neuropathy is a common complication of end stage kidney disease ( eskd ) , typically presenting with a distal symmetric pattern with greater involvement of the lower extremities compared to the upper extremities ( 1 ) . however , in addition to the distal symmetric peripheral neuropathy ( pn ) , mononeuropathies have been reported to occur with increased frequency in patients with eskd , and most typically affect the median , ulnar , and femoral nerves ( 2 ) . carpal tunnel syndrome ( cts ) is the most common mononeuropathy in patients with eskd with a frequency of 8% to 31% ( 3 , 4 ) . microglobulin amyloidosis has been reported as the major cause of the development of cts ( 5 ) . in addition , there is an increase in the frequency of cts associated with increasing durations of hemodialysis ( hd ) ( 5 ) . other factors proposed as causes of cts include : uremic tumoral calcinosis ( 6 ) and placement of an arteriovenous ( a - v ) fistula inducing diversion of blood from the distal limbs ( 7 , 8) . in a recent study ( 9 ) , the frequency of cts was 30.5% in the limbs with a fistula and 12.2% in the contralateral limb . however , the exact causes of the development of cts in eskd are not known . in addition , many prior studies did not perform electrophysiological studies for the diagnosis of cts and did not consider the differential diagnosis for coexisting pn and cts . this study was designed to identify the mechanisms of the development of cts using electrophysiological studies in patients with eskd . sixty four patients were on hd and 48 were on peritoneal dialysis ( pd ) . there were 34 females and 30 males with a mean age of 57.8  13.0 ( range : 24 - 78 yr ) in the hd group and 23 females and 25 males ( mean age , 52.7  12.4 ; range , 25 - 79 yr ) in the pd group . exclusion criteria were : 1 ) a history of fracture or trauma of an upper limb that could cause focal nerve injury , 2 ) metabolic disease other than diabetes mellitus , 3 ) patients that could not tolerate electrical stimulation . data on the duration of eskd and dialysis , site of the a - v fistula in the patients on hd and additional medical illness were noted after review of the medical records . in addition , laboratory data such as blood urea nitrogen , creatinine , and beta-2-microglobulin were recorded . clinical evaluation included the symptoms and signs of cts and electrophysiological studies for diagnosis of cts and pn were performed in less than 2 weeks after the laboratory examinations . the clinical and electrophysiological evaluations were conducted by two experienced physiatrists . for the clinical evaluation , subjective symptoms such as numbness of lateral four fingers , pain and stiffness of the hands were assessed . muscle strength of the abductor pollicis brevis ( apb ) , sensory impairment of median nerve distribution , and the tinel 's sign and phalen test were assessed objectively . the patients who had more than two symptoms and/or signs of five ( numbness of lateral four fingers , apb weakness , hypesthesia of median nerve distribution , tinel sign , phalen test ) were considered to have ' clinical cts ' . the patients who also had numbness and hypesthesia of little finger and those revealed the provocative tests only were not diagnosed with clinical cts . nerve conduction studies were performed using a counterpoint mk2 ( dantec , copenhagen , denmark ) . the median , ulnar , peroneal , and tibial motor nerves and median , ulnar , and sural sensory nerves were evaluated using standard conduction techniques . the distance between the recording electrode and stimulation was 8 cm in all of the compound muscle action potential ( cmap ) recordings and was 14 cm for the sensory nerve action potential ( snap ) recordings . the f waves of all the motor nerves and the h reflex were also evaluated . skin temperature was maintained at 32 or above in the upper extremity nerves and 30 or above in the lower extremity nerves . pn was diagnosed and graded i to iv based on the criteria of our laboratory , a modification of the diabetes control and complication trial ( dcct ) research group ( 10 ) . cts was diagnosed when the findings met at least one of the following regardless of the presence or absence of a pn : 1 ) ratio of median sensory latency of a 7 cm wrist segment to a 7 cm palm segment > 2.0 , 2 ) ratio of distal latency of a median snap to that of an ulnar snap > 1.2 , 3 ) ratio of the amplitude of a median sensory snap with wrist stimulation to that with palm stimulation < 0.5 , 4 ) ratio of the distal latency of a median cmap to an ulnar cmap > 1.5 , 5 ) ratio of the amplitude of a median cmap to an ulnar cmap < 0.6 . these cut off values are obtained from the 50 healthy volunteers aging from 26 to 75 ( mean age , 55.2  12.0 yr ) . the frequency of cts was compared between pd and hd groups using the chi - square test . the correlation between beta-2-microglobulin levels and the duration of eskd was analyzed ; the levels of beta-2-microglobulin were analyzed using the independent t - test . the software used for statistical analysis was spss 12.0 ( spss inc . , chicago , il , usa ) and the significance level was set at a p < 0.05 . the health service human research ethics committee and the committee on experimental procedures