Robert M. Lindsay

In-center hemodialysis six times per week versus three times per week

BACKGROUND In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis. METHODS Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access. RESULTS Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents. CONCLUSIONS Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Acute Interstitial Nephritis Due to Drugs: Review of the Literature with a Report of Nine Cases

Acute interstitial nephritis due to drugs commonly presents as acute renal failure and may be commoner than is presently realized. Drugs implicated include not only methicillin and other penicillins but also diuretics and nonsteroidal anti-inflammatory agents. The mechanism of injury likely involves an immunologic disturbance, possibly a delayed hypersensitivity reaction. Differential diagnosis from other causes of acute renal failure may be difficult, but coincident evidence of an acute allergic reaction may help, as may the detection of eosinophils in the urine or avid uptake of 67Ga by the kidneys. Definitive diagnosis may require renal biopsy, which will reveal normal glomeruli and a patchy but usually heavy interstitial infiltrate with lymphocytes, plasma cells, and eosinophils. Diagnosis of acute interstitial nephritis is important, because withdrawal of the offending agent will usually result in rapid improvement in renal function, and steroid therapy may reduce residual chronic renal damage.

Daily hemodialysis: a systematic review.

Several studies have reported improved outcomes with daily hemodialysis (DHD), but the strength of this evidence has not been evaluated. The published evidence on DHD was synthesized and its quality rated to inform need and sample size calculations for a randomized trial. Citations were identified in MEDLINE and EMBASE using validated search strategies. Dialysis journals that were not indexed and bibliographies of relevant articles were hand-searched. Two authors reviewed all citations. Articles that reported original data on five or more adults who were receiving DHD (1.5 to 3 h, 5 to 7 d/wk) for > or = 3 mo were included. Twenty-five articles reporting 14 unique populations with 268 patients (five to 72 per study) met inclusion criteria. Of the 14 cohorts, 13 were studied with an observational design, 10 were studied prospectively, and four had parallel control groups. Mean age ranged form 41 to 64 yr, mean time on dialysis was 2 to 11 yr, 0 to 28% of patients had diabetes, > 90% had arteriovenous fistulae, and > 50% were dialyzed at home. Most data were described at < or = 12 mo of follow-up. Outcomes included quality of life, cardiovascular disease, erythropoiesis, nutritional status, hospitalizations, and vascular access failures. Reporting was too heterogeneous to allow pooling of data. Ten of 11 studies suggested improvements in blood pressure; findings for other outcomes varied. Discontinuation of DHD occurred in 0 to 57% in-center and 0 to 15% home patients. Studies of DHD are limited by small sample size, nonideal control groups, selection and dropout biases, and paucity of data on potential risks. Randomized trials with adequate statistical power are required to establish the efficacy and the safety of DHD.

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Volume control and blood pressure management in patients undergoing quotidian hemodialysis

BACKGROUND Hypertension and interdialytic weight gain are associated with left ventricular hypertrophy (LVH), an important predictor of cardiovascular mortality in hemodialysis (HD) patients. METHODS In the London Daily/Nocturnal Hemodialysis Study, a group of patients receiving quotidian HD, either short daily (n = 11) or long nocturnal (n = 12), were followed for up to 18 months. Patients were assessed for effects of quotidian HD therapy on blood pressure, interdialytic weight gain, extracellular fluid volume (ECFV), intensity of antihypertensive therapy, and homocysteine levels. RESULTS Significant reductions in predialysis mean arterial blood pressure were observed in the daily HD group at 6 months (P < 0.04) and in the nocturnal HD group at 9 months (P < 0.03); these improvements persisted throughout the study period. The daily HD group had a 60% reduction in mean number of antihypertensive tablets per day at 1 month and an 8.8-fold reduction by 18 months. Nocturnal HD patients experienced a 3.3-fold reduction, and control patients, a 1.4-fold increase in mean number of tablets per day by 18 months. By 3 months, the daily HD group showed a significant decrease in interdialytic weight gain (P < 0.0005) and lower ECFV than controls (P < 0.05). The nocturnal HD group had a transient, but significant, increase in interdialytic weight gain at 6 and 15 months (P < 0.05) and no difference in ECFV compared with controls, suggesting a different mechanism of blood pressure control. Homocysteine levels were significantly lower for both quotidian HD groups compared with conventional HD patients. CONCLUSION Quotidian HD is a promising therapy with potent antihypertensive effects, resulting in improved blood pressure control. This, together with improved homocysteine levels, may be beneficial in the long term with regard to cardiovascular mortality.

