Thirty-Five Years of Hemodialysis: Two Case Reports as a Tribute to Nils Alwall

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    vivyeNephrology Department, and in 1984 from the

    Am48, he attempted to create an arteriovenousunt; however, the available materials wereombogenic and the shunts clotted after only a

    usages.3 In 1960, Alwall initiated a long-m hemodialysis program; unfortunately, earlyrvival failed to exceed five months.4 In 1965,ly a few years after the Quinton-Scribner shuntd been developed,5 Alwall wrote: All theronic cases have come for treatment in theal stage of the disease, and it has been impos-le to carry out dialysis at sufficiently shortervals. It is only in the last 2 years that weve been able to give 7 patients with arterio-

    private Ellenbogen clinic), in the reports of twopatients initially treated by Alwall (Fig 2). Thesepatients still continue on HD to the present day.

    From the 1Department of Nephrology, Lund UniversityHospital, Lund; and 2Department of Nephrology and Trans-plantation, Malm University Hospital, Malm, Sweden

    Support: None. Potential conflicts of interest: None.Address reprint requests to Jan Kurkus, Department of

    Nephrology, Lund University Hospital, SE-221 85 Lund,Sweden. E-mail:

    2007 by the National Kidney Foundation, Inc.0272-6386/07/4903-0016$32.00/0doi:10.1053/j.ajkd.2007.01.022

    erican Journal of Kidney Diseases, Vol 49, No 3 (March), 2007: pp 471-476 471Thirty-Five Years of HemodiaTribute to

    Jan Kurkus, MD,1Marie Nykvist, RN,2 Birge

    Two patients with long-term (35 years) survival otherapy for these patients was initiated by a pionerespectively. Kidney transplantation was attempteinterval was less than 18 months in both patients.survivors on hemodialysis worldwide. Factors that mthe complications that have occurred over the yearsAm J Kidney Dis 49:471-476. 2007 by the Nation

    INDEX WORDS: Long-term, survival, hemodialysis

    hen Nils Alwall started his animal experi-ments in the basement of the Depart-

    nt of Medicine at Lund University Hospital atbeginning of the 1940s,1 treatment of acute

    al failure with dialysis was considered to be apia, and long-term survival with an artificialney was beyond the imagination of most

    ople practicing medicine. Alwalls ideas werenifest at a time when the Second World Warhibited closer contact with contemporary Wil-

    lm Kolff in Holland, who developed the rotat-drum artificial kidney. Initially tested in rab-

    s, Alwall=s stationary drum artificial kidneys enhanced for use in humans (Fig 1). In 1946,

    ing the stationary drum artificial kidney, herformed the first treatment combining bothlysis and controlled ultrafiltration.2Alwall continued his work to provide help fortients with renal failure, and during his remark-le career he was able to achieve goals thats: Two Case Reports as aAlwall

    ergrd, MD,1 Mrten Segelmark, MD1

    odialysis are described. Kidney replacementemodialysis, Nils Alwall, in 1968 and 1971,in both patients; however, the dialysis-free

    patients represent two of the longest knowne influenced their survival are discussed, andesented.ey Foundation, Inc.

    nous shunts satisfactory treatment. The sur-al time is approaching 2 years.6

    The turning point arrived in 1966 when Bres-, Cimino and others published their ideas foreriovenous (AV) fistulas,7 opening the possibil-for long-term hemodialysis (HD). Alwall fore-

    the rapidly increasing demand for HD. In65, about 3,500 dialysis treatment sessionsre carried out in Sweden, and at that time heticipated approximately 50,000 treatments in68 and 100,000 in 1969.8 In the decades since,ormous development has occurred, increasing

    quality of dialysis techniques and medicalatment and allowing the survival of over 1.5llion dialysis patients worldwide.Despite the many limitations in the early yearslong-term HD, the care provided by Alwalls sufficiently good to enable long-term sur-al. This conclusion is evident in 2007, over 35

    ars after Alwalls retirement (in 1971 from

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    Kurkus et al472CASE REPORTS

    tient 1atient 1 is a 51-year-old woman who developed chroniclonephritis in 1962, at the age of 7, probably due to refluxhropathy. Her kidney function deteriorated gradually,, at the age of 13, an AV fistula was created in her leftst; HD was initiated when signs of pericarditis mani-ted. Six months later, bilateral native nephrectomy wasformed to treat uncontrollable hypertension. At the age ofcadaveric kidney transplantation was performed; how-r, this kidney failed to function satisfactorily and sherned to HD after 6 months. In the interim, splenectomy

    s performed because of signs of hypersplenism (anemia).age 23, a second cadaveric kidney transplantation wasformed. In the postoperative course she experiencedltiple infection complications and she returned to hemodi-sis one year later (total dialysis-free interval 18 months).

