Gašić B. at al.

RESEARCH ARTICLE
UDC 616.833-009-073:616.6-008.64-78

CORRELATION OF RENAL IMPAIRMENT AND DURATION OF HEMODIALYSIS WITH

ELECTROMYONEUROGRAPHIC FINDINGS IN CHRONIC KIDNEY DISEASE

KORELACIJA STEPENA OŠTEĆENJA BUBREŽNE FUNKCIJE I DUŽINE TRAJANJA

HEMODIJALIZE SA EMNG NALAZOM

Branislav Gašić 1, Aleksandra Dominović-Kovačević 2, Irena Balaban 1, Vlastimir Vlatković1, Siniša

Miljković 2, Vlado Đajić 2, Aleksandra Grbić 3

Abstract: Uremic polyneuropathy (PN) is a common concomitant sign of chronic kidney disease (CKD).
Numerous studies have demonstrated improvement of symptoms and signs of polyneuropathy on hemo-
dialysis. The aim of this study was to evaluate association between duration of hemodialysis (HD) treat-
ment and the type of polyneuropathy, and association between duration of hemodialysis and sensory and
motor nerve conduction velocities for the sural and peroneal nerve. We also examined correlation between
glomerular filtration rate (GFR) as an indicator of renal impairment and the type of polyneuropathy, and
the correlation between GFR and sensory and motor nerve conduction velocities of the sural and peroneal
nerve in patients with CKD not treated with HD. This study was carried out with 30 patients, 12 females
and 18 males, average age 62.67 ± 13.2 years. Patients were divided into 3 groups, each consisting of 10 pa-
tients: CKD patients with no need for HD; patients on HD for one year; and CKD patients on HD for 2-12
years. Sensory nerve conduction velocity of the sural nerve and motor nerve conduction velocity of the per-
oneal nerve were measured by electromyoneurography. Twenty patients were treated with HD for an aver-
age 3.85 ± 1.5 years (median 1.5, range 1-12 years). Results showed that 19 out of all patients had sensory
polyneuropathy, eight patients had sensorimotor polyneuropathy, and three patients had no signs of neu-
ropathy. We found a negative but statistically insignificant association between sensory and motor nerve
conduction velocities and the degree of renal impairment and duration of HD treatment. Possible explana-
tions for such findings could be the existence of extreme values of studied variables, the older age of study
subjects, and an inadequate HD treatment.

Keywords: Uremic polyneuropathy, chronic kidney disease, sensory and motor nerve conduction velocity

Sažetak: Uremijska polineuropatija je čest prateći znak hronične bubrežne insuficijencije. Brojne studije
su pokazale da adekvatnom hemodijalizom (HD) može da dođe do poboljšanja znakova i simptoma poli-
neuropatije. Osnovni cilj ovog istraživanja je utvrđivanje korelacija između dužine trajanja HD i vrste po-
lineuropatije, te korelacija između dužine trajanja HD i senzorne i motorne nervne brzine provodljivosti.
Istraživanjem je obuhvaćeno 30 pacijenata (12 žena i 18 muškaraca), prosječne starosti 62.67 ± 13.2 godi-

1 Clinical Centre Banja Luka, Clinic for Nephrology, Banja Luka, Bosnia and Herzegovina
2 Clinical Centre Banja Luka, Clinic for Neurology, Banja Luka, Bosnia and Herzegovina
3 Clinical Centre Banja Luka, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Banja Luka, Bosnia and
Herzegovina
Correspondence to: Gašić Branislav, MD, Clinical Centre Banja Luka, 12 Beba, 78000 Banja Luka, E-mail:
branislavgasic@yahoo.com
* Received April 2,2010; accepted June 6, 2010.

24 Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010
 Gašić B. at al.

