Clinical risk factors of recurrent kidney stone disease: a cohort retrospective study in a tertiary referral hospital

Widi Atmoko¹, Febriyani¹, Ary Indriana Savitri², Cuno Uiterwaal², Siti Setiati³, Agus Rizal Ardy Hariandy Hamid¹, Ponco Birowo¹, Nur Rasyid¹

Background

Nephrolithiasis or kidney stone disease (KSD) is common worldwide. Despite various effective treatment strategies, KSD recurrence remains a problem. This study aimed to investigate the risk factors of KSD recurrence.

 

Methods

This retrospective cohort study used medical records of all patients who came to the Department of Urology, Cipto Mangunkusumo Hospital, Jakarta, from January 2014 to December 2019, with asymptomatic and symptomatic KSD. Demographic information, clinical data, exposure to risk factors, and recurrent KSD diagnosis were collected. Univariate and multivariate analyses using logistic regression were performed to determine the significant risk factors.

 

Results

We reported 325 patients with a median age of 52 years. More than half of the patients were males and from Java. Staghorn stone dominated the KSD types found in 181 patients (55.7%). After undergoing percutaneous nephrolithotomy, 214 patients (65.8%) became stone-free. However, about 40.6% of them later developed recurrent KSD. The adjusted odds ratio in recurrent KSD were 1.46 (95% confidence interval [CI] 1.33–1.59) for younger age, 1.86 (95% CI 1.61–2.07) for overweight–obese, 2.13 (95% CI 1.89–2.31) for less fluid intake, 1.81 (95% CI 0.97–2.12) for routine tea consumption, 1.24 (95% CI 1.06–1.84) for routine vegetables consumption, 2.27 (95% CI 1.83–2.84) for a family history of KSD, and 2.08 (95% CI 1.77–2.39) for diabetes mellitus (DM).

 

Conclusions

Most patients with recurrent KSD were younger, overweight/obese, had less fluid intake, a family history of KSD, and DM. Modifying a healthy lifestyle and a balanced diet is important to prevent KSD recurrence.

 

Keywords

kidney calculi, nephrolithiasis, urolithiasis

Kidney stone disease (KSD) and nephrolithiasis are among the most common urological diseases, affecting approximately 5–9% of Europeans, 7–13% of North Americans, and 1–19.1% of Asians.1–3 Decreased kidney function, which can result in chronic kidney disease and end-stage renal failure, is one of the main negative consequences of KSD. Furthermore, it is associated with an increased risk of other comorbidities such as malignancy and cardiovascular disease events, thus leading to a financial burden resulting from increased healthcare costs.4,5 Due to lifestyle, dietary habits, and climate change, the incidence of KSD is increasing.6

The main goal of treatment is to maintain a stone-free condition, leaving no residual fragments.7,8 There are various established treatment options for KSD, including conservative management, open surgery, percutaneous nephrolithotomy (PCNL), ureterorenoscopy, and extracorporeal shock wave lithotripsy (ESWL). Despite the satisfactory outcome after treatment, the recurrence of KSD remains high.9,10 Studies have reported that the recurrence rate is 6–7% after 1 year and 21–53% after 3–5 years, and the lifetime risk of recurrence is estimated to be 60–80%.11,12

The high recurrence rate remains a challenge for clinicians treating patients with KSD. Identifying high-risk stone patients and preventing KSD are important for reducing further complications. However, data on the risk factors for recurrent KSD are still lacking, especially in Indonesia, despite the high prevalence of patients. This study is among the first to explore whether demographics, dietary habits, and lifestyle play a role as significant risk factors for recurrent KSD. The results of this study contribute to the existing knowledge regarding KSD as benchmark data for further studies and serve as clinician guidelines for preventing recurrent KSD.

