Giusy Chiarelli

Novel Biomarkers Do Not Correlate with Severity of Vascular Stiffness in CKD Patients with Severe Co-Morbid Disease

Background/Aims: Novel biomarkers may help explain the pathobiology of vascular disease in chronic kidney disease, and thus set the stage for identification of therapeutic targets, potential reversibility, and improved outcomes in this population. Methods: 124 subjects with GFR <60 ml/min or on renal replacement therapy underwent measurement of inflammatory, vascular and cardiac biomarkers as well as aortic pulse wave velocity (PWV) testing. A subset of patients (n = 60) had repeat PWV measured at 6 months. Results: Thirty-four percent of the patients were diabetic, and 50% had a history of cardiovascular disease or congestive heart failure. Median PWV was 9.8 (IQR 8.3–12.7) m/s. No significant correlations between the measured biomarkers and baseline PWV was observed. An increase in PWV (>1.5 m/s) over 6 months was observed in those subjects with diabetes, a higher brain natriuretic peptide level, lower cholesterol and lower phosphate level. Age (HR 1.086, p = 0.0028), fetuin (0.024, p = 0.0448), and interleukin-10 (top tertile HR 4.720, p = 0.0359) were associated with mortality. Conclusions: In this cohort of patients with chronic kidney disease and diabetes and/or heart disease, we were unable to demonstrate that select biomarkers can inform processes leading to vascular disease. Biomarkers do appear to have utility in predicting future events in this population.

Clinical significance of FGF-23 measurement in dialysis patients

AIMS Considering the growing relevance of fibroblast growth factor-23 (FGF-23) in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD-MBD), an analysis was performed to determine the relative importance of C-terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the first place and the relationship between FGF-23 and mortality as a secondary aim. METHODS In 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D, FGF-23 (C-terminal and intact molecule) were measured and their correlations were analyzed. The relationship between FGF-23 levels and patient survival was also analyzed. RESULTS A significant correlation was found between cFGF-23 and 1,25D, PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23 independent predictors were phosphate and 25D. No significant relationship was found between FGF-23 and mortality. CONCLUSIONS C-terminal or intact FGF-23 levels are weakly correlated and thus not clearly indicative of FGF-23 effects on PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF-23 showed a good correlation, but the intact molecule was not superior in defining interactions with CKD-MBD molecules. Measuring FGF-23 on a regular basis with the current assays in CKD and dialysis patients does not yet seem clinically useful.

Vascular stiffness in incident peritoneal dialysis patients over time.

OBJECTIVE Vascular stiffness is prevalent in end-stage renal disease patients and predicts adverse events. This study describes the prevalence of vascular stiffness and its associated factors in a cohort of incident peritoneal dialysis (PD) patients. METHODS In a prospective observational study of 50 patients, carotid-femoral pulse wave velocity (PWV) were conducted at baseline, 3, 6 and 12 months after initiation of PD. Aortic calcification scores (ACS) were derived using plain lateral abdominal films. We examined the association of significant changes in PWV (defined as 1 m/s or 15% change from baseline) over 6 months in conjunction with demographic and clinical data. RESULTS The mean age was 58 years, 67% were male, and 48% were Caucasian. One third was diabetic, and 23% had pre-existing cardiovascular disease. Median eGFR was 8.7 ml/ min. ACS was strongly correlated with PWV (r = 0.62, p < 0.0001). Over 6 months, 42% demonstrated significant increases, while 23% demonstrated decreases in their PWV. Factors shown to be associated with increasing PWV were Caucasian race (OR = 4.50; CI: 0.97 - 20.83), higher phosphate (OR = 8.36; CI: 1.10 - 63.51) and a lower baseline PWV (OR = 0.67; CI: 0.45 - 0.99). Decrease in PWV was associated with the absence of calcium based phosphate binder usage (OR = 0.11; CI: 0.02 - 0.73). Changes in weight and PWV at 12 months were significantly correlated (p = 0.007, r = 0.57). CONCLUSION In this group of incident PD patients, we demonstrate a lower prevalence of vascular calcification than in hemodialysis patients, a correlation of calcification with PWV, and an important finding that PWV can change in either direction over a short period of time, which are associated with modifiable risk factors.

