Metabolic syndrome (MetS) has become a growing global health concern, characterized by a cluster of metabolic abnormalities such as central obesity, insulin resistance, hypertension, hyperglycemia, and dyslipidemia. These abnormalities significantly increase the risk of chronic conditions including cardiovascular diseases, type 2 diabetes mellitus, and renal disorders (1) One notable renal complication associated with MetS is nephrolithiasis, commonly known as kidney stones, which involves the formation of calculi within the renal parenchyma or urinary tract. The association between MetS and nephrolithiasis has gained increasing attention in recent years due to shared pathophysiological mechanisms and their combined impact on clinical outcomes. With the global prevalence of MetS on the rise, understanding its link to nephrolithiasis has become an important focus in nephrology (2).

Nephrolithiasis is a widespread urological condition that causes considerable morbidity through recurrent pain, urinary tract infections, and impaired kidney function. While stone formation is influenced by genetic, environmental, and dietary factors (3), emerging evidence suggests that metabolic disturbances characteristic of MetS may play a central role in its development. Components of MetS such as insulin resistance, obesity, hypertension, and dyslipidemia are believed to contribute to significant alterations in urinary biochemistry. These alterations, including changes in the levels of calcium, oxalate, citrate, and uric acid, create a favorable environment for stone formation (4). A better understanding of these biochemical shifts is critical to developing effective prevention and management strategies, especially for patients with MetS.

Kidney stone formation is largely driven by the supersaturation of urine with lithogenic substances like calcium, oxalate, phosphate, and uric acid. In individuals with MetS, insulin resistance reduces renal ammonium production, resulting in lower urinary pH and a higher tendency to form uric acid stones (5). Obesity further contributes by increasing the urinary excretion of oxalate and uric acid, along with lowering urinary pH. Hypertension and dyslipidemia, commonly seen in MetS, also play a role by disrupting renal calcium handling and increasing oxidative stress and inflammation (6).

Biochemical parameters such as serum and urinary levels of calcium, oxalate, citrate, uric acid, and Ph are essential markers in understanding the link between MetS and nephrolithiasis (7). For instance, hypercalciuria, or elevated urinary calcium levels, is often observed in patients with kidney stones. This may result from increased intestinal calcium absorption, reduced renal calcium reabsorption, or enhanced bone resorption (8).

The presence of MetS may also influence treatment outcomes in patients with nephrolithiasis. Common treatment approaches include medical management, lifestyle modifications, and surgical interventions like extracorporeal shock wave lithotripsy (ESWL), ureteroscopy, and percutaneous nephrolithotomy (PCNL) (9). However, patients with MetS may respond differently to these treatments. Obesity and insulin resistance, for example, may reduce the efficacy of ESWL by affecting stone composition or the body's ability to eliminate stone fragments. Additionally, the recurrence rate of nephrolithiasis may be higher in individuals with MetS due to persistent metabolic derangements. Therefore, treating nephrolithiasis in this population requires a comprehensive strategy that addresses both stone formation and the underlying metabolic issues through targeted lifestyle and pharmacological interventions (10).

The relationship between metabolic syndrome and nephrolithiasis is a complex interplay involving metabolic, biochemical, and clinical dimensions (11). This study aims to investigate the association between MetS and the biochemical factors involved in nephrolithiasis, as well as how MetS influences treatment outcomes. By deepening our understanding of these relationships, the study aims to support the development of more effective prevention and management strategies, ultimately improving patient outcomes and reducing the public health burden of both conditions.

Study Design: This observational study was conducted in the Department of Urology at a tertiary care medical institute in Khammam. The objective was to investigate the association between metabolic syndrome and biochemical and urinary factors contributing to urolithiasis, as well as to evaluate treatment outcomes in affected individuals.

Study Duration and Population: The study was conducted over a period of 24 months, from September 2022 to August 2024 with 210 participants; a convenient sampling method was adopted for patient recruitment. All patients who presented to the Department of Urology during the study period and were diagnosed with urolithiasis were considered for inclusion.

Inclusion and Exclusion Criteria: All patients presenting with urolithiasis to the urology department were eligible for inclusion. Exclusion criteria included patients below 16 years of age, pregnant women, and individuals who were unwilling to participate or provide informed consent.

Ethical Approval and Consent: The study protocol, informed consent forms, and case report formats were approved by the Institutional Ethics Committee. Written informed consent was obtained from all participants. For illiterate individuals, consent was documented via left thumb impression in the presence of a witness.

Study Procedure: Each participant underwent clinical evaluation, including age, sex, symptom duration, and anthropometric measurements (height, weight, waist circumference). Blood pressure was measured per JNC VII guidelines. Fasting blood samples were collected to assess lipid profile, fasting glucose, serum calcium, magnesium, phosphorus, and uric acid. Urine analysis included pH, calcium, sodium, potassium, urea, creatinine, uric acid, citrate, and oxalate. Metabolic syndrome was diagnosed using ATP-III criteria.

Data Management and Analysis: Data were entered in MS Excel 2013 and analyzed using IBM SPSS version 25.0. Results were expressed as mean ± SD for continuous variables and percentages for categorical data. Unpaired t-test and Z-test were used for group comparisons, and Pearson’s correlation coefficient assessed associations. A p-value < 0.05 was considered statistically significant.

Table 3: Association of Metabolic Parameters with Metabolic Syndrome in Urolithiasis Cases

Table 3 shows a strong association between metabolic syndrome and key metabolic risk factors in urolithiasis patients. Elevated waist circumference, triglycerides, blood pressure, fasting blood sugar, and low HDL levels were significantly more common in the MetS group (all p = 0.000). These findings confirm that classic MetS traits are highly prevalent among stone formers with MetS and may contribute to increased stone risk and complexity.

