Does the 5-Item Modified Frailty Index Predict Adverse Outcomes after Retrograde Intrarenal Surgery? A Case—Control Study by the RIRSearch Group

Introduction

With the increase in the aging population worldwide, the concept of frailty has attracted scientific interest over the past few decades. Frailty is defined as a deterioration in the physiological capacity of several organ systems. It is a strong predictor of not only morbidity but also mortality after a surgery, ¹ and clinicians usually have difficulty managing these cases. In a high-volume population-based study, frail patients were at a higher risk of developing urinary tract stones when compared with non-frailty-specific rates in the literature. ² Apart from the well-known comorbidities associated with frailty, the optimal management of urinary stone disease in frail patients is essential for preventing the bothersome systemic effects of these conditions and achieving optimal quality of life. Frail patients can undergo minimally invasive treatments such as shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotripsy (PCNL). However, a high-volume single-center study indicated that the risk of postoperative infectious and hemorrhagic complications might be higher in frail patients after PCNL. ³ Therefore, RIRS might be more suitable for frail renal stone patients because it can be performed in the supine position, and the absence of specific contraindications makes it feasible even for patients receiving anticoagulant therapy. ⁴ However, no study has directly examined the safety, feasibility, and efficacy of RIRS for frail individuals. To fill this gap, this study aimed to examine whether severely frail patients have an increased risk of adverse events and worse surgical outcomes during and after RIRS.

Materials and Methods

This was a multicenter study with a case-control design. The study was approved by the Ethics Committee of Canakkale Onsekiz Mart University, Çanakkale, Türkiye (approval number: 03.06.2024/06-13), and was conducted according to the principles of the Declaration of Helsinki. Written informed consent has been obtained from all patients involved in this study. The data of 1551 consecutive patients undergoing RIRS for upper urinary tract stones at five referral centers between February 2016 and May 2023 were analyzed. All operations were performed by surgeons with a minimum of five years’ experience in RIRS. Patients younger than 18 years, patients with solitary kidneys, congenital kidney anomalies, or previous PCNL surgery, and patients with missing data were excluded from the study. After the exclusions, the data of 912 patients were included before case-control matching.

The 5-item modified frailty index (mFI-5) was used to assess frailty status. The index score ranged from 0 to 5, with one point assigned for each of the following comorbidities: history of congestive heart failure within 30 days before surgery, presence of insulin- or non-insulin-dependent diabetes mellitus, history of chronic obstructive pulmonary disease or pneumonia, partially or totally dependent functional health status at the time of surgery, and presence of hypertension requiring medication. The patients were divided into a non-frail group (Group 1; mFI-5 score of <2) and a frail group (Group 2; mFI-5 score of ≥2). Case-control matching was then performed to minimize potential selection bias and control for confounding factors. The matching criteria were age, sex, lower pole stone location, stone volume, stone number, use of a ureteral access sheath, and use of anticoagulant therapy. A total of 85 patients from Group 2 were matched in a 1:3 manner to 255 patients from Group 1 using a matching algorithm. Thus, 340 patients were included in the subsequent analysis.

The preoperative evaluation of the patients included a detailed anamnesis, a physical examination, routine laboratory studies consisting of serum creatinine levels, urinalysis, and a urine culture, and radiological evaluation using non-contrast computed tomography (NCCT). If the urine culture was positive, appropriate antibiotics were prescribed according to the patient’s sensitivity profile. The operation was performed only after the patient’s urine was confirmed to be sterile. The stone volume was calculated based on the NCCT images using the following formula: length × width × height × π (3.14) × 0.167 (in cubic millimeters). In cases with multiple stones, stone size was calculated as the sum of the volumes of all stones. In terms of location, the stones were classified as lower pole and non—lower pole stones based on the NCCT images.

The patients’ demographic characteristics, stone-related parameters (volume, density, location, and number), and operative and postoperative outcomes were analyzed retrospectively. The primary objective was to assess the safety of RIRS for frail patients. Complications were classified as intraoperative and postoperative and were graded according to the modified Satava classification system and the modified Clavien classification system (MCCS), respectively.^5,6 Postoperative complications were further divided into two groups: Grade 1 and 2 complications were classified as minor, and Grade 3, 4, and 5 complications were classified as major. The secondary objective was to determine whether a higher mFI-5 score negatively affected the stone-free rate after RIRS. Stone-free status was defined as no evidence of residual fragments of >2 mm on first-month postoperative NCCT. The surgical technique used has been described in our previous study. ⁷

Results

Before matching, the demographic and clinical characteristics of 1555 patients were analyzed. After exclusions, the non-frail group comprised 1153 patients, and the frail group comprised 146 patients. After 1:3 matching, there were no statistically significant differences between the two groups in terms of age, sex, preoperative urinary tract infection, anticoagulant use, or stone characteristics (volume, number, and location; Table 1). The groups were also similar in terms of pre-stenting and SWL history. Likewise, there were no significant differences between the two groups in terms of operative outcomes, such as operation and fluoroscopy screening times, length of stay, and complication rates (Table 2).

In the non-frail group, 19 patients (7.6%) experienced intraoperative complications. The most common complication in this group was mucosal ureteral injury requiring ureteral stent placement (n = 6, 2.3%). In the frail group, eight patients (9.4%) experienced intraoperative complications, the most common of which was mild hematuria (n = 3, 4.7%). There were no Grade 3 complications (complications requiring open or laparoscopic surgery) in either group. The intraoperative complication rates did not differ significantly between the two groups (7.6% and 9.4%, respectively; P = .47). Details on the intraoperative complications are provided in Table 3.

