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1.  Effect of Lowering Dialysate Sodium Concentration on Interdialytic Weight Gain and Blood Pressure in Patients Undergoing Thrice-Weekly In-center Nocturnal Hemodialysis: A Quality Improvement Study 
Background
Patients on in-center nocturnal hemodialysis therapy typically experience higher interdialytic weight gain (IDWG) than patients on conventional hemodialysis therapy. We determined the safety and effects of decreasing dialysate sodium concentration on IDWG and blood pressure in patients on thrice-weekly in-center nocturnal hemodialysis therapy.
Study Design
Quality improvement, pre-post intervention.
Settings & Participants
15 participants in a single facility.
Quality Improvement Plan
Participants underwent three 12-week treatment phases, each with different dialysate sodium concentrations, as follows: phase A, 140 mEq/L; phase B, 136 or 134 mEq/L; and phase A+, 140 mEq/L. Participants were blinded to the exact timing of the intervention.
Outcomes
IDWG, IDWG/dry weight (IDWG%), and blood pressure.
Measurements
Outcome data were obtained during the last 2 weeks of each phase and compared with mixed models. The fraction of sessions with adverse events (eg, cramping and hypotension) also was reported.
Results
IDWG, IDWG%, and predialysis systolic blood pressure decreased significantly by 0.6 ± 0.6 kg, 0.6% ± 0.8%, and 8.3 ± 14.9 mm Hg, respectively, in phase B compared with phase A (P < 0.05 for all comparisons). No differences in predialysis diastolic and mean arterial or postdialysis blood pressures were found (P > 0.05 for all comparisons). The proportion of treatments with intradialytic hypotension was low and similar in each phase (P = 0.9). In phase B compared with phase A, predialysis plasma sodium concentration was unchanged (P > 0.05), whereas postdialysis plasma sodium concentration decreased by 3.7 ± 1.9 mEq/L (P < 0.05).
Limitations
Modest sample size.
Conclusion
Decreasing dialysate sodium concentrations in patients undergoing thrice-weekly in-center nocturnal hemodialysis resulted in a clinical and statistically significant decrease in IDWG, IDWG%, postdialysis plasma sodium concentration, and predialysis systolic blood pressure without increasing adverse events. Prolonged exposure to higher than required dialysate sodium concentrations may drive IDWG and counteract some of the purported benefits of “go-slow” (longer session length) hemodialysis.
doi:10.1053/j.ajkd.2011.06.030
PMCID: PMC4124938  PMID: 21875769
Nocturnal hemodialysis; interdialytic weight gain; sodium gradient; dialysate sodium; sodium set point; hypertension
2.  Spurious Hyperphosphatemia in Patients on Hemodialysis With Catheters 
doi:10.1053/j.ajkd.2008.03.033
PMCID: PMC4088958  PMID: 18534730
Hyperphosphatemia; spurious hyperphosphatemia; alteplase; catheter; hemodialysis
3.  Prevalence and significance of stroke symptoms among patients receiving maintenance dialysis 
Neurology  2012;79(10):981-987.
Objective:
The purpose of this cross-sectional study was to determine the prevalence and potential significance of stroke symptoms among end-stage renal disease (ESRD) patients without a prior diagnosis of stroke or TIA.
Methods:
We enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and functional status, basic and instrumental activities of daily living (ADL, IADL), were ascertained by validated questionnaires. Cognitive function was assessed with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs below norms for age and education in 2 domains. IADL impairment was defined as needing assistance in at least 1 of 7 IADLs.
Results:
Among the 126 participants without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke symptoms. After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had lower scores on tests of attention, psychomotor speed, and executive function, and more pronounced dependence in IADLs and ADLs (p ≤ 0.01 for all). After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had a higher likelihood of cognitive impairment (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03–5.92) and IADL impairment (OR 3.86, 95% CI 1.60–9.28).
