Neuropathic Pain, Polyneuropathy, and Quality of Life in Patients Receiving Dialysis

Introduction

Neuropathy associated with metabolic disorders presents as distal symmetric sensorimotor polyneuropathy (PNP) characterized by paresthesia, vibration sensory disorders, muscle loss, loss of strength, and decreased deep tendon reflexes. It is usually progresses quite slowly, over months, rarely progresses rapidly, and can result in crucial disability [1]. Patients receiving hemodialysis are predisposed to several PNP causes, such as drug-induced neuropathies, autoimmune diseases, infections, and diabetic neuropathy. Furthermore, uremic PNP, which is caused by the accumulation of toxic metabolites, can develop in hemodialysis patients [2]. PNP is highly prevalent in patients receiving hemodialysis. Studies indicate that 60% to 100% of patients with chronic kidney disease receiving hemodialysis encounter this complication. A cross-sectional study on Iraqi patients with uremia revealed a 63.7% prevalence of uremic PNP, ranging from mild to severe [3]. Likewise, another study reported neuropathic pain in 61.5% of patients receiving hemodialysis [4].

Neuropathic pain is a prevalent and challenging issue among patients in hemodialysis, often leading to a significant reduction in various aspects of quality of life, including mood, sleep, and social interactions [5]. PNP has a substantial effect on the quality of life of patients receiving hemodialysis. Studies have demonstrated an association between the severity of PNP and lower quality of life scores, such as those using the Short Form-36 (SF-36) [6].

In our study, unlike other studies, the Ferrans & Powers Quality of Life Index (F&P QLI)-Dialysis Version III was used instead of the SF-36 to analyze patient quality of life. Of all the scales applied to measure quality of life in research involving dialysis patients in foreign countries, F&P QLI is one of the most commonly used [7].

Most individuals with kidney failure have subclinical peripheral neuropathy, according to electromyography (EMG) assessments. Sensorimotor peripheral neuropathy is the type that is most commonly recognized [1]. Although nerve dysfunctions are seen more frequently in electrophysiological evaluations, which are quantitative indicators of PNP, the percentage of symptomatic patients is relatively low [8]. A methodical approach is required to diagnose and treat patients who have PNP [9].

In this study, we aimed to evaluate if patients receiving hemodialysis experience neuropathic pain and to compare the pain intensity, quality of life, and electrophysiological tests of patients with and without neuropathic pain. This study demonstrates the clinical contribution of detecting PNP in the asymptomatic period using EMG. Early EMG-based identification allows for timely supportive interventions, enhances patient awareness, and may contribute to preserving quality of life before symptom onset.

Material and Methods

This cross-sectional study, conducted from July 2021 to January 2022, included 74 hemodialysis patients from physical medicine, rehabilitation, and internal medicine clinics. Based on Ezzeldin et al [1], Power Analysis and Sample Size 11 software was used to calculate the required sample size as 60 (α=0.05, CI=85%, case rate=0.55, d=0.2). Patients older than 18 years on regular dialysis were included; exclusions were malignancy, pregnancy, diabetes, and neurological disorders. Patients with diabetes mellitus were excluded from the study due to the potential presence of diabetes-induced peripheral neuropathy, which could confound the evaluation of PNP related to chronic kidney disease. Laboratory screening for hemoglobin, B12, folate, electrolytes, and minerals was performed, and abnormal results led to exclusion.

The F&P QLI, Neuropathic Pain Questionnaire (NPQ), and Brief Pain Inventory-Short Form (BPI-SF) were completed by all patients receiving hemodialysis. The F&P QLI, for which validity and reliability studies have been conducted for the Turkish version, is answered by responses to 6-point Likert-type items and consists of 2 main sections, each containing 34 items. Part 1 evaluates “how satisfied you are” in various areas of life, and part 2 evaluates “how important” that area is for that person. The 6-point Likert-type items in the first and second parts are answered from “very satisfied” to “not satisfied at all” and from “very important” to “not important at all”, respectively. The scale consists of 4 subscales: family, health and functioning, psychological/spiritual, social and economic. Total quality of life scores and subscale scores, satisfaction, and importance scores are obtained using a specific formula [7]. The F&P QLI scale was selected because it provides a disease-specific, multidimensional assessment of quality of life in dialysis patients, allowing for a more nuanced and clinically relevant evaluation than that offered with generic quality of life tools.

