Fourteen patients, aged 19-56 years, (with chronic renal failure caused by isolated renal diseases) were treated with hemodialysis. The frequency and duration of dialyses were adjusted to obtain adequate hemodialysis. Adequate hemodialysis was defined as a method of treatment that could relieve the patient of all clinical manifestations of uremia as well as provide complete rehabilitation. The results of this study were published in three parts in 1974 and 1975.1–3
It was decided that the following clinical manifestations of uremia would be taken into account in the classification of adequacy: nausea, vomiting, loss of appetite, bad taste in mouth, gastric pain, restless legs syndrome, burning feet syndrome, motor neuropathy, bone pains, pathological fractures of bones, metastatic calcifications, pseudogout attacks, diastolic arterial pressure above 95 mm Hg before dialysis and 90 mm Hg after dialysis, circulatory failure, arrhythmia due to hyperkalemia, pericarditis, exudative pleuritis, amenorrhea in women below the age of 40 years, impotence in males, hemorrhagic diathesis, insomnia, dizziness, and headaches during dialysis. Also, a degree of rehabilitation was taken into account when assessing dialysis adequacy. A full rehabilitation was accepted if patients were able to work without sickness absences due to uremia. The following symptoms and signs were considered as complications of dialysis: insomnia only at the time of dialysis, muscle cramps, hypotension, and weakness after dialysis.
Hemodialysis was performed on RSP Travenol artificial kidney and Ultra Flo145 coil dialyzers. The blood flow was kept at 200 mL/min and the dialysate flow at 500 mL/min. A single dialyzer was reused several times during 3 weeks in a given case.4 No blood transfusions or anabolic steroids were given. Erythropoietin-stimulating agents were not available at that time. Using this method it was possible to achieve adequate hemodialysis with two procedures of 12 hours each twice weekly in three patients with a 24 hour urine output of greater than 500 mL. These patients preserved urine output over 500 mL/day extremely well for many years. In the remaining cases with a lower urinary output, adequate hemodialysis could be achieved with three sessions of 8 or 9 hours per week. In some patients with uremic manifestations refractory to treatment, four sessions of 6 or 7 hours each were required weekly. Since the post-dialysis body weight of study patients ranged between 47 and 76 kg, it was not possible to predict the number of procedures per week necessary for a patient.1
There was excellent correlation between the hemodialysis adequacy and following measurements: serum albumin concentrations, blood pressure before and after dialysis, serum albumin concentration, hematocrit, nerve conduction values, and residual kidney function. The correlation with urine output in the range of 100−750 mL/day was better than with creatinine clearance in the range of 0.5-5.5 mL/min.1 This indicates that it is more important to measure urine output than creatinine clearance below 15 mL/min to predict the appropriate dialysis dose in a patient. There was no correlation between the clinical condition of the patient and the following variables: pre dialysis serum urea (86-172 mg/100 mL) and post-dialysis serum urea (18-64 mg/100 mL), and pre dialysis serum creatinine (6.7-14.3 mg/100 mL) and post-dialysis serum creatinine (2.3-6.8 mg/100 mL).1 Our third publication3 presented the correlation of various parameters with dialysis frequency or duration. The correlation between various parameters and dialysis frequency and duration was calculated with Student’s t-test for paired samples.5, 6 This kind of statistic is useful for comparison of two methods applied consecutively (before and after design; A-B or A-B-A) in the same, small, group of patients. The paired t statistic, is also very reliable since it reduces intersubject variability by comparing observations between the same subjects. This method cannot compare mortality, but there is more to life than absence of death.
The blood samples for determining urea, creatinine and hematocrit were obtained before and after dialysis whenever required. The total blood loss caused by sample taking, insertion of needle into the internal fistula, and blood remaining in the dialyzer was about 20 mL per dialysis. The additional blood loss caused by sample taking for routine determinations was about 90 mL monthly. After increasing the frequency or duration of dialyses no more transfusions of donor blood were given to the patients. No androgens were administered.
The conclusions in this publication were as follows: (i) Frequent and short-lasting dialyses are much more effective in treatment of uremic manifestations than longer but less frequent dialyses. (ii) Increased frequency of dialyses has a very favorable effect on hematocrit value, albumin concentration, motor nerve conduction velocity and dry body weight. (iii) Prolongation of dialysis duration without changing the frequency improves the value of hematocrit and albumin concentration, although this improvement is less pronounced than after increased frequency of dialyses. (iv) Increase in the frequency as well as duration of dialyses causes a drop of arterial blood pressure, particularly in hypertensive patients. Increasing the frequency of dialyses by once a week, or duration of dialysis by 17.5%, had no significant effect on the concentration of pre or post urea and creatinine when these parameters were determined after a mean period of 6.4 months after increasing the frequency of dialyses or after a mean time of 6.9 months after increasing the duration of dialyses. At the same time, the patients gained dry body weight so the increased removal of urea and creatinine were compensated by increased protein intake and creatinine production with higher muscle mass. Cramps, hypotensive episodes during dialysis, and prolonged recovery time after dialysis were very rare. Almost all patients accepted longer and/or more frequent dialyses as they felt better and could change diet. With longer and more frequent dialyses the patients could change diet to one containing more salt. One of our patients in whom the necessity of dietary restrictions was particularly stressed in view of arterial hypertension explained that the recommended low-salt diet caused loss of appetite, abdominal pains, weakness and irritability. The patient accepted an increase in the frequency of dialyses and reduction of dietary restrictions for relief from troublesome symptoms. Lately the diet has been made much less strict. The mean protein intake calculated on the basis of a weekly diary given to patients ranged from 0.90 to 1.25 g/kg/24 hours. The intake of sodium exceeded 100 mEq/24 hours in many patients, judging from the weight gains in the intervals between dialyses. One patient had headaches during dialyses. The headaches were, undoubtedly, a consequence of disequilibrium syndrome of small intensity since they disappeared after a short trial of increasing the frequency of dialyses. However, this patient considered the intensity of this symptom so insignificant that he ruled out switching to more frequent hemodialysis sessions. As a result of these studies, we came to the conclusion that adequate dialysis with blood flow of 200 mL/min on coil dialyzers (in patients with 24-hours urine output exceeding 500 mL) may be achieved with two procedures of 12 hours each twice weekly. However, patients with less urinary output will require at least 24 hours of dialysis per week (3× 8-9 hours), preferably more than 3 times per week (4 × 6-7 hours).
I predicted “that in the near future, the main form of treatment of uremia will be short daily hemodialysis”.3 This prediction has not come to pass, mainly because the development went toward short dialysis but only limited to three times a week. Only recently there has been is a movement toward more frequent dialysis; however, using more efficient dialyzers, the time of dialysis does not need to be as long as on coil dialyzers.
Zbylut J. Twardowski received medical degree Summa cum laude from the Jagiellonian University, became full Professor of Medicine in Poland and Professor Emeritus of Medicine at the University of Missouri, Columbia, MO, USA. He has published 397 articles, 185 abstracts, 16 discussions, 28 letters, 23 patents, and an autobiography. He has made 550 presentations all over the world and received multiple rewards. He retired in 2014 as octogenarian.