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1.  Cost Analysis of Hemodialysis and Peritoneal Dialysis Access in Incident Dialysis Patients 
♦ Background: Although several studies have demonstrated the economic advantages of peritoneal dialysis (PD) over hemodialysis (HD), few reports in the literature have compared the costs of HD and PD access. The aim of the present study was to compare the resources required to establish and maintain the dialysis access in patients who initiated HD with a tunneled cuffed catheter (TCC) or an arteriovenous fistula (AVF) and in patients who initiated PD.
♦ Methods: We retrospectively analyzed the 152 chronic kidney disease patients who consecutively initiated dialysis treatment at our institution in 2008 (HD-AVF, n = 65; HD-CVC, n = 45; PD, n = 42). Detailed clinical and demographic information and data on access type were collected for all patients. A comprehensive measure of total dialysis access costs, including surgery, radiology, hospitalization for access complications, physician costs, and transportation costs was obtained at year 1 using an intention-to-treat approach. All resources used were valued using 2010 prices, and costs are reported in 2010 euros.
♦ Results: Compared with the HD-AVF and HD-TCC modalities, PD was associated with a significantly lower risk of access-related interventions (adjusted rate ratios: 1.572 and 1.433 respectively; 95% confidence intervals: 1.253 to 1.891 and 1.069 to 1.797). The mean dialysis access-related costs per patient-year at risk were €1171.6 [median: €608.8; interquartile range (IQR): €563.1 - €936.7] for PD, €1555.2 (median: €783.9; IQR: €371.4 - €1571.7) for HD-AVF, and €4208.2 (median: €1252.4; IQR: €947.9 - €2983.5) for HD-TCC (p < 0.001). In multivariate analysis, total dialysis access costs were significantly higher for the HD-TCC modality than for either PD or HD-AVF (β = -0.53; 95% CI: -1.03 to -0.02; and β = -0.50; 95% CI: -0.96 to -0.04).
♦ Conclusions: Compared with patients initiating HD, those initiating PD required fewer resources to establish and maintain a dialysis access during the first year of treatment.
PMCID: PMC3862096  PMID: 23455977
Cost analysis; health economics; hemodialysis; dialysis access; vascular access; peritoneal catheter
3.  Concerted Action of ANP and Dopamine D1-Receptor to Regulate Sodium Homeostasis in Nephrotic Syndrome 
BioMed Research International  2013;2013:397391.
The edema formation in nephrotic syndrome (NS) is associated with a blunted response to atrial natriuretic peptide (ANP). The natriuretic effects of ANP have been related to renal dopamine D1-receptors (D1R). We examined the interaction between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN-NS). Urinary sodium, cyclic guanosine monophosphate (cGMP) excretion, and D1R protein expression and localization in renal tubules were evaluated in PAN-NS and control rats before and during volume expansion (VE). The effects of zaprinast (phosphodiesterase type 5 inhibitor), alone or in combination with Sch-23390 (D1R antagonist), were examined in both groups. The increased natriuresis and urinary cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in increased urinary excretion of cGMP and sodium to similar levels of control rats and increased expression of D1R in the plasma membrane of renal tubular cells. Combined administration of Sch-23390 and zaprinast prevented natriuresis and increased cGMP excretion induced by zaprinast alone. We conclude that D1R may play a major role in the ANP resistance observed in PAN-NS.
PMCID: PMC3727124  PMID: 23956981
4.  Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study 
BMC Nephrology  2012;13:88.
Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation.
A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC.
Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024).
Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.
PMCID: PMC3476986  PMID: 22916962
5.  Renalase Lowers Ambulatory Blood Pressure by Metabolizing Circulating Adrenaline 
Blood pressure is acutely regulated by the sympathetic nervous system through the action of vasoactive hormones such as epinephrine, norepinephrine, and dopamine. Renalase, a recently described, secreted flavoprotein, acutely decreases systemic pressure when administered in vivo. Single‐nucleotide polymorphisms present in the gene are associated with hypertension, cardiac disease, and diabetes. Although renalase's crystal structure was recently solved, its natural substrate(s) remains undefined.
Methods and Results
Using in vitro enzymatic assays and in vivo administration of recombinant renalase, we show that the protein functions as a flavin adenine dinucleotide– and nicotinamide adenine dinucleotide–dependent oxidase that lowers blood pressure by degrading plasma epinephrine. The enzyme also metabolizes the dopamine precursor l‐3,4‐dihydroxyphenylalanine but has low activity against dopamine and does not metabolize norepinephrine. To test if epinephrine and l‐3,4‐dihydroxyphenylalanine were renalase's only substrates, 17 246 unique small molecules were screened. Although the search revealed no additional, naturally occurring compounds, it identified dobutamine, isoproterenol, and α‐methyldopa as substrates of renalase. Mutational analysis was used to test if renalase's hypotensive effect correlated with its enzymatic activity. Single–amino acid mutations that decrease its enzymatic activity to varying degrees comparably reduce its hypotensive effect.
Renalase metabolizes circulating epinephrine and l‐3,4‐dihydroxyphenylalanine, and its capacity to decrease blood pressure is directly correlated to its enzymatic activity. These findings highlight a previously unrecognized mechanism for epinephrine metabolism and blood pressure regulation, expand our understanding of the sympathetic nervous system, and could lead to the development of novel therapeutic modalities for the treatment of hypertension. (J Am Heart Assoc. 2012;1:e002634 doi: 10.1161/JAHA.112.002634.)
PMCID: PMC3487338  PMID: 23130169
catecholamines; hypertension; kidney; norepinephrine

Results 1-5 (5)