[Show abstract][Hide abstract] ABSTRACT: Once an arteriovenous fistula is established, the blood vessels are subjected to marked changes in hemodynamic forces that trigger remodeling to re-establish baseline parameters of sheer and hoop stress. These homeostatic processes culminate in two requirements that define an adequate and enduring access. First, blood flow must increase to provide amounts that will provide adequate delivery of blood to the artificial kidney. Second, the vessel wall must undergo changes that will allow it to withstand repeated cannulation. Hence, a fistula is mature when it can do what it sets out to do (flow readiness) despite what is being done to it (cannulation readiness). Although flow has been measured with Doppler, high-frequency ultrasound is needed to measure vessel wall thickness to determine hoop stress. Beyond the wall of the vessel, the concept of cannulation readiness depends on the skill and expertise of the cannulator.
Seminars in Nephrology 11/2012; 32(6):564-571. DOI:10.1016/j.semnephrol.2012.10.008 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The creation of buttonhole tracks with Supercath Safety Clampcath is a novel and simple technique that allows dull fistula needle insertions with relative ease and diminished pain. As greater experience with this procedure develops, new issues arise for consideration. We report an unexpected complication of Supercath Safety Clampcath catheter breakage that may be due to physical distortions as a result of its location in the antecubital fossa just proximal to the elbow joint. We present a review of our experience and a framework for the safe ongoing use of this device for creation of buttonholes in fistula for hemodialysis.
Hemodialysis International 08/2012; 17(3). DOI:10.1111/j.1542-4758.2012.00735.x · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether venous wall thickness and hoop (circumferential) stress, as determined with high-frequency ultrasonography (US), can predict cannulation readiness in arteriovenous fistulas (AVFs).
Institutional review board approval and informed consent were obtained for this prospective study. To determine the US appearance of the venous wall, an AVF specimen was excised and scanned in a bath of degassed lactated Ringer solution with a 55-MHz probe. The appearance of the wall at high-frequency US was correlated with histologic findings. High-frequency (40-55-MHz) US was used to image the near-field AVF venous wall of 14 men (mean age, 59 years ± 11 [standard deviation]) and six women (mean age, 55 years ± 14) with newly created AVFs within 1 week of cannulation between January 2008 and December 2009. Measurements of the intima-media thickness (IMT) were generated by three independent observers who were blinded to outcomes. Intraclass correlation analysis was performed. Cannulation readiness was defined as no extravasation during the first dialysis treatment.
By using high-frequency US, the IMT was defined as the sum of a thin echogenic blood-intima interface and a uniform hypoechoic media. The mean IMT of the no extravasation group (0.16 mm ± 0.03) was greater than that of the extravasation group (0.10 mm ± 0.02) (P < .001). A minimum threshold IMT of 0.13 mm (P < .001) was associated with successful cannulation. The mean hoop stress of the no extravasation group (246 kPa ± 57) was lower than that of the extravasation group (530 kPa ± 199) (P < .001). A maximum hoop stress threshold of 248 kPa was associated with successful cannulation (P = .009).
Venous IMT and hoop stress assessed with high-frequency US can predict cannulation readiness in AVFs that are clinically deemed mature.
[Show abstract][Hide abstract] ABSTRACT: Buttonhole cannulation is a method of cannulation of native arteriovenous fistulae traditionally practiced by self-cannulators. At St Michael's Hospital, this method has been modified to allow its use in problematic fistulae by multiple cannulators. In a busy dialysis unit, the need for a few specific cannulators to establish the tunnel tracks in combination with the variable dialysis schedules creates logistical challenges. A new method of creating tunnel tracks with the use of the BioHole™ device was evaluated. Buttonhole tracks were created in 12 patients using a peg of polycarbonated material with a holder (BioHole™ kit). The peg was inserted into the path left by the hemodialysis sharp needle following the index cannulation. Four of the 12 patients had an alternate access. Buttonhole tracks were successfully created in all the patients, albeit in 2 patients, the initial attempt to establish buttonhole tracks was aborted due to complications and the procedure was rescheduled. Compared with the modified buttonhole technique, pain on cannulation following track creation was significantly less in the BioHole™ group (P < 0.001). Ease of cannulation was significantly improved in the BioHole™ group (P<0.05) when compared with that in thrice-weekly patients using the modified buttonhole technique. Hemostasis postdialysis did not differ between the study groups. The use of the BioHole™ device is effective in the creation of tunnel tracks for buttonhole cannulation, is associated with less pain, and simplifies the logistics of arranging patient and nurses' schedules.
