ACUTE EFFECT OF HEMODIALYSIS ON SYMPATHETIC SKIN RESPONSE

Abstract

Sympathetic skin response (SSR) is a useful and simple test for unmyelinated axon function in peripheral sensorimotor neuropathies. SSR was tested on a group of patients undergoing chronic regular hemodialysis before and after a single dialysis session. Nineteen patients in hemodialysis for more than three months were included. Nine patients were on dialysis with cellulosic membranes (CA, 3 male and 6 female, aged 57.7 ± 16.4 years) and ten ones were on dialysis with non-cellulosic membranes (NC, 4 male and 6 female, aged 50.2 ± 15.9 years) were studied. There were no differences neither in Kt/V values (NC 1.37 ± 0.34 vs. CA 1.22 ± 0.27) nor in TAC ones (NC 41.5 ± 18.2 vs. CA 41.3 ± 14.1 mg/dL). After hemodialysis with NC amplitude significantly increased (994 ± 1015 vs. 382 ± 465 μv baseline, p < 0.05). Latency did not change (1.76 ± 0.83 vs. 2.07 ± 0.50 s baseline). After hemodialysis with CA neither amplitude changed (1368 ± 1074 vs. 1240 ± 1594 μv baseline), nor did latency (1.79 ± 0.35 vs. 1.94 ± 0.59 s baseline). Hemodialysis with non-cellulosic membranes (but not with cellulose acetate) yields a short-term improvement of sympathetic skin response. This effect is similar to those seen in nerve conduction velocities and it may be related to increased middle-molecules depuration.

• Chronic renal failure
• Hemodialysis
• Polyneuropathy
• Sympathetic skin response

INTRODUCTION

Peripheral and autonomic neuropathies are common complications of chronic renal failure [1-2]. In most dialysis centers, nerve conduction studies (NCS) are routinely used to monitor the response of uremic polyneuropathy to chronic dialysis therapy. A simple non-invasive test, SSR, has been shown to be a useful and simple test of unmyelinated axon function in peripheral sensorimotor neuropathies [[3]]. This test is easily performed on an electromyograph with successful correlations with NCS in uremic neuropathy [4-7]. In hemodialysis patients SSR shows to be more severely impaired than either motor or sensory conduction velocities [[7]].

Usually, nerve conduction studies has been used to evaluate acute and chronic effects of hemodialysis on uremic neuropathy. Hemodialysis seems to acutely enhance nerve conduction velocities, but only when non-cellulosic membranes are used [8-11]. Chronic hemodialysis improves nerve conduction velocities when the patient has not been treated with dialysis or when, in spite of dialytic treatment, the patient is not adequately treated [12-13]. When the patient is receiving an adequate dosage of dialysis, no changes at long term should be expected [[10]].

We have studied the short-term effects of hemodialysis on SSR in asymptomatic uremic patients on chronic regular hemodialysis, comparing the effect of cellulosic membranes and non-cellulosic ones.

MATERIAL AND METHODS

SSR were studied in 19 uremic patients on conventional hemodialysis (7 male and 12 females, mean age 57.3 ± 16.3). Nine patients were on dialysis with cellulosic membranes (3 male and 6 female, aged 57.7 ± 16.4 years) and ten ones were on dialysis with non-cellulosic membranes (4 male and 6 female, aged 50.2 ± 15.9 years) were studied. No patients with diabetes mellitus or other systemic disease were included. Patients remain with the same membrane for more than three months before the study was performed. Cellulose acetate was the cellulosic membrane used (Acepal, Hospal, Switzerland). Six patients were dialyzed with polyacrylonitrile (Filtral, Hospal, Switzerland) and four more with polysulphone (Fresenius, Germany).

The most common urea kinetics related parameters (time-averaged concentration of urea (TAC), normalized protein catabolic rate (PCR) and whole-blood urea clearance (Kt/V)) were calculated monthly by computer using the simplified Daugirdas formulation which included the ultrafiltration rate at the midweek dialysis session [[14]]. The values of TAC, PCR, and Kt/V, and mean time on hemodialysis are listed in Table 1 for all groups. The patients with variation of Kt/V higher of 10% between studies or with inadequate values were excluded.

Table 1. Dialysis Adequacy

	Cellulose Acetate	Non-cellulosic Membranes
Kt/V	1.22 ± 0.27	1.37 ± 0.34
PCR	0.94 ± 0.16	1.03 ± 0.47
TAC	41.3 ± 14.1	41.5 ± 18.2
Session length	240.0 ± 0.0	243.0 ± 9.5

Differences are not significant. TAC expressed as mg/dL, PCR as mg/kg/day, session length in minutes.

SSR studies were performed before and after the midweek dialysis session (either Wednesday or Thursday) as described previously [[3]]. Surface electrodes were attached to the palm and dorsum of the right hand and to the sole and dorsum of the right foot. Stimuli, delivered to the left wrist, consisted of single square pulses of 200 μs duration and 50–150 V intensity. The stimuli were given at irregular intervals. The amplitude and latency were determined a number of times to give an average value. The skin temperature was monitored and maintained at 34° to 35°C during the tests. All studies were performed with a Medelec MS92a electromyograph.

A computer program performed statistical evaluation. Students' “t” test for paired and non-paired data was used to compare continuous data. All values are expressed as the mean ± 1 SD.

RESULTS

There were not differences between non-cellulosic membranes and cellulose acetate dialysis neither in TAC of urea values, nor protein catabolic rate ones nor Kt/V ones (see values in Table 1). Dialysis session length was not different between the groups (Table 1).

Taken all results altogether, the amplitude of SSR shows a small increment after hemodialysis but it was not significant (baseline 788 ± 1197 μv vs. 1171 ± 1033 μv). Neither was significant the small decrease detected in latency (baseline 2.01 ± 0.53 s vs. 1.76 ± 0.62 s, p < 0.1).

