Blood Urea Nitrogen Stability: A Feasibility Study for Home Hemodialysis Adequacy Testing Through Mail

Urea kinetic modeling measures the delivered dose of hemodialysis and is used to monitor dialysis adequacy. Obtaining samples for adequacy calculations is a challenge for home hemodialysis (HHD) patients. Ideally, the urea reduction ratio (URR) should be measured at a typical dialysis session; therefore, for HHD patients test specimens should be drawn at home and transferred to a clinical laboratory. Would blood urea nitrogen (BUN) remain stable if samples were mailed to the laboratory? To answer this question, BUN was measured in pre- and postdialysis samples from 20 patients over 8 days of laboratory storage. While BUN values varied among the patient population, neither pre- nor postdialysis values showed any significant variation during the 8-day storage time. These results suggest that BUN values are sufficiently stable for specimens to be drawn at home and mailed to a testing laboratory.     

What is a surrogate marker for optimal dialysis?

To find a surrogate marker to obtain optimal dialysis delivery from the viewpoint of nutrition, 180 maintenance hemodialysis patients (109 males/71 females) were enrolled between October 1999 and June 2006 at our kidney center. In the 449 hemodialysis treatments, ultrapure dialysis solutions and high-flux synthetic membranes were utilized. Parameters were measured by Kt/V(urea) and postdialysis urea rebound, Kc (the cellular membrane clearance for urea), urea clear space (CS), %creatinine generation rate, %lean body mass, total body water, and so on. We examined the correlation between dialysis delivery and nutritional parameters: Kt/V(urea) and postdialysis urea rebound were found to be strongly and negatively correlated with nutritional parameters. However, Kc and CS have shown positive and strong correlations with nutritional parameters such as %creatinine generation rate, %lean body mass, and total body water as well. In addition, the age factor was correlated with Kt/V(urea) positively, and it influenced Kc and CS negatively. As a conventional dialysis parameter, Kt/V(urea) did not reflect nutrition, but Kc was found to improve nutrition due to the increase of the dialysis delivery. Therefore, Kc might be a reliable surrogate marker for optimal dialysis.     

Comparison of urea clearance in low‐efficiency low‐flux vs. high‐efficiency high‐flux dialyzer membrane with reduced blood and dialysate flow: An in vitro analysis

Rapid removal of small molecules during hemodialysis places an acutely ill patient with kidney failure at an increased risk of hemodynamic instability and for dialysis disequilibrium syndrome. The use of high‐flux, high‐efficiency (HEF) dialyzers may increase this risk despite reductions in blood and dialysate flow. We performed in vitro experiments to compare urea clearance at low dialysate flow and various blood flows using a low‐efficiency low‐flux (LEF) and a HEF membrane. Compared to LEF, there was a significant increase in the clearance of urea at all blood flows with the HEF (all P values < 0.005). HEF dialyzer (F180NR) had higher urea clearance at a blood flow of 150 mL/min than LEF dialyzer (F5) at blood flow of 300 mL/min (144.1 ± 0.99 vs. 130.1 ± 0.001 mL/min for F180 vs. F5, respectively, P < 0.002). Our data suggest that use of HEF dialyzer are not as safe as LEF in high‐risk acute dialysis patients since these are associated with more rapid removal of urea despite reduction in blood and dialysate flow as compared to LEF.     

Measurement of Hemodialysis Adequacy in a Changing World

Defining adequacy of dialysis remains an elusive goal. The application of the Kt/V_urea concept to clinical dialysis was a major improvement in trying to define a dialysis dose. Intuitively, the Kt/V concept makes a great deal of sense: the urea clearance of the dialyzer during dialysis (K), multiplied by the time (t) of dialysis, divided by the patient's urea distribution volume (V) ought to give the best number to compare the efficiency of dialyses that patients receive. There are, however, many pitfalls associated with the whole Kt/V_urea concept.     

