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.

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.

Vascular access planning in peritoneal dialysis patients.

Peritoneal dialysis (PD) is a well-established renal replacement therapy for end-stage renal disease patients. Nonetheless, on an annual basis, at least 10% of patients shift from PD to hemodialysis for a variety of reasons. Thus the issue of vascular access creation needs to be addressed for this small but significant group of patients. Despite the relatively consistent number of dropouts, the creation of an arteriovenous fistula prior to transfer remains suboptimal, and variable from center to center. Literature for this specific area is poor and dated. Guidelines seem to suggest vascular access creation in high-risk failure patients, but they have no detailed criteria to select patients that would likely fail PD and therefore take advantage of a backup access. There is a need to better understand and predict patients that require conversion to hemodialysis to develop a plan that focuses on wellness and maximum quality of life in the lifecycle of PD patients. This review addresses the issue of vascular access planning in adult PD patients, presents the available literature on the topic and the current guidelines and recommendations, and describes a research agenda to guide decision making in clinical practice.

Management of secondary hyperparathyroidism in uremic patients: the role of the new vitamin D analogs.

Secondary hyperparathyroidism - a common comorbid condition in patients with chronic renal insufficiency - is considered a consequence of critical determinants such as hypocalcemia, phosphate retention and reduced levels of calcitriol production. In this complex mechanism, the skeletal apparatus and the nonskeletal targets such as vascular and heart valves are often involved, thus explaining the increased risk of cardiovascular morbidity and mortality of uremic patients. In this review we will focus on the major role played by Calcitriol deficiency as a trigger of secondary hyperparathyroidism and the crucial need for obiquitous vitamin D receptor activation in order to have an optimal PTH control and to obtain a modulation between inhibitors and inducers of soft tissue calcification. This review will also elucidate the possible role of paricalcitol - a new vitamin D analog - in conditioning morbidity and mortality of patients on renal replacement therapy (RRT).

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.

[Cardiovascular calcification and accelerated atherosclerosis in chronic kidney disease]. / Calcificazioni cardiovascolari e aterosclerosi accelerata in corso di uremia.

Cardiovascular disease is the first cause of morbidity and mortality in dialysis patients. Hyperphosphatemia and elevated serum calcium-phosphate levels have recently been investigated as inducing factors on extraskeletal calcification in this population. In vitro studies demonstrated that human aortic smooth muscle cells calcify when incubated in a high phosphate medium, where calcium and calcitriol are not changed. Furthermore, the lack of inhibitory proteins, such as fetuin and matrix Gla protein, is a possible main determinant of calcium-phosphate deposition in soft tissues. The classical treatment of hyperphosphatemia and secondary hyperparathyroidism in dialysis patients consists of calcium-based phosphate binders and calcitriol administration. Unfortunately, this "first-generation" therapy is not free of dramatic side effects. New free-calcium and -aluminum phosphate binders, new vitamin D metabolites, and calcimimetics are examples of "second-generation" therapies that may prevent vascular calcification and possibly prevent some of the burden of cardiovascular disease in uremia.