DAILY DIALYSIS

Daily Hemodialysis Is Best: Why Did We Stop at Three?

Carl M. KjellstrandAksys, Ltd, Lincolnshire, and Department of Medicine, Loyola University School of Medicine, Chicago, Illinois

At the 7th annual meeting of the American Society ofArtificial Internal Organs in 1961, Hegstrom and a co-worker from Scribner’s group in Seattle reported the firstsuccessful trial of prolongation of life in patients withend stage renal disease (ESRD) with hemodialysis (1).Dialysis was done for symptoms every 5–7 days for 20–24 hours. Within the next year, they had discovered thatintervals between dialysis were too long and were per-forming dialysis twice weekly on most of their patients(2). Soon thereafter, thrice weekly hemodialysis becamethe standard and has remained so to this day. This oc-curred despite the fact that every time dialysis frequencywas increased, major improvement in patient well-beingwas noted. O’Brien and colleagues had noted improvedsurvival of “prophylactic daily dialysis” in acute renalfailure already in 1959, 40 years ago (3).

However, all were not satisfied with the rather medio-cre results of chronic hemodialysis; in 1967, John De-Palma began a five-year program of daily hemodialysis,defined as five or more dialysis treatments per week, inLos Angeles. He noted major improvements in dialysistolerance, general well-being, hypertension, hematocrit,nutrition and shunt survival (4). Bonomini undertook atwo-year research study in Bologna in 1972 and 1973(5), and shortly thereafter a group at Maimonides Hos-pital in New York began an almost decade-long programthat ultimately involved 11 patients (6–8). All of thesetrailblazing efforts ended for technological, financial orpersonal reasons; machines malfunctioned, patient ser-vice chores became too great, or teams split up and mem-bers went their separate ways. Dr. John DePalma elo-quently describes what happened to his pioneer programin the next article in this issue ofSeminars in Dialysis.

Initiating his program in 1984, Dr. Buoncristiani hashad the world’s longest continuous daily hemodialysisexperience (9, 10); in 1994 the Toronto group, originallyunder the late Dr. Uldall and later directed by Dr. Pier-ratos, introduced long nightly dialysis done five to seventimes per week (11). The latter experience is summarizedin this issue by Dr Pierratos.

In 1975, we described the theory of “unphysiology ofdialysis” and suggested that daily hemodialysis is the

very best dialysis one could offer patients (12–14). Thesame year, Dr. Zbylut Twardowski in Poland showedthat it was much better for patients well-being to increasethe frequency of dialysis per week rather than to increasethe time or dose (15).

There is currently an explosion in interest in dailyhemodialysis. Over 20 centers are now doing daily di-alysis in over 150 patients in the world (Fig. 1), on fourcontinents (16, 17).

In this edition ofSeminars in Dialysis, Dr. DePalma’sfirst, trailblazing article is reproduced with a personalrecounting of how the treatment came about and how,ultimately, it failed. Dr. Kooistra reports his thoroughinvestigation in the Netherlands of short daily dialysis,the largest such study in the world. Dr. Perriatos reviewshis results with long nightly hemodialysis from Toronto.Clearly, the method developed there allows not only thebenefits of frequency, but also permits Kt/Vs that areunattainable by any other method. Dr. Pinciaroli reportson her very thorough hormonal studies; the general find-ing shows a remarkable metabolic improvement. Everyone of the 16 hormones she has measured slowly driftsinto a normal or near-normal range as patients switchfrom three to six times weekly hemodialysis.

Dr. George Ting, a daily hemodialysis pioneer in theUnited States, argues for short, daily, in-center hemodi-alysis, and suggests that most patients will probably havedifficulties doing long nightly unattended home dialysis.(Parenthetically, this latter method was tried by Dr. De-Palma 22 years ago.) Dr. Robert Lockridge, the pioneerof long nightly home dialysis in the United States, re-ports on his economic and logistical troubles and solu-tions. In the U.S.A., it is clear that daily hemodialysiswill result in overall lower cost. Because of the superiorclinical result, medical costs will decrease for intercur-rent illness; this decrease will exceed the cost increasesfor materials necessary to supply more frequent hemo-dialysis. Dr. Amy Williams reports on the first prelimi-nary comparison between daily short and long nightlyhemodialysis.

