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ASE REPORTS
Thirty-Five Years of Hemodialysis: Two Case Reports as aTribute to Nils Alwall
Jan Kurkus, MD,1Marie Nykvist, RN,2 Birger Lindergård, MD,1 Mårten Segelmark, MD1
Two patients with long-term (35 years) survival on hemodialysis are described. Kidney replacementtherapy for these patients was initiated by a pioneer in hemodialysis, Nils Alwall, in 1968 and 1971,respectively. Kidney transplantation was attempted twice in both patients; however, the dialysis-freeinterval was less than 18 months in both patients. These patients represent two of the longest knownsurvivors on hemodialysis worldwide. Factors that may have influenced their survival are discussed, andthe complications that have occurred over the years are presented.Am J Kidney Dis 49:471-476. © 2007 by the National Kidney Foundation, Inc.
INDEX WORDS: Long-term, survival, hemodialysis.
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hen Nils Alwall started his animal experi-ments in the basement of the Depart-
ent of Medicine at Lund University Hospital athe beginning of the 1940s,1 treatment of acuteenal failure with dialysis was considered to be atopia, and long-term survival with an artificialidney was beyond the imagination of mosteople practicing medicine. Alwall’s ideas wereanifest at a time when the Second World War
rohibited closer contact with contemporary Wil-elm Kolff in Holland, who developed the rotat-ng drum artificial kidney. Initially tested in rab-its, Alwall=s stationary drum artificial kidneyas enhanced for use in humans (Fig 1). In 1946,sing the stationary drum artificial kidney, heerformed the first treatment combining bothialysis and controlled ultrafiltration.2
Alwall continued his work to provide help foratients with renal failure, and during his remark-ble career he was able to achieve goals thatrobably exceeded even his own expectations. In948, he attempted to create an arteriovenoushunt; however, the available materials werehrombogenic and the shunts clotted after only aew usages.3 In 1960, Alwall initiated a long-erm hemodialysis program; unfortunately, earlyurvival failed to exceed five months.4 In 1965,nly a few years after the Quinton-Scribner shuntad been developed,5 Alwall wrote: “All thehronic cases have come for treatment in thenal stage of the disease, and it has been impos-ible to carry out dialysis at sufficiently shortntervals. It is only in the last 2 years that we
ave been able to give 7 patients with arterio-merican Journal of Kidney Diseases, Vol 49, No 3 (March), 2007
enous shunts satisfactory treatment. The sur-ival time is approaching 2 years”.6
The turning point arrived in 1966 when Bres-ia, Cimino and others published their ideas forrteriovenous (AV) fistulas,7 opening the possibil-ty for long-term hemodialysis (HD). Alwall fore-aw the rapidly increasing demand for HD. In965, about 3,500 dialysis treatment sessionsere carried out in Sweden, and at that time he
nticipated approximately 50,000 treatments in968 and 100,000 in 1969.8 In the decades since,normous development has occurred, increasinghe quality of dialysis techniques and medicalreatment and allowing the survival of over 1.5illion dialysis patients worldwide.Despite the many limitations in the early years
f long-term HD, the care provided by Alwallas sufficiently good to enable long-term sur-ival. This conclusion is evident in 2007, over 35ears after Alwall’s retirement (in 1971 fromephrology Department, and in 1984 from therivate Ellenbogen clinic), in the reports of twoatients initially treated by Alwall (Fig 2). Theseatients still continue on HD to the present day.
From the 1Department of Nephrology, Lund Universityospital, Lund; and 2Department of Nephrology and Trans-lantation, Malmö University Hospital, Malmö, SwedenSupport: None. Potential conflicts of interest: None.Address reprint requests to Jan Kurkus, Department of
ephrology, Lund University Hospital, SE-221 85 Lund,weden. E-mail: [email protected]© 2007 by the National Kidney Foundation, Inc.0272-6386/07/4903-0016$32.00/0
doi:10.1053/j.ajkd.2007.01.022: pp 471-476 471
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CASE REPORTS
atient 1Patient 1 is a 51-year-old woman who developed chronic
yelonephritis in 1962, at the age of 7, probably due to refluxephropathy. Her kidney function deteriorated gradually,nd, at the age of 13, an AV fistula was created in her leftrist; HD was initiated when signs of pericarditis mani-
ested. Six months later, bilateral native nephrectomy waserformed to treat uncontrollable hypertension. At the age of6, cadaveric kidney transplantation was performed; how-ver, this kidney failed to function satisfactorily and sheeturned to HD after 6 months. In the interim, splenectomyas performed because of signs of hypersplenism (anemia).t age 23, a second cadaveric kidney transplantation waserformed. In the postoperative course she experiencedultiple infection complications and she returned to hemodi-
lysis one year later (total dialysis-free interval 18 months).he has continued uninterrupted on hemodialysis since this
ime, having refused further attempts at kidney transplanta-ion.