    has continued uninterrupted on hemodialysis since thise, having refused further attempts at kidney transplanta-.

    alysis Accesshe initial AV fistula that had been placed in 1968 ceased

    function after 13 years; new fistulas were created in thewrist in 1981 and right wrist in 1982. This latter fistula

    s revised in 1982, 1988 and 1989. Since then, the functionthe AV fistula has been good and repeated angiographicminations (because of edema of the arm, signs of collat-l circulation) have not revealed significant stenoses, al-ugh several short periods with a temporary catheter forlysis were needed.

    igure 1. Nils Alwall examining one of his early dialyz-used in animals experiments in the early 1940s. This

    del was later scaled up for use in humans.ood Pressureer blood pressure was difficult to control, with periods

    hypertension followed by periods of hypotension, whichs unresponsive to weight adjustment, increase in sodiumcentration in the dialysate, correction of anemia or nutri-al parameters. She responded partially to treatment with

    ydroergotamine. Her blood pressure is currently accept-e without treatment.

    emiauring the first 20 years of hemodialysis, hemoglobin

    els occasionally dropped as low as 5-6 g/dL (50-60 g/L)she required multiple blood transfusions, sometimes one

    t every week or every other week. Altogether she re-ved 150 units of blood between 1968 and 1987. During

    period, she was probably infected with hepatitis B andatitis C viruses. In 1988 erythropoietin treatment was

    rted and she has been successfully maintained at targetoglobin levels of 11-13 g/dL (110-130 g/L).

    ne Diseaseone densitometry monitoring was performed from 1972

    il 1998 with a single-photon technique, and thereafter

    igure 2. Nils Alwall (1904-1986). Reproduced withmission from Kjellstrand CM: Dedication to Nils Alwall.phron 39(2):71-72, 1985. Copyright S. Karger.

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    Table 1. Selected complications in two patients during 35 years of hemodialysis.

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    Long-term Survival on Hemodialysis 473h dual-energy-X ray absorptiometry (DEXA). Over timere has been a slow decrease in bone mineral content of up20%; however, vertebral morphometry of the T4-L4ion has remained normal. She underwent parathyroidec-y in 1977. Late in 1979 she developed joint pain andtment with analgesics was started. In 1989-1990, treat-

    nt with methotrexate, prednisolone and cyclosporine wasiated based on the incorrect assumption of reactive arthri-The diagnosis was later changed to dialysis-related

    yloidosis. In 1991 arthroscopic acromioplasty of her leftulder was performed, but resulted in only brief andignificant pain relief. Operations for carpal tunnel syn-me were performed on the right wrist in 1983, left wrist985, right wrist again in 1987, and again in the left wrist

    1999. Since 1986 joint manifestations have consisted ofgressive pain in the shoulders, spine and small joints, andfening and effusions. Radiological examination showedtructive joint changes (erosion and periarticular bonets), and treatment with antidepressants and morphine-likegs in slowly increasing doses was initiated. The full listomplications is presented in Table 1.he is currently quite satisfied with her quality of life,pite the pain in her bones and joints requiring frequentcotic administration. In spite of the signs of dialysis-ted amyloidosis, she refuses to increase the frequency of

    lysis therapies beyond 5 hours twice weekly. Althoughrelies on a wheelchair for mobility, she describes her

    sent situation as being relatively calm, despite undergo-long-term HD for over 35 years.

    rgan/system Patient Type of event/c

    rgical 1 Splenectomy1 Cholecystectomy1 Appendectomy1 Uterine dilation and curet1 GI-bleeding1 Fasciotomy (posttraumati1 Cataract surgery2 Hysterectomy and bilatera

    salpingo-oophorectomyurological 1 Epilepsy

    1 Acute hearing loss, right e2 Sleep apnea

    neral 2 Aluminium intoxicationctions 1 Septic arthritis

    1 Septicemia1 Hepatitis B1 Hepatitis C1 VRE1 Extraction of eight teeth d2 Hepatitis B2 Septicemia2 Severe shoulder infection