Dr. Twardowski reviews the experience with bloodaccess, because the first question always asked is howthe “Achilles heel” of any hemodialysis, the vascularaccess, will hold up when the number of connects isdoubled. Extensive experience now indicates that for apatient with a well-functioning native vessel fistula, it isinconsequential whether it is punctured three times or sixtimes per week. There are now over 3000 patient-monthsof experience and careful comprisons. The results from

Address correspondence to: Carl M. Kjellstrand M.D., Aksys,Ltd., 2 Marriott Drive, Lincolnshire, IL 60069. E-mail:Ckjellstrand@aksys.comSeminars in Dialysis—Vol 12, No 6 (November–December)1999 pp. 403–405

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Dr. Pierratos’ program indicate that central venous cath-eters probably are also having no more problems with thedaily connect. There are not enough data as yet to assesssynthetic grafts such as Teflon, Gore-Tex, and bovinegrafts.

Dr. Depner analyzes the pharmacokinetic advantagesof daily hemodialysis. For the same weekly time andwith the same clearance one gets “bigger bang for thebuck” in Kt/V as frequency increases. Unfortunately, itleads to further complications of an already complicatedconcept, the Kt/V; it appears that the benefits of in-creased frequency often exceed that which might reason-ably be attributed to the rather modest gains in Kt/V. Idiscuss this point in the final article in this symposium.

Two methods of daily hemodialysis are now crystal-lizing: the first method, short, daily hemodialysis, is mostoften done in-center with less stable patients who poorlytolerate the longer dialysis intervals of hemodialysis per-formed three times per week. Dr. George Ting’s center inMountain View, California, illustrates the type of centerthat performs this method. In general, this population, asevident from the literature, is older and sicker. The sec-ond method is long, nightly hemodialysis, which offersthe advantage of very high Kt/V. In Dr. Lockridge’sprogram in Lynchburg, Virginia, patients’ weekly Kt/Vlevels now regularly exceed 10 (!), or three times therecommended hemodialysis dose in the NKF-DOQIdocument (18). In general, these patients are younger andhealthier.

This is again an exciting time in hemodialysis, wherethe last couple of decades have been fairly unexciting,mainly concentrating on large population studies andmodest improvements. There continues to be much con-fusion about the reason for these improvements and, atleast in the United States, the focus has been almostexclusively on Kt/V. This concept, as the lone determi-nant to measure dialysis adequacy, appears to miss mostof the points. Long, slow dialysis is much better thanshort, fast dialysis, and more frequent dialysis appears tobest of all, none of which is reflected in the Kt/V num-bers.

I firmly believe that daily hemodialysis will becomethe new standard of dialysis. It is interesting to note thatthe process has been carried out by small centers byenthusiastic, diligent, intelligent and devoted nephrolo-gists, mostly away from academic centers. Non-clinicalpurists can always point out that the data are often col-lected from a small number patients and are not ideallycontrolled, that some of the studies took place a longtime ago, and so forth. But the clinical case for morefrequent dialysis is overwhelming. Almost all the studiesare crossover studies where the patients are their owncontrols (the strongest of all clinical research protocols),and, very convincingly, everyone “sings the same song”:hematocrit improves, transfusion and erythropoietindoses decrease, blood pressure becomes easy to controlwith fewer or no medications, nutrition improves, andbody weight and albumin levels rise. Dialysis tolerance

FIG. 1. Development of daily hemodialysis. From 1982–1997, the figures are cumulative. For 1998 and 1999, they are prevalence figures frompublished literature and a personal registry.

404 Kjellstrand

and need for nursing intervention during dialysis im-prove markedly, and the annoying post-dialysis fatigue,cramps and other problems basically disappear. Thesechanges result in marked improvement of the quality oflife; hospitalization rates fall and rehabilitation increasesand overall costs will come down.

This issue ofSeminars in Dialysisis dedicated to thegood workers who have labored with daily hemodialysisfor three decades and whose labor has improved so manypatients’ quantity and quality of life. A salute to thetrailblazers!

References1. Hegstrom RM, Murray JS, Pendras JP, Burnell JM, Scribner BH: Hemodi-

alysis in the treatment of chronic uremia.Trans Am Soc Artif Intern Organs7:136–149, 1961

2. Hegstrom RM, Murray JS, Pendras JP, Burnell JM, Scribner BH: Two years’experience with periodic hemodialysis in the treatment of chronic uremia.Trans Am Soc Artif Intern Organs8:266–280, 1962

3. O’Brien TF, Baxter CR, Teschan PE: Prophylactic daily hemodialysis.TransAm Soc Artif Intern Organs5:77–81, 1959

4. DePalma JR, Pecker EA, Maxwell MH: A new automatic coil dialyzer sys-tem for ‘daily’ dialysis.Proc Eur Dial Transplant Assoc6:26–34, 1969