Kinetic Studies on Urea Extraction with Hemodialysis in Adolescents by On‐line Monitoring of Dialysate Urea

Kinetics of urea extraction during a single dialysis session in children are unknown, because analysis of solutes in dialysate is difficult due to their extreme dilution. >Objective: A novel urea monitor of the Gambro Company might be of help in studying urea kinetics also in children. Methods: We studied 107 urea kinetics in 5 adolescents aged 13–19 years, weighing 26–58 kg, and looked for influences of membrane size, blood flow, and duration of one dialysis session. Urea measurement applies to the change of electric dialysate conductivity due to ionization because of urea splitting by urease. Bicarbonate dialysis regimen was 4–5 h each, 3 times a week, using polysulfone high‐flux dialyzers (Fresenius F60 or F80, depending on body size). Results: Average 4‐h urea Kt/V values for F60 (n = 85) were 1.69±0.53 and for F80 (n = 21) 1.63±0.25, extracted urea mass was 16.0±5.4 g and 32.5±5.4 g, respectively (p < 0.05); Kt/V urea results for blood flows of 180–220 mL/min were 1.36±0.52 and for <180 mL/min 1.10±0.43; extracted urea mass was 17.3±8.0 and 11.7±4.9 g, respectively (p < 0.05). Total average urea extraction ratio after 2 h of dialysis (n = 107) was 64.8±5.6%. Extraction ratio during the 4^th h of dialysis was only 15.3±4.1% and during the 5^th h not more than 9.0±3.6% of total urea extraction. Conclusion: Kinetics of urea extraction helps understanding dialysis processes in children. Adapting the size of the dialyzer according to body size raises urea extraction and maintains urea clearance Kt/V at the desired quality level. An inadequate blood flow lowers both urea extraction and urea clearance Kt/V. Prolonging dialysis beyond 4 h is, at least in concern of urea kinetic modelling, a rather ineffective means. We speculate that children with blood flow problems should be dialysed more often.     

Effect of dialysis dose and membrane flux on hemoglobin cycling in hemodialysis patients

Many studies found that hemoglobin (Hb) fluctuation was closely related to the prognosis of the maintenance hemodialysis patients. We investigated the association of factors relating dialysis dose and dialyzer membrane with Hb levels. We undertook a randomized clinical trial in 140 patients undergoing thrice‐weekly dialysis and assigned patients randomly to a standard or high dose of dialysis; Hb level was measured every month for 12 months. In the standard‐dose group, the mean (±SD) urea reduction ratio was 65.1% ± 7.3%, the single‐pool Kt/V was 1.26 ± 0.11, and the equilibrated Kt/V was 1.05 ± 0.09; in the high‐dose group, the values were 73.5% ± 8.7%, 1.68 ± 0.15, and 1.47 ± 0.11, respectively. The standard deviation (SD) and residual SD (liner regression of Hb) values of Hb were significantly higher in the standard‐dose group and low‐flux group. The percentage achievement of target Hb in the high‐dose dialysis group and high‐flux dialyzer group was significantly higher than the standard‐dose group and low‐flux group, respectively. Patients undergoing hemodialysis thrice weekly appear to have benefit from a higher dialysis dose than that recommended by current KDQQI (Kidney Disease Qutcome Quality Initiative) guidelines or from the use of a high‐flux membrane, which is in favor of maintaining stable Hb levels.     

The anticoagulant activity of enoxaparin sodium during on-line hemodiafiltration and conventional hemodialysis

