Schiffl, Helmut

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Universität München: Elektronischen Publikationen

Carpal Tunnel Syndrome in Patients on Intermittent Hemodialyis

Helmut Schiffl

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Blood Purification

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Fax +41 61 306 12 34E-Mail karger@karger.chwww.karger.com Letter to the Editor / Reply  Blood Purif 2012;34:332–333  DOI: 10.1159/000343569  Carpal Tunnel Syndrome in Patients on Intermittent Hemodialyis  Helmut Schiffl   Department of Medicine IV, University of Munich,  Munich , Germany less than 60.3 months. By comparison, other authors reported the prevalence of CTS as 0 at 5 years  [2] when low-flux membranes and commercial (potential-ly contaminated) dialysis fluid were used. Busch et al.  [1]  clearly overestimat-ed the prevalence of CTS in their pa-tients (median follow-up 31 months).  (2) Cross-sectional studies may establish associations, but not causality. Due to the nonrandomized design, confound-ers may be unequally distributed among subgroups. Indeed, in the study by Busch et al.  [1] , patients treated with high-flux biocompatible dialyzer membranes had the highest dialysis duration, the lowest residual diuresis, and the highest circu-lating   2 -microglobulin concentrations. Moreover, the use of high-flux mem-branes was associated with a higher prevalence of CTS in the multivariate lo-gistic regression analysis. These data are in contrast to other reports demonstrat-ing lower   2 -microglobulin levels in high-flux HD compared to low-flux HD of similar HD vintage and a lower preva-lence of CTS in these patients  [3, 4] .  Busch et al.  [1] report a high prevalence of carpal tunnel syndrome (CTS) in hemo-dialysis (HD) patients in spite of the use of high-flux dialyzer membranes and ultra-pure dialysis fluid. The article is of interest as dialysis-related amyloidosis (DRA) has been out of focus in the last decade. The interpretation of the data present-ed is, however, hampered by the disadvan-tages of the cross-sectional study design they chose. (1) One major pitfall of this descriptive study is the absence of a clear, specific and reproducible disease definition. The gold standard for the diagnosisof DRA manifestations remains the im-munohistological detection of amyloid. Clinical assessment of symptoms and signs may pave the way to the diagnosis, but do not prove the presence of amyloid deposits in CTS. The authors do not dif-ferentiate between different causes (dia-betes) of CTS nor grade the severity of destructive arthropathy, which may lead to overdiagnosis. The authors found a prevalence of CTS of 28.7% in HD patients with a dialysis vintage of  Published online: January 9, 2013  Prof. Helmut Schiff l  University of Munich, Department of Medicine IV  Ziemssenstrasse 1  DE–80336 Munich (Germany)  E-Mail h-schiff l   @   t-online.de  © 2013 S. Karger AG, Basel0253–5068/12/0344–0332$38.00/0  Accessible online at:www.karger.com/bpu  (3) Cross-sectional studies ascertain ex-posure and outcome at the same time. There is convincing evidence that the microbiological quality of the dialysis fluid is an important determinant of DRA  [5] . Unfortunately, the authors were not able to analyze the impact of the dialysis fluid purity on the preva-lence of CTS. They had no information on this variable when their patients were dialysed before their investiga-tions had started.  Our retrospective analysis of compara-ble HD patient groups (1995–2010, a total of 147 patients, dialysis vintage at least 10 years) undergoing predominantly (more than 75% of all sessions) either low-flux HD utilising commercial dialysis fluid or receiving ultrapure high-flux HD revealed a decrease in histologically proven CTS from 68 to 28% (unpublished data). This trend is in line with other studies  [6, 7] re-porting a decreased prevalence of CTS over time. We agree with Busch et al.  [1] that DRA remains an unsolved problem of long-term maintenance HD.  References  1 Busch M, Schwenzky A, Franke S, Stein G, Wolf G: Advanced glycation end products and 2-microglobulin as predictors of carpal tunnel syndrome in hemodialysis patients. Blood Purif 2012; 34: 3–9.  2 Koch KM: Dialysis-related amyloidosis. Kidney Int 1992; 41: 1416–1429.  3 Kuchle C, Fricke H, Held E, Schiffl H: High-flux hemodialysis postpones clinical mani-festation of dialysis-related amyloidosis. Am J Nephrol 1996; 16: 484–488.  4 Schiffl H, Fischer R, Lang SM, Mangel E: Clinical manifestations of AB-amyloidosis: effects of biocompatibility and flux. Nephrol Dial Transplant 2000; 15: 840–845.  5 Baz M, Durand C, Ragon A, Jaber K, Andrieu D, Merzouk T, Purgus R, Olmer M, Reynier JP, Berland Y: Using ultrapure water in he-modialysis delays carpal tunnel syndrome. Int J Artif Organs 1991; 14: 681–685.  6 Schwalbe S, Holzhauer M, Schaeffer J, Ga-lanski M, Koch KM, Floege J: Beta 2-micro-globulin associated amyloidosis: a vanishing complication of long-term hemodialysis? Kidney Int 1997; 52: 1077–1083.  7 Cianciolo G, Coli L, La MG, Donati G, D’Addio F, Comai G, Ricci D, Dormi A, Wratten M, Feliciangeli G, Stefoni S: Is beta-2-microglobulin-related amyloidosis of he-modialysis patients a multifactorial disease? A new pathogenetic approach. Int J Artif Or-gans 2007; 30: 864–878.   