5. Bonomini V, Mioli V, Albertazzi A, Scolari P: Daily-dialysis programme.Indications and results.Proc Eur Dial Transplant Assoc9:44–52, 1972 (Re-printed inNephrol Dial Transplant13:2779–2778, 1998)

6. Snyder D, Louis BM, Gorfien P, Mordujovich J: Clinical experience withlong-term brief, “daily” haemodialysis.Proc Eur Dial Transplant Assoc11:128–135, 1975

7. Louis B, Patel TG, Pinedo A, Snyder D, Gorfein P: Clinical experience withlong-term 5 days-a-week hemodialysis.Proc Dial Transplant Forum5:58–60, 1975

8. Manohar NL, Louis BM, Gorfien P, Lipner HI: Success of Frequent ShortHemodialysis.Trans Am Soc Artif Intern Organs27:604–609, 1981

9. Buoncristiani U, Giombini L, Cozzari M, Carobi C, Quintaliani G, BrugnanoR: Daily recycled bicarbonate dialysis with polyacrylonitrile.Trans Am SocArtif Intern Organs29:669–672, 1983

10. Buoncristiani U: Fifteen years of clinical experience with daily hemodialysis.Nephrol Dial Transplant13(Suppl. 6):148–151, 1998

11. Uldall R, Ouwendyk M, Francoeur R, Wallace L, Sit W, Vas S, Pierratos A:Slow nocturnal home hemodialysis at the Wellesley Hospital.Adv Renal ReplTher 3:133–136, 1996

12. Kjellstrand CM: Reflections on dialysis side effects.Fein et Foie, MaladNutr 16B:327–335, 1974

13. Kjellstrand CM, Evans RL, Petersen RJ, Shideman JR, von Hartitzsch B,Buselmeier TJ: The ‘unphysiology’ of dialysis: a major cause of dialysis sideeffects?Kidney Int2(Suppl 7):S30–S34, 1975

14. Kjellstrand CM, Rosa AA, Shideman JR, Rodrigo F, Davin TD, Lynch RE:Optimal dialysis frequency and duration: The “unphysiology hypothesis”.Kidney Int8 (Suppl 13):S120–S124, 1978

15. Twardowski Z: Effect of long-term increase in the frequency and/or prolon-gation of dialysis duration on certain clinical manifestations and results oflaboratory investigations in patients with chronic renal failure.Acta Med Pol16:236–249, 1975

16. Kjellstrand C, Ing T: Daily hemodialysis − history and revival of a superiordialysis method and literature review.ASAIO J44:117–122, 1998

17. Kjellstrand C, Ting G: Daily hemodialysis: dialysis for the next century.AdvRenal Repl Ther5:267–274, 1998

18. National Kidney Foundation–Dialysis Outcomes Quality Initiative: Clinicalpractice guidelines for hemodialysis adequacy.Am J Kidney Dis30:S22–S63, 1997

Announcement

Reports of methicillin-resistantStaphylococcus aureus(MRSA) strains with intermediate susceptibility to van-comycin (VISA; minimum inhibitory concentration[MIC] 8 mg/mL) have increased recently. All 4 VISAsisolated in the United States were from patients under-going dialysis. It is important to note thatnot all anti-microbial susceptibility testing methods used in clinicalmicrobiology laboratories detect VISA isolates. Disk dif-fusion, for example, is ineffective for detecting VISA. In1998, the Hospital Infections Program (HIP), centers forDisease Control and Prevention (CDC), developed a sen-tinel network (SEARCH) to provide a service of confir-matory diagnostics and expedited susceptibility testingfor Staphylococcus aureuswith reduced susceptibility tovancomycin (MIC$ 4 mg/mL). This service is meant toaid laboratory researchers with identification of patho-gens that may be difficult to detect.

In summary:● Isolates ofS. aureuswith vancomycin MICs$ 4

mg/mL should be retested locally by broth micro-dilution or Etest methods and may be sent to CDCfor confirmatory testing.

● Information on sending isolates to the CDC may beobtained by sending an E-mail to SEARCH@cdc.gov with your name, title, telephone number,and fax number, or by calling Jeff Hageman at(404) 639-4951.

● All U.S. healthcare organizations and practitionersare encouraged to report such isolates to the StateHealth Department and CDC.

● Patients with isolates ofS. aureusconfirmed withCDC with a vancomycin MIC$ 4 mg/mL are eli-gible for enrollment into a nationwide epidemio-logical study.

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