The NPQ, validated and adapted into Turkish, is a screening tool including 10 questions assessing the quality of pain and 12 questions evaluating changes in sensitivity. Each item is scored on a continuous scale from 0 (not at all) to 100 (extremely), allowing for a nuanced evaluation of symptom severity. The final score is calculated by multiplying each item by a specific coefficient derived from regression analysis and summing the results. A total score equal to or above zero indicates the presence of neuropathic pain, whereas a score below zero indicates the absence of neuropathic pain. The NPQ covers a wide range of symptoms, including burning sensations, electric shocks, tingling, and numbness, as well as changes in touch or temperature sensitivity. These elements reflect the sensory disturbances often observed in patients with PNP or nerve injury. The tool not only quantifies the intensity of symptoms but also aids in distinguishing neuropathic pain from other types of chronic pain in clinical practice [10]. It was preferred in this study because it captures sensory alterations and neuropathic pain descriptors through a validated scoring method, enhancing the reliability of neuropathic pain detection in the dialysis population. The BPI-SF, for which validity and reliability studies have been conducted for the Turkish version, is used to indicate pain severity (0=no pain to 10=worst pain imaginable) and pain interference with daily functions (0=no interference to 10=interferes completely) [11]. Its inclusion was based on its brevity, ease of administration, and ability to assess pain intensity and its interference with daily functions, which are essential for evaluating patient-centered outcomes. Additionally, EMG was performed on all patients regardless of the presence of neuropathic symptoms.

Data analysis was performed using the IBM SPSS 25.0 (IBM Corp, Armonk, NY, USA) package program. The assumption of normality was assessed using the Shapiro-Wilks test, and the homogeneity of variances was assessed using the Levene test. Descriptive statistics are shown as mean ± standard deviation for variables with normal distribution, median (min–max) for variables with abnormal distribution, and frequency and (%) for nominal variables. The significance of the difference between the 2 groups in terms of means was assessed using the t test, and the significance of the difference between the median values was assessed using the Mann-Whitney U test. Nominal variables were assessed using the Pearson chi-square or Fisher exact test, as appropriate. The association between numerical variables was examined using Spearman correlation. Results were considered statistically significant at P<0.05.

The Clinical Research Ethics Committee of Erzincan Binali Yıldırım University Faculty of Medicine approved the study (decision No: 06/07 Date: 26/04/2021). All participants provided written informed consent prior to enrollment in the study, and the study was conducted in accordance with the principles of the Declaration of Helsinki. In cases in which clinical information or images were used, additional written consent for publication was obtained from the patients to ensure confidentiality.

Results

Clinical neurological evaluation and EMG results of 74 patients receiving hemodialysis, 38 men (51.4%) and 36 women (48.6%), with a mean age of 59.72±12.33 years and a mean dialysis duration of 6.29±4.66 years, were analyzed.

Female patients were significantly more likely to have neuropathic pain (P=0.010). Patients on dialysis for a long time (>7 years) were much more likely to have neuropathic pain, at 69.2% (P=0.004). There was a small negative correlation between dialysis duration and F&P QLI total score (r: −0.242, P=0.038). Likewise, a small negative correlation of dialysis duration with the F&P QLI psychospiritual subscale (r: −0.259, P=0.026), and a small negative correlation with the family subgroup (r: −0.233, P=0.046) were obtained. Other F&P QLI subscales did not reveal any correlation with dialysis duration (P>0.05).

Patients were categorized into 2 groups based on their NPQ screening results, which assess symptoms indicative of distal symmetrical PNP. The NPQ-positive group (n=38; 51.4%) reported pain predominantly localized to the distal, symmetrical regions of the lower and upper extremities – most commonly in the feet and hands – described as burning, tingling, shooting, or electric-like sensations, often accompanied by numbness and hypersensitivity to touch (allodynia). In contrast, the NPQ-negative group (n=36; 48.6%) did not exhibit these characteristic distal, symmetrical pain patterns or associated sensory changes. BPI-SF assessments were compared between the 2 groups, and the results are presented in Tables 1 and 2. In Table 1, higher values indicate an increase in pain scores. Table 2 shows the effect of pain on activities and daily life, where higher values reflect greater interference of pain with activities.