 

 

Study design and participants

This retrospective cohort study used medical records from January 2014 to December 2019 from the Urology Outpatient Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The inclusion criteria were patients with asymptomatic or symptomatic KSD who visited the hospital and aged 18–80 years. The diagnosis of KSD was made by a urologist based on clinical and radiological examinations, which included ultrasonography, plain abdominal photography, and computed tomography, referring to the Indonesian Urological Association guidelines for KSD. Patients with incomplete medical records were also excluded. The sample size was calculated using the formula for the cohort study, which resulted in a minimum sample size of 273. The patient's demographic and dietary information, clinical symptoms, and stone-free status were collected and assessed. Data were obtained from medical records, interviews, and online questionnaires. Patients with KSD recurrence after treatment for the first stone episode were identified.

This study was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia–Cipto Mangunkusumo Hospital, Jakarta, Indonesia (No: KET-199/UN2.F1/ETIK/PPM.00.02/2022). Written informed consent was obtained from all participants prior to their participation. If a participant was illiterate, a written informed consent was obtained from a legal representative.

 

Assessment of the variables

Based on their stone-free status after PCNL, the participants were classified into stone-free or residual stone groups. Stone-free status was defined as the absence of residual stone fragments or fragments ≤4 mm in diameter. Stone recurrence was diagnosed when patients with symptomatic stones presented to the emergency department or urology clinic and asymptomatic patients with radiological recurrence after stone intervention with a stone-free status. A radiological recurrence was defined as new stones reported from imaging studies after surgery.13 The recurrent and non-recurrent KSD groups were then compared to the following variables: age, sex, ethnicity, family history of KSD, fluid intake, tea consumption, vegetable consumption, diabetes mellitus (DM), hypertension, hypercholesterolemia, physical activity, and body mass index (BMI).14–16

The mean/median age of the participants was first evaluated and became the cut-off value for categorizing the age group. Subjective variable data, such as dietary habits, were collected using either online or direct questionnaire forms filled out by the participants. Fluid intake was evaluated using the approximate fluid intake within 24 hours. After determining the mean/median value, the participants were categorized into two groups based on the cut-off value. The tea and lean/fatty meat consumption variables were categorized into routine, defined by ≥3 times/week, and non-routine, defined by <3 times/week. A nonstop and minimum of 30 min of physical exercise can be defined as physical activity. They were then categorized into routine (≥3 times/week) or non-routine (<3 times/week). Vegetable consumption included any vegetable intake, defined as routine (≥7 times/week) or non-routine (not daily or <7x/week).

 

Statistical analysis

Data normality was assessed using the Kolmogorov–Smirnov test. Normally distributed continuous variables are presented as mean (standard deviation) and were tested using Student’s t-test. Medians and ranges were used to represent non-normally distributed data. Categorical variables are presented as numbers (percentages) and were tested using the chi-square test. Univariate analysis using logistic regression was performed to evaluate the crude association between each factor and the occurrence of recurrent KSD. Variables with p<0.25 were then included in the multivariate analysis using logistic regression. The results are expressed as odds ratios (ORs) with 95% confidence intervals and corresponding p-values. Statistical significance was a 2-sided p-value of <0.05. All analyses were performed using SPSS software version 25 (IBM Corp., USA).

 

 

Within 5 years, 479 patients with kidney stones visited the Urology Outpatient Clinic, Cipto Mangunkusumo Hospital. However, owing to incomplete medical record data for 154 patients, 325 patients were included in the analysis. The baseline characteristics of the study participants are shown in Table 1. Normality test results for some variables, such as age, were not normally distributed; therefore, a nonparametric test was used. The median patient age was 52 years (ranged from 18–80 years). Most of the patients were males and from Java. Approximately 32.6% of the patients were office workers. Staghorn stones were more common than non-staghorn stones. The mean stone size before the intervention was 24.3 mm. None of the patients had undergone any prior surgical intervention. PCNL was the treatment of choice for all patients. After PCNL, 214 (65.8%) patients became stone-free; the remaining patients still had residual stones. Among patients with a stone-free status, follow-up visits or monitoring were performed for a mean duration of 30.7 (3.2) months, and 40.6% of them later developed recurrence from the prior KSD.