Table 4: Correlation between MeS traits and Metabolic syndrome in urolithiasis

Table 4 presents the correlation between metabolic syndrome traits and the presence of MetS in urolithiasis patients. All components showed statistically significant correlations. Triglycerides (r = 0.630), systolic blood pressure (r = 0.541), fasting blood sugar (r = 0.514), diastolic blood pressure (r = 0.401), and waist circumference (r = 0.246) were positively correlated with MetS. HDL cholesterol showed a negative correlation (r = -0.269), indicating lower HDL levels in MetS patients. These findings reinforce the strong link between MetS components and stone risk.

Table 5: Relation between Blood investigations and Metabolic syndrome in urolithiasis

Among blood investigations, serum uric acid levels were significantly higher in patients with metabolic syndrome (6.1 ± 1.5 mg/dl) compared to those without (5.4 ± 1.4 mg/dl), with a p-value of 0.006 indicating statistical significance. In contrast, serum sodium, potassium, calcium, magnesium, phosphorus, and creatinine levels did not show significant differences between the two groups, with p-values indicating no significant associations (Table 5).

Table 6: Correlation between Blood investigations and Metabolic syndrome in urolithiasis

The correlation analysis shows that serum uric acid has a significant positive correlation with metabolic syndrome (correlation coefficient of 0.188, p = 0.006). Other blood investigations, including serum sodium, potassium, calcium, magnesium, phosphorus, and creatinine, did not show significant correlations with metabolic syndrome, as indicated by their p-values (Table 6).

Table 7: Correlation between Urinary parameters and Metabolic syndrome in urolithiasis

Table 7 presents the correlation between urinary parameters and metabolic syndrome in urolithiasis patients. Significant positive correlations were observed for urinary uric acid (r = 0.630, p = 0.000) and oxalate (r = 0.601, p = 0.000), indicating higher excretion of these lithogenic substances in MetS patients. Urinary citrate showed a significant negative correlation (r = -0.375, p = 0.000), suggesting reduced levels of this protective factor. Urinary pH showed no significant correlation with MetS (r = -0.047, p = 0.498). These findings reflect a pro-lithogenic urinary environment in individuals with metabolic syndrome.

Table 8: Association between Treatment outcome and Metabolic syndrome in urolithiasis

The stone-free rate (SFR) was 85% for patients with metabolic syndrome compared to 92% for those without, with a p-value of 0.15 indicating no significant difference. The complication rate was higher in patients with metabolic syndrome (23%) compared to those without (10%), with a p-value of 0.01, indicating a statistically significant difference. The need for additional procedures was also higher among patients with metabolic syndrome (30%) compared to those without (15%), with a p-value of 0.02, reflecting a significant difference. Hospital stay duration was longer for patients with metabolic syndrome (3.8 ± 1.1 days) compared to those without (2.5 ± 0.8 days), with a p-value of 0.001, indicating a statistically significant difference (Table 8).

This study evaluated the association between metabolic syndrome (MetS) and biochemical, urinary, and clinical parameters in urolithiasis patients, along with its effect on treatment outcomes. MetS, a constellation of obesity, dyslipidemia, hypertension, and hyperglycemia, is known to increase the risk of cardiovascular, diabetic, and renal disorders. Urolithiasis, a common and often recurrent condition, shares multiple pathophysiological links with MetS.

Among the 210 patients studied, 22.4% had MetS, aligning with previous findings (12, 13). Age was significantly associated with MetS prevalence (p < 0.001), similar to Chang et al (12) reported no age-related difference. Gender was not significantly associated with MetS (p = 0.607), in line with Hood et al (14).

Anthropometric factors such as weight, BMI, and waist circumference were significantly higher in MetS patients, supporting obesity's central role in MetS pathogenesis. These findings are consistent with Rams et al (15) and Chang et al (12). Dyslipidemia was evident with elevated triglycerides (p = 0.000) and reduced HDL levels (p = 0.000), showing strong correlations (r = 0.630 and r = -0.269 respectively), as reported by Hood et al (14).

MetS patients also showed significantly higher systolic and diastolic blood pressures and fasting blood sugar levels (all p = 0.000), consistent with insulin resistance, and similar to reports (14, 15). Serum uric acid was elevated (p = 0.006, r = 0.188), highlighting its contribution to uric acid stone formation, as supported by Hood et al (14).

Serum sodium, potassium, calcium, magnesium, phosphorus, and creatinine levels showed no significant difference between groups, echoing findings by Rendina et al (16). Urinary markers were more strongly associated with MetS. Urinary uric acid and oxalate were significantly higher (p < 0.001), while citrate was lower (p = 0.000), indicating a lithogenic profile (r = 0.630, r = 0.601, and r = -0.375 respectively). These findings are consistent with Rendina et al (16) and Hood et al (14). Urinary pH showed no significant variation (p = 0.498).

Though stone-free rates were similar between groups (85% vs. 92%, p = 0.15), MetS patients experienced more complications (23% vs. 10%, p = 0.01), required more additional procedures (30% vs. 15%, p = 0.02), and had longer hospital stays (3.8 vs. 2.5 days, p = 0.001). This suggests that MetS increases the clinical burden in urolithiasis management, likely due to systemic comorbidities.

Metabolic syndrome was present in a significant proportion of patients with urolithiasis and was associated with key metabolic disturbances such as higher BMI, waist circumference, blood pressure, triglycerides, fasting glucose, and serum uric acid, along with altered urinary parameters. Although stone clearance rates were similar, patients with MetS had more complications, longer hospital stays, and required additional procedures. These findings underscore the importance of early identification and management of MetS to improve outcomes in urolithiasis.

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