Hemodialysis International 04/2011; 15(2):243-9. DOI:10.1111/j.1542-4758.2010.00506.x · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with Stage 5 Chronic Kidney Disease who require renal replacement therapy a major decision concerns modality choice. However, many patients defer the decision about modality choice or they have an urgent or emergent need of RRT, which results in them starting hemodialysis with a Central Venous Catheter. Thereafter, efforts to help patients make more timely decisions about access choices utilizing education and resource allocation strategies met with limited success resulting in a high prevalent CVC use in Canada. Providing decision support tailored to meet patients' decision making needs may improve this situation. The Registered Nurses Association of Ontario has developed a clinical practice guideline to guide decision support for adults living with Chronic Kidney Disease (Decision Support for Adults with Chronic Kidney Disease.) The purpose of this study is to determine the impact of implementing selected recommendations this guideline on priority provincial targets for hemodialysis access in patients with Stage 5 CKD who currently use Central Venous Catheters for vascular access.
A non-experimental intervention study with repeated measures will be conducted at St. Michaels Hospital in Toronto, Canada. Decisional conflict about dialysis access choice will be measured using the validated SURE tool, an instrument used to identify decisional conflict. Thereafter a tailored decision support intervention will be implemented. Decisional conflict will be re-measured and compared with baseline scores. Patients and staff will be interviewed to gain an understanding of how useful this intervention was for them and whether it would be feasible to implement more widely. Quantitative data will be analyzed using descriptive and inferential statistics. Statistical significance of difference between means over time for aggregated SURE scores (pre/post) will be assessed using a paired t-test. Qualitative analysis with content coding and identification of themes will be conducted for the focus group and patient interview data.
Coupling the SURE tool with a decision support system structured so that a positive test result triggers providers to help patients through the decision-making process and/or refer patients to appropriate resources could benefit patients and ensure they have the opportunity to make informed HD access choices.
[Show abstract][Hide abstract] ABSTRACT: We examined whether retinal vessel diameter in persons with type 1 diabetes mellitus is associated with changes in subclinical anatomical and functional indicators of diabetic nephropathy.
Persons with type 1 diabetes mellitus had gradable fundus photographs and renal biopsy data at baseline and 5-year follow-up (n = 234). Retinal arteriolar and venular diameters were measured at baseline and follow-up. Central retinal arteriole equivalent (CRAE) and central retinal venule equivalent (CRVE) were computed. Baseline and 5-year follow-up renal structural variables were assessed by masked electron microscopic morphometric analyses from percutaneous renal biopsy specimens. Variables assessed included: mesangial fractional volume, glomerular basement membrane width, mesangial matrix fractional volume and glomerular basement membrane width composite glomerulopathy index.
While controlling for other covariates, baseline CRAE was positively associated with change in the glomerulopathy index over the 5-year period. Change in CRAE was inversely related to a change in mesangial matrix fractional volume and abnormal mesangial matrix fractional volume, while change in CRVE was directly related to change in the volume fraction of cortex that was interstitium [Vv((Int/cortex))] over the 5-year period. Baseline CRAE or CRVE or changes in these diameters were not related to changes in other anatomical or functional renal endpoints.
Independently of other factors, baseline CRAE correlated with changes in glomerulopathy index, a composite measure of extracellular matrix accumulation in the mesangium and glomerular basement membrane. A narrowing of the CRAE was related to mesangial matrix accumulation. Changes in CRVE were related to changes in Vv((Int/cortex),) a measure of interstitial expansion in persons with type 1 diabetes mellitus.
[Show abstract][Hide abstract] ABSTRACT: Human serum paraoxonase (PON1) activity is reduced in standard hemodialysis (SHD) (4 hours, 3 days/week) patients. Home nocturnal hemodialysis (HNHD) (8 hours, 6 days/week), provides a greater dialysis dose resulting in a greater clearance of metabolites. Whether improvements in the metabolic milieu of HNHD patients results in different PON1 activity levels compared to SHD patients is unclear. We determined serum PON1 mass and arylesterase activities in a group of HNHD patients and compared them to SHD patients and a group of healthy controls (HC).
