Background and Aims Peritoneal fibrosis can limit long term peritoneal membrane function in peritoneal dialysis (PD) patients. It has been related to bioincompatible PD fluids and peritoneal infections. There are no prospective studies regarding correlation between effluent biomarkers and peritoneal biopsy findings. Our aim was to study the possible relation of peritoneal effluent biomarkers and peritoneal morphology alterations. Method Multicenter prospective study in a cohort of stable PD patients treated with biocompatible PD fluids who received a kidney transplant. We collected in each patient peritoneal biopsy samples and peritoneal effluent fluid. We analyzed the relation between effluent biomarkers, phenotype of mesothelial cells (MC) cultured ex vivo, and peritoneal biopsy parameters (mesothelial integrity, fibrosis and hyalinizing vasculopathy). We compared them with patient characteristics, including peritoneal transport parameters. The biomarkers tested were Collagen-1 (COL-1), Fibronectin (FN), Collagen-13 (COL-13), Interleukin-6 (IL-6), Trombospondin-1, Cadherin 13 (CDH-13), CA-125, Gremlin-1 (GREM-1), Matrix metalloproteinase 2 (MMP-2), CC chemokine ligand 18 (CCL18), Plasminogen activator inhibitor 1 (PAI-1) and Vascular endothelial growth factor A (VEGF-A). Results Forty patients were included (mean age 54.5±15 years, 64% male, 24.1% diabetics). Mean time on PD was 25.5±27 months, 62.1% were on automated PD (APD) and 17.2% had prior peritonitis episodes. A normal MC culture phenotype was observed in 78% of patients. In peritoneal biopsies samples we found partial or total mesothelium preservation in 39%, submesothelial thickness in 42% and vasculopathy in 14% of cases. Effluent PAI-1 levels were significantly lower in patients with mesothelial cell loss than in those with mesothelial preservation (21.62 vs. 38.59 pg/ml respectively; p = 0.031). Patients with peritoneal fibrosis showed significantly higher effluent CDH-13 levels (3.51 vs. 2.32 pg/ml; p = 0.048) and supernatant PAI-1 levels (1183 vs. 72.73; p = 0.000) than those without fibrosis. No other statistical differences were found in other biomarkers analysed. Conclusion Most patients treated with biocompatible peritoneal dialysis fluids showed normal mesothelial cell phenotype in peritoneal effluent culture. Lower PAI-1 effluent levels were associated with mesothelial cell loss and higher effluent CDH-13 levels were related to peritoneal fibrosis.
Background and Aims The FGF-23/Klotho ratio increases from early stages of chronic kidney disease (CKD) in parallel with kidney function declined. In some cases, serum FGF-23 levels increase is unbalanced, causing organ damage and increasing cardiovascular risk. The aim of our study was to evaluate the intact FGF-23 (iFGF-23) levels in a cohort of CKD patients and to establish its correlation with cardiovascular and bone mineral metabolism parameters. Method A prospective observational study in 59 adult normophosphatemic patients with CKD stage 2-4, was performed. Clinical and analytical variables (serum calcium, phosporus, intact parathyroid hormone (iPTH), iFGF-23, calcidiol and calcitriol) were evaluated. Basal transthoracic echocardiogram, bone densitometry (Lunar prodigy, GE iDXA), software trabecular bone score (TBS), iNsight clinical data analyzer and carotid Doppler ultrasound were performed. We excluded patients with background of primary hyperparathyroidism, hepatorenal polycystic disease, kidney transplant, tumoral nephrectomy, active neoplasm, tubulopathies or treatment with active vitamin D or calcimimetics. For statistical analysis, we use SPSS software (T Student, Xi2, Fisher test, ANOVA test, U-Mann Whitney test and correlations of Pearson and Spearman) Results Mean age was 62,7±10,5 years, 82,5% were men; 17,7% have CKD stage 2, 28,8% stage 3a, 42,3% stage 3b and 9,6% stage 4. The main CKD etiology was vascular (25%) and diabetes (22%). Previous cardiovascular disease was observed in 11% (ischemic heart disease 6,3%, cerebrovascular disease 3,2% and descompensated heart failure with hospitalization 1,6%). Mean iFGF-23 levels in CKD stage 2 were 80,4±38 ng/l (38-170, median 71 ng/l), in CKD stage 3a 95,5±39,7 ng/l (46-178,9 ng/l, median 85,5 ng/l), in CKD stage 3b 118,8±55,06 (35,5-285 ng/l, median 124,6 ng/l) and in stage 4 134,8±50,9 ng/l (65,25-216,5 ng/l, median 136,1 ng/l). We found correlation between iFGF-23 levels and glomerular filtration rate (Rho:-0,390, p: 0,003), as well as with CKD stages (ANOVA test, p: 0,057). We performed 48 carotid doppler ultrasound and observed mild carotid atheromatosis in 58,7%, mainly bilateral, and intima-media thickness >0,9 mm in 7,9%. In patients with atheromatosis, 38,9% showed iFGF-23 levels in second tertil and 36% in the third. We observed left ventricular hypertrophy (LVH) in 46% of patients, mostly mild degree. In bone densitometry, we found mean femoral neck T-Score of -1±1,1 and lumbar spine T-Score of -0,07±1,5, mean mineral bone density (DMO) in femoral neck of 0,89±0,25 g/cm2 and 1,17±0,20 g/cm2 in lumbar spine. Only 40% of patients had normal TBS score. We found correlation between serum iFGF-23 levels and phosphorus tubular reabsorption (r:-0,396, p: 0,002), calcidiol (Rho: 0,264, p:0,047), calcitriol (r: -0,412, p:0,002), iPTH (Rho: 0,296, p:0,025), lumbar T-Score (r: -0,320 p:0,022), lumbar DMO (r:-0,267, p:0,049) and TBS (r: -0,396, p:0,005). Conclusion We confirm an association between a glomerular filtration rate decline and an increase in serum iFGF-23 levels. The inverse correlation observed between iFGF-23 serum levels and lumbar T-Score, lumbar DMO and trabecular microarchitecture suggests a negative effect of iFGF-23 in bone mineralization.
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