To study and compare the anticoagulant activity of enoxaparin sodium during on-line hemodiafiltration (OL-HDF) and conventional hemodialysis (C-HD). Enoxaparin was administered as an anticoagulant to 21 hemodialysis patients at the beginning of a single 4-hour OL-HDF session as an intravenous bolus dose of 80 mg/kg. On-line hemodiafiltration was performed using a high-flux polyester polymer alloy dialyzer and a total of 18 L replacement fluid (session A). One week later, the study was repeated in the same patients during a single 4-hour session of C-HD using a low-flux polysulfone dialyzer (session B). Blood samples for the measurement of Hb, blood urea and nitrogen (BUN), activated partial thromboplastin time (APTT), and anti-Xa levels were taken before each study session and 5-minute postdialysis. In 13 more patients, the same study was performed during OL-HDF using a high-flux polysulfone dialyzer (session C). No differences were found between sessions A, B, and C when predialysis values for Hb, BUN, APTT, and anti-Xa were compared. The mean postdialysis APTT and anti-Xa values were 32.5±3.8 seconds and 0.19±0.11 IU/mL, respectively, in session A, 39.0±5.0 seconds and 0.71±0.17 IU/mL in session B, and 33.8±3.1 seconds and 0.35±17 IU/mL in session C (A vs. B, P<0.0001, for both parameters, A vs. C, P<0.003 for anti-XA, and B vs. C, P<0.005, for both parameters). The anticoagulant activity of enoxaparin sodium is decreased significantly during a 4-hour OL-HDF session compared with to a similar session of C-HD. The degree of the reduction seems to depend on the dialyzer's membrane.     

Does Increasing Dialyzer Blood Flow Always Improve Dialysis Efficiency?

As dialyzer blood flow is increased during hemodialysis, diminishing increments in clearance are inevitable. In addition, as clearance increases, diminishing increases in solute removal from the patient are inevitable. The causes of these equally self-defeating and additive effects are the fundamental self-limitation of the dialysis itself due to first-order kinetics, membrane-limited diffusion within the dialyzer, and disequilibrium within the patient. Access recirculation is a specialized cause of solute disequilibrium that is separately measurable and preventable. Cardiopulmonary recirculation (CPR) is a predictable form of solute disequilibrium that is found in all patients with peripheral arteriovenous shunts and is absent during vein-to-vein dialysis. Other forms of blood flow-dependent disequilibrium probably also play a role in diminishing the efficiency of hemodialysis. Sequestration of urea in muscle during hemodialysis is suggested by reduction in the magnitude of rebound when patients exercise (and increase muscle blood flow) during hemodialysis. This discussion is not intended to discourage attempts to increase solute removal by increasing blood flow, but rather to place this maneuver in a proper perspective. Other maneuvers such as increasing dialysis frequency may be more effective as a means of improving dialysis efficiency.     

Biocompatibility of heparin-grafted hemodialysis membranes: impact on monocyte chemoattractant protein-1 circulating level and oxidative status

This prospective observational study aimed at evaluating efficacy and biocompatibility performances of the new heparin-coated Evodial dialyzers with/without systemic heparin reduction. After a 4-week wash-out period with reference polysulfone F70S dialyzers, 6 hemodialysis patients were sequentially dialyzed with Evodial, F70S, and Evodial dialyzers using 30% heparin reduction, each period of treatment was 4 weeks. Removal rates (RR) (urea, creatinine, and β2-microglobulin), dialysis dose, and instantaneous clearances (urea and creatinine) were measured as well as inflammatory (C-reactive protein, fibrinogen, interleukin 6, tumor necrosis factor α, and monocyte chemoattractant protein-1) and oxidative stress (OS) (superoxide anion, homocysteine, and isoprostanes) parameters at the end of each study period. Patients treated with Evodial or F70S dialyzers for 4 weeks presented comparable dialysis efficacy parameters including urea and creatinine RR, dialysis dose and instantaneous clearances. By contrast, a significantly lower but reasonably good β2-microglobulin RR was achieved with Evodial dialyzers. Regarding biocompatibility, no significant difference was observed with inflammation and OS except for postdialysis monocyte chemoattractant protein-1 which significantly decreased with Evodial dialyzers. Thirty percent heparinization reduction with Evodial dialyzers did not induce any change in inflammation but led to an improvement in OS as demonstrated by a decrease in postdialysis superoxide production and predialysis homocysteine and isoprostane. This bioactive dialyzer together with heparin dose reduction represents a good trade-off between efficacy and biocompatibility performance (improvement in OS with a weak decrease in efficacy) and its use is encouraging for hemodialysis patients not only in reducing OS but also in improving patient comorbid conditions due to lesser heparin side effects.     