ialysis AccessThe initial AV fistula that had been placed in 1968 ceased
o function after 13 years; new fistulas were created in theeft wrist in 1981 and right wrist in 1982. This latter fistulaas revised in 1982, 1988 and 1989. Since then, the functionf the AV fistula has been good and repeated angiographicxaminations (because of edema of the arm, signs of collat-ral circulation) have not revealed significant stenoses, al-hough several short periods with a temporary catheter for
Figure 1. Nils Alwall examining one of his early dialyz-rs used in animals experiments in the early 1940s. Thisodel was later scaled up for use in humans.
ialysis were needed.pN
lood PressureHer blood pressure was difficult to control, with periods
f hypertension followed by periods of hypotension, whichas unresponsive to weight adjustment, increase in sodium
oncentration in the dialysate, correction of anemia or nutri-ional parameters. She responded partially to treatment withihydroergotamine. Her blood pressure is currently accept-ble without treatment.
nemiaDuring the first 20 years of hemodialysis, hemoglobin
evels occasionally dropped as low as 5-6 g/dL (50-60 g/L)nd she required multiple blood transfusions, sometimes onenit every week or every other week. Altogether she re-eived 150 units of blood between 1968 and 1987. Duringhis period, she was probably infected with hepatitis B andepatitis C viruses. In 1988 erythropoietin treatment wastarted and she has been successfully maintained at targetemoglobin levels of 11-13 g/dL (110-130 g/L).
one DiseaseBone densitometry monitoring was performed from 1972
ntil 1998 with a single-photon technique, and thereafter
Figure 2. Nils Alwall (1904-1986). Reproduced with
ermission from Kjellstrand CM: Dedication to Nils Alwall.ephron 39(2):71-72, 1985. Copyright © S. Karger.
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Long-term Survival on Hemodialysis 473
ith dual-energy-X ray absorptiometry (DEXA). Over timehere has been a slow decrease in bone mineral content of upo 20%; however, vertebral morphometry of the T4-L4egion has remained normal. She underwent parathyroidec-omy in 1977. Late in 1979 she developed joint pain andreatment with analgesics was started. In 1989-1990, treat-ent with methotrexate, prednisolone and cyclosporine was
nitiated based on the incorrect assumption of reactive arthri-is. The diagnosis was later changed to dialysis-relatedmyloidosis. In 1991 arthroscopic acromioplasty of her lefthoulder was performed, but resulted in only brief andnsignificant pain relief. Operations for carpal tunnel syn-rome were performed on the right wrist in 1983, left wristn 1985, right wrist again in 1987, and again in the left wristn 1999. Since 1986 joint manifestations have consisted ofrogressive pain in the shoulders, spine and small joints, andtiffening and effusions. Radiological examination showedestructive joint changes (erosion and periarticular boneysts), and treatment with antidepressants and morphine-likerugs in slowly increasing doses was initiated. The full listf complications is presented in Table 1.She is currently quite satisfied with her quality of life,
espite the pain in her bones and joints requiring frequentarcotic administration. In spite of the signs of dialysis-elated amyloidosis, she refuses to increase the frequency ofialysis therapies beyond 5 hours twice weekly. Althoughhe relies on a wheelchair for mobility, she describes herresent situation as being relatively calm, despite undergo-
Table 1. Selected complications in tw
Organ/system Patient Type of eve
urgical 1 Splenectomy1 Cholecystectomy1 Appendectomy1 Uterine dilation and cur1 GI-bleeding1 Fasciotomy (posttraum1 Cataract surgery2 Hysterectomy and bilat
salpingo-oophorectomeurological 1 Epilepsy
1 Acute hearing loss, righ2 Sleep apnea
eneral 2 Aluminium intoxicationnfections 1 Septic arthritis
1 Septicemia1 Hepatitis B1 Hepatitis C1 VRE1 Extraction of eight teeth2 Hepatitis B2 Septicemia2 Severe shoulder infecti
ardiovascular 2 Myocardial infarction
Abbreviations: HD, hemodialysis; GI, gastrointestinal; VR
ng long-term HD for over 35 years. f
atient 2This is a 76-year-old woman with kidney failure due to
-linked Alport syndrome of juvenile type, confirmed byetection of causative splice site mutation in the COL4A5ene.9 She has had a history of hematuria and proteinuriarom early childhood, and beginning at age 23, after givingirth to her second child, gradually decreasing renal func-ion, hypertension, and hearing loss ensued. Kidney biopsyave a diagnosis of chronic pyelonephritis. In 1971 an AVstula was created in the left wrist and HD was started soon
hereafter, when she was 42 years old. A cadaveric kidneyransplant was performed 3 months after start of HD, butas unsuccessful. She has been menopausal since 1975 and
otally deaf on the left side since 1978. In 1984, at the age of5, a second cadaveric kidney transplant was carried out;ne year later the graft was lost because of sepsis and sheeturned to HD. Her total dialysis-free interval was 15onths, and she refused further kidney transplantation. HDas carried out at home (self-care) between 1979 and 1984
nd again between 1986 and 1989. Between 1991 and 2005D was performed at a satellite dialysis unit in Lund,weden.