involving human subjects of the korea university medical center reviewed and approved this study protocol . the frequency of cts was compared between pd and hd groups using the chi - square test . the correlation between beta-2-microglobulin levels and the duration of eskd was analyzed ; the levels of beta-2-microglobulin were analyzed using the independent t - test . the software used for statistical analysis was spss 12.0 ( spss inc . , chicago , il , usa ) and the significance level was set at a p < 0.05 . the health service human research ethics committee and the committee on experimental procedures involving human subjects of the korea university medical center reviewed and approved this study protocol . the mean duration on hd and pd was 45.6  41.9 and 59.4  44.7 months , respectively . the duration of dialysis , bun , creatinine , potassium , and uric acid were not significantly different between hd and pd groups . on clinical evaluation , 18 patients were categorized as having clinical cts in the patients on hd and 11 in patients on pd . based on the electrophysiological studies , 42 out of 64 patients on hd were classified with a pn and/or cts ; 22 with a pn only , 8 with cts only ; and 12 with both . among the 48 patients on pd a pn developed in 16 , cts in 4 , and both in 8 ( table 1 ) . the frequency of cts was not different in comparisons between the hd and pd groups ( p = 0.823 ) . among the patients with ' clinical cts ' , three in the hd group and four in the pd group had no electrophysiological abnormalities ; the other patients were electrophysiologically diagnosed with cts and/or a pn ( table 2 ) . the frequency of cts was not different between the limb with an a - v fistula and the contralateral limb ( table 3 ) ( p = 0.816 ) . the duration of eskd , dialysis and beta-2-microglobulin levels were not significantly different between the cts group and non - cts group ( table 4 ) . the development of uremic neuropathy has been related previously to the retention of neurotoxic molecules in the middle molecular range . nerves of uremic patients have shown to exist in a chronically depolarized state prior to dialysis , with subsequent improvement and normalization of resting membrane potential after dialysis . the degree of depolarization correlates with serum potassium , suggesting that chronic hyperkalemic depolarization plays an important role in the development of nerve dysfunction in eskd ( 1 ) . patients with eskd frequently complain of a numbness and tingling sensation of the hands and feet . distal symmetric pn may cause symptoms more frequently in the feet ; the symptoms in the upper extremity may be caused by an a - v fistula or mononeuropathies . recently , mononeuropathies in patients on dialysis , caused by entrapment at sites that are physiologically prone to stenosis , has become a topic of interest , such as ulnar neuropathy at the elbow and median neuropathy at the carpal tunnel ( 11 , 12 ) . however , the etiology remains unknown and the frequency varies widely according to the criteria and methods used for the diagnosis . in a report on the association between cts and a - v fistulas in patients on hd ( 13 ) , clinical cts was more frequently diagnosed in the wrist with an a - v fistula ; however , electrodiagnostic studies did not indicate any significant association between the frequency of cts and the a - v fistula or its duration . such reports raise questions about the validity of electrodiagnostic results in patients with an a - v fistula , because of the discrepancy between the clinical and electrodiagnostic findings . however , only median and ulnar motor conduction studies were performed for the diagnosis of cts . in this study , precise criteria for the diagnosis of pn and cts , with or without a pn , were used . the frequencies of clinical and electrodiagnostic cts were similar : 24/4 , 20/64 and 13/48 , 12/48 in the hd and pd groups , respectively . however , there was some discrepancy between the clinical and electrophysiological diagnosis ; the patients with clinical cts had pn due to eskd but some of the patients diagnosed electrophysiologically were asymptomatic . the electrophysiological findings are more objective than the clinical symptoms and/or signs ; the clinical findings of pn can be due to eskd even with normal electrodiagnostic findings . therefore , we investigated the frequency and correlation of cts with the clinical variables based on the electrodiagnosis . a prior study found no difference in the frequency of cts in patients undergoing pd or hd ( 14 ) . similarly , the electrodiagnostic confirmation of cts was not associated with the type of dialysis in this study . many investigators have reported a positive correlation between the frequency of cts and the duration of hd ( 3 , 5 ) , and have also reported that the side of the a - v fistula could affect the frequency of cts ( 12 , 13 ) . however , the results of this study do not reveal the relationship between the frequency of electrodiagnostic cts and the duration of eskd , dialysis , and the side of the a - v fistula . these differences could be explained by the fact that most of the prior investigators used the clinical findings only for the diagnosis of cts . since both pn and cts can cause