Quotidian dialysis Survival in 221 patients treated by short daily hemodialysis for 315 patient years

Scanty data suggests that large solutes show a kinetic behavior that is different from urea. The question investigated in this study is whether other small water‐soluble solutes such as some guanidino compounds show a kinetic behavior comparable or dissimilar to that of urea. This study included 7 stable conventional hemodialysis patients without residual diuresis undergoing low flux polysulphone dialysis (F8 and F10HPS). Blood samples were collected from the inlet and outlet blood lines before the dialysis session, after 5, 15, 30, 120 minutes, and immediately after discontinuation of the session. Plasma concentrations of urea, creatinine (CTN), creatine (CT), guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), and methylguanidine (MG) were used to calculate corresponding dialyzer clearances. A two‐pool kinetic model was fitted to the measured plasma concentration profiles, resulting in the calculation of the perfused volume (V₁), the total distribution volume (V_tot), and the inter‐compartmental clearance (K₁₂); solute generation and ultrafiltration were determined independently. No significant differences were observed between V₁ and K₁₂ for urea (6.4 ± 3.3 L and 822 ± 345 mL/min) and for the guanidino compounds. However, with respect to V_tot, GSA was distributed in a smaller volume (30.6 ± 4.2 L) compared to urea (42.7 ± 6.0 L ? P < 0.001), while CTN, CT, GAA, G, and MG showed significantly larger volumes (54.0 ± 5.9 L, 98.0 ± 52.3 L, 123.8 ± 66.9 L, 89.7 ± 21.4 L, and 102.6 ± 33.9 L, respectively). These differences resulted in markedly divergent effective solute removal: 67%(urea), 58%(CTN), 42%(CT), 76%(GSA), 37%(GAA), 43%(G), and 42%(MG). In conclusion, the kinetics of the guanidino compounds under study are different from that of urea; hence, urea kinetics are not representative for the removal of other uremic solutes, even if they are small and water‐soluble like urea.     

Half the V by 120: A practical approach to the prevention of the dialysis disequilibrium syndrome

The dialysis disequilibrium syndrome (DDS) results from osmotic shifts between the blood and the brain compartments. Patients at risk for DDS include those with very elevated blood urea nitrogen, concomitant hypernatremia, metabolic acidosis, and low total body water volumes. By understanding the underlying pathophysiology and applying urea kinetic modeling, it is possible to avoid the occurrence of this disorder. A urea reduction ratio (URR) of no more than 40%–45% over 2 h is recommended for the initial hemodialysis treatment. The relationship between the URR and Kt/V is useful when trying to model the dialysis treatment to a specific URR target. A simplified relationship between Kt/V and URR is provided by the equation: Kt/V = −ln (1 − URR). A URR of 40% is roughly equivalent to a Kt/V of 0.5. The required dialyzer urea clearance to achieve this goal URR in a 120-min treatment can simply be calculated by dividing half the patient's volume of distribution of urea by 120. The blood flow rate and dialyzer mass transfer coefficient (K₀A) required to achieve this clearance can then be plotted on a nomogram. Other methods to reduce the risk of DDS are reviewed, including the use of continuous renal replacement therapy.     