Carpal Tunnel Syndrome in Patients on Intermittent Hemodialyis  Blood Purif 2012;34:332–333 333 We thank Dr. Helmut Schiffl and col-leagues for their comments on our study [1]. We absolutely agree that our study has several shortcomings being typical of many descriptive studies. The critique on the absence of a clear disease definition is correct. Due to the fact that our data were obtained from living subjects, no immu-nohistological staining of amyloid was possible, as it was also clearly discussed in the study [1]. In the same context, an un-pleasant and partly invasive nerve conduc-tion testing of the median nerve was not done because it should have been per-formed in all 385 participants, whether they had symptoms or not. Certainly, this test could have been applied only in pa-tients having clinical signs because the combination of clinical symptoms and electrodiagnostic findings is the most val-id way of diagnosing carpal tunnel syn-drome (CTS) [2]. However, the outpatient nature of our study prohibited such de-sign. It was not possible to examine all pa-tients from the different dialysis centers by the same equipment and examiner which is a necessary prerequisite for correct diag-nosis. Moreover, most patients declined additional diagnostic tests. It should be mentioned that the quoted reference re-ported only on CTS in HD if patients re-quired operation (0%  ! 8 years, 50% after 14 years and 100% after 20 years) [3]. Rates reporting clinical findings are expected to be higher. Moreover, in our study, the rate of patients who were already treated by op-eration was substantially higher (8.8%). Especially in these cases, the diagnosis of CTS should have been previously con-firmed and thus indicate the higher rate of CTS in our HD population. Nevertheless, we agree with the assumption that several cases of CTS might have been caused by diseases other than dialysis-related amy-loidosis (DRA). But unfortunately, the main clinical symptoms of CTS in DRA are identical to those of idiopathic CTS, or CTS accompanying other diseases [3]. Since age is a strong predictor of CTS and DRA [3, 4], it should be taken into account that our dialysis population was substan-tially older (median 65.1 years) than in most other studies [3]. Moreover, several other known risk factors for CTS/ DRA could be confirmed in our trial [1]. The (paradoxical) findings concerning DRA and the use of high-flux dialyzers were ad-equately discussed in our paper [1].  Reply  Martin Busch, MD, Günter Stein, MD, Gunter Wolf, MD  Department of Internal Medicine III, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany  The cross-sectional and retrospective character of our study implies the non-randomized design. This includes the ab-sence of information concerning the use and the quality of dialysis fluid in the past which is an obvious limitation of our study [1]. Prospective studies strictly using dif-ferent types of dialyzers in different pa-tient groups are welcome and would help to solve some of the open questions. Dueto limitations regarding the length of our paper, these points could not be discussed in depth. The presented retrospective and currently unpublished observation in HD groups by Schiffl et al. showed a decrease in histologically proven CTS from 68% in the period 1990–2000 to 28% in the period 2000–2010. Although details on these re-sults are lacking, our clinical finding of 31.7% CTS cases seems not quite different from their results [1].  Besides discussion about rates, it should be noticed that our study was di-rected to the potential causes of CTS in HD like malnutrition or increased serum concentrations of 2-microglobulin and advanced glycation end products. References  1 Busch M, Schwenzky A, Franke S, Stein G, Wolf G: Advanced glycation end products and 2-microglobulin as predictors of carpal tunnel syndrome in hemodialysis patients. Blood Purif 2012; 34: 3–9.  2 Aroori S, Spence RA: Carpal tunnel syn-drome. Ulster Med J 2008; 77: 6–17.  3 Koch KM: Dialysis-related amyloidosis. Kidney Int 1992; 41: 1416–1429.  4 Stein G, Schneider A, Thoss K, Ritz E, Schae-fer K, Huller M, Sperschneider H, Marzoll I: Beta 2-microglobulin serum concentration and associated amyloidosis in dialysis pa-tients. Nephrol Dial Transplant 1991; 6(suppl 3):57–61. 

2 Ar o o r i S , S p e n c e RA : C arp al t un n e l s yn -drome. Ulster Med J

Artif Organs

Beta 2-microglobulin associated amyloidosis: a vanishing complication of long-term hemodialysis? Kidney Int

E: Clinical manifestations of AB-amyloidosis: effects of biocompatibility and flux. Nephrol Dial Transplant

Marzoll I: Beta 2-microglobulin serum concentration and associated amyloidosis in dialysis patients. Nephrol Dial Transplant 1991; 6(suppl 3):57–61.

S: Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach.

Schiffl H: Highflux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis.

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Carpal Tunnel Syndrome in Patients on Intermittent Hemodialyis

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