After hemodialysis with non-cellulosic membranes amplitude significantly increased (baseline 382 ± 465 vs. post-hemodialysis 994 ± 1015 μv, p < 0.05) (Figure 1). Latency did not change after dialysis (baseline 2.07 ± 0.50 vs. post-hemodialysis 1.76 ± 0.83 s, the difference is not significant).

Figure 1. SSR amplitude did not change after hemodialysis with cellulose acetate.

After hemodialysis with cellulose acetate amplitude showed a slight increase, but it was not statistically significant (baseline 1240 ± 1594 vs. 1368 ± 1074 μv) (Figure 2). The latency also remains statistically unchanged in spite of a small improvement (baseline 1.94 ± 0.59 vs. 1.79 ± 0.35 s).

Figure 2. SSR shows a small improvement after hemodialysis with non-cellulosic membranes (p < 0.05).

DISCUSSION

SSR is a useful method of evaluating a part of the peripheral nervous system – small unmyelinated C fibers – that cannot be assessed by current clinical electroneurographic laboratory techniques. It has been found a linear correlation between the NCS and SSR values in patients on chronic hemodialysis [[7]]. The SSR, however, seems to be more impaired than NCS in uremic patients, so that it might be a more sensitive test to monitor polyneuropathy in chronic renal failure. Until nowadays the effects of hemodialysis on SSR has not been evaluated. We have found an enhancement of amplitude of SSR without changes in latency, and this change occurred just in patients treated with non-cellulosic membranes. Hemodialysis with cellulose acetate could not elicit any change on SSR.

Changes in electrical nerve conduction occur in chronic renal failure even in the absence of clinical signs. In most dialysis centers, NCS are routinely used to monitor the response of uremic polyneuropathy to renal replacement therapy. The appearance or worsening of neuropathy while the patient is on dialysis is usually taken as an indication to increase dialysis time [15-16]. However, it has been reported that conduction velocities do not change appreciably after more frequent and improved dialysis, despite the clinical improvement that is usually seen [[17]]. In most cases, SCV is more sensitive than MCV as indicator of peripheral neuropathy in uremic patients [[7]], [[18]] and sensory changes tend to appear earlier in the course of renal failure [[19]].

There are a few reports on the effect of a dialysis on uremic polyneuropathy evaluated using changes on nerve conduction velocities. When this problem has been studied using cellulosic membranes, either no significant changes in nerve conduction velocities [[8]], or an isolated increase in the MCV were found [[9]]. A third report, comparing polysufphone and cuprophan effects on uremic polineuropathy before and after dialysis, showed a statistically significant enhancement of SCV after hemodialysis with polysulphone but not with cuprophan. Also an increase of MCV with both membranes was shown [[10]]. More recently, it has been shown an acute improvement of both SCM and MCV after hemodialysis with polyacrilonitrile, but not with cellulose acetate membrane [[11]]. These results agreed with the observed effects of hemodialysis on SSR and pointed to the ability of non-cellulosic membranes to depurate middle-molecules. The scanty effects of hemodialysis on SSR could be explained by the more severe impairment of SSR parameters seems in hemodialysis patients compared to nerve conduction velocities [[7]]. Acute hemodialysis with non-cellulosic membranes can just mildly improve the effects of uremia on small unmyelinated fibers and the result is a minor effect comparing with the changes reported on motor and sensory conduction velocities. Long term effects of hemodialysis on SSR remains to be evaluated, but no significant changes should be expected since they had not been shown for nerve conduction velocities, which are much more acutely improved after hemodialysis [9-11].

Sympathetic skin activity mediates sudomotor function and the SSR has been used to evaluate autonomic function in patients with suspected dysautonomia. It is a common clinical observation that sudomotor function is disordered in peripheral neuropathies such as diabetic neuropathy, even when there is no evidence of other autonomic function abnormalities, in other words, it is a sensitive way to test peripheral autonomous nervous function [20-21]. The observed lack of effect of hemodialysis on autonomous neuropathy shows the limited effects of current dialytic schedules to completely correct uremic derangements.

We have selected a Kt/V (∼ 1.2), according to current guidelines [[22]]. There were no differences on Kt/V and dialysis session length between CA and non-cellulosic membranes. So that, differences in the amount of dialysis received by the patients cannot explain the improving positive effect of non-cellulosic membranes on SSR amplitude. The remaining question is whether increased Kt/V values could improve SSR parameters after hemodialysis.

All referred studies were performed using conventional hemodialysis procedures, without increased convective transport [8-11]. This kind of hemodialysis technique was again used for our comparative study. So that, an increasing of convective transport of solutes due to higher ultrafiltration rates when hemofiltration or hemodiafiltration is used could be carried out as an explanation of the observed differences.

Many candidate toxins has been suggested as the responsible of the altered nerve function due to chronic renal failure, however there is no convincing proof of their neurotoxicity and it has been emphasized the importance of overall retention [[23]]. It seems likely that the accumulation of toxins in the middle-molecules range can cause the neuropathy [[24]]. These molecules cross cellulose dialysis membrane only slowly, and are more effectively cleared when dialysis time is prolonged or high-flux membranes (such as polysulphone or polyacerilonitrile) are used [25-26]. This special ability of polysulphone and polyacrylonitrile could explain the increase in amplitude of SSR seen after hemodialysis, which was not seen with a cellulosic membrane.

In conclusion, we found evidence that hemodialysis with non-cellulosic membranes (but not with cellulose acetate) yields a short-term improvement of sympathetic skin response, an electroneurographic technique which deals with peripherical small unmielinated nervous fibers. This effect is similar to those seen in nerve conduction velocities and it may be related to increased middle-molecules depuration.