Phosphorus Clearance Using Two Hemodialyzers Placed in Parallel

Control of hyperphosphatemia is a major goal in patients with end‐stage renal disease. However, removal of retained inorganic phosphorus during hemodialysis remains a major problem. We compared clearances and total phosphate removal in large patients treated with two F‐80 dialyzers (Fresenius Medical Care of North America, Lexington, MA, U.S.A.) placed in parallel, and small patients dialyzed with a single F‐80 dialyzer (SD). Clearances were obtained using total dialysate collections. Eight dialysate collections (5 patients) using double parallel dialyzers (DD group) were compared with 5 dialysate collections (4 patients) using single dialyzers (SD group). Blood and dialysate flow rates and time of dialysis treatment were identical between the groups. The DD group's Kt/V _urea was 1.46 ± 0.13; SD group's Kt/V _urea was 1.35 ± 0.09 (p = 0.2). Absolute phosphorus removal was 1594 ± 300 mg for the DD group, compared to 1108 ± 285 mg in the SD group (p = 0.03). Urea clearance in the DD group was 285 ± 25 mL/minute and 251 ± 27 mL/ min in the SD group (p = 0.082). Phosphorus clearance was 178 ± 32 mL/min in the DD group and 149 ± 38 mL/min in the SD group (p = 0.039). There was no correlation between phosphorus clearance and dialyzer reuse. The bulk of phosphorus removal was achieved during the first 2 hours of hemodialysis. This finding is consistent with the hypothesis that there are at least two pools of body phosphorus. Using hemodialyzers placed in parallel led to higher phosphate clearance and total phosphorus removal. This higher phosphate removal may be related in part to increasing the concentration gradient for transfer out of a second compartment.     

Kinetic Modeling of “Go Slow” Dialysis in Acute Renal Failure

Go slow” dialysis is a gentle, intermittent hemodialysis therapy for acute renal failure patients, with advantages compared to slow, continuous therapies. It employs a recirculating closed dialysate circuit. A two-pool urea kinetic model is elaborated to determine kinetic parameters from blood and dialysate concentrations. This will allow quantification of the therapy. Variable clearance is included to accurately describe the kinetic process. The model is tested in an acute renal failure patient. Solute removals, as determined from direct dialysis quantification and by the model, are comparable. Variable clearance is not required to determine the kinetic parameters, because the constant mean clearance delivers equal results. The dialysis dose, as defined, allows comparison with chronic renal therapies. It requires solute removal determined from dialysate sampling and time-averaged concentration (TAC) from the urea kinetic modeling. In the test patient, dialysis dose is lower compared to standard thrice-weekly therapies because of its lower efficiency and higher TAC, a result of his highly catabolic state.     

Development of a high performance parallel-plate hemodialyzer

Early dialyzer development work had shown that a membrane support consisting of a square array of pyramids with a spatial density of 164/in² reduced fluid film resistances to 39 per cent of the total resistance to diffusion of chloride ion with a corresponding increase in dialyzer efficiency of 50 per cent. Subsequent experiments with small tests cells containing pyramidal membrane supports with densities of 256 and 576/in² have shown that even further reductions in fluid film resistance could be attained without adversely affecting other parameters in the dialyzer-patient system. These data have been used to calculate the dimensions of a dialyzer with a chloride clearance of 150 cc/min at 200 cc/min blood flow and 500 cc/min dialysate flow. In vitro performance of dialyzers fabricated to these dimensions have met design objectives. Clinical testing has shown comparable in vivo clearance rates of 126 cc/min for BUN and 102 cc/min for creatinine and the potential for ‘single-shift’ dialysis with a parallel-plate dialyzer.     

Daily Hemodialysis versus Standard Hemodialysis: TAC,TAD, Weekly eKt/V,std(Kt/V), and PCRn