ialysis AccessThe initial AV fistula was surgically revised, because of
neurysmatic changes, in 1983, 1996, 2002 and 2004. Sev-ral radiological procedures were carried out to maintain the
nts during 35 years of hemodialysis.
lication Years after initiation of long-term HD
31920
(hypermenorrhea) 8 times (19-29)21
matoma) 222925
223317183 times (33-35)14-181723 (serological diagnosis)25
infection 286 (serological diagnosis)3 times (13,14,24)2431
comycin-resistant Enterococcus.
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nemiaDuring the first 17 years of HD the patient neededultiple blood transfusions; however, these were less fre-
uent than in patient 1. Recombinant erythropoietin treat-ent was initiated in 1988; thereafter, anemia was managedithout transfusions.
one DiseaseThe patient was monitored using a single-photon tech-
ique beginning in 1972. Her bone mineral content slowlyecreased over her first several years on dialysis; this pro-ess accelerated after 1979, such that by 1991 she had lost7% of her bone mineral content in both arms, and, by 1996,7% in her right arm. She has lost 5 cm in height, fractureder right lower arm in 1979, both lower arms in 1985, rightip in 1991, left hip in 1996 and suffered a pelvis fracture in000. She underwent parathyroidectomy in 1980. Surgeryas performed for carpal tunnel syndrome in the left wrist in986 and in the right wrist in 1992 and 1994. Since 1990 sheas experienced increasing pain in multiple joints, initiallyreated with analgesics, and, more recently, with narcotics.he full list of complications is presented in the Table 1.espite these complications, she lives at home with herusband, and with the use of a wheelchair, she can attend toctivities of daily living with only limited assistance fromocal social services.
DISCUSSION
There are several breathtaking testimonies ofatients describing long-term survival on HD,ncluding those of Judy Weintraub, Peter Lundin,ichard Faber and Robin Eady (all available on
he internet). There are also many publicationsbout long-term survival on HD.10-13 Graddennd Ahmed10 presented in 2001 a patient treated0 years with HD; unfortunately, this patientied while the paper was in press. These authorspined: “It is unlikely that we will see manyatients on such long-term haemodialysis in Eu-ope in the future”. The cases presented hererove that it is possible, and that there may evene other such long-term survival cases.In 1996, Avram et al14 presented a unique
nalysis of long-term survivors on hemodialysis.oung age at the onset of kidney failure, nondia-etic status, black race, male gender, good nutri-ional status, and adequate dose of dialysis allredicted better survival for periods up to 30ears. According to the Swedish Uraemia Regis-ry, there are 5 patients in Sweden who startedD in Sweden at the beginning of the 1970s,
ho remain on hemodialysis over 30 years later; wof these individuals have received hemodialy-is for 35 years or more.15
Several factors may be crucial for the long-erm survival of our patients. To date, neither hasanifested any clinical signs of advanced isch-
mic heart disease or peripheral vascular disease;owever, both have significant limitations inobility and have refused coronary artery dis-
ase screening. Neither patient is diabetic, andhere has been no prolonged hypertension oryperlipidemia. Patient 1 is a light smoker, whileatient 2 has never smoked. All this could beesponsible for the lack of cardiovascular symp-oms and could contribute to their long-termurvival.16-18
A second factor is vascular access. Both pa-ients have had well-functioning AV fistulas forhe vast majority of their time on HD, withatient 2 using the same AV fistula since 1971.his likely is a prerequisite for effective dialysis,s judged by the high rate of blood flow throughhe dialysis membrane, consistently acceptableialysis adequacy, and excellent nutrition param-ters.