    rdiovascular 2 Myocardial infarctionbbreviations: HD, hemodialysis; GI, gastrointestinal; VREtient 2his is a 76-year-old woman with kidney failure due to

    inked Alport syndrome of juvenile type, confirmed byection of causative splice site mutation in the COL4A5e.9 She has had a history of hematuria and proteinuria

    m early childhood, and beginning at age 23, after givingth to her second child, gradually decreasing renal func-, hypertension, and hearing loss ensued. Kidney biopsye a diagnosis of chronic pyelonephritis. In 1971 an AVula was created in the left wrist and HD was started soonreafter, when she was 42 years old. A cadaveric kidneysplant was performed 3 months after start of HD, but

    s unsuccessful. She has been menopausal since 1975 andlly deaf on the left side since 1978. In 1984, at the age ofa second cadaveric kidney transplant was carried out;year later the graft was lost because of sepsis and sherned to HD. Her total dialysis-free interval was 15

    nths, and she refused further kidney transplantation. HDs carried out at home (self-care) between 1979 and 1984

    again between 1986 and 1989. Between 1991 and 2005was performed at a satellite dialysis unit in Lund,


    alysis Accesshe initial AV fistula was surgically revised, because ofurysmatic changes, in 1983, 1996, 2002 and 2004. Sev-l radiological procedures were carried out to maintain thection of the fistula.

    tion Years after initiation of long-term HD


    ypermenorrhea) 8 times (19-29)21

    toma) 222925

    223317183 times (33-35)14-181723 (serological diagnosis)25

    fection 286 (serological diagnosis)3 times (13,14,24)2431

    mycin-resistant Enterococcus.TX-ldetgenfrobirtiongavfistthetranwa









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    Kurkus et al474emiauring the first 17 years of HD the patient needed

    ltiple blood transfusions; however, these were less fre-nt than in patient 1. Recombinant erythropoietin treat-nt was initiated in 1988; thereafter, anemia was managedhout transfusions.

    ne Diseasehe patient was monitored using a single-photon tech-

    ue beginning in 1972. Her bone mineral content slowlyreased over her first several years on dialysis; this pro-s accelerated after 1979, such that by 1991 she had lost

    of her bone mineral content in both arms, and, by 1996,in her right arm. She has lost 5 cm in height, fractured

    right lower arm in 1979, both lower arms in 1985, rightin 1991, left hip in 1996 and suffered a pelvis fracture in0. She underwent parathyroidectomy in 1980. Surgery

    s performed for carpal tunnel syndrome in the left wrist in6 and in the right wrist in 1992 and 1994. Since 1990 sheexperienced increasing pain in multiple joints, initiallyted with analgesics, and, more recently, with narcotics.

    e full list of complications is presented in the Table 1.spite these complications, she lives at home with herband, and with the use of a wheelchair, she can attend toivities of daily living with only limited assistance fromal social services.

    DISCUSSIONThere are several breathtaking testimonies oftients describing long-term survival on HD,luding those of Judy Weintraub, Peter Lundin,

    chard Faber and Robin Eady (all available oninternet). There are also many publications

    out long-term survival on HD.10-13 Graddend Ahmed10 presented in 2001 a patient treated

    years with HD; unfortunately, this patientd while the paper was in press. These authorsined: It is unlikely that we will see manytients on such long-term haemodialysis in Eu-e in the future. The cases presented hereve that it is possible, and that there may evenother such long-term survival cases.In 1996, Avram et al14 presented a uniquealysis of long-term survivors on hemodialysis.ung age at the onset of kidney failure, nondia-tic status, black race, male gender, good nutri-nal status, and adequate dose of dialysis alldicted better survival for periods up to 30

    ars. According to the Swedish Uraemia Regis-, there are 5 patients in Sweden who started

    in Sweden at the beginning of the 1970s,o remain on hemodialysis over 30 years later;f these individuals have received hemodialy-for 35 years or more.15

