Assessment of HRQoL and its Determinants for Kidney Stone Formers

Background Quality of life is the central health-improving goal. Urolithiasis is a complex disease signicantly related to disease-related morbidity and impacting patient’s health-related quality of life (HRQoL). The study aims to evaluate the HRQoL and markers of HRQoL of kidney stone formers using a disease-specic instrument. Methods We compared the HRQoL of kidney stone formers with healthy individuals using Wisconsin stone quality of life (WISQoL) questionnaire. A prospective, cross-sectional, case-control study was conducted at different urological settings of Rawalpindi. Result Multivariate analysis of variance (MANOVA) analysis depicted that compared with healthy individuals stone formers reported statistically signicant (p = 0.000) differences in HRQoL in overall health and all the domains of WISQoL i.e. social, emotional, disease impact and impact on vitality. Further regression analysis evaluated that demographic factors, clinical features of the disease and surgical procedure for active removal of stone are also determinants of QoL of stone formers (p < 0.05).


Introduction
Health-related quality of life (HRQoL) is a multidisciplinary approach and as a patient-reported outcome measure is considered a more reliable indicator of a patient's health status compared to physician objective assessment of the patient. (1) Urolithiasis or kidney stone disease is a complex disease signi cantly related to disease-related morbidity (2). The complex nature of disease range for an acute stone event that may remain asymptomatic, to symptomatic (3). Further, the highly recurrent nature of the stone disease, with 50% chances of recurrence in the next 5 years (4), requiring lifelong medication and dietary modi cation explains the chronic nature of the disease. With all this complexity urolithiasis is reported to compromising patients HRQoL.
Kidney stone disease is typically associated with renal colic. Although renal colic, the most common presentation of kidney stones is short-lived still the acute event is associated with frequent hospital evaluation, emergency department visits, hospitalization, and surgical intervention causing depression, stress, absence form workdays, or impaired work performance, nancial burden and social dysfunction (3,5,6). Management of urolithiasis involves medical and surgical intervention. Although the advent of completely noninvasive and minimally invasive procedures like extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and ureterorenoscopy (URS) have improved surgical removal of stone as compared to historically used open surgical methods these interventions are still associated with side effects and complications (7). Consequently, the disease itself and various interventions for its management can impact patient HRQoL (8).
Quality of life is the central health-improving goal. Assessment of HRQOL is therefore necessary for measuring progress toward achieving goals. Different generic and disease-speci c instruments are used for the assessment of HRQoL in patients (9)(10)(11). ]. Quality of life in stone formers has been assessed for a long time with generic instruments (8), Until 2013 a disease-speci c quality of life instrument namely Wisconsin stone quality of life (WISQoL) questionnaire was developed, tested and validated in kidney stone population (9,12,13). The present study aims to evaluate the HRQoL of kidney stone formers in the local population and to determine various factors that are epitope of HRQoL in urolithic patients using WISQoL.

Methodology
A prospective, cross-sectional, case-control study was conducted at the Department of Urology, Benazir Bhutto Hospital, and Holy Family Hospital Rawalpindi, Pakistan, for a period of 6 months (from April 2018 to October 2018). Ethical review board (ERB) approval for the study was obtained from the ERB committee of Quaid-I-Azam University, Islamabad, Pakistan. Informed consent was obtained from all individual participants included in the study. The sample size for the study was 238 calculated through the G-power sample size calculator.

Study Population
The study population constitutes cases and controls. Cases constitute the individuals who were admitted to Hospitals for surgical removal of kidney stones. Case-mix includes stable interventional patients of urolithiasis. Control group constitute healthy individuals from the general population whose stone-free was con rmed via ultrasound technique. Cases and controls were matched in terms of age and gender.

Inclusion and Exclusion Criteria
For Cases patients with stable stone disease admitted to urology departments for surgical removal of kidney stones were included in the study irrespective of their age. For Controls healthy individuals from the general population that were matched with cases in terms of age and gender were included in the study. Controls with a personal history of kidney stone disease or any renal disease were excluded from the study.

Data collection
Data was collected via patient's medical reports and direct interviews with the participants both cases and controls. Information was collected on the data collection form, about subject's demographics, associated comorbidity, past medical history, clinical features of kidney stone disease (including the size of kidney stone, type of kidney stone and location of stone within urinary tract) and procedure used for active removal of stone. Lastly, WISQoL, a 28-item disease-speci c questionnaire, was self-administered to access HRQoL in kidney stone formers. The questionnaire was translated into the local language and validated as per WHO guidelines for ease of understanding of the study participants. The validated local language WISQoL had a Crohn Balch alpha value of 0.78 (α = 0.78).

Statistical analysis
Data were analyzed via SPSS v20. Data were expressed as counts and percentages for categorical variables while as mean and standard deviation for scale variable. Multivariate analysis of variance (MANOVA) was used to compare the mean score of WISQoL domains while linear regression analysis was used to derive any relation between demographic and clinical variables of disease with the WISQoL domains using 95% con dence interval and considering p-value less than 0.05 as statistically signi cant.

