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Clinical |
Institute of Urology and Nephrology1 and Institute of Physical Medicine and Rehabilitation,2 Clinical Center of Serbia, Belgrade, Serbia
Correspondence to: D. Jovanovic, Akademska 8, 11080 Belgrade, Zemun, Serbia. dijanaj{at}eunet.yu
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ABSTRACT |
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Background: It is well known that patients with uremia,
as well as patients with diabetes mellitus, develop polyneuropathy. Objectives: The signs of polyneuropathy in diabetic and
nondiabetic patients on continuous ambulatory peritoneal dialysis (CAPD) and
their relation with age, duration of dialysis, biochemical parameters,
dialysis adequacy, and health-related quality of life (HRQOL) were analyzed in
the present study. Patients and Methods: 65 CAPD patients (37 men, age 29
– 85 years, duration on dialysis 3 months to 14 years) were divided into
two groups: group 1 was comprised of 20 diabetic patients (mean age 50.1
± 13.2 years); group 2 was comprised of 45 nondiabetic patients (mean
age 62.3 ± 9.7 years). Biochemical parameters, dialysis adequacy, and
clinical signs were determined. Motor conduction velocity on the peroneal and
tibial nerves and sensitive conduction velocity on the sural nerve were
measured. The Kidney Disease Quality of Life Short Form (KDQOL-SF) was used to
measure the CAPD patients' self-assessment of functioning and well-being using
4 component scores: physical component summary (PCS), mental component summary
(MCS), kidney disease target issues, and patient satisfaction. Results: Subjective symptoms were more intense in the
diabetic patients and correlated with changes in peroneal and tibial distal
motor latency (DML). Diabetic patients were significantly younger, had lower
creatinine and higher glucose levels, and all analyzed pathological
neurophysiological parameters were higher. Nondiabetic patients had prolonged
latency of the F-wave on the peroneal nerve and the tibial nerve and reduced
sensitive conduction velocity on the sural nerve. Significant correlations
were found between the analyzed neurophysiological parameters and duration of
dialysis and diabetes, glucose concentration, and dialysis adequacy in
diabetic patients, and between neurophysiological parameters and age and
dialysis adequacy in nondiabetic patients. Analysis of the 4 component scores
of the KDQOL-SF revealed that diabetic patients had significantly better
scores for PCS and MCS, which can be explained by their younger age. Patient
satisfaction was worse in diabetic patients and correlated with duration of
diabetes. In addition, significant correlations were established between PCS,
MCS, and tibial DML (late neuropathic changes) in diabetic patients, and
between MCS and tibial F-wave (early neuropathic changes) in nondiabetic
patients. Conclusion: Polyneuropathy was significantly worse in
diabetic than in nondiabetic patients on CAPD. DML on the tibial nerve
correlated with glucose concentration, dialysis adequacy, PCS, and MCS in
diabetic patients, whereas in nondiabetic patients, dialysis adequacy and
azotemia correlated with F-waves on the peroneal nerve and the tibial nerve
but MCS only with F-wave on the tibial nerve.
KEY WORDS: Polyneuropathy; diabetic patients; KDQOL; dialysis adequacy.
Uremic neuropathy, recognized since the 1960s (1), is presently known as an important cause of disability in patients with advanced chronic renal failure, as well as in those maintained on hemodialysis and peritoneal dialysis (2–4).
Peritoneal dialysis remains an important renal replacement therapy for end-stage renal disease (ESRD) patients with diabetes mellitus (DM) (5). These patients are prone to diabetic neuropathy and vasculopathy. In addition, when they develop uremia their peripheral nervous system becomes more affected, especially the sensory parts (6). Despite improvements in dialysis treatment of diabetic patients, their health-related quality of life (HRQOL) is lower than that in patients with other kidney diseases (nondiabetic patients) and much lower than in the general population (7–11).
The signs of polyneuropathy in diabetic and nondiabetic patients on continuous ambulatory peritoneal dialysis (CAPD) and their relation with age, duration of dialysis, biochemical parameters, dialysis adequacy, and HRQOL were analyzed in the present study.
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PATIENTS AND METHODS |
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The present study was carried out according to the ethics regulations of the Helsinki Declaration.
METHODS
Clinical findings and subjective symptoms were evaluated using a simple
questionnaire that we formulated for this population of patients to determine
the presence (1) or absence (0) of the following subjective symptoms of
neuropathy (one or more) in each patient: paresthesia, tingling, prickling,
cramps, itch, and pain. There were also questions about the presence or
absence of diseases that might exclude patients from the study.
Blood samples were taken from fasting patients. The biochemical parameters hemoglobin, HbA1c (normal range 3.9% – 6.1%), serum glucose, urea, and creatinine were determined using standard biochemical methods.