    Several factors may be crucial for the long-m survival of our patients. To date, neither hasnifested any clinical signs of advanced isch-ic heart disease or peripheral vascular disease;wever, both have significant limitations inbility and have refused coronary artery dis-

    se screening. Neither patient is diabetic, andre has been no prolonged hypertension orperlipidemia. Patient 1 is a light smoker, whiletient 2 has never smoked. All this could beponsible for the lack of cardiovascular symp-s and could contribute to their long-term

    rvival.16-18A second factor is vascular access. Both pa-nts have had well-functioning AV fistulas for

    vast majority of their time on HD, withtient 2 using the same AV fistula since likely is a prerequisite for effective dialysis,judged by the high rate of blood flow through

    dialysis membrane, consistently acceptablelysis adequacy, and excellent nutrition param-rs.Kidney transplantation was performed twiceboth patients but their dialysis-free time wasatively short, failing to exceed 18 months inher patient. Subsequently, the total doses ofrticosteroids and other immunosuppressiondications given with kidney transplantation,re relatively low.The most disabling complication for both pa-nts has been bone disease, manifested withlysis-related amyloidosis in patient 1 and with

    teopenia in patient 2. The sharp contrast be-een the very low mineral content in the armsd hips compared with the normal to highntent in the spine in both cases is very interest-. This could be explained by the long periodhyperparathyroidism (at least 9 years in bothtients, from the start of HD to parathyroidec-

    y), which mainly affects the cortical bonesch as in the arms and hips.19 As the main factordialysis-related amyloidosis seems to be 2-croglobulin, convective dialysis (hemodiafil-tion/hemofiltration) has been used in our pa-nts; however we were unable to reverse thegression of osteoarthropathy in either pa-

    nt.20 Both patients underwent parathyroidec-y; subsequently, they had limited problems

    th calcium-phosphate metabolism. This may

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    Table 2. Evolution of dialysis prescription in two patients during 35 years of hemodialysis



    Pat 89 whe


    A hemod

    Long-term Survival on Hemodialysis 475ve reduced vascular calcification but likelyntributed to their skeletal problems.A change from acetate-based to bicarbonate-sed dialysate was made at our unit in 1988,d both patients were treated with convectivelysis methods (with highly permeable andcompatible membranes in dialyzers) wherelacement fluid was prepared from dialysate

    -line. Thus ultra-pure dialysate has been usedring the last 15 years of treatment in bothtients. However, signs of dialysis-related amy-dosis are progressing, mostly in the shoulderions. Dialyzers were never reused in our unit.

    Both patients were profoundly anemic untildevelopment of recombinant erythropoietin.

    ey required blood transfusions as often asery 1 to 6 weeks; subsequently both developedpatitis B surface antibody and hepatitis B coretibody positivity (patient 1 in 1985 and patientn 1979). Patient 1 tested positive for hepatitisin 1989. Fortunately, no signs of liver diseasere observed in either patient. Both patientsre initiated on recombinant erythropoietinrapy in 1988 with uncomplicated anemia man-

    ement since.Malnutrition has been observed in long-term

    survivors21 and although the nutritional sta-of our patients can be described as satisfac-

    y on the basis of constant body weight, oral

    ient 1 (treatment in center only)

    Year Modality Membrane8 HD Cuprophane0 HD Cuprophane9 HD Cuprophane6 HD Cuprophane1 HF Polyamide8 HDF Polyamide0 HF Polyamide

    ce 2002 HDF Polyamide

    ient 2 (treatment in center except intervals 1979-1984 and 1986-19

    Year Modality Membrane1 HD Cuprophane7 HD Cuprophane9 Home HD Cuprophane1 HD Cuprophane6 HDF Polyamidece 2003 HDF Polyamidebbreviations: HD, hemodialysis; HF, hemofiltration; HDF,ake and nutritional parameters, they have lostbstantial muscle mass during treatment. Pa-nt 1 needed intradialytic parenteral nutritionring a period of several months.Both patients were treated according to thehniques available at the time. Initially, theyre treated with parallel plate-dialyzers, acetatelysate, long duration twice weekly sessions,

    d dialysis monitors without ultrafiltration con-l. By the end of 1970s, hollow fiber dialyzers,dified monitors and high flux membranes be-

    me available followed by on-line monitoringhemofiltration and hemodiafiltration (TableBoth patients have been participants in nearlyentire historical development of chronic he-

    dialysis therapy.Finally, what needs to be stressed is bothtients strong will to live. This has providedm the strength and determination to cope withlong list of complications presented above.hope that this will encourage other patientsHD to regard their treatment with greater

    timism and give them more hope for the fu-e.The patients presented above show thatwalls prediction of long-term survival on

    could indeed be realized and honor hisacy as a founder of chronic hemodialysisrapies.