 

 

The associations between the evaluated factors and KSD recurrence are shown in Table 2. Younger age, less fluid intake, routine vegetable consumption, a family history of KSD, and DM were associated with recurrent KSD. The risk of recurrent KSD increased more than 2-fold with less fluid intake, routine vegetable consumption, and a family history of KSD. Male sex, overweight/obesity, tea consumption, fatty meat consumption, hypercholesterolemia, hypertension, and lack of routine physical activity tended to increase the odds of recurrent KSD, although the difference was not statistically significant. Multivariate analysis was performed with age, BMI, fluid intake, vegetable consumption, tea consumption, family history of KSD, and DM as independent variables. The adjusted OR for BMI was higher than the crude OR, and patients who were overweight and obese had a recurrent KSD 1.86 times higher compared to the underweight and normal BMI groups.

 

 

 

 

In this study, patients with kidney stone ranged from 18 to 80 years old. In line with previous studies,14–17 52 years old was the median age of patients, and younger patients (18–51 years) had a higher risk of KSD. All patients in this study underwent PCNL as the first method for active stone removal and as the treatment of choice for kidney stones >20 mm based on the guidelines, with no history of surgical intervention. Some patients had undergone prior ESWL and a trial with oral medication. This study reported the successful stone-free rate following PCNL. Only the stone-free status group after the intervention was included in the risk factor analysis to minimize the confounding effect of stone history. However, almost half of the patients experienced recurrence.

Varying KSD recurrence rates have been reported. In a retrospective study, Rule et al14 presented that KSD recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively. Compared to the present study, the recurrence rate was higher (40.6%) after >2 years of follow-up. The present study found a strong positive association between KSD recurrence and age, BMI, fluid intake, vegetable consumption, a family history of KSD, and DM.

In the present study, patients with a family history of KSD had 2.09 times higher odds of recurrence than those without a family history of KSD. This finding was consistent with a previous study reporting a higher prevalence of stone disease in patients with a family history of KSD (hazard ratio 1.64, p<0.001).14 This is probably because of genetic factors contributing to the recurrence of KSD.14 Metabolic disease has been associated with KSD. Chronic inflammation and insulin resistance lead to complex metabolic derangements that contribute to the pathogenesis of various diseases. Recent studies have shown that the early processes of kidney stone formation involve inflammatory responses, including the expression of inflammatory molecules such as monocyte chemoattractant protein-1 and osteopontin and macrophage infiltration.18

DM was a significant risk factor for recurrent KSD. Insulin resistance, which plays a role in type 2 DM, has been linked to the formation of uric acid stones. It results in a deficit in ammonium production in the kidney, which lowers urinary pH, thus generating a milieu for the stone formation.18 However, it is not a surprising fact that the prevalence of patients with diabetes is increasing globally, including Indonesia. Unfortunately, Indonesia has low public health.19 This should attract the attention of all clinicians, especially those in primary healthcare. Prevention and management of diabetes are needed to avoid KSD and its recurrence.

In a previous study of 146 patients with KSD recurrence, 100 (68.5%) were males;20 this aligns with the finding that KSD occured more frequently in men than in women. However, sex was not a significant risk factor in this study. This suggests that well-known lifestyle factors for KSD in male patients explain only a fraction of the observed risk, indicating that other factors, such as genetics or hormones, might also play a role.

