We Should Strive for Optimal Hemodialysis: A Criticism of the Hemodialysis Adequacy Concept

Adequacy of hemodialysis is frequently equated with Kt/V_urea , the amount of urea clearance (K) multiplied by time (t) and divided by urea distribution volume (V). Several formulas have been developed to calculate Kt/V_urea from the pre‐ and post‐dialysis urea concentrations. In three‐times‐weekly hemodialysis, a single pool (spKt/V_urea) value of 1.3 per treatment is commonly considered to indicate adequate therapy.
Despite providing the recommended spKt/V_urea of 1.3 per treatment, short dialysis with rapid ultrafiltration is associated with multiple intradialytic and interdialytic complications. Patients experience cramps, nausea, vomiting, headaches, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control, left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality.
According to Webster's dictionary, "optimal" means most desirable or satisfactory; "adequate" means sufficient for a specific requirement or barely sufficient or satisfactory. Optimal dialysis is the method of dialysis yielding results that cannot be further improved. New approaches, including hemeral quotidian or long nocturnal dialysis, provide opportunities to abandon the notion that adequate dialysis is "good enough" for our patients. Optimal dialysis should be our goal. Dialysis sessions should be long and frequent enough to provide excellent intra‐ and interdialytic tolerance of hemodialysis, normalization of serum calcium and phosphorus, blood pressure control, normal myocardial morphology and function, and hormonal balance, and to eliminate all, even subtle, uremic symptoms.     

Normalization of Dialysis Dose for Daily Dialysis

The equilibrated Kt/V (eKtV) is widely used in hemodialysis (HD) as a measure of the intensity (magnitude) of an individual dialysis treatment. Adequate eKt/V for thrice‐weekly hemodialysis (twHD) has been extensively studied, and a value in the range 1.0 – 1.1 per treatment (3.0 – 3.3 weekly) is generally considered to represent adequate therapy for this specific frequency of dialysis. However, for other schedules, summing eKt/V's and time‐averaging the clearance is not appropriate. This was first demonstrated several years ago by the observation that a weekly eKt/V of 2.0 in continuous ambulatory peritoneal dialysis (CAPD) is therapeutically equal to a weekly eKt/V of 3.0 in twHD. That paradox has been resolved by the standard Kt/V (stdKt/V), which accounts for the first order nature of solute removal by dialysis, and which correctly predicts a normalized weekly stdKt/V of 2.0 for both CAPD and twHD. The equivalent renal clearance (EKR) has also been advanced as a method to normalize dose for varying treatment schedules. However, mathematical consideration shows that EKR is an exact time‐averaged clearance. Analysis of data reported for daily dialysis by Piccoli et al. in the present issue of Hemodialysis International shows that the EKR_ct/V calculated for daily dialysis is identical to the sum of eKt/V's for the individual dialyses. We therefore conclude that EKR is not a suitable parameter for normalizing the dialysis dose, because it fails to reflect the effect of dialysis frequency in HD therapy.     

The Case for Every‐Other‐Day Dialysis

Until daily dialysis becomes widely available, we believe that hemodialysis patients would benefit enormously from every‐other‐day dialysis (EODD), which may be implemented both by home patients and in centers. Benefits of EODD over the routine, three‐times‐weekly schedule would include decreased mortality after the weekend interval without dialysis; increased weekly dose of dialysis, resulting in better rehabilitation; and improved blood pressure control.     

Quantitating Dialysis in the Home Hemodialysis Patient: A Simple and Practical Approach