Seven patients, mean age 42.57 ± 15.69 years (range 21 – 67 years), on standard hemodialysis (SHD), 4 – 5 hours, three times per week for 11.0 ± 6.63 years (range 1 – 18 years), were switched to daily hemodialysis (DHD), 2 – 2.5 hours, six times per week. For each type of treatment similar parameters were applied, and the total weekly time was the same. Mean duration of DHD was 15.4 ± 4.98 months (range 7 – 20 months). We report here our results of quantification in each method, including time-averaged concentration (TAC), normalized protein catabolic rate (PCRn), equilibrated Kt/V (eKt/V), equivalent normalized continuous standard clearance [std(Kt/V)], equivalent renal urea clearance (eKRn), and time-averaged deviation (TAD). With DHD, urea TAC was reduced from 19.09 ± 3.47 to 15.16 ± 3.21 mmol/L (p = 0.026), urea TAD diminished from 4.76 ± 1.04 to 2.52 ± 0.57 mmol/L (p = 0.000 53), PCRn increased from 1.11 ± 0.23 to 1.42 ± 0.24 g/kg/day (p = 0.001), weekly eKt/V increased from 4.11 ± 0.31 to 4.74 ± 0.43 (p = 0.000 25), std(Kt/V) rose from 2.17 ± 0.06 to 4.02 ± 0.25 (p = 0.0001), and eKRn increased from 12.96 ± 0.60 to 21.7 ± 3.09 mL/min (p = 0.000 45). On DHD the most important quantitative variation is the decrease of urea TAD (closer to that of a healthy kidney), due to the increased frequency of dialysis; std(Kt/V) practically doubled and represents 30% of that of normal renal function. These changes are probably the main explanation for the clinical improvements, but it is difficult to dissociate the effects of increased dialysis dose from the effects of decreased TAD.     

Removal of vancomycin administered during dialysis by a high‐flux dialyzer

Introduction: Hemodialysis patients frequently receive vancomycin for treatment of gram‐positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high‐flux polyamide dialyzers. Methods: This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high‐flux (Polyflux 24R) dialyzer (Phase 2). There was a three‐week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. Findings: Dialysis removed 35 ± 15% (range 18‐56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0‐44.5 hours from the start of infusion were similar between the two phases (AUC_{Phase 1} 884 ± 124 mg‐hr/L, mean ± SD; AUC_{Phase 2} 856 ± 208 mg‐hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). Discussion: When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high‐flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra‐dialysis dosing is empirically increased to account for intra‐dialytic drug removal.     

Unphysiology Is the Major Factor Influencing Cardiovascular Instability during Hemodialysis

Background: Hemodialysis is often complicated by cardiovascular instability (CVI). We studied factors contributing to this problem during 720 hemodialyses (HDs) in 20 patients; 480 dialyses were 6/week and 240 were 3/week. Methods: Dependent variables were increase in pulse rate (PR) and maximal (MAX) and overall (OV) fall of systolic blood pressure (BP). Independent variables were dialyses/week (DIAL), ultrafiltration (Uf), % of body weight (BW), pre‐post BUN (ΔBUN), time on dialysis (T), speed of dialysis (K/V in mL min^–1 kg^–1 BW), target‐postdialysis BW (Ta‐Po BW), Kt/V, ΔPO4, Δbicarbonate, Δpotassium, ΔBUN, an ‘unphysiology index’ summing up changes in electrolytes, and BUN and BW during dialysis (UPI). The relations were analyzed by backward multiple regression analysis. Results: PR increased 0.5 ± 11/min; MAX BP fall was 23 ± 17 mmHg; OV BP fall was 12 ± 19 mmHg. In multiple stepwise backward regression analysis, independents in order of importance: PR = 38 – DIAL × 4 + T × 0.1 + Uf × 1.8 +ΔPO4 × 1.8 – UPI× 0.2 – K/V × 2, r = 0.30, p < 0.0001; MAX BP = UPI × 0.4 – ΔBUN × 0.3 + ΔPO4 × 2.6 + 11, r = 0.34, p < 0.0001; OV BP = UPI × 0.4 – ΔBUN × 0.3 +ΔPO4 × 2.7 + 1, r = 0.33, p < 0.0001. Conclusion: To prevent BP fall and tachycardia during hemodialysis, the most important factor to decrease is unphysiology, i.e., the oscillations in electrolytes, fluid spaces, and osmolality that occur during dialysis. The best way to do this is to dialyze patients daily. An unexpected finding worthy of further investigation was the large detrimental influence of ΔPO4 on CVI.     

The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.