We measured PON1 arylesterase activity and mass, C-reactive protein (CRP), cystatin C, total and high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins A-I and B in 15 HNHD, 15 SHD and 15 HC participants.
PON1 arylesterase activity (p < 0.001) and mass (p < 0.05) were significantly higher in HC participants compared to SHD and HNHD participants, although no significant differences were noted between HD groups. CRP (p < 0.05) was significantly higher in SHD compared to HC participants and there were no significant differences noted between HD groups. Cystatin C (p < 0.001) was significantly different among the 3 groups. There were no significant differences noted in any lipoprotein parameters among the groups. PON1 activity (r = -0.636, p < 0.001) and mass (r = -0.425, p = 0.019) were inversely correlated with CRP in HD patients.
PON1 is reduced in HNHD patients compared to HC subjects, independent of the concentration of HDL cholesterol. Within subjects on HD, the combination of increased CRP and reduced PON1 may identify subjects at a high risk for cardiovascular complications.
[Show abstract][Hide abstract] ABSTRACT: To examine the relationship of blood pressure (BP) and use of angiotensin-receptor blocker or angiotensin-converting enzyme inhibitor to retinal vessel diameter in normotensive, normoalbuminuric persons with type 1 diabetes mellitus.
In a randomized, controlled clinical trial, clinic and 24-hour ambulatory BPs were measured in persons with type 1 diabetes mellitus and gradable fundus photographs both at baseline (n = 147) and at 5-year follow-up (n = 124). Retinal arteriole and venule diameters were measured by a computer-assisted technique. Individual arteriole and venule measurements were combined into summary indexes that reflect the average retinal arteriole (central retinal arteriole equivalent [CRAE]) and venule (central retinal venule equivalent [CRVE]) diameter of an eye, respectively.
While controlling for age, study site, glycosylated hemoglobin level, and ambulatory pulse rate, the daytime ambulatory systolic (-0.29-microm effect per 1 mm Hg; P = .02), daytime ambulatory diastolic (-0.44-microm effect per 1 mm Hg; P = .04), nighttime ambulatory systolic (-0.27-microm effect per 1 mm Hg; P = .03), and 24-hour ambulatory systolic (-0.31-microm effect per 1 mm Hg; P = .03) BPs were cross-sectionally associated with a smaller CRAE. While controlling for age, study site, glycosylated hemoglobin level, ambulatory pulse rate, and baseline CRAE, no BP measure was associated with a change in CRAE or CRVE during 5 years of follow-up. Treatment with losartan potassium or enalapril maleate was not associated with a statistically significant change in CRAE or CRVE.
Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy does not affect retinal arteriole or venule diameter in normotensive persons with type 1 diabetes mellitus. Trial Registration clinicaltrials.gov Identifier: NCT00143949.
Archives of ophthalmology 02/2010; 128(2):198-205. DOI:10.1001/archophthalmol.2009.391 · 4.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients on conventional hemodialysis (HD) have elevated markers of oxidative stress and chronic inflammation, which may contribute to a high prevalence of cardiovascular disease. Glutathione (GSH), an important intracellular antioxidant, requires cysteine as a rate-limiting amino acid for its synthesis and riboflavin for its regeneration.
We aimed to examine whether erythrocyte GSH (eGSH) concentrations and riboflavin status are influenced by the increased dialysis dose provided to vitamin-supplemented patients receiving home nocturnal hemodialysis (HNHD) (6-8 hours/session, 5-7 nights/week) compared with patients on standard hemodialysis (SHD) (4 hours/session, 3 days/week).
This was a cross-sectional comparative study involving 30 patients undergoing SHD or HNHD regimens and a group of 15 healthy control subjects (HC). We measured eGSH concentration by liquid chromatography-tandem mass spectrometry, riboflavin status by eGSH reductase activity coefficient (EGRAC) as well as plasma total cysteine (Cys) and total homocysteine (Hcy), vitamin C by high-performance liquid chromatography, and C-reactive protein (CRP) by standard method. Estimated dietary protein and energy intakes were determined by 3-day food records, and nutritional status was assessed by subjective global assessment (SGA).