Home hemodialysis is the most cost-effective form of dialysis and is associated with the lowest mortality. Home hemodialysis patients are usually highly motivated, independent, and actively employed. Because of the minimal supervision they require and the fact that they are not in a controlled environment, it is easy to overlook the measurement of their dialysis adequacy. We studied 6 home hemodialysis patients and demonstrated that blood urea measured 30 min before the end of dialysis (Ct-30) is equivalent to that measured 30 min after the end of dialysis (Ct+30). The Kt/V results using Ct-30, Kt/V(Ct-30), were almost equivalent to Kt/V(Ct+30) (p = 0.5). The Kt/V Kt/V(Ct) using blood urea measured at the end of dialysis (Ct) significantly overestimated Kt/V(Ct-30) and Kt/V(Ct+30) (p = 0.007) The calculated percent reduction of urea (PRU) was about 5% less when using Ct-30 compared with Ct (p = 0.001). Taking blood samples 30 min before the end of dialysis for urea kinetics is more convenient for the home dialysis patients, since no other technical aspects of dialysis need their attention. The samples can be delivered to the laboratory the following day, because the blood may be stored in heparinized tubes at 4°C without deterioration of urea and creatinine concentrations. The Kt/V(Ct-30) was almost equal to Kt/V(Ct+30), so there is no longer any concern for the errors introduced by urea rebound. The blood pump must be reduced to 80 mL/min for about 10 sec to eliminate the errors due to fistula and cardiopulmonary recirculation. A simple programmable calculator will facilitate the calculation of accurate results using the Daugirdas second-generation formula.     

The History of Home Hemodialysis: A View From Seattle

Home hemodialysis was first used for the treatment of end-stage renal disease in the early 1960s, primarily as a means of reducing the cost of treatment. It was soon found to be an effective form of treatment that provided patient independence, greater opportunity for rehabilitation, and better survival. In 1973, when the Medicare End-Stage Renal Disease Program began, some 40% of all U.S. dialysis patients were on home hemodialysis, but since then the percentage of patients on this treatment has steadily decreased. There are several reasons for this, one in particular being the lack of availability of suitable equipment. There is now renewed interest in home hemodialysis sparked by the knowledge that new equipment specifically designed for this is being developed, that this is the modality with the best survival rate, greatest opportunity for adequate dialysis and best quality of life, and an interest in the use of daily (or nightly) home hemodialysis. Consequently, more than 30 years later, it appears that home hemodialysis may again become the preferred treatment for many more patients.     

Nightly Home Hemodialysis: Fifteen Months of Experience in Lynchburg,Virginia

What constitutes adequate dialysis has been debated in the nephrology literature over the past eight years. The mortality rate of patients on dialysis in the United States is about 20% per year. We believed that short and infrequent dialysis sessions contributed to poor outcomes. To improve the results, Lynchburg Nephrology started the nightly home hemodialysis (NHHD) program in September 1997. Ten patients were trained in the first 15 months of the program. Patients dialyzed 7 – 9 hours, 6 nights/week, using the Fresenius 2008H machine. A standard dialysis solution with 2.0 mEq/L potassium, calcium concentration of 3.0 – 3.5 mEq/L was used. Dialysis solution flow rates were 200 – 300 mL/min. Serum phosphate levels were maintained above 2.5 mg/dL by adding 0 – 45 mL Fleet's Phosphosoda to the bicarbonate bath. Patients had marked improvement in quality of life as measured with the SF-36. Blood pressure was better controlled with fewer medications. All phosphate binders were eliminated. Caloric intake and protein intake increased to normal levels as measured by three-day dietary histories pre-NHHD, and at 3, 6, and 12 months on NHHD. Epoetin alfa dosages were reduced by about 50%. Nightly home hemodialysis should be considered as a valuable modality option for end-stage renal disease patients; it is potentially superior to conventional thrice-weekly hemodialysis.     

Choice Reaction Time and Adequacy of Dialysis: A New Application of an Old Method

Background:  Choice Reaction Time (CRT) is the time it takes for a subject to accurately respond to a flashing panel of lights. The CRT has been used to assess the quality of dialysis in hemodialysis patients and to assess the neurological impairments in patients with Parkinson's disease.
Methods:  Three groups of end‐stage renal disease (ESRD) patients on three different renal replacement therapies were tested using CRT: intermittent peritoneal dialysis (IPD, n = 11), thrice weekly hemodialysis (HD, n = 22), and well‐functioning kidney transplant (Tx, n = 6). A group of volunteers with normal renal function (NL, n = 12) was also tested.
Results:  The CRT was significantly longer in IPD patients (618 ± 89 ms) than observed in the other three groups (p < 0.0001). CRT in HD patients was 461 ± 50 ms, which was significantly longer than in Tx patients (396 ± 25 ms, p = 0.05). However, the CRT in the Tx patients was no different from the NL (382 ± 22, p = 0.32). There was a strong negative correlation between CRT and weekly creatinine clearance in the IPD group (r =− .96) and between the dialysis index and CRT in HD (r =− 0.79).
Conclusions:  CRT may be a useful tool in assessing the adequacy of dialysis.     