Obesity is a significant risk factor for the development of KSD. Moyano et al21 revealed that 41.6% of men were overweight, with a BMI ranging from 25 to 30, and 9.6% had a BMI of 30 or greater. In the present study, 59.8% of the patients had an abnormally high BMI, supporting the notion that a high BMI is a risk factor for recurrent KSD. However, the exact mechanism through which obesity increases the risk of incident stone formation remains unclear. However, obesity, which has been suggested to be associated with insulin resistance, can alter urine composition. Insulin resistance may manifest in the kidneys as defects in ammonium production and the ability to excrete acid.22

Interestingly, diet was also associated with the recurrence of KSD. Contrary to Zhuo et al,15 who reported that a high dietary intake of vegetables was a protective factor against urolithiasis (OR 0.856), the present study found that routine vegetable consumption increased the risk of recurrent KSD. This might be caused by high oxalate-rich consumption, as dietary oxalate is mainly derived from plant-based foods. The oxalate-rich vegetables, such as spinach, soybeans, green beans, nuts, and sweet potatoes, are common in Indonesia.22 However, a certain kind or specific concentration amount of the consumed vegetables was not evaluated, and the retrospective design of study might lead to bias. In addition, these contrary findings might be promoted by combining other imbalanced diets, such as lean/fatty meat consumption and less fluid intake. Further research exploring specific kinds of vegetables and determining the cut-off value for consumption is still needed.

A fluid intake of less than 1.8 liter in 24 hours independently increased the odds of recurrent episodes of KSD by more than 2-fold. Our findings were consistent with those of a previous study, which indicated that high fluid intake decreased the risk of stone formation (OR 0.758). High fluid intake has been shown to increase urine volume and reduce the concentration of calcium oxalate in urine, consequently reducing the risk and recurrence rate of stone formation by 50% and 60–80%, respectively.15

In the present study, tea consumption more than 3 times/week also affected urinary stone recurrence. Another study also investigated whether black tea consumption increased the risk of stone formation due to increased oxalate intake.23 On the contrary, a study in Southern China found that strong tea preference might be a protective factor for urolithiasis (OR 0.793).18 This contrary finding might be caused by certain kinds of tea from different demographic regions and specific concentrations of tea consumption. The mechanism by which tea exerts protective effects against urolithiasis remains unclear and requires further investigation.

Other risk factors contributing to KSD recurrence, including stone composition, have also been observed. Few studies have examined the risk of recurrence with different stone compositions. The genetic basis of cystine stones reasonably leads to greater stone recurrence than most other stone compositions.24 Unfortunately, stone analysis is still generally unavailable in all regions of Indonesia and not routinely performed in all patients after PCNL. Therefore, this study did not include these factors in the risk factor analyses.

A limitation of this retrospective study was the possibility of recall bias. Further prospective studies are needed to confirm the causal relationships between these variables. Several variables such as dietary intake may have resulted in high individual subjectivity. The sample size was limited to 325 participants because many other patients who visited over 5 years ago had incomplete medical records, leading to insufficient data. This might have reduced the power of the study and increased the margin of error.

In conclusion, most patients with recurrent KSD were younger, overweight/obese, had less fluid intake, a family history of KSD, and DM. Modifying a healthy lifestyle and maintaining a balanced diet are important in preventing KSD recurrence. Further studies and prospective or clinical trials are needed for a better understanding, and a more specific exploration, such as the role of genetics and hormones, will become an area of interest.

 

 

 

 

 

 

 

1. Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y. Epidemiology of stone disease across the world. World J Urol. 2017;35(9):1301–20.
2. Edvardsson VO, Indridason OS, Haraldsson G, Kjartansson O, Palsson R. Temporal trends in the incidence of kidney stone disease. Kidney Int. 2013;83(1):146–52.
3. Liu Y, Chen Y, Liao B, Luo D, Wang K, Li H, et al. Epidemiology of urolithiasis in Asia. Asian J Urol. 2018;5(4):205–14.
4. Fan X, Kalim S, Ye W, Zhao S, Ma J, Nigwekar SU, et al. Urinary stone disease and cardiovascular disease risk in a rural Chinese population. Kidney Int Rep. 2017;2(6):1042–9.
5. Gambaro A, Lombardi G, Caletti C, Ribichini FL, Ferraro PM, Gambaro G. Nephrolithiasis: a red flag for cardiovascular risk. J Clin Med. 2022;11(19):5512.
6. Aune D, Mahamat-Saleh Y, Norat T, Riboli E. Body fatness, diabetes, physical activity and risk of kidney stones: a systematic review and meta-analysis of cohort studies. Eur J Epidemiol. 2018;33(11):1033–47.
7. Alelign T, Petros B. Kidney stone disease: an update on current concepts. Adv Urol. 2018;2018:3068365.
8. Torricelli FCM, Monga M. Staghorn renal stones: what the urologist needs to know. Int Braz J Urol. 2020;46(6):927–33.
9. Sorokin I, Pearle MS. Medical therapy for nephrolithiasis: state of the art. Asian J Urol. 2018;5(4):243–55.
10. Zisman AL. Effectiveness of treatment modalities on kidney stone recurrence. Clin J Am Soc Nephrol. 2017;12(10):1699–708.
11. Taguchi K, Cho SY, Ng AC, Usawachintachit M, Tan YK, Deng YL, et al. The Urological Association of Asia clinical guideline for urinary stone disease. Int J Urol. 2019;26(7):688–709.
12. Tae BS, Balpukov U, Cho SY, Jeong CW. Eleven-year cumulative incidence and estimated lifetime prevalence of urolithiasis in Korea: a national health insurance service-national sample cohort based study. J Korean Med Sci. 2018;33(2):e13.
13. D’Costa MR, Pais VM, Rule AD. Leave no stone unturned: defining recurrence in kidney stone formers. Curr Opin Nephrol Hypertens. 2019;28(2):148–53.
14. Rule AD, Lieske JC, Li X, Melton LJ 3rd, Krambeck AE, Bergstralh EJ. The ROKS nomogram for predicting a second symptomatic stone episode. J Am Soc Nephrol. 2014;25(12):2878–86.
15. Zhuo D, Li M, Cheng L, Zhang J, Huang H, Yao Y. A study of diet and lifestyle and the risk of urolithiasis in 1,519 patients in Southern China. Med Sci Monit. 2019;25:4217–24.
16. Zeng J, Wang S, Zhong L, Huang Z, Zeng Y, Zheng D, et al. A retrospective study of kidney stone recurrence in adults. J Clin Med Res. 2019;11(3):208–12.
17. Deutsch PG, Subramonian K. Conservative management of staghorn calculi: a single-centre experience. BJU Int. 2016;118(3):444–50.
18. Kohjimoto Y, Sasaki Y, Iguchi M, Matsumura N, Inagaki T, Hara I. Association of metabolic syndrome traits and severity of kidney stones: results from a nationwide survey on urolithiasis in Japan. Am J Kidney Dis. 2013;61(6):923–9.
19. Indrahadi D, Wardana A, Pierewan AC. The prevalence of diabetes mellitus and relationship with socioeconomic status in the Indonesian population. J Gizi Klinik Indones. 2021;17(3):103–12.
20. Wang W, Fan J, Huang G, Li J, Zhu X, Tian Y, et al. Prevalence of kidney stones in mainland China: a systematic review. Sci Rep. 2017;7:41630.
21. Moyano MF, Wendel GH, del Carmen Trujillo L, Orellano GO, Fuentes LB. Weight gain as a potential risk factor in kidney stones formers. Int Res J Nat Sci. 2015;3(4):54–65.
22. Siener R. Nutrition and kidney stone disease. Nutrients. 2021;13(6):1917.
23. Siener R, Hesse A. Effect of black tea consumption on urinary risk factors for kidney stone formation. Nutrients. 2021;13(12):4434.
24. Daudon M, Jungers P, Bazin D, Williams JC Jr. Recurrence rates of urinary calculi according to stone composition and morphology. Urolithiasis. 2018;46(5):459–70.

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