Conclusions:
Stroke symptoms are common among patients with ESRD and strongly associated with impairments in cognition and functional status. These findings suggest that clinically significant stroke events may go undiagnosed in this high-risk population.
doi:10.1212/WNL.0b013e31826845e9
PMCID: PMC3430712  PMID: 22875090
4.  Individualized reduction in dialysate sodium in conventional in-center hemodialysis 
Recent studies have focused on the association between dialysate sodium (Na+) prescriptions and interdialytic weight gain (IDWG). We report on a case series of 13 patients undergoing conventional, thrice-weekly in-center hemodialysis with an individualized dialysate Na+ prescription. Individualized dialysate Na+ was achieved in all patients through a stepwise weekly reduction of the standard dialysate Na+ prescription (140 mEq/L) by 2–3 mEq/L until reaching a Na+ gradient of −2 mEq/L (dialysate Na+ minus average plasma Na+ over the preceding 3 months). Interdialytic weight gain, with and without indexing to dry weight (IDWG%), blood pressure, and the proportion of treatments with cramps, intradialytic hypotension (drop in systolic blood pressure >30 mmHg) and intradialytic hypotension requiring an intervention were reviewed. At the beginning of the observation period, the pre-hemodialysis (HD) plasma Na+ concentration ranged from 130 to 141 mEq/L. When switched from the standard to the individualized dialysate Na+ concentration, IDWG% decreased from 3.4% ± 1.6% to 2.5% ± 1.0% (P = 0.003) with no change in pre- or post-HD systolic or diastolic blood pressures (all P > 0.05). We found no significant change in the proportion of treatments with cramps (6% vs. 1.3%), intradialytic hypotension (62% vs. 65%), or intradialytic hypotension requiring an intervention (29% vs. 33%). Individualized reduction of dialysate Na+ reduces IDWG% without significantly increasing the frequency of cramps or hypotension.
doi:10.1111/j.1542-4758.2012.00701.x
PMCID: PMC3660723  PMID: 22554224
Hemodialysis; dialysate sodium; individualized dialysate sodium; sodium gradient; interdialytic weight gain
5.  Determinants of Left Ventricular Mass in Patients on Hemodialysis: the Frequent Hemodialysis Network (FHN) Trials 
Background
An increase in left ventricular mass (LVM) is associated with mortality and cardiovascular morbidity in patients with end-stage renal disease.
Methods and Results
The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to 12 months of 6 times per week daily in-center hemodialysis or conventional hemodialysis; the FHN Nocturnal Trial randomized 87 patients to 12 months of 6 times per week nocturnal hemodialysis or conventional hemodialysis. The main cardiac secondary outcome was change in LVM. In each trial, we examined whether several pre-defined baseline demographic or clinical factors, as well as change in volume removal, blood pressure or solute clearance influenced the effect of frequent hemodialysis on LVM. In the Daily Trial, frequent hemodialysis resulted in a significant reduction in LVM (13.1(95% CI 5.0 to 21.3) g, p=0.002), LVM index (6.9 (2.4 to 11.3) g/m2, p=0.003) and percent change in geometric mean of LVM (7.0 (1.0 to 12.6)%, p =0.02). Similar trends were noted in the Nocturnal Trial but did not reach statistical significance. In the Daily Trial, a more pronounced effect of frequent hemodialysis on LVM was evident among patients with left ventricular hypertrophy at baseline. Changes in LVM were associated with changes in blood pressure (conventional hemodialysis: R=0.28, P=0.01, daily hemodialysis: R=0.54, P<0.001) and were not significantly associated with changes in other parameters.
Conclusions
Frequent in-center hemodialysis reduces LVM. The benefit of frequent hemodialysis on LVM may be mediated by salutary effects on blood pressure.
doi:10.1161/CIRCIMAGING.111.969923
PMCID: PMC3328963  PMID: 22360996
Left Ventricular Mass; Frequent Hemodialysis; Daily Hemodialysis; Nocturnal Hemodialysis; Blood Pressure
6.  An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients 
BMC Nephrology  2012;13:95.
Background
Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently.
Methods
Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa–to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline.
Results
A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2–13) to 54% (Weeks 18–25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents.
Conclusions
The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.
Trial registration
ClinicalTrials.gov registration: NCT00228449
doi:10.1186/1471-2369-13-95
PMCID: PMC3511162  PMID: 22935486
Anemia; Chronic kidney disease; Erythropoiesis-stimulating agent; Epoetin alfa; Hemodialysis; Peginesatide
7.  Impact of Sleep Quality on Cardiovascular Outcomes in Hemodialysis Patients: Results from the Frequent Hemodialysis Network Study 
American Journal of Nephrology  2011;33(5):398-406.
Background
Poor sleep quality is a common, persistent, and important problem to patients with end-stage renal disease (ESRD). This report examines whether sleep quality is associated with dialysis treatment factors and other modifiable clinical factors in a large group of hemodialysis (HD) patients.
Methods
Cross-sectional analyses were conducted on baseline data collected from participants in the Frequent Hemodialysis Network trials. Sleep quality was measured using the Medical Outcomes Study Sleep Problems Index II (SPI II), a 9-item measure of sleep quality with higher scores reflecting poorer sleep quality.
Results
The participants had an age of 51.2 ± 13.6 years, 61% were male, 38% were black, and 42% had diabetes. Higher pre-dialysis serum phosphorus (per 0.5 mg/ml) (OR 0.91; 95% CI 0.85, 0.96) and depression (OR 0.16; 95% CI 0.10, 0.25) were independently associated with decrements in sleep quality. There was also a difference in time to recovery from dialysis for the fourth versus the first SPI II quartile (5.1 h; p < 0.0001).
Conclusion
These findings underscore the link between sleep and daytime function and suggest that improving sleep may provide an opportunity to improve outcomes in ESRD. Whether sleep problems may be improved by reduction of serum phosphorus or treatment of depression in the HD population merits further investigation.
doi:10.1159/000326343
PMCID: PMC3080580  PMID: 21474924
Hemodialysis; Sleep; Quality of life; Cognitive function; Cardiac magnetic resonance imaging
8.  Dialysate sodium and sodium gradient in maintenance hemodialysis: a neglected sodium restriction approach? 
Nephrology Dialysis Transplantation  2011;26(4):1281-1287.
Background. A higher sodium gradient (dialysate sodium minus pre-dialysis plasma sodium) during hemodialysis (HD) has been associated with sodium loading; however, its role is not well studied. We hypothesized that a sodium dialysate prescription resulting in a higher sodium gradient is associated with increases in interdialytic weight gain (IDWG), blood pressure (BP) and thirst.
Methods. We conducted a cross-sectional study on 1084 clinically stable patients on HD. A descriptive analysis of the sodium prescription was performed and clinical associations with sodium gradient were analyzed.
Results. The dialysate sodium prescription varied widely across dialysis facilities, ranging from 136 to 149 mEq/L, with a median of 140 mEq/L. The mean pre-HD plasma sodium was 136.7 ± 2.9 mEq/L, resulting in the majority of subjects (n = 904, 83%) being dialyzed against a positive sodium gradient, while the mean sodium gradient was 4.6 ± 4.4 mEq/L. After HD, the plasma sodium increased in nearly all patients (91%), reaching a mean post-HD plasma sodium of 141.3 ± 2.5 mEq/L. We found a direct correlation between IDWG and sodium gradient (r = 0.21, P < 0.0001). After adjustment for confounders and clustering by facilities, the sodium gradient was independently associated with IDWG (70 g/mEq/L, P < 0.0001). There were no significant associations among sodium gradient and BP, whether measured as pre-HD systolic (r = −0.02), diastolic (r = −0.06) or mean arterial pressure (r = −0.04). Post-HD thirst was directly correlated with sodium gradient (r = 0.11, P = 0.02).
Conclusion. Sodium gradient is associated with statistically significant and clinically meaningful differences in IDWG in stable patients on HD.
doi:10.1093/ndt/gfq807
PMCID: PMC3108351  PMID: 21303968
dialysate sodium; hemodialysis; hypertension; interdialytic weight gain; sodium gradient
9.  Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis  
The Journal of Experimental Medicine  1998;188(7):1353-1358.
Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface.
PMCID: PMC2212493  PMID: 9763614
complement regulation; Heymann nephritis; Crry; autoantibodies; glomerulus

Results 1-9 (9)