ne. Pacijenti su podijeljeni u tri grupe od po 10 pacijenata : grupa sa HBI bez potrebe za HD, grupa na di-
jalizi od godinu dana i grupa na dijalizi duže od godinu dana). Elektromioneurografijom je praćena sen-
zorna brzina provođenja za n. suralis i motorna brzina provođenja za n. peroneus, uz analizu senzornog
neurograma i motornog akcionog potencijala. Na intermitentnoj HD prosječne dužine trajanja 3.85 ± 1.5
godina je bilo 20 bolesnika (medijana 1.5, opseg 1-12 god). Dobijeni podaci su pokazali da je senzornu po-
lineuropatiju imalo 19 pacijenata, senzomotornu osam, dok su bez neuropatije bila tri pacijenta. Iako bro-
jne studije pokazuju povezanost senzorne i motorne nervne brzine provodljivosti sa stepenom oštećenja
bubrežne funkcije i dužinom trajanja HD, u našem istraživanju smo uočili negativnu ali ne i statistički
značajnu povezanost među ovim varijablama. Moguć razlog je postojanje ekstremnih vrijednosti među is-
pitivanim varijablama, starija dob ispitivanih pacijenata, a kod hemodijaliziranih pacijenata jedan od ra-
zloga negativne korelacije između ispitivanih varijabli mogla bi da bude i neadekvatna dijalizna terapija.

Ključne riječi: Uremijska polineuropatija, hronična bubrežna insuficijencija, senzorna nervna brzina pro-
vodljivosti, motorna nervna brzina provodljivosti

INTRODUCTION Asbury and colleagues first described pathomorp-

Chronic kidney disease (CKD) is a major and ra-
pidly growing global health and financial problem
in developed countries. Improved quality of heal-
th care has significantly increased the population
life span, and consequently greater numbers of pa-
tients with renal disease live to the stage when the-
ir renal impairment has advanced so as to requi-
re hemodialysis or kidney transplantation. Diabe-
tes as the most common cause of CKD in deve-
loped countries accounts for the majority of these
patients. Primary nephropathies, collagenoses and
vasculitides are other important causes of renal fa-
ilure. It is predicted that patients with renal disea-
se will further increase in number (1-4).
Clinical manifestations of CKD are heterogene-
ous and have been subject to numerous studies.
One of these manifestations is uremic polyneuro-
pathy (PN). Charcot suggested the existence of an
association between neurological manifestations
and CKD as early as 1880, and Osler came to the
same conclusions in 1892. The advent of hemodi-
alysis and renal transplantation has considerably
increased the life span of these patients and ena-
bled studying the evolution of uremic neuropathy,
which was previously impossible because the pa-
tients died early and the progression of neuropat-
hy could not be monitored. The first detailed cli-
nical features of uremic neuropathy were provided
by Asbury, Victor and Adams in the 1960s (5-7).
hology of peripheral nerve injury in patients with
clinical manifestations of uremic PN (7). Forno
and Alston demonstrated in 1967 that the main
pathohistological nerve lesion is axonal degenera-
tion with distal distribution. Dreyfus postulated a
role of transketolase in the genesis of demyelina-
ting neuropathy (8,9).
In this study we investigated the type of neuro-
pathy in CKD patients not needing hemodialysis
and those on hemodialysis, correlation between
the degree of renal impairment and sensory nerve
conduction velocity of the sural nerve and motor
nerve conduction velocity of the peroneal nerve in
patients with CKD without need for hemodialysis,
and correlation between the duration of hemodi-
alysis treatment and these nerve conduction velo-
cities among hemodialysis patients.
PATIENTS AND METHODS
This study was carried out with 30 patients. The-
re were 18 males (60%) and 12 females (40%),
mean age 62.67 ± 13.2 years. Patients were divided
into 3 groups, each consisting of 10 patients: pati-
ents with chronic kidney disease (CKD) not nee-
ding dialysis treatment (non-HD); patients on he-
modialysis for 1 year; and patients on hemodial-
ysis more than 1 year (2-12 years). A total of 20
patients (66.67%) were treated with hemodialysis

Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010 25
Gašić B. at al.

