiva: revisión de nuestra serie.

OBJECTIVES: To evaluate the association of positive margins in the intraoperative biopsy during radical cystectomy (RC) with the risk of recurrence in the uretero-ileal anastomosis or upper urinary tract (UUT), and identify potential risk factors for positive ureteral margins. METHODS: A retrospective, descriptive study was performed in patients treated with radical cystectomy due to transitional cell carcinoma (TCC), who underwent a cold biopsy of the ureteral margin at the time of cystectomy. A descriptive analysis and frequency distribution was performed. Fisher's test was used to calculate sensitivity and specificity and a survival analysis was performed. RESULTS: 230 patients were included. Prior to RC, transurethral resection of the bladder tumor and a CT scan were done. The percentage of positive margins was 4.81% for the right ureter and 4.27% for the left. Recurrence was detected in the anastomosis in 2.64% of the cases. In a 0.88% recurrence was found in the UUT (2 cases) at the level of left renal pelvis (1 case) and left kidney (1 case). In the multivariate analysis, neither recurrence in the anastomosis (p=1) or at the UUT (p=1) level during follow-up were significantly associated with the presence of positive margins. An association was found between the pathological biopsy of the right ureter and carcinoma in situ (CIS) of the bladder wall with UUT involvement. We found only association between the cold biopsy of the left ureter and tumor in left UTT. Reimplantation with positive margins was not statistically associated with neither ureteroileal anastomosis or UTT relapse. A relationship was found between the cold biopsy of both ureters and the definitive pathology. CONCLUSIONS: In our study, the presence of positive ureteral margins was not associated with an increased risk of recurrence in the anastomosis or UUT. Although it remains a topic for debate, a strategy to follow may be to adapt ureteral cold biopsies to individual risk, thus perform it in patients with bladder CIS.

Utilidad de la biopsia fría ureteral durante la cistectomía radical como predictor de riesgo de recidiva: revisión de nuestra serie / Usefulness of cold ureteral biopsy during radical cystectomy as a predictor of recurrence risk: Review of our series

OBJETIVOS: Evaluar la asociación de márgenes positivos en la biopsia intra-operatoria al tiempo de la cistectomía radical (CR) con el riesgo de recidiva en la anastomosis urétero-ileal o a nivel del tracto urinario superior (TUS), y estudiar posibles factores de riesgo preoperatorios asociados con el margen ureteral positivo. MÉTODO: Estudio descriptivo retrospectivo de pacientes tratados mediante CR debido a carcinoma de células transicionales (CCT), a los que se les realizó al tiempo de la CR una biopsia fría del margen ureteral. Se realizó un análisis descriptivo y distribuciones de frecuencias. Se empleó el test de Fisher, se calcularon los valores de sensibilidad (Se) y especificidad (Sp) de la prueba, y se realizó un análisis de supervivencia. RESULTADOS: Se incluyeron 230 pacientes que fueron sometidos a CR. Previamente a la CR se les realizó resección transuretral (RTU) de vejiga y tomografía axial computarizada (TC). El porcentaje de márgenes positivos fue de 4,8% para el uréter derecho y de 4,7% para el izquierdo. Se detectó recidiva en la anastomosis en el 2,6% de los casos. En un 0,8% se encontró recidiva en el TUS (2 casos) a nivel de pelvis renal izquierda (1 caso) y riñón izquierdo (1 caso). En el análisis multivariante, ni la recidiva en la anastomosis (p=1) ni a nivel del TUS (p=1) a lo largo del seguimiento, se asociaron de forma significativa con la presencia de márgenes positivos. De forma secundaria se estudiaron los posibles factores anatomopatológicos preoperatorios asociados con el riesgo de margen positivo, encontrando asociación entre la anatomía patológica (A-P) intraoperatoria del uréter derecho y CIS en la RTU vesical y con tumor del TUS asociado. La reimplantación con margen positivo no se asoció estadísticamente con recidiva en la anastomosis ni con recidiva en el TUS. Hubo relación entre A-P intraoperatoria de ambos uréteres y la definitiva. CONCLUSIONES: En nuestro estudio, la presencia de márgenes ureterales positivos no se asociaron con mayor riesgo de recidiva en la anastomosis o en el TUS. Aunque sigue siendo un tema a debate, una estrategia a seguir puede ser adaptar la biopsia fría ureteral al riesgo individual y realizarla a pacientes con CIS vesical

OBJECTIVES: To evaluate the association of positive margins in the intraoperative biopsy during radical cystectomy (RC) with the risk of recurrence in the uretero-ileal anastomosis or upper urinary tract (UUT), and identify potential risk factors for positive ureteral margins. METHODS: A retrospective, descriptive study was performed in patients treated with radical cystectomy due to transitional cell carcinoma (TCC), who underwent a cold biopsy of the ureteral margin at the time of cystectomy. A descriptive analysis and frequency distribution was performed. Fisher's test was used to calculate sensitivity and specificity and a survival analysis was performed. RESULTS: 230 patients were included. Prior to RC, transurethral resection of the bladder tumor and a CT scan were done. The percentage of positive margins was 4.81% for the right ureter and 4.27% for the left. Recurrence was detected in the anastomosis in 2.64% of the cases. In a 0.88% recurrence was found in the UUT (2 cases) at the level of left renal pelvis (1 case) and left kidney (1 case). In the multivariate analysis, neither recurrence in the anastomosis (p=1) or at the UUT (p=1) level during follow-up were significantly associated with the presence of positive margins. An association was found between the pathological biopsy of the right ureter and carcinoma in situ (CIS) of the bladder wall with UUT involvement. We found only association between the cold biopsy of the left ureter and tumor in left UTT. Reimplantation with positive margins was not statistically associated with neither ureteroileal anastomosis or UTT relapse. A relationship was found between the cold biopsy of both ureters and the definitive pathology. CONCLUSIONS: In our study, the presence of positive ureteral margins was not associated with an increased risk of recurrence in the anastomosis or UUT. Although it remains a topic for debate, a strategy to follow may be to adapt ureteral cold biopsies to individual risk, thus perform it in patients with bladder CIS