Left ventricular assist device patient maintained on home hemodialysis: A novel class of patients to the home dialysis population

Severe heart failure is increasingly being managed by cardiac transplantation, and in some cases mechanical support devices serve as destination therapies. Left ventricular assist devices (LVADs) were approved for destination therapy for end stage heart failure patients before the more advanced total artificial heart modality became available. One common complication of mechanical assist device placement is acute kidney injury. Historically, patients with mechanical support devices have had to have inpatient hemodialysis until combined heart kidney transplant. Though, some units have started accepting LVAD patients in outpatient dialysis clinics. The cost of in center hemodialysis remains high and home dialysis modalities are becoming increasingly popular. We report the first patient with an LVAD to undergo training and successful home hemodialysis while awaiting combined heart kidney transplantation.     

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.     

A Composite Index of Compliance for Chronic In‐Center Hemodialysis Patients

We developed a composite compliance index as the sum of the compliance scores for interdialytic weight gain (IDWG), pre‐dialysis serum potassium and phosphorus concentrations (each scored from zero to 3, with 3 indicating the poorest compliance), and skipping hemodialysis sessions (scored from zero to 9, with 9 indicating the poorest compliance). We used this composite score to prospectively evaluate compliance in 25 prevalent hemodialysis patients over a period of 1 year. We then followed these patients for another 3.5 years. The patients studied were divided into two groups: group A (poor compliance) consisted of 9 subjects with composite score ≥ 9 (13.2 ± 3.2); group B (better compliance) consisted of 16 subjects with composite score < 9 (4.7 ± 1.8). Age, duration of hemodialysis, and frequency of diabetes mellitus did not differ between the groups. Group A contained higher fractions of subjects with history of alcoholism (66.7% vs 12.5%, p = 0.010), other substance addiction (44.4% vs 0%, p = 0.010), and severe psychosocial problems (88.9% vs 18.8%, p = 0.002). Mean survival from the beginning of observation, estimated by actuarial life‐table survival analysis, was 1.19 years in group A and 2.60 years in group B (p = 0.0265). A composite compliance index incorporating domains indicating adherence to diet, medications, and dialysis schedule identified other behavioral problems in poorly compliant patients. Hemodialysis patients characterized by this composite index as poorly compliant had shortened survival.     

The Neglect of Sodium Restriction in Dialysis Patients: A Short Review

In end-stage renal failure, natriuresis decreases, sodium accumulates, and extracellular volume (ECV) excess develops. In 1962, Scribner, reporting about the first maintenance hemodialysis (HD) patient, observed that ECV control using a low-salt diet and ultrafiltration led to blood pressure (BP) normalization. Thus, the concept of dry weight, the ideal postdialysis weight allowing for a stable normal BP, was born. Achieving dry weight requires a combination of negative diffusive sodium balance, adequate ultrafiltration, and a low-salt diet. Unfortunately, the low-salt diet is very often neglected today. In the late 1960s, BP control was achieved in 90% of HD patients using low-sodium dialysis and a low-salt diet. As time passed and HD duration was reduced, there was a worsening BP control and subsequent increasing in morbidity and mortality.
In recent years, interventional studies have examined the effects of reducing sodium in dialysate, in diet, or in both. All of them show that low-salt diet is essential for BP control in HD. While the healthy population is advised to eat a reasonably low-salt diet (5 g of NaCl), the K/DOQI Guidelines and the European Best Practice Guidelines surprisingly do not even mention salt restriction.
To achieve dry weight under the present conditions, with short HD duration and a frail population, it is mandatory to reduce the interdialytic weight gain. A low-salt diet is, more than ever, a necessity.     