There were no significant differences among groups in eGSH concentration, EGRAC, dietary protein intake, and SGA score. SHD patients had significantly higher plasma Cys (P < .001) and Hcy compared with HNHD and HC groups (P = .048). Vitamin C was significantly lower (P = .01) and CRP significantly higher (P = .048) in both HD groups compared with HC.
eGSH concentration appears to be unaffected by dialysis dose in well-nourished HD patients.
[Show abstract][Hide abstract] ABSTRACT: Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin-angiotensin system.
We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models.
A total of 90% and 82% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P=0.38) or the losartan group (0.026, P=0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6% in the placebo group; the incidence was higher with losartan (17%, P=0.01 by the log-rank test) but not with enalapril (4%, P=0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65% with enalapril (odds ratio, 0.35; 95% confidence interval [CI], 0.14 to 0.85) and by 70% with losartan (odds ratio, 0.30; 95% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo.
Early blockade of the renin-angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy. (ClinicalTrials.gov number, NCT00143949.)
New England Journal of Medicine 08/2009; 361(1):40-51. DOI:10.1056/NEJMoa0808400 · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The preference for fistulae as the hemodialysis access of choice has led to a significant number of accesses that are less than ideal for cannulation. Buttonhole cannulation is ideal for such accesses, but the technique for creation provides major challenges. In 12 patients, buttonhole tunnel tracks were created by leaving the polyurethane catheter of a Clampcath hemodialysis needle indwelling for 10 days after the initial cannulation. After each dialysis the catheter was flushed, and dressed with an antibacterial ointment and gauze. Dialysis was carried out via the catheter during that time. After day 10, the catheter was removed, the tunnel track covered with an antibacterial dressing and the tunnel track was cannulated with a dull buttonhole needle at the next dialysis. Successful buttonhole accesses were created in 11 patients after 10 days, the 12th patient required a single sharp needle cannulation before using dull needles. During the first 2 weeks of dull needle cannulation both pain experienced on cannulation and the difficulty cannulating the access were significantly less than in the classical buttonhole technique (P<0.01). Complications during the follow-up period (6 months-1.5 years) included difficulty cannulating with a dull needle (22) and antibacterial agent induced contact dermatitis (4). There was no episode of sepsis or tunnel track infection. Initial cannulation of the fistula using a Clampcath hemodialysis needle, leaving the polyurethane catheter indwelling for 10 days, is a simple, safe, and effective technique for the creation of buttonhole tunnel tracks.
Hemodialysis International 06/2009; 13(3):316-21. DOI:10.1111/j.1542-4758.2009.00373.x · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Some patients are not optimally treated by conventional in-center hemodialysis (HD) and are unable to perform home HD. We examined the effect of in-center thrice-weekly nocturnal HD (INHD) on patient outcomes.
Patients who were not optimally treated on conventional HD were offered INHD. Thirty-nine patients' laboratory data and medication use were analyzed for the 12 mo before and after conversion to INHD until September 1, 2007. Quality of life on conventional HD and INHD was compared.
After conversion to INHD, median values for phosphorus decreased from 5.9 to 3.7 mg/dl (P < 0.01), alkaline phosphatase level increased from 84 to 161 U/L (P < 0.01), and percentage reduction in urea increased from 74 to 89% (P < 0.01). The mean number of antihypertensive drugs prescribed declined from 2.0 to 1.5 (P < 0.05) during the course of INHD, and the mean daily dosage of phosphate binders declined from 6.2 to 4.9 at study end (P < 0.05). There was a significant reduction in erythropoietin-stimulating agent use of 1992 U/wk (P < 0.01). There was no significant change in median hemoglobin, iron saturation, corrected calcium, or parathyroid hormone levels. Overall, quality of life, sleep, intradialytic cramps, appetite, and energy level all improved significantly on INHD.
INHD offers an effective form of HD for long-term dialysis patients who are unable to perform home HD.
Clinical Journal of the American Society of Nephrology 04/2009; 4(4):778-83. DOI:10.2215/CJN.05221008 · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The creation of a vascular access is necessary in hemodialysis patients, including those with marginal vessels. Upper arm fistulae are attractive due to the ease of creation and of achieving high access flow rates. Cephalic arch stenosis (CAS) can lead to failure of upper arm fistulae and is increasingly identified. We hypothesized that CAS is promoted by high blood flow rates, brachiocephalic fistulae, and an angle of cephalic vein insertion approaching 90 degrees.