Unsuccessful application of taurolidine in the treatment of fungal peritonitis in peritoneal dialysis

Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients, determining hospitalization, technique failure, catheter loss and death. In the 2005 update, treatment recommendations for FP from the International Society of Peritoneal Dialysis (ISPD) advocate catheter removal immediately after fungi are identified by microscopy or culture. The availability of more effective medical treatments could therefore be of great importance. The aim of this report is to describe a case of a 43-year-old, diabetic, HIV positive PD patient with fluconazole resistant Candida peritonitis, who was treated with an i.p. taurolidine solution. Taurolidine is a non-antibiotic antimicrobial, with broad bactericidal and fungicidal properties. It has been used during surgery for lavage of the peritoneum in cases of peritonitis. Its mechanism of action is related to direct toxic action on micro-organisms, through a chemical reaction between active taurolidine derivatives and structures on the cell wall. Treatment failed because the patient had severe burning pain during i.p. administration of the drug, limiting its dose. PD catheter removal allowed complete recovery. It remains undetermined if, with different doses and methodology, taurolidine could be more effective in treating bacterial and/or fungal peritonitis. Currently, catheter removal remains the most effective therapy of fungal peritonitis.

Calcium and phosphate handling in peritoneal dialysis.

In the last 10 years, it has been well documented that mineral metabolism abnormalities in dialysis patients are associated with an enhanced risk of morbidity and mortality for cardiovascular disease. Extraskeletal calcifications represent one of the major risk factors involved in the pathogenesis of cardiovascular disease in this population. In fact, secondary hyperparathyroidism and hyperphosphatemia associate with increased cardiovascular mortality in uremic patients for two reasons: first for the passive deposition of calcium and phosphate in soft tissues; second for the active role of inorganic phosphate on direct induction of extraskeletal mineralization of the tunica media in the vasculature of these patients. In peritoneal dialysis patients, many unbalances of calcium and phosphate metabolism are present. In particular, recent cohort studies indicate that most patients do not reach targets indicated by clinical practice guidelines. Further efforts to control hyperphosphatemia are essential, in order to reduce the impact of secondary hyperparathyroidism both on bone and cardiovascular system.

Elimination of BNP by peritoneal dialysis: investigation of analytical issues.

1. Zareie M, hekking l, Welten AG, Driesprong BA, Schadeeeestermans Il, Faict D, et al. Contribution of lactate buffer, glucose and glucose degradation products to peritoneal injury in vivo. Nephrol Dial Transplant 2003; 18:2629–37. 2. rippe B, Simonsen o, heimburger o, Christensson A, haraldsson B, Stelin G, et al. long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products. Kidney Int 2001; 59:348–57. 3. Jones S, holmes CJ, Krediet rT, Mackenzie r, Faict D, Tranæus A, et al. Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels. Kidney Int 2001; 59: 1529–38. 4. Zweers MM, de Waart Dr, Smit W, Struijk DG, Krediet rT. Growth factors VeGF and TGF-beta1 in peritoneal dialysis. J lab clin med 1999; 134:124–32. 5. Cooker lA, luneburg P, holmes CJ, Jones S, Topley n; the Bicarbonate/lactate Study Group. Interleukin-6 levels decrease in effluent from patients dialyzed with bicarbonate/lactate-based peritoneal dialysis solutions. Perit Dial Int 2001; 21(Suppl 3):S102–7. 6. Mortier S, Faict D, Schalkwijk CG, lameire nh, De Vriese AS. long-term exposure to new peritoneal dialysis solutions: effects on the peritoneal membrane. Kidney Int 2004; 66:1257–65. 7. ho-dac-Pannekeet MM, hiralall JK, Struijk DG, Krediet rT. longitudinal follow-up of CA125 in peritoneal effluent. Kidney Int 1997; 51:888–93. 8. Topley n. Membrane longevity in peritoneal dialysis: impact of infection and bio-incompatible solutions. adv ren replace Ther 1998; 5:179–84. 9. ho-dac-Pannekeet MM, Krediet rT. Inflammatory changes in vivo during CAPD: what can the effluent tell us? Kidney Int Suppl 1996; (56):S12–16. 10. McIntyre CW. Update on peritoneal dialysis solutions. Kidney Int 2007; 71:486–90. doi:10.3747/pdi.2009.00139