Adequacy of dialysis was calculated from 24-hour dialysate and urine collections for urea and creatinine. Peritoneal creatinine clearance (pCcr) was corrected to a body surface area of 1.73 m2 and urea clearance was expressed as dialysis dose (Kt/V, where K is solute clearance, t is duration of the exchange, and V is the volume of dialysate drained at the end of the exchange) using the Watson formula for body water. Renal creatinine clearance (rCcr) was calculated from the mean of creatinine and urea clearances corrected to a body surface area of 1.73 m2, while total Ccr was calculated as the sum of pCcr and rCcr (12). Total weekly Ccr and weekly pCcr were expressed in liters per 1.73 m2. Residual Ccr of 1 mL/minute is equivalent to a weekly clearance of 10 L/1.73 m2. A minimum of 50 – 60 L/1.73 m2 has been recommended based on clinical observations and experience (12).
Motor conduction velocity (CV) on the peroneal and tibial nerves and sensitive CV on the sural nerve were measured on a Medelec Sapphire ME 4 instrument (Medelec, Old Woking, Surrey, UK) using surface electrodes. Skin temperature was more than 32°C. For the peroneal nerve, motor CV and distal motor latency (DML) were measured by stimulating the popliteal region and ankle joint. The recording electrodes were on the extensor digiti brevis muscle for the peroneal nerve and on the abductor hallucis muscle for the tibial nerve. The DML was taken as the latency of any change from the baseline of the compound muscle action potential recorded after stimulation of the ankle joint 8 cm proximal to the recording electrode. The F-wave was obtained by stimulating the ankle joint and recording on the extensor digiti brevis muscle for the peroneal nerve and on the abductor hallucis muscle for the tibial nerve. The minimal F-wave latency was recorded in all trials. Sensitive CV was determined antidromically on the sural nerve using surface electrodes 14 cm proximal to the recording electrode below the lateral malleolus. All neurophysiological parameters were recorded with reference to values for volunteer healthy subjects.
The HRQOL was measured using the self-administered Kidney Disease Quality of Life Short Form (KDQOL-SF) version 1.1 (13) converted into Serbian according to the translation process (http://gim.med.ucla.edu/kdqol/page8.html). The questionnaire consisted of 79 items divided into 19 domains and included both general aspects and sections specific to patients with kidney disease. The general sections were based on questions from the Short Form Health Survey (SF-36) and included 36 items in 8 domains. Specific sections involved kidney disease targeted questions and included 43 items in 11 domains. These 19 health-related domains were categorized into 4 components of HRQOL by Bakewell et al. (7). The physical component summary (PCS) is composed of the following seven domains: physical functioning, work status, role limitations due to physical health, general health perception, pain, energy/fatigue, and social function. The mental component summary (MCS) consists of five domains: emotional well-being, quality of social interactions, burden of kidney disease, social support, and role limitations due to emotional problems. The kidney disease target issues section consists of cognitive function, symptoms/problems, effect of kidney disease, sexual function, and sleep. Patient satisfaction is composed of patient self-satisfaction and perceptions of staff encouragement (7,11).
The KDQOL-SF version 1.1. questionnaires were given to the patients, who completed them during their monthly control in the clinic or at home and returned them at the next control. To make sure the patients adequately understood the surveys, the directions were read out. Approximately 10% of the patients needed the assistance of nurses, physicians, or family members.
STATISTICAL ANALYSIS
Values are expressed as mean ± standard deviation. Pearson's or
Spearman's rank correlation was used to test for correlation between the
variables. Unpaired Student's t-test and the Mann–Whitney U test were
used to test for differences between the groups.
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RESULTS |
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There were no significant differences in gender, CAPD duration, hemoglobin, serum protein, urea, Kt/V, or total Ccr between the groups.
Subjective symptoms such as paresthesia, tingling, prickling, cramps, itchiness, and pain tended to be more intense in DM than in non-DM patients (ratio 65%:53%) but the difference was not significant. The most common subjective symptom in both groups of patients was paresthesia. Only 2 (3%)non-DM patients had all examined neurophysiological parameters in the normal range. Mean values of all analyzed neurophysiological parameters were pathological in the DM patients and were significantly different from the non-DM group (p < 0.01; Table 2). In non-DM patients, prolonged latency of the F-wave on the peroneal and tibial nerves and reduced sensitive CV on the sural nerve were found.
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After dividing the patients into two groups according to the presence or absence of subjective symptoms, we found a relationship between subjective symptoms and peroneal and tibial DML (p < 0.035, r = 0.514; p < 0.05, r = 0.472, respectively).
Analysis of the four component scores of the KDQOL-SF revealed that diabetic patients had significantly better scores for PCS and MCS (Table 3).
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In DM patients, significant correlations were found between the analyzed neurophysiological parameters and duration of dialysis, duration of diabetes, glucose concentration, HbA1c, and dialysis adequacy (Table 4).
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In addition, significant correlations were established between tibial DML and PCS and MCS. Duration of diabetes was associated with age (p < 0.029) and patient satisfaction (p < 0.015). In non-DM patients, significant correlations were found between neurophysiological parameters and age and dialysis adequacy (Table 5), and also between MCS and tibial F-wave.
