Hypertension is a major modifiable determinant of cardiovascular disease, stroke, heart failure, and kidney dysfunction. Contemporary hypertension guidelines emphasize accurate blood pressure classification, global cardiovascular risk assessment, and identification of hypertension-mediated organ damage as central components of patient evaluation.1 Despite improvements in diagnosis and treatment, substantial residual vascular and renal risk remains, particularly in individuals with metabolic abnormalities. Serum uric acid, the end product of purine metabolism in humans, has gained attention as one such metabolic factor because elevated concentrations frequently coexist with hypertension, obesity, dyslipidaemia, diabetes, and impaired kidney function.2 Uric acid has traditionally been considered primarily in relation to gout and nephrolithiasis. However, epidemiological and mechanistic evidence has expanded its relevance to cardiovascular, metabolic, and renal disorders.3 Proposed biological mechanisms linking hyperuricaemia with elevated blood pressure include reduced endothelial nitric oxide availability, oxidative stress, vascular smooth-muscle proliferation, renal microvascular injury, and activation of the renin-angiotensin-aldosterone system. These