(HD), with HD duration 3.85 ± 1.5 years (median
1.5, range 1-12 years). Duration of hemodialysis
was determined from patients’ histories and me-
dical records. Biochemical analyses were perfor-
med in the central laboratory of the Clinical Cen-
tre Banja Luka. Glomerular filtration rate (GFR) is
the best test to measure renal function and deter-
mine the stage of renal disease. According to the
National Kidney Foundation (NKF) Kidney Di-
sease Outcomes Quality Initiative (KDOQI), the-
re are five stages of chronic kidney disease (CKD)
expressed in ml/min/1.73 m2: stage 1 - GFR > 90;
stage 2 - GFR 60-89; stage 3 - GFR 30-59; stage 4 -
GFR 15-29; and stage 5, or end-stage renal disea-
se - GFR<5ml/min/1.73 m2 or hemodialysis (10).
In this study GFR was calculated with a GFR cal-
culator (11), with the following parameters: se-
rum creatinine levels, age, sex and race of patients.
HD patients had three four-hour sessions weekly,
Kt/V 1.43±0.33, and protein catabolic rate (PCR)
was not determined. Bicarbonated solutions (con-
centrate PGS21-Ca 1.75mmol/l, K 2mmol/l) were
used. The dialyzer used was Fresenius Polysulfo-
ne High-flux F60S and Low-flux F8HPS. Sensory
nerve conduction velocity of the sural nerve and
motor nerve conduction velocity of the perone-
al nerve were measured by electromyoneurograp-
hy (EMNG) in the same centre. All EMNG stu-
dies were performed with a Medelec Sinergy ap-
paratus. Electroneurography (ENG) was perfor-
med with superficial bipolar electrodes, and elec-
Table 1 Distribution of CKD patients according to the duration of HD treatment and the type of polyneuropathy
tromyography (EMG) with disposable concentric
needle electrodes. Normal values for motor pero-
neal nerve conduction velocity were 50±4.0m/s
and for sensory sural nerve conduction velo-
city 50±5.0m/s (the lowest tolerable value was
40m/s for both conduction velocities) (12). Stati-
stical evaluation was carried out using the SPSS
for Windows statistical package (13). In addition
to descriptive statistics for the selected variables,
comparison of groups was evaluated by tests such
as Pearson correlation and linear regression anal-
ysis. The mean values, standard deviation, median
with maximum and minimum values were used as
measures of central tendency. P value of 0.05 was
considered statistically significant.
RESULTS
This study was carried out with 30 patients with
different degrees of renal impairment (CKD sta-
ge 3, 4, and 5). There were 18 males (60%) and 12
females (40%), mean age 62.67 ± 13.2 years. Only
patients with primary renal disease were inclu-
ded, and patients with diabetes mellitus or syste-
mic diseases were excluded. In total, 20 patients
(66.67%) were treated with hemodialysis, on ave-
rage for 3.85 ± 1.5 years (median 1.5, range 1-12
years). Sensory polyneuropathy was found in 19
patients (63.33%), sensorimotor polyneuropathy
in 8 (26.67%), and no signs of neuropathy in 3 pa-
tients (10%) (Table 1).

CKD patients
Polyneuropathy No HD HD = 1 year HD = 2-12 yrs Total
No neuropathy 2 (6.67%) 1 (3.33%) 0 3 (10%)
Sensitive 7 (23.33%) 6 (20%) 6 (20%) 19 (63.33%)
Sensorimotor 1 (3.33%) 3 (10%) 4 (13.33%) 8 (26.67%)
Total 10 10 10 30 (100%)

CKD-chronic kidney disease HD- hemodialysis

Results of correlating sensory nerve conduction velocity of the sural nerve and motor nerve conduction
velocity of the peroneal nerve with GFR and duration of HD are presented in Table 2 and 3.
Table 2 Sensory nerve conduction velocity of the sural nerve
Patients Sensory nerve conduction velocity of the sural nerve
Non-HD CKD patients 22.92 ± 24.99
CKD patients on HD for 1 year 27.43 ± 24.40
CKD patients on HD for 2-12 years 21.69 ± 23.00
HD patients 24.56 ± 23.27
Total 24.013 ± 23.44

CKD-chronic kidney disease HD- hemodialysis

26 Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010
 Gašić B. at al.

Table 3 Motor nerve conduction velocity of the perone- Figure 2. Regression test for peroneal MNCV and GFT
al nerve in non-HD patients
MNCV
60
Motor nerve con-
duction velocity 50
Patients
of the peroneal
40
nerve
Non-HD CKD patients 38.33 ± 20.62 30