Kidney transplantation was performed twicen both patients but their dialysis-free time waselatively short, failing to exceed 18 months inither patient. Subsequently, the total doses oforticosteroids and other immunosuppressionedications given with kidney transplantation,ere relatively low.The most disabling complication for both pa-
ients has been bone disease, manifested withialysis-related amyloidosis in patient 1 and withsteopenia in patient 2. The sharp contrast be-ween the very low mineral content in the armsnd hips compared with the normal to highontent in the spine in both cases is very interest-ng. This could be explained by the long periodf hyperparathyroidism (at least 9 years in bothatients, from the start of HD to parathyroidec-omy), which mainly affects the cortical bonesuch as in the arms and hips.19 As the main factorn dialysis-related amyloidosis seems to be �2-
icroglobulin, convective dialysis (hemodiafil-ration/hemofiltration) has been used in our pa-ients; however we were unable to reverse therogression of osteoarthropathy in either pa-ient.20 Both patients underwent parathyroidec-omy; subsequently, they had limited problems
ith calcium-phosphate metabolism. This may
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Long-term Survival on Hemodialysis 475
ave reduced vascular calcification but likelyontributed to their skeletal problems.
A change from acetate-based to bicarbonate-ased dialysate was made at our unit in 1988,nd both patients were treated with convectiveialysis methods (with highly permeable andiocompatible membranes in dialyzers) whereeplacement fluid was prepared from dialysaten-line. Thus ultra-pure dialysate has been useduring the last 15 years of treatment in bothatients. However, signs of dialysis-related amy-oidosis are progressing, mostly in the shoulderegions. Dialyzers were never reused in our unit.
Both patients were profoundly anemic untilhe development of recombinant erythropoietin.hey required blood transfusions as often asvery 1 to 6 weeks; subsequently both developedepatitis B surface antibody and hepatitis B corentibody positivity (patient 1 in 1985 and patientin 1979). Patient 1 tested positive for hepatitisin 1989. Fortunately, no signs of liver diseaseere observed in either patient. Both patientsere initiated on recombinant erythropoietin
herapy in 1988 with uncomplicated anemia man-gement since.
Malnutrition has been observed in long-termD survivors21 and although the nutritional sta-
us of our patients can be described as satisfac-
Table 2. Evolution of dialysis prescription
atient 1 (treatment in center only)
Year Modality Membra968 HD Cupropha970 HD Cupropha979 HD Cupropha986 HD Cupropha991 HF Polyamid998 HDF Polyamid000 HF Polyamidince 2002 HDF Polyamid
atient 2 (treatment in center except intervals 1979-1984 and 1986
Year Modality Membra971 HD Cupropha977 HD Cupropha979 Home HD Cupropha991 HD Cupropha996 HDF Polyamidince 2003 HDF Polyamid
Abbreviations: HD, hemodialysis; HF, hemofiltration; HD
ory on the basis of constant body weight, oral t
ntake and nutritional parameters, they have lostubstantial muscle mass during treatment. Pa-ient 1 needed intradialytic parenteral nutritionuring a period of several months.Both patients were treated according to the
echniques available at the time. Initially, theyere treated with parallel plate-dialyzers, acetateialysate, long duration twice weekly sessions,nd dialysis monitors without ultrafiltration con-rol. By the end of 1970s, hollow fiber dialyzers,odified monitors and high flux membranes be-
ame available followed by on-line monitoringf hemofiltration and hemodiafiltration (Table). Both patients have been participants in nearlyhe entire historical development of chronic he-odialysis therapy.Finally, what needs to be stressed is both
atients’ strong will to live. This has providedhem the strength and determination to cope withhe long list of complications presented above.
e hope that this will encourage other patientsn HD to regard their treatment with greaterptimism and give them more hope for the fu-ure.