All patients requiring a fistulogram between January 2004 and May 2006 had surveillance fluoroscopy of the central veins. Demographic, clinical and laboratory parameters were collected and the angle of the cephalic vein insertion measured by 3 blinded independent observers.
Fifty-eight patients had fistulograms and CAS was detected in 18 subjects. Significant differences between the CAS and non-CAS groups were brachiocephalic fistula site (p = 0.046), access flow (mL/min) (p = 0.012), and absence of diabetes (p = 0.03). Univariate predictors of CAS include access flow (per 100 mL/min) (p = 0.042), platelet count (p = 0.031) and calcium-phosphate product (p = 0.026). The relationship of brachiocephalic site and CAS was confounded by access flow [(per 100 mL/min)*brachiocephalic fistula site (p = 0.016)] and fistula age [brachiocephalic fistula site*fistula age (p = 0.017)]. In multivariate analysis, renovascular disease, calcium-phosphate product, platelet count and access flow (per 100 mL/min)*brachiocephalic fistula predicted CAS (p < 0.001, Negelkerke's R-Square = 0.55). The angle of insertion of the cephalic vein was not predictive for CAS.
CAS may be a long-term consequence of high blood flow rates. The interaction of access flow and brachiocephalic fistula supports the hypothesis that high flow through a brachiocephalic fistula promotes CAS. The multiple factors influencing cephalic arch remodeling require further research.
The journal of vascular access 10/2007; 8(4):287-95. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the association of ambulatory blood pressure (ABP) and ambulatory pulse rate (APR) with diabetic retinopathy (DR) in persons with type 1 diabetes in the Renin-Angiotensin System Study (RASS), a multicenter primary diabetic nephropathy (DN) prevention trial.
One hundred ninety-four normotensive RASS participants in 3 centers who are 16 years of age or older with type 1 diabetes mellitus (DM) of 2 to 20 years' duration.
Ambulatory blood pressure and APR were monitored using standardized protocols. Patients were defined as nondippers if the night-to-day ratios for both systolic and diastolic blood pressures were >0.9. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of 7 standard fields using the Early Treatment Diabetic Retinopathy Study severity scale.
Severity of DR.
No DR was present in 32%, mild nonproliferative DR (NPDR) was present in 55%, and moderate to severe NPDR or proliferative DR was present in 13% of the cohort. Neither 24-hour systolic ABP or diastolic ABP, daytime systolic or diastolic ABP, nor nighttime diastolic ABP were related to severity of DR. Statistically significant associations were found between nighttime systolic ABP and mean ABP and DR. Among those with no DR, 19% were nondippers; for those with mild NPDR, 28% were nondippers; and for those with severe NPDR or proliferative DR, 36% were nondippers (P = 0.08). The ratio of nighttime to daytime APR, but not the 24-hour APR or daytime or nighttime APR, was related positively to the severity of DR. In multivariable analyses, only the nighttime systolic ABP was related to severity of DR (P<0.05).
These data suggest that ABP, especially during the night, may provide a better measure than clinical BP regarding the relationship of BP to the severity of retinopathy in normotensive persons with type 1 DM without clinical DN.
[Show abstract][Hide abstract] ABSTRACT: We describe the St Michael's Hospital (SMH) modified buttonhole (BH) cannulation technique as a method that offers a solution for fistulae with aneurysmal dilatation due to repetitive cannulation in a restricted area. This is a prospective cohort study of 14 chronic hemodialysis (HD) patients with problematic fistulae (marked aneurysmal formation and thinning of the overlying skin, bleeding during treatment, and prolonged hemostasis post-HD) because of repetitive, localized cannulation. Each patient was followed for 12 months. The protocol was as follows: creation of tunnel tracks by 1 to 3 experienced cannulators per patient, using sharp needles. After the tunnel tracks were established and cannulation was easily achieved with dull needles, additional cannulators were incorporated with the guidance of a mentor. Bleeding from cannulation sites during dialysis ceased within 2 weeks and skin damage resolved within 6 months in all patients. Hemostasis time postdialysis decreased from 24 to 15 min. Cannulation pain scores decreased significantly. Access flows and dynamic venous pressure measurements remained unchanged. No interventions were required to maintain access patency. In 2 cases, the aneurysms became much less evident. Complications included one episode of septic arthritis and one contact dermatitis. A third patient developed acute bacterial endocarditis 9 months following completion of her follow-up. The SMH modified BH cannulation technique can salvage problematic fistulae, prevent further damage, and induce healing of the skin in the areas of repetitive cannulation. This technique can be successfully achieved by multiple cannulators in a busy full-care HD unit.