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DISCUSSION |
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TOPABSTRACTPATIENTS AND METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Diabetes mellitus is one of the most common causes of ESRD, especially in CAPD patients, and is associated with considerable morbidity (5). The peripheral nervous system of diabetic patients becomes more affected when these patients develop uremia (6). The prevalence of neuropathy increases with age and duration of diabetes (5), as verified here; that is, the DML on the tibial nerve was longer with PD duration, diabetes duration, and higher creatinine concentrations, but shorter with better glycemic control and higher total Ccr (Table 4).
Prolonged latency of the F-wave on peroneal and tibial nerves and reduced sensitive CV on the sural nerve were found in non-DM patients (Table 2). This confirms the work of Laaksonen et al. (14), who also showed that the most sensitive parameters for diagnosis of uremic neuropathy were the sural nerve sensory action potential amplitude and the F-wave from the lower limbs, and that they are early signs of polyneuropathy. Our study indicated that, in nondiabetic patients, serum creatinine concentration was most closely related to pathological changes in the F-wave in addition to dialysis adequacy (Kt/V, total Ccr) and serum urea concentration (Table 5).
Neurophysiological signs of uremic polyneuropathy varied from 10% to 85% (15). Makkar and Kochar (16) and Bazzi et al. (17) found that uremic neuropathy is often subclinical and detectable only by electrophysiological studies. Moreover, approximately 60% – 80% of patients with advanced chronic renal failure have electrophysiological signs of impaired nerve function at the beginning of dialysis (18,19), although only half are symptomatic (6,20). Almost all our patients (97%) had pathological neurophysiological parameters, but they were subclinical in 35% of the diabetic and 47% of the nondiabetic patients.
Polyneuropathy syndrome in our CAPD patients consisted of typical symptoms such as paresthesia, cramps, and fasciculations (21) but pain in connection with cramps in only two cases. That was why our patients did not take medications for pain, such as NSAID or other specific nerve pain medications (22). Symptoms, if present, are generally more manifest as the neuropathy worsens (23), beginning in the distal lower extremities (4) and evolving slowly over many months (24). In our study, subjective symptoms were worse in diabetic patients than in nondiabetic patients (65% vs 53%) and in patients with pathological prolonged DML on the peroneal and tibial nerves, that is, in patients with advanced polyneuropathy.
Interest in HRQOL in patients with ESRD has risen in recent years. The traditional assessment of patient outcome after ESRD treatment is generally based on the results of biochemical tests, hospitalization rates, techniques for survival, and mortality. In recent years, evaluation of the impact of ESRD treatment on patients' quality of life has become recognized as an important outcome measurement (7). However, the connection between neurophysiological parameters and HRQOL has not been investigated, even though many studies indicate that diabetes and its complications are major risk factors associated with poorer survival rates, higher morbidity, and decreased quality of life (5).
The grade of polyneuropathy influenced HRQOL (PCS and MCS) in our CAPD patients. In the diabetic patients, PCS and MCS were better with favorable neurophysiological results (Table 4), while in the nondiabetic patients, MCS was better with favorable or normal neurophysiological results (Table 5). However, our diabetic patients enjoyed significantly better PCS and MCS (Table 3) than nondiabetic patients, which can be explained by their younger age. Patient satisfaction worsened with duration of DM (p < 0.015).
From a review of many studies, as well as our results, it can be seen that
improved glycemic control may lessen neuropathic changes in diabetic patients
(25). In our patients,
glycemic control was not adequate, as seen with their high HbA1c levels, and
our next steps will be closer collaboration with endocrinologists and better
glycemic control (food intake, exercise, correction of therapy). On the other
hand, in both groups of analyzed CAPD patients, adequate dialysis (Kt/V, total
Ccr) was important for slowing the development of polyneuropathy (Tables
4 and
5). Only a few of our diabetic
patients were treated with 
-lipoic acid but not with any other specific
nerve medications, which may be a limitation of this study and must be
improved in the future.
Balducci et al. (26) and Fisher et al. (27) showed that moderate exercise training can prevent the onset or modify the natural history of diabetic neuropathy and can improve nerve function in patients with DM types I and II, including significant improvement in nearly all electrophysiological parameters evaluated post-exercise, including motor CV and amplitudes, sensitive CV, and F-wave latencies. Many of our patients with diabetic and uremic neuropathy who had suffered from DM for more than 20 years are blind and several of them are without one lower limb, so it will be difficult for them to do much exercise. However, for the few diabetic patients that are able to exercise, as well as for the nondiabetic patients, we must consider recommending moderate exercise, which might decrease their neuropathy and improve their quality of life.
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CONCLUSION |
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ACKNOWLEDGMENTS |
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Received 17 August 2007; accepted 5 May 2008.
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