CKD patients on HD for 1 year 45.5 ± 4.19 20

CKD patients on HD for 2-12 years 38.52 ± 14.38 10

HD patients 41.92 ± 14.94 0

Observed
Total 40.78 ± 14.59 -10 Linear
0 10 20 30 40 50 60

CKD-chronic kidney disease HD- hemodialysis GFR

In CKD patients with no need for HD treatment, MNCV - Motor nerve conduction velocity of the peroneal
a negative correlation was found between sensory nerve GFR- Glomerular filtration rate
nerve conduction velocity of the sural nerve and
GFR (correlation coefficient – 0.318) and between Figure 3. Regression test for sural SNCV and duration
motor nerve conduction velocity of the perone- of hemodialysis
al nerve and GFR (correlation coefficient -0.287). SNCV
However, t-test did not show a statistically signifi- 70

cant association for these variables (P>0.05) (Fi- 60

gures 1 and 2). 50

40

In HD patients, there was a negative correlati- 30

on between duration of HD and sensory ner- 20
ve conduction velocity of the sural nerve (corre-
10
lation coefficient -0.180) and a negative correlati-
0 Observed
on between duration of HD and motor nerve con-
-10 Linear
duction velocity of the peroneal nerve (correlation 0 2 4 6 8 10 12 14

coefficient -0.232). However, t-test did not show a DHD

statistically significant association for these varia- SNCV - Sensory nerve conduction velocity of the sural nerve
bles (P>0.05) (Figures 4 and 5).
DHD- Duration of hemodialysis
Figure 1. Regression test for sural SNCV and GFR rate
in non-HD patients Figure 4. Regression test for peroneal MNCV and dura-
tion of hemodialysis
SNCV MNCV
60
60

50
50

40
40

30
30

20
20
10
10
0
Observed
0
Observed
-10 Linear
0 10 20 30 40 50 60 -10 Linear
0 2 4 6 8 10 12 14
GFR DHD
SNCV - Sensory nerve conduction velocity of the sural nerve MNCV - Motor nerve conduction velocity of the peroneal
GFR - Glomerular filtration rate nerve DHD-Duration of hemodialysis

Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010 27
Gašić B. at al.
DISCUSSION
Polyneuropathy in patients with chronic kidney
disease (CKD) is a distal symmetric sensorimo-
tor peripheral polyneuropathy, usually insidious
in onset and with slow progression. The periphe-
ral nerve degeneration is more prominent in dis-
tal than in proximal nerve parts, and in lower lim-
bs. Biopsy of the sural nerve has shown primary
axonal degeneration with secondary demyelina-
tion (7,8,14,15). Some authors noted primary de-
myelination on analyzed biopsy samples in CKD
patients (8,16). It is assumed that axonal disrup-
tion leads to reduction in the diameter of axonal
cylinder with segmental demyelination in axonal
degeneration. Retraction of myelin sheath at the
nodes of Ranvier leads to secondary loss of mye-
lin that actually causes segmental demyelination
and eventually nerve fiber degeneration (8,15,17).
As disease progresses, symptoms move proximally
to involve the upper extremities, and sensory and
motor nerve conduction velocities are reduced
(5,18,19). Unlike most other published studies, in
our study there were more patients with sensory
than sensorimotor polyneuropathy. There was a
negative correlation between sensory and motor
nerve conduction velocities and duration of he-
modialysis, and a negative correlation between
these velocities and the degree of renal impair-
ment as measured by glomerular filtration rate in
non-HD CKD patients. A possible explanation for
our results could be the existence of extreme va-
lues among the examined variables, as seen on Fi-
gures 1-4. Furthermore, the older age of our pati-
ents also could have influenced the results. Chro-
nic hemodialysis and peritoneal dialysis have been
shown to stabilize or recover nerve function in
most patients with CKD, especially in those with
mild symptoms of polyneuropathy (5,8). Another
explanation for the negative correlation found in
our study could therefore be inadequate dialysis
regimens (although the dialysis membranes used
were in accordance with the European standar-
ds). It is also possible that our results have been
influenced by inadequate Kt/V in each individu-
al patient and a uniform use of hemodialysis solu-
tion. Previous studies have suggested that optimi-
zing dialysis treatment through increasing frequ-
ency or duration of dialysis sessions or changing
the type of membranes may improve symptoms of
polyneuropathy (5,20). Renal transplantation re-
28 Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010
mains the best treatment for uremic neuropathy
and should be considered in any patient with pro-
gressive neuropathy. Sensory symptoms recover
shortly following renal transplantation, whereas
the recovery of motor and sensory nerve function
takes much longer (1,21,22). It has been suggested
that improvement in neuropathy occurs mainly as
a result of segmental remyelination (21) and re-
covery of renal metabolic function (23). Therefo-
re, it is essential to dedicate special attention to an
adequate therapeutic regimen for uremic polyne-
uropathy.
REFERENCES:
1. Arun VK, Matthew CK. Neurological complica-
tions of chronic kidney disease. Nature Reviews Neu-
rology 5.October 2009.542-551
2. Chadban SJ, et al.Prevalence of kidney damage in
Australian adults: the AusDiab kidney study.J Am Soc
Nephrol.2009.14, S131-S138
3. Barsoum RS. Chronic kidney disease in the devel-
oping world.N Engl J Med. 2006. 354.997-999
4. ANZDATA [ homepage on the Internet], 31st An-
nual Report.2008 [cited 2010 March]. Available from:
http://www.anzdata.org.au/v1/report2008.html(2008)
5. Yi Pan. Uremic Neuropathy [serial on the Internet].
Updated 2009 Dec [ cited 2010 March]. Available from:
http://emedicine.medscape.com/article/1175425-over-
view (2009)
6. Charcot JM. Lecons sur les maladies du systeme
nerveux.XVI Des paraplegies urinares.3rd ed.Paris.
1880. 295
7. Asbury AK, Victor M, Adams RD. Uremic poly-
neuropathy.Arch Neurol. Apr 1963. 8: 413-28
8. Kopitović A, Mitić I, Ilin M, Čurić S, Banić-Horvat
S, Cvijanović M i sar. Polyneuropathy in patients with
chronic renal failur. Medicina danas 2004. 3 (1-2): 135-
139
9. Potić-Dimić J. Uremijske polineuropatije.
Beograd,br 25; MK Beograd.Zagreb, 1989.
10. National Kidney Fondation (NKF).Am J Kidney
Dis 2002. 39 (Suppl): S1-S266
11. GFR kalkulator KDOQI ( United states National
Kidney Foundation ‘ Kidney Disease Outcomes Qual-
ity Initiative’)[homepage on the Internet]. [ cited 2010
March]. Available from: http://www.kidney.org/profes-
sionals/kdoqi/gfr_calculator.cfm