The electrophysiological examination revealed that PNP was detected in all patients in the NPQ-positive group, whereas PNP was identified in 28 patients (77.8%) in the NPQ-negative group. PNP was detected in a total of 66 patients (89.2%) with nerve conduction studies, 51.4% of all patients in the NPQ-positive group and 37.8% in the NPQ-negative group. These findings demonstrate the prevalence of uremic PNP in patients, even during the asymptomatic period. Table 3 displays the distribution of electrophysiological examination findings from the patients’ nerve conduction studies by group. According to these results, the distribution of PNP types detected by EMG was similar between patients with positive and negative neuropathic pain screening outcomes, and no statistically significant difference was observed between the groups.

A strong negative correlation was found between NPQ scores and the F&P QLI total score (r=−0.809, P<0.001). Similarly, strong negative correlations were observed across all subscales, including health-performance, socioeconomic, psychospiritual, and family domains.

The outcomes of the NPQ-positive and NPQ-negative intergroup comparison of F&P QLI total and subgroup values are presented in Table 4. According to these findings, quality of life was statistically significantly lower in the NPQ-positive group in all subgroups.

Discussion

This study was planned to detect neuropathic pain in patients receiving hemodialysis, to determine the rates of PNP in dialysis patients with EMG studies, and to compare the types between those with and without clinical neuropathy. The study results showed that even if neuropathic pain was not detected in clinical examination in dialysis patients, PNP was detected in EMG studies in 89.2% of all patients. In a review study by Lambourg et al showed that although most of the studies used validated scales in the assessment of chronic pain and neuropathic pain, very few studies relied on a tool specifically designed to investigate neuropathic pain, such as the NPQ, in the assessment of neuropathic pain [12]. In our study, NPQ was used as a screening tool for neuropathic pain, allowing symptoms to be systematically and comprehensively assessed. Despite the abundance of research on neuropathy in patients on dialysis, there are not enough studies evaluating how this disorder affects quality of life. The present observational cross-sectional study was conducted for this aim and demonstrated the impact of neuropathic pain in dialysis patients on overall quality of life, including its socioeconomic, psychospiritual, familial, functional, and health-related domains.

Research studies in the literature have not determined the effect of patient sex on neuropathy [3,8,13]. On the other hand, our research revealed that women were more likely than men to experience neuropathic pain (P=0.010). Sex-based differences in neuropathic pain among patients receiving hemodialysis remain a subject of clinical interest. In our study, female patients were significantly more likely to experience neuropathic symptoms. This finding may be related to known differences in hormonal status, psychosocial factors, and pain perception between the sexes. Variations in sample characteristics, assessment tools, and reporting behavior may also contribute to this result. These findings highlight the need for further research to better understand the role of patient sex in neuropathic pain within this population.

A recently published study of 96 patients on dialysis revealed no association between dialysis duration and neuropathic pain [14]]. By contrast, in our study, the probability of developing neuropathic pain was found to be higher in patients with dialysis duration of more than 7 years. (P=0.004). When Mizher et al examined the association between pain severity and dialysis-related factors, such as dialysis duration, weekly dialysis number, and duration, instead of neuropathic pain using the BPI-SF, they detected no association between pain severity and hemodialysis-related factors [15]. This difference between the results can be hypothesized to be due to the increased probability of uremic neuropathic pain due to the accumulation of uremic toxic substances as dialysis duration increases. Neuropathic pain may have a higher association with dialysis duration than chronic pain.

Chronic pain has been associated with impairments in daily functioning, particularly physical disability, poor mood, and problems with concentration and sleep at night [16–18]]. In the present study, pain in patients receiving hemodialysis restricted activities such as general activities, emotional status, human relationships, sleeping, and enjoying life, and these restrictions were more pronounced in the group with neuropathic pain, as seen in the BPI-SF results in Tables 1 and 2. There was a significant difference in the group with neuropathic pain only in daily work activities, and this may be related to the fact that individuals focused on their responsibility to complete their daily work despite experiencing neuropathic pain.

According to a study in the literature, 55% of all patients receiving hemodialysis had clinical symptoms of PNP. When EMG was performed, PNP was detected in 92.5% of the clinically asymptomatic group and in 100% of the symptomatic group [1]. In our study, similar to this study, PNP detected in EMG was reported in 100% of the NPQ-positive group, while it was reported in 72.8% of the NPQ-negative group. With EMG, we can detect PNP earlier in patients receiving hemodialysis, before neuropathic pain symptoms begin, and determine the treatment options recommended by the guidelines earlier. This study provides an overview to improve patients’ awareness and sensitivity regarding PNP, which, by using EMG, was identified in 89.2% of dialysis patients. The high rate of PNP detected through EMG in patients without overt symptoms underscores the value of early screening during the asymptomatic period. Identifying neuropathic changes at this stage allows for timely interventions that can prevent further nerve damage and functional decline.