Results
A total of 246 individuals participated in the study, of which 219 were enrolled who were compliant with the inclusion criteria of the study. Within 219 enrolled participants 146 were cases and 73 were controls. The ratio of the case to control was 2:1. The demographic detail of cases and control is expressed in Table 1. The kidney stone formers belong to all the age groups with a range of 7 to 82 and mean age of 40.45 ± 16.7. The age group most affected by kidney stone disease was 31-50 years constituting 42.5% of the cases. The majority of stone formers 52.1% constitute male.       The trends in the prevalence of urolithiasis in Asian subcontinent show a variable response with overall prevalence of 1-5% while some Asian countries like Saudi Arabia have also reported prevalence up to 20.1% (14). Pakistan being situated in the middle of Afro-Asian stone forming belt show a high incidence of kidney stone formation with study reporting urolithiasis workload of 40-50% in the urological settings of Pakistan (15). Quality of life of kidney stone formers has been a concern in this regard. HRQoL in kidney stone patients have been assessed in different urologic setting in different regions of the world but to the best of our knowledge this is rst attempt to assess the HRQoL of stone formers using disease speci c instrument in native community with such vast ethnic inclusiveness.
Study reveal that quality of life of stone formers is affected as kidney stone formers scored lower than healthy study participants in all the major domains of HRQoL i.e. social, emotional, disease impact and vitality. These results are consistent with Bryant and Micheal (2) who also reported same nding using SF 36 questionnaire.
Results indicated an age related decline in the HRQoL of kidney stone formers as shown in Fig. 1, similar ndings were reported by Arafa and Mostafa (5). That is particularly true for age, this decline in QoL of stone formers with advancing age can be attributed to the compromised ability of coping with the emotional and physical trauma associated with kidney stone disease. On contrary the pediatric stone formers scored very high in all the domains of WISQoL as depicted in gure, More evidence are needed to support the argument that either urolithiasis does not compromise the HRQoL of pediatric stone formers to the extent the QoL of other age groups is affected or the appropriateness of WISQoL for this particular age group need to be addressed as WISQoL was originally validated for adult stone formers. Clinical features of kidney stone disease were also observed as markers of HRQoL. Among diseases feature patients having stone localized at more than one site in the body (for example; patients having a stone in kidney and ureter at the same time) scored lowered in WISQoL domains than those with stone localized at a single site (either kidney, ureter or bladder). Moreover, stone type (either staghorn stone or non-staghorn stone) also yielded a statistically signi cant association with the HRQoL. Arafa and Mostafa (5) in their study also reported a signi cant relation of stone location and stone size with the HRQoL of urolith formers, However, in our study, a statistically insigni cant association was found with the kidney stone size that could be possibly the limitation of scale. Although stone formers having larger stone within their body scored lower in major domains of WISQoL (52.7 vs 50.9 for the standard score, 55.3 vs 49.5 for emotional impact and 51.0 vs 46.9 for disease impact) while almost similar and converse results were observed in social impact (54.1 vs 54.9) and impact on vitality ( 37.9 vs 45.2) respectively. This difference may be due to the accommodation process involving response shift that results in a change in internal standard and values (16).
Interestingly the patient's perception of current stone status showed contradictory results, as patients who reported that they do not currently have stone within their body scored lower in WISQoL domains (standard score; 54.5 vs 46.3, Social impact; 55.8 vs 48.8, emotional impact; 58.1 vs 44.4, disease impact; 53.2 vs 42.7, impact on vitality; 38.0 vs 39.4) compared with those who reported the presence of stone within their body. These contradictory results could be due to sampling size limitation or these lower scores can be accredited to the fact that patients who responded were asked about their perception for the stone presence within their body a couple of days after surgery, so the post-surgical impairment and stent placement (17) maybe associated with the current nding. Notably procedure for active removal of stone was critical for determining the patient's HRQoL. Depending on clinical features of disease different surgical techniques including PCNL, URS, Pyelolithotomy, cystolithotomy, and open surgery were used for active stone removal, ndings report a statistically signi cant relation of surgical procedure with WISQoL domains. Patients receiving different minimally/partially invasive procedures (e.g. PCNL and URS) for active stone removal scored better than patients who were subjected to invasive or completely invasive surgical procedures like pyelolithotomy, cystolithotomy or laparoscopic procedures respectively.

Conclusion
The overall advancement in the treatment modalities for urolithiasis has improved the clinical practices in this domain but HRQoL remains a major concern. Urolithiasis itself along with different patient-related factors and disease-related variable are proven to be playing an equivalent role in the divination of patient's quality of life, affecting the HRQoL of stone formers in all the major domain of health impacting not only patient's vitality but also affecting stone formers socially and psychologically. WISQoL was proved to be a reliable disease-speci c instrument in assessing the HRQoL of kidney stone formers but more investigation is recommended for the generalizability of the instrument for all age groups particularly for pediatric stone formers. The ratio of cases and control and the follow up for the patients who competed WISQoL post-surgically has been a limitation for the current study. We recommend more such types of studies in multiple settings with longitudinally evaluating the disease impact, pre and postsurgical with appropriate follow-up time to overcome the potential limitation of this study.