12. Maksimovic D. Praktikum za asistente iz elektomi-
oneurografije. Beograd,2008.
13. SPSS for Windows, Chicago: SPSS Inc.
14. Thomas PK, Hollinrake K, Lascelles RG, et al. The
polyneuropathy of chronic renal failure. Brain.1971.
94: 761-80
15. Dyck PJ, Johnson WJ, Lambert EH, O’Brien PC.
Segmental demyelination secondary to axonal degen-
eration in uremic neuropathy. Mayo Clin Proc 1971.
46: 400-31
16. Said G, Hontebeyrie-Joskowicz M. Nerve lesions
induced by macrophage activation. Res Immunol 1992.
143 (6): 589-99
17. Dayan AD, Gardner-Thorpe C, Down PF, Glead-
le RI. Peripherial neuropathy in uremia: pathological
studies on peripherial nerves from 6 patients. Neurol-
ogy 1970. 20: 649-58
18. Krishnan AV, Phoon RK, Pussell BA, Charlesworth
JA, Kiernan MC. Sensory nerve excitability and neu-
ropathy in end-stage kidney disease. J Neurol Neuro-
surg Psychiatry. 2006. 117: 992-9
Curr Top Neurol Psychiatr Relat Discip. Vol 18, No. 2, June 2010
Gašić B. at al.
19. Krishnan AV, Phoon RK, Pussell BA, Charlesworth
JA, Bostock H, Kiernan MC. Altered motor nerve ex-
citability in end-stage kidney disease. Brain.2005. 128:
2164/74
20. Djukanovic LJ, Mimic-Oka JI, Potic JB. The effects
of hemodialysis with different membranes on middle
molecules and uremic neuropathy. Int J Artif Organs.
Jan 1989. 12 (1): 11-9
21. Bolton CF. Electrophysiologic changes in uremic
neuropathy after successful renal transplantation. Neu-
rology. 1976. 26, 152-161
22. National Kidney Foundation. NKF-DOQI clinical
practice guidelines for hemodialysis adequacy. Am J
Kidney Dis. 1977. 30 (2): S15-S66
23. Shin J, Oh. Clinical electromyography: nerve con-
duction studies [monograph on the Internet]. Phila-
delphia: Library of congress cataloging-in-publication
data. 2003. [cited 2010 March]. Available from: http://
www.amazon.com/Clinical-Electromyography-Nerve-
Conduction-Studies/dp/0781736811#reader_0781736
811.
29