The patients presented above show thatlwall’s prediction of long-term survival onD could indeed be realized and honor his
egacy as a founder of chronic hemodialysis
patients during 35 years of hemodialysis
Duration (hours) Frequency/week6.5 28 2
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hen hemodialysis at home was performed)
Duration (hours) Frequency/week8 29 26 34 34 33.5 3
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ACKNOWLEDGMENTSThe authors would like to express their gratitude to theedical staff of the Department of Nephrology, Lund Univer-
ity Hospital, involved in the daily activities of the dialysisnit. They would like also to thank especially Ulla Radler,N, Ulla-Berit Olsson, RN and Kerstin Wingren, RN, whoave accompanied these two patients during almost all theseears of dialysis.
REFERENCES1. Alwall N, Norwiit L: On artificial kidney II. The
ffectivity of the apparatus. Acta Med Scandinavica 196:250-58, 19472. Alwall N: Therapeutic and diagnostic problems in
evere renal failure. Scandinavian University Books, Munks-aard, Copenhagen, Svenska Bokförlaget-Boniers, Stock-olm, and Universitetsförlaget, Oslo, 19633. Cameron JS: History of the treatment of renal failure
y dialysis. Oxford, England, Oxford University Press, 20024. Alwall N: On the organization of treatment with the
rtificial kidney and clinical nephrology in the 1940s andollowing decades: a contribution to the history of medicine.V. The nineteen-sixties, first part. Dial Transplantation(7):669-676, 19805. Quinton W, Dillard D, Scribner BH: Cannulation of
lood vessels for prolonged hemodialysis. Trans ASAIO J:104-113, 19606. Alwall N: A unit for simultaneous dialysis of fourteen
atients. Proc Eur Dial Transplant Assoc 2:93-95, 19657. Brescia MJ, Cimino JE, Appel K, Hurwich BH:
hronic hemodialysis using venepuncture and a surgi-ally created arteriovenous fistula. N Engl J Med 275;1089-092, 19668. Alwall N: Development of dialysis activity in Sweden,
eed for dialysis, and planning for the future. Proc Eur Dialransplant Assoc 3:149-152, 19669. Persson U, Hertz JM, Wieslander J, Segelmark M:
lport syndrome in southern Sweden. Clin Nephrol 64:85-
0, 2005 110. Gradden C, Ahmad R: Thirty years on hemodialysis:ne patients’ story. Dial Transplantation, 30(6):374-378,00111. Gutman RA: Characteristics of long-term (14 years)
urvivors of maintenance dialysis. Nephron 33:111-115,98312. Piccoli GB, Mezza E, Anania P, et al: Patients on
enal replacement therapy for 20 or more years: a clinicalrofile. Nephrol Dial Transplant 17:1440-1449, 200213. Harris S, Brown E: Patients surviving more than 10
ears on haemodialysis. The natural history of the complica-ions of treatment. Nephrol Dial Transplant 13:1226-1233,99814. Avram MM, Bonomini LV, Sreedhara R, Mittman N:
redictive value of nutritional markers (albumin, creatinine,holesterol and hematocrit) for patients on dialysis for up to0 years. Am J Kidney Dis 28:910-917, 199615. Schön S: Swedish Uremia Registry 1991-2004. Pub-
ication 2005 (in Swedish)16. Owen WF, Madore F, Brenner BM: An observa-
ional study of cardiovascular characteristics of long-termnd-stage renal disease survivors. Am J Kidney Dis8:931-936, 199617. Iseki K, Shinzato T, Nagura Y, Akiba T: Factors
nfluencing long-term survival in patients on chronic dialy-is. Clin Exp Nephrol 8:89-97, 2004
18. Pozzoni P, Del Vecchio L, Pontoriero G, Di Filippo S,ocatelli F: Long-term outcome in hemodialysis: Morbiditynd mortality. J Nephrol 17:87-95, 2004
19. Parisien M, Silverberg SJ, Shane E, et al: The histo-orphometry of bone in primary hyperparathyroidism: pres-
rvation of cancellous bone structure. J Clin Endocrinoletab 70:930-938, 199020. Gejyo F, Narita I: Current clinical and pathogenetic
nderstanding of beta2-m amyloidosis in long-term haemodi-lysis patients: Nephrology 8:S45-49, 2003 (Suppl 2)
21. Chazot C, Laurent G, Charra B, et al: Malnutrition inong-term haemodialysis survivors. Nephrol Dial Transplant
6:61-69, 2001Recommended