    Duration (hours) Frequency/week6.5 28 2

    12 25 34 34, 5 35 25 2

    n hemodialysis at home was performed)

    Duration (hours) Frequency/week8 29 26 34 34 33.5 3




  • ACKNOWLEDGMENTSThe authors would like to express their gratitude to the

    medical staff of the Department of Nephrology, Lund Univer-sity Hospital, involved in the daily activities of the dialysisunit. They would like also to thank especially Ulla Radler,RN, Ulla-Berit Olsson, RN and Kerstin Wingren, RN, whohave accompanied these two patients during almost all theseyears of dialysis.

    REFERENCES1. Alwall N, Norwiit L: On artificial kidney II. The

    effectivity of the apparatus. Acta Med Scandinavica 196:250-258, 1947

    2. Alwall N: Therapeutic and diagnostic problems insevere renal failure. Scandinavian University Books, Munks-gaard, Copenhagen, Svenska Bokfrlaget-Boniers, Stock-holm, and Universitetsfrlaget, Oslo, 1963

    3. Cameron JS: History of the treatment of renal failureby dialysis. Oxford, England, Oxford University Press, 2002

    4. Alwall N: On the organization of treatment with theartificial kidney and clinical nephrology in the 1940s andfollowing decades: a contribution to the history of medicine.IV.9(7







    10. Gradden C, Ahmad R: Thirty years on hemodialysis:One patients story. Dial Transplantation, 30(6):374-378,2001

    11. Gutman RA: Characteristics of long-term (14 years)survivors of maintenance dialysis. Nephron 33:111-115,1983

    12. Piccoli GB, Mezza E, Anania P, et al: Patients onrenal replacement therapy for 20 or more years: a clinicalprofile. Nephrol Dial Transplant 17:1440-1449, 2002

    13. Harris S, Brown E: Patients surviving more than 10years on haemodialysis. The natural history of the complica-tions of treatment. Nephrol Dial Transplant 13:1226-1233,1998

    14. Avram MM, Bonomini LV, Sreedhara R, Mittman N:Predictive value of nutritional markers (albumin, creatinine,cholesterol and hematocrit) for patients on dialysis for up to30 years. Am J Kidney Dis 28:910-917, 1996

    15. Schn S: Swedish Uremia Registry 1991-2004. Pub-lication 2005 (in Swedish)

    16. Owen WF, Madore F, Brenner BM: An observa-tional study of cardiovascular characteristics of long-termend-stage renal disease survivors. Am J Kidney Dis28:








    Kurkus et al476The nineteen-sixties, first part. Dial Transplantation):669-676, 1980. Quinton W, Dillard D, Scribner BH: Cannulation ofod vessels for prolonged hemodialysis. Trans ASAIO J04-113, 1960. Alwall N: A unit for simultaneous dialysis of fourteen

    ients. Proc Eur Dial Transplant Assoc 2:93-95, 1965. Brescia MJ, Cimino JE, Appel K, Hurwich BH:

    ronic hemodialysis using venepuncture and a surgi-ly created arteriovenous fistula. N Engl J Med 275;1089-2, 1966. Alwall N: Development of dialysis activity in Sweden,d for dialysis, and planning for the future. Proc Eur Dialnsplant Assoc 3:149-152, 1966. Persson U, Hertz JM, Wieslander J, Segelmark M:ort syndrome in southern Sweden. Clin Nephrol 64:85-2005931-936, 19967. Iseki K, Shinzato T, Nagura Y, Akiba T: Factorsuencing long-term survival in patients on chronic dialy-Clin Exp Nephrol 8:89-97, 20048. Pozzoni P, Del Vecchio L, Pontoriero G, Di Filippo S,

    catelli F: Long-term outcome in hemodialysis: Morbiditymortality. J Nephrol 17:87-95, 20049. Parisien M, Silverberg SJ, Shane E, et al: The histo-rphometry of bone in primary hyperparathyroidism: pres-ation of cancellous bone structure. J Clin Endocrinoltab 70:930-938, 19900. Gejyo F, Narita I: Current clinical and pathogeneticerstanding of beta2-m amyloidosis in long-term haemodi-

    sis patients: Nephrology 8:S45-49, 2003 (Suppl 2)1. Chazot C, Laurent G, Charra B, et al: Malnutrition ing-term haemodialysis survivors. Nephrol Dial Transplant61-69, 2001

    Thirty-Five Years of Hemodialysis: Two Case Reports as a Tribute to Nils AlwallCASE REPORTSPatient 1Dialysis AccessBlood PressureAnemiaBone DiseasePatient 2Dialysis AccessAnemiaBone Disease



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