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Assistant Professor of Medicine
Division of Renal Diseases and Hypertension
University of Texas McGovern Medical School
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In-center hemodialysis (HD) is no walk in the park. Treatment-related symptoms are common and often inadequately addressed. The burden of unpleasant symptoms increases with progression of chronic kidney disease, and includes the emergence of new hemodialysis-related symptoms once treatment is initiated (Kalantar-Zadeh et al, Nat Rev Nephrol 2022). Patients on in-center HD report symptoms such as fatigue, itching, cramping, restless legs, bone pain, dry mouth, nausea, and difficulty concentrating during both the intra- and interdialytic periods. A recent prospective, single-center observational study by Chauhan et al. in KI Reports surveyed adult patients who receive thrice weekly in-center HD on their intra-dialytic symptoms. The researchers’ main objective was to determine if symptom frequency and severity correlated to the long (2-day versus 1-day) interdialytic period.
Participants completed twelve surveys over a four-week period; surveys obtained on Mondays or Tuesdays were considered surveys from after the long interdialytic period. The survey instrument was based on the Dialysis Symptom Index. It asked patients to identify presence (within the prior 24 hours) and severity (5 point scale, 0-4) of twenty common dialysis-related symptoms. A symptom severity index for each survey was calculated by a sum of all severity scores from each reported symptom. Then the mean severity scores for short and long interdialytic intervals were calculated for each participant. Factors such as intradialytic weight gain, systolic blood pressure, and ultrafiltration rate were captured for multivariate analysis and adjustment.
In total, 97 patients completed the study. Their baseline demographics and characteristics are listed in Table 1. Throughout the study period, across all collected surveys, the most commonly reported symptoms were fatigue, cramping, dry skin, muscle soreness, itching, and cough. The least commonly reported symptoms were constipation, decreased concentration, vomiting, and diarrhea.
Figure 1. Percent of participants that experienced a symptom on any of the 12 completed surveys
Comparing surveys obtained after the short vs long interdialytic period, 10 of the 20 symptoms were significantly more frequent after the long interval. Fatigue (22% vs 15%, p<0.001) and cramping (21% vs 16%, p=0.003) were prominent. The association of higher symptom frequency after the long interdialytic period remained a significant 37% higher incidence even after multivariable adjustment (IRR 1.37, 95%CI 1.24-1.51, p<0.001), see Table 2. Symptom severity was also higher after long interdialytic periods with significantly higher mean severity scores when compared to the short interdialytic periods (6 ± 4.9 vs. 4.6 ± 3.8, p<0.001). Symptom frequency and symptom severity were both higher in female participants.
Figure 2. Percent of long and short treatments where patient reported symptoms.
The authors acknowledged a few limitations of the results of their study. An important one to consider is that residual kidney function (RKF) was unknown for the study participants so its effect on the symptom burden findings herein is unknown. The 24-hour urine output and residual kidney function are not routinely measured or monitored in patients on in-center hemodialysis. Studies on RKF and intra-dialytic symptom burden specifically are few. In the 2010 CHOICE study, the presence of >250 mL/day urine output was associated with a survival benefit, but also better quality of life scores (questionnaire included questions relating to pain and fatigue). Similarly, a 2022 study by Elgendy et al. found increased quality of life scores for patients on HD with urine production >100 mL/day compared to anuric patients. Additionally, CHOICE showed that patients with higher RKF also have lower erythropoietin stimulating agent (ESA) requirements. High ESA doses to maintain target hemoglobin levels could contribute to symptoms such as bone and muscle pain, these being known medication side effects. How might RKF affect the observed increase in symptom frequency after the long interdialytic interval? The survival benefit associated with RKF is likely closely tied to advantages in fluid management (Mathew et al, Kidney Int 2016). It is possible that the commonly reported symptoms of cramping and fatigue are related to increased ultrafiltration rate (UFR) sometimes required after the long interdialytic interval. While Chauhan et al., did not find a difference in UFR and the increased symptom frequency/severity, they were notably unable to capture treatment data such as ultrafiltration discontinuation of UFR reduction occurring in response to patient symptoms.
Knowing the potential impact of the long interdialytic interval, what could be done to help alleviate symptoms or symptom severity? Pain, specifically bone pain, is a commonly reported severe symptom identified here and in other studies. Prior reviews have addressed pharmacological and non-pharmacological approaches to pain management (Vajjala & Shah, KI Reports Community 2022; Raina et al, Hemodial Int 2018) Interestingly, increased dialysis frequency is not remarked on as an option to manage pain. A cross-over study suggested symptomatic benefit of short daily hemodialysis, but implementation was limited by compliance and vascular access complications (Goldfarb-Rumyantzev AS et al, NDT 2006). As such, discussion with patients about dialysis options that include daily treatments (e.g. home hemodialysis and peritoneal dialysis) might help to reduce symptom burden, particularly in patients who have a spike in symptoms during the long interdialytic period.
Chauhan et al. proposed guidance for consideration in future research on symptom burden in patients undergoing in-center hemodialysis. First, timing survey distribution after the long interdialytic period may help capture maximum symptom burden. Interestingly, a similar study conducted in the UK (published only 1 week prior to study described above by Chauhan et al) found that when measuring symptom severity, they did not have to account for the HD schedule. Instead, they found differences and potential bias introduction on whether the survey was administered on a hemodialysis or non-hemodialysis day (Hnynn Si et al, PLoS One 2022; @Pannei_Hnynnsi). The study by Chauhan et al., did not survey patients on non-hemodialysis days to make any similar comparison. Second, trials testing treatments for these hemodialysis-related symptoms would benefit from longitudinal assessment of patient symptoms to identify those with the highest symptom burden. Indeed, it is likely all can agree the annual quality of life assessments performed in most dialysis centers in the US are inadequately capturing patients’ true symptom burden.
As we cannot change our seven-day week, in continuing with thrice weekly hemodialysis we are left to contend with a long interdialytic period. Prior studies have shown that cardiac-related hospital admissions and mortality events occur more frequently after the long interdialytic period (Georgianos PI et al, Am J Nephrol 2015), and this study highlights that increased intradialytic symptom burden coincides.
Visual Abstract by Eric Au, MD
AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.