Hemodialysis International 05/2006; 10(2):193-200. DOI:10.1111/j.1542-4758.2006.00094.x · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.
[Show abstract][Hide abstract] ABSTRACT: A decrease in the lifespan of erythrocytes has been accepted universally as one of the contributory factors to anemia in patients with chronic renal failure. This observation was made in the 1950s and 1960s when continuous renal replacement therapy was at its infancy. Based on the premise that a reduced red blood cell (RBC) lifespan in renal disease is primarily caused by the toxic uremic milieu, the purpose of this study is 2-fold: to compare the RBC survival in today's renal patients with that in the existing literature and to explore if there are differential RBC survival benefits with various dialysis dosages.
This is an observational study. Patients with end-stage renal disease were recruited from the dialysis program at the University Health Network and St Michael's Hospital in Toronto. The patients were stratified into 3 groups including conventional thrice-weekly, nocturnal, and short-daily hemodialysis. Healthy subjects were recruited to validate the normal range for RBC lifespan. Red cell survival was assessed using radiolabeled sodium chromate (Na2 51CrO4).
Twenty-two patients and 2 healthy control subjects were recruited. The average red cell half-lives in thrice-weekly, nocturnal, short-daily, and healthy subjects were 14.5 +/- 1.6, 17.1 +/- 4.7, 15.9 +/- 2.2, and 23.5 days, respectively. All 3 patient groups exhibited reduced RBC lifespan (P < 0.05). Further, the overall RBC lifespan was not different from that reported half a century ago. Despite better urea clearances among the nocturnal and short-daily dialysis groups, no RBC survival benefit was observed.
A reduced RBC lifespan continues to contribute to renal anemia despite technologic advancements and improved uremic environment.
American Journal of Kidney Diseases 11/2004; 44(4):715-9. DOI:10.1053/j.ajkd.2004.06.018 · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The normal hematocrit is not a random number, but one that maximizes oxygen delivery. While the feedback loop wherein tissue oxygen pressure determines the production of erythropoietin, which further drives the production of red blood cells in the bone marrow, explains how the hematocrit is generated, it does not speak to how the hematocrit is regulated. The regulation of the hematocrit requires the coordination of the plasma volume and the red cell mass. By controlling red cell mass via erythropoietin and plasma volume through excretion of salt and water, the kidney is able to generate the hematocrit. It is hypothesized that the kidney functions as a critmeter by sensing the relative volumes of each component of the blood through the common signal of tissue oxygen tension. The kidney's unique ability to sense ECF volume through tissue oxygen signal allows it to coordinate these two volumes to produce the normal hematocrit. Hence, it may be the kidneys ability to report a measure of ECF volume as a tissue oxygen signal and thus to regulate the hematocrit that establishes it as the logical site of erythropoietin production. The critmeter is proposed to be a functional unit located at the tip of the cortical labyrinth at the juxta-medullary region of the kidney where erythropoietin is made physiologically. Renal vasculature and nephron segment heterogeneity in sodium reabsorption likely provides the anatomical construct to generate the marginal tissue oxygen pressure required to trigger the production of erythropoietin. The balance of oxygen consumption for sodium reabsorption and oxygen delivery is reflected by the tissue oxygen pressure. This balance hence determines RBC mass adjusted to plasma volume. Factors that affect blood supply and sodium reabsorption in a discordant manner may modulate the critmeter, e.g. angiotensin II. The objective of this work is to describe the hypothesis of the kidney's function as a critmeter, including the anatomical and physiological components, and the role of the renin-angiotensin system in modulating erythropoietin. Clinical examples of the dysregulation of the critmeter may be found in the anemia of renal failure and in sports anemia.
Advances in Experimental Medicine and Biology 02/2003; 543:73-87. DOI:10.1007/978-1-4419-8997-0_6 · 2.01 Impact Factor