Postoperative complications were seen in 35 patients in the non-frail group and 10 patients in the frail group. In the non-frail group, most complications were minor (MCCS Grade 2 or lower). The rates of major complications were 1.3% and 1.1%, respectively. The most common postoperative complications were renal colic in the non-frail group (n = 15, 5.8%) and postoperative hematuria in the frail group (n = 4, 4.7%). Two patients in the non-frail group developed obstructive urosepsis due to steinstrasse and were treated with ureteral stent placement (MCCS Grade 3b). In the frail group, 1 patient developed urosepsis requiring intensive care management (MCCS Grade 4a). The rates of postoperative complications were similar in the non-frail and frail groups (13.8% and 11.8%, respectively; P = 0 .71). The overall (intraoperative and postoperative) complication rates were also similar. Detailed descriptions of the postoperative complications are provided in Table 4.

Stone-free status was achieved in 181 patients (70.9%) in the matched non-frail group and 62 patients (72.9%) in the matched frail group. The difference was not statistically significant (P = .73). The frail patients had a slightly higher re-treatment rate than the non-frail patients (11.8% and 8.4%, respectively), but the difference was not statistically significant (P = .42).

Discussion

This retrospective multicenter study investigates the association between frailty status and RIRS outcomes. We examined whether RIRS is a safe, feasible, and effective treatment option for severely frail renal stone patients. We found that the stone-free and operative complication rates of severely frail patients were comparable to those of non-frail patients. This suggests that RIRS can be performed safely and successfully on frail patients, with outcomes similar to those of their non-frail counterparts.

As frailty is closely associated with adverse patient outcomes after a surgery, many scales have been developed to determine its severity. In 2004, the Canadian Study of Health and Aging (CSHA) developed a 70-factor clinical frailty scale. Despite its great predictive validity, this scale includes too many factors, which makes data collection from a clinical database difficult. ⁸ For this reason, the mFI-5 and mFI-11 (which are composed of 11 comorbidities) ⁹ scales were developed based on the CSHA scale for simpler and faster data collection. Many studies in various fields have shown that the mFI-5 and mFI-11 scales have equal power in predicting postoperative outcomes, including mortality.^10,11 Therefore, the mFI-5 was used in this study for easier data collection with fewer variables from the patients’ charts to minimize errors.

Operative complications are one of the most important parameters showing clinicians whether a surgical procedure can be safely used under different circumstances. As frailty makes patients vulnerable to complications, many studies have investigated the efficacy of both the mFI-5 and mFI-11 in predicting operative complications. A retrospective case-controlled study using the mFI-11 found that frail patients had a significantly higher incidence of postoperative complications and mortality within 30 days of radical pelvic surgery than their non-frail counterparts. The authors encouraged clinicians to measure frailty preoperatively to predict adverse outcomes in patients undergoing major pelvic surgery such as proctectomy or radical cystectomy. ¹² Similarly, in a retrospective minimally invasive partial nephrectomy series, Goldwag et al. found that patients with an mFI-5 score of ≥2 had a 2.26 times greater risk of postoperative morbidity than non-frail patients. These findings suggest that frailty, as measured by the mFI-5, is a reliable preoperative predictor of overall surgical complications. ¹³

In a high-volume prospective percutaneous nephrolithotomy series, Bhatia et al. divided patients into frail and non-frail groups using the Hopkins Frailty Index, which is based on the additive score of five components: exhaustion, weight loss, grip strength, activity level, and walking speed. This study suggested that the risks of sepsis, bacteremia, and postoperative bleeding might be higher in frail patients after PCNL than in normal ones. ³ Conversely, in our study, after matching confounding factors, we found that higher mFI-5 scores had no significant effect on either intraoperative or postoperative complications associated with RIRS. The overall complication rate in the severely frail group was 14.1%, which is consistent with the overall, non-frailty-specific rates reported in the literature (8%–24.9%).^14,15 Our findings suggest that RIRS can be confidently recommended to severely frail patients suffering from upper urinary tract stones.

Achieving stone-free status with a single RIRS session is one of the primary objectives of current endourologic stone management. Several stone- and patient-related factors have been evaluated to predict optimal stone clearance after RIRS. A retrospective single-center study highlighted five factors that might directly affect stone clearance: stone volume, stone number, lower pole stone location, hydronephrosis, and the surgeon’s experience. The authors also suggested that a nomogram including these factors could be used to predict stone-free status after RIRS and guide clinicians in selecting the optimal treatment. ¹⁶ In our study, the secondary objective was to determine whether a high mFI-5 score negatively affected the stone-free rate after RIRS. We found no correlation between higher mFI-5 scores and stone-free status. In fact, the stone-free rate in the severely frail patients was slightly higher than in the non-frail patients, although the difference was not statistically significant. These findings also suggest that RIRS can be successfully performed on severely frail patients.

Certain limitations of this study should be acknowledged. First, the study’s retrospective nature entails possible selection bias. However, we used the RIRSearch study group database, which was prospectively developed with detailed evaluations. Moreover, we used a 1:3 matching ratio to minimize selection bias and matched confounding factors as covariates. Second, as this was a multicenter study, the surgeons at the different centers may have influenced the clinical outcomes. However, all procedures were performed using the same surgical technique and equipment, standardized since 2015. Finally, despite the 1:3 matching, the limited number of patients resulted in insufficient statistical power to reach definitive conclusions. A high-volume prospective study could have arrived at more reliable conclusions. Despite these limitations, our study is the first to investigate the association between frailty and RIRS outcomes, showing that greater frailty is not related to worse outcomes. Our findings can guide clinicians in the management of these patients.

Conclusions

This multicenter study shows that higher frailty scores have no significant effect on operative complications or stone-free rates after RIRS. Although previous studies in various specialties have suggested an association between severe frailty and a higher likelihood of morbidity and mortality, this study suggests that RIRS can be safely and successfully performed to treat renal stones in severely frail patients.