pain and/or numbness of the hands , the differentiation of the two entities is important in the management of patients . we used separate electrodiagnostic criteria to diagnose the pn and the cts , because eskd can induce uremic neuropathy . we also investigated the frequency of cts according to the severity of the pn , and found no significant association . this might in part be due to the difficulty in the differentiation of the two entities in severe cases with a pn . the effect of cervical complications such as spondyloarthropathy , common in patients on long term hd , can induce cervical radiculopathy or myelopathy ( 15 ) . these factors are also an important consideration in patients with symptoms and/or signs without evidence of cts or a pn . we performed nerve conduction studies without needle electromyography in this study , to avoid patient discomfort , the cases with clinical cts and normal electrophysiological findings might have had a cervical radiculopathy . in the reports on patients receiving long - term hd , the frequency of beta-2-microglobulin related osteoarthropathy increased steadily with the length of survival , and the frequency of cts increased with the number of years on dialysis ( 5 ) . another investigation on patients undergoing hd reported no correlation between cts and the site of vascular access and synovial biopsy of the flexor tendons demonstrated edema without inflammation . these findings suggest that extracellular fluid volume excess in the presence of flexion and immobility during dialysis may be important to the pathogenesis rather than osteoarthropathy ( 16 ) . in this study , we did not find an association between the frequency of cts and the level of beta-2-microglobulin or between the side of a - v fistula and the development of cts . in this investigation , we considered the effect of diabetes mellitus on pn and/or cts in patients with diabetes and eskd . we also analyzed the patients without diabetes mellitus separately , however , the results neither revealed the correlations between the variables . we do not think that the development of cts in patients with preexisting uremic peripheral neuropathy is a special condition , but rather think that the patients with generalized peripheral neuropathy are prone to the development of entrapment neuropathy . ( 4 ) reported that nerve dysfunction was independent of the disease underlying renal failure , the side of dialysis access shunt , and the presence or absence of osteodystrophy . they recommended that dialysis patients need frequent nerve conduction studies from the beginning of dialysis to identify cts early and to avoid irreversible nerve damage . in a report on the management of patients with entrapment neuropathy , surgical intervention successfully relieved all symptoms , but return of normal renal function based on the results of previous recommendations and investigations on the management of entrapment neuropathy in patients with eskd , early and accurate diagnosis of cts is important in planning the treatment of such patients . in conclusion , the results of this study do not support that microglobulins , involved in the development of amyloidosis , and placement of an a - v fistula , are associated with the development of cts in patients with eskd . carpal tunnel syndrome and peripheral polyneuropathy in patients with end stage kidney disease hee - kyu kwon , sung - bom pyun , won yong cho and chang su boo neuropathy is a common complication of end stage kidney disease ( eskd ) , and carpal tunnel syndrome ( cts ) is most common . this study was designed to identify the mechanisms of the development of cts in patients with eskd . the electrophysiological studies do not support that microglobulin induced amyloidosis or placement of an a - v fistula are associated with an increase in cts . the cause of cts in patients with eskd is supposed to be a vulnerability of nerves for the development of entrapment neuropathy in the cases with preexisting peripheral neuropathy .
this study was designed to identify the causes of the development of carpal tunnel syndrome ( cts ) associated with end stage kidney disease ( eskd ) . 
 a total of 112 patients with eskd , 64 on hemodialysis ( hd ) and 48 on peritoneal dialysis ( pd ) , were enrolled . 
 the duration of eskd and dialysis , the site of the arteriovenous ( a - v ) fistula for hd , laboratory data such as blood urea nitrogen , creatinine , and beta-2-microglobulin were determined . 
 clinical evaluation of cts and electrophysiological studies for the diagnosis of cts and peripheral neuropathy were performed . 
 the electrophysiological studies showed that the frequency of cts was not different in the hd and pd groups ( p = 0.823 ) and the frequency of cts was not different in the limb with the a - v fistula compared to the contralateral limb ( p = 0.816 ) . 
 the frequency of hd and pd were not related to beta-2-microglobulin levels , an indicator of amyloidosis . 
 the frequency of cts did not increase as the severity of the peripheral neuropathy and the duration of eskd and dialysis increased ( p = 0.307 ) . 
 the results of this study do not support that microglobulin induced amyloidosis or placement of an a - v fistula are associated with an increase in cts .