Hemodialysis: a therapeutic option for severe attacks of acute intermittent porphyria in developing countries

Acute intermittent prophyria (AIP) is an autosomal dominant disease that results from a defect in the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the most common of hepatic porphyrias and can tax the therapeutic capabilities of the physician to the limit. Motor weakness is a major feature of an acute attack, and flaccid paralysis of all extremities can occur rapidly, within a matter of days. The acute attacks may be life threatening. Hematin (Heme Arginate) should be given early during an acute attack to prevent neurologic sequel. Hemodialysis and hemoperfusion have been tried in the treatment of acute attacks of AIP with success. As hematin is not available in India, a severe acute attack of AIP in a patient was managed with hemodialysis successfully. Later, hematin was imported and provided to the patient. An 18-year-old girl was admitted to our hospital with recurrent abdominal pain and 2 episodes of convulsions. She had undergone an appendectomy earlier at another hospital for abdominal pain. On evaluation, she had hyponatremia, episodic abnormal behavior, generalized muscle pain, hypertension, and sinus tachycardia. In view of the above clinical picture, a clinical diagnosis of acute intermittent porphyria was made. Her 24-hr urinary porphobilinogen was 90.8 mg/day (<2 mg-normal) and alpha amino levalunic acid was 108.8 mg/day (1-7 mg-normal), consistent with the diagnosis. Her hyponatremia was corrected. Arrangements were made to import hematin and she was managed with dextrose infusion. Meanwhile, she developed flaccid quardriparesis with urinary incontinence and bulbar palsy. Her brain MRI was normal. Her nerve conduction study was suggestive of motor radiculoneuropathy. Specific treatment for severe porphyric crisis was planned. She failed to improve with dextrose infusion alone. As hematin was not readily available in the country, other therapeutic options were considered. As few case reports of AIP being successfully treated with hemodialysis were available, the option of dialytic support was explained to the family. After procuring informed consent, she was subjected to hemodialysis for 4 hr in the first day, increasing to 6 hr a day for the next 6 days. Her abdominal pain and myalgia subsided on the third day of dialysis. Her lower limb muscle power improved and she became ambulant by the fourth day. Urinary retention improved within 4 days. Hematin was imported by then from the United States. Later, 2 doses of hematin (4 mg/kg-160 mg in 20% albumin) were given via a central vein. She was maintained on physiotherapy. Repeat nerve conduction study revealed recovery. She has been provided with a list of drugs that have to be avoided. Currently, she is on outpatient follow-up with occasional abdominal pain, which subsides with intravenous dextrose therapy.     

Challenges of long-term vascular access in pediatric hemodialysis: Recommendations for practitioners

Kidney transplantation is the preferred treatment of end-stage renal disease in children. However, time to transplant varies, making a well-functioning long-term vascular access essential for performing hemodialysis efficiently and without disruption until a kidney becomes available. However, establishing long-term vascular access in pediatric patients can present distinct challenges due to this population's unique characteristics, such as smaller body size and lower-diameter blood vessels. There are three main pediatric long-term vascular access options, which include central venous catheters (CVC), arteriovenous fistula (AVF), and arteriovenous graft (AVG). CVC are currently the most widely used modality, although various studies and guidelines recommend AVF or AVG as the preferred option. Although AVF should be used whenever possible, it is crucial that clinicians consider factors such as patient size, physical exam findings, comorbidities, predicted duration of treatment to decide on the most optimal long-term vascular access modality. This article reviews the three long-term vascular access methods in children and the benefits and complications of each.     

Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.     

Intensive dialysis and blood pressure control: A review

The prevalence of hypertension in hemodialysis (HD) patients has increased over the years. In the early days of maintenance HD blood pressure (BP) control was achieved in most patients. As sessions were shortened, the prevalence of hypertension increased. Yet, in principle, dialysis is able to control hypertension. Today, in programs using long HD, most patients are normotensive without antihypertensive medication. The same is true for patients on daily dialysis, but not for those on short thrice‐weekly HD. In all studies reporting BP normalization, dry weight is regularly achieved. Why the poor control of hypertension now? At first sight the shortened session duration is the culprit. This is suggested by several epidemiologic observations and strongly supported by a prospective experience of changing the HD schedule (short to long HD or conversely) in the same group of patients. Recent studies, however, using strict volume control show that BP normalization can be obtained in conventional 3 x 4 hr/week dialysis with relatively low delivered Kt/V_urea. Therefore, prolonging the dialysis time and/or increasing the dialysis dose are not required to achieve BP control. Intensive dialysis most probably normalizes BP by getting the extracellular volume and the amount of sodium in the body back to normal. It acts in conjunction with a moderate dietary sodium restriction and the use of reasonably low dialysate sodium. With this approach improved BP control can be achieved in the vast majority of HD patients.