Uremic neuropathy in patients receiving dialysis is assumed to be caused by oxidative stress and secondary nerve damage resulting from uremic toxin accumulation. It typically presents as sensorimotor PNP, mostly affecting the lower extremities [19]. Nerve conduction studies help identify neuropathy patterns, distinguish between axonal and demyelinating pathology, and assess the severity of neuropathy [1]. In the present study, we classified the neuropathy in patients receiving hemodialysis as axonal, demyelinating, mixed, motor, sensory, and sensorimotor and analyzed the comparison of all subgroups in NPQ-positive and NPQ-negative groups. No significant differences were identified among the groups in terms of the various types of PNP. Conversely, Ezzeldin et al conducted a study comparing clinically symptomatic and asymptomatic groups based on PNP classification and reported significant differences not only in the demyelinating and sensorimotor types but also in the mixed PNP group – unlike our findings [1]. The increased frequency of isolated motor and sensory PNP subtypes in this study raises the question of whether other underlying pathological conditions may be contributing factors in these patients and warrants further investigation [1].

Quality of life in patients with end-stage renal disease undergoing dialysis has been evaluated in the literature using the health-related quality of life instrument SF-36 [20,21]. In the study by Alencar et al, the quality of life in patients receiving hemodialysis was assessed using the Self-Realization and Pleasure Questionnaire (CASP-16) [22]. In our study, more specific results were obtained because the F&P QLI Dialysis III, which was specifically defined for patients receiving dialysis, was used to assess quality of life. Since neuropathic pain is one of the most difficult pain conditions to treat, patients usually report disappointing results. Untreated pain negatively affects dialysis adherence, increases healthcare utilization and mortality, and reduces health-related quality of life [23]. When the quality of life of the NPQ-positive and NPQ-negative groups were compared, as presented in Table 4, the quality of life of patients with neuropathic pain was significantly lower both in total scores and in the health and performance, socioeconomic, psychospiritual, and family subgroups (P<0.001 for all groups).

Evidence-based guidelines recommend gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors for neuropathic pain management, with similar efficacy reported among agents. In clinical trials, a 30% reduction in pain is generally considered a meaningful treatment response. Combination therapy can be considered if monotherapy fails after an adequate trial period [24–26]. Based on our findings, early EMG screening in asymptomatic patients and timely initiation of supportive treatments may help prevent the emergence of chronic, treatment-resistant neuropathic pain.

This study stands out as one of the few investigations that holistically examine the impact of neuropathic pain and PNP on the quality of life of dialysis patients, using clinical assessments and electrophysiological data. Unlike previous studies that often limited their scope to symptom prevalence or general quality of life metrics, our research incorporated a disease-specific quality of life index, the F&P QLI Dialysis III, and systematically evaluated pain characteristics with a validated screening tool, the NPQ. In addition to these methodological strengths, the study benefited from a relatively large sample size, the use of validated multidimensional assessment tools, and detailed EMG-based subgroup analyses, which collectively enhanced the robustness and generalizability of the findings. Furthermore, by including asymptomatic patients and identifying early polyneuropathic changes through EMG, the study highlights a critical opportunity for timely intervention before irreversible functional deterioration occurs. These findings not only enrich current understanding of the hidden burden of neuropathic complications in this population but also emphasize the importance of integrating comprehensive pain and nerve evaluations into routine dialysis care protocols. One of the shortcomings of the study is that the pain areas in the body were not examined and analyzed in detailed sections, such as the head, chest, foot, knee, upper extremities, waist, and neck. The pain areas can be determined separately, and their effect on quality of life can be investigated in future studies.

Conclusions

PNP findings can be detected in EMG studies during the asymptomatic period in patients receiving hemodialysis. The presence of neuropathic pain in patients receiving hemodialysis reduces quality of life across all domains, including physical health, functional performance, socioeconomic status, psychological well-being, and family relationships. The activities of patients undergoing hemodialysis are restricted by pain, and this restriction is particularly pronounced in those experiencing neuropathic pain. Routine use of EMG in dialysis patients can facilitate the early detection of PNP and support timely interventions to improve quality of life. Prospective research is required in the future to examine patient quality of life, using hemodialysis-specific measures, especially before and after dialysis treatment.