Intradialytic Blood Volume Monitoring in Ambulatory Hemodialysis Patients: A Randomized Trial

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non-access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non-access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non-access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.

Calcium and phosphate balance with quotidian hemodialysis

BACKGROUND Conventional hemodialysis (HD) is associated with profound disturbances in calcium and phosphate metabolism and abnormal parathyroid hormone (PTH) levels. Effects of more frequent HD on calcium and phosphate balance have not been fully elucidated. METHODS The London Daily/Nocturnal Hemodialysis Study examined effects of quotidian HD, either daily HD (n = 11) or nocturnal HD (n = 12), on calcium and phosphate metabolism, bone alkaline phosphatase levels, and intact PTH (iPTH) levels. RESULTS Daily HD patients showed a slight decrease in predialysis serum phosphate levels, no changes in phosphate-binder requirements or serum calcium levels, and slight increases in serum bone alkaline phosphatase and iPTH levels. Nocturnal HD patients showed a trend for decreased predialysis phosphate levels, with significantly lower values than daily HD and matched control patients on conventional HD therapy at several times. Phosphate-binder use by nocturnal HD patients was significantly reduced. Both quotidian HD groups showed decreases in calcium x phosphate product, with significantly lower values for nocturnal HD patients (38.11 mg(2)/dL(2)) compared with daily HD and control patients (53.99 and 52.51 mg(2)/dL(2), respectively) at 18 months. Bone alkaline phosphatase levels increased slightly and attained statistical significance compared with baseline values for both quotidian HD groups. A trend for increases in serum iPTH levels, coupled with increasing levels of bone alkaline phosphatase in nocturnal HD patients, led to the decision to increase the dialysate calcium concentration from 5.0 to 7.0 mg/dL. This 1-time adjustment resulted in a reversal of the trend and a return to baseline values. CONCLUSION This study shows the superior control of serum phosphate levels in nocturnal HD patients compared with daily HD or conventional HD patients and the benefits of dialysate with a greater calcium concentration in slow nocturnal HD.

Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American clinical trial

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.

The London Daily/Nocturnal Hemodialysis Study--study design, morbidity, and mortality results.

BACKGROUND Despite the growing interest in more frequent hemodialysis (HD), to date, there have been no randomized prospective studies comparing outcomes in patients dialyzed using conventional thrice-weekly therapy with either the short hours daily or long slow nocturnal HD modalities. METHODS The London Daily/Nocturnal Hemodialysis Study, a prospective, comparative, nonrandomized study, directly compared outcomes of quotidian HD patients with conventional thrice-weekly HD patients. Patients were assigned to either daily HD (n = 11) or nocturnal HD (n = 12) and followed up for 5 to 36 months; all data were directly compared with matched control patients receiving conventional HD. This report describes the study design, morbidity and mortality results, and vascular access results. RESULTS There were no significant differences between patient groups in total numbers of hospital admissions or hospital days. Likewise, there was no significant difference in number of emergency visits per patient-year. There were 3 patient deaths in each of the nocturnal HD and control groups, although none of the deaths was deemed related to HD treatment. No deaths occurred in the daily HD group. Vascular access differences between study groups were not statistically significant. Among patients with arteriovenous (AV) fistulae, more than 80% of daily HD and nocturnal HD patients elected to use the buttonhole technique and successfully performed quotidian HD through their buttonhole at the 18-month follow-up. Patients with AV fistulae had the lowest annual rates of access complications and interventions. The annual access infection rate for quotidian HD patients using catheters decreased significantly after patients switched from in-center conventional HD to more frequent HD treatments at home. CONCLUSION Results from this comprehensive and pioneering study support the hypothesis that quotidian HD is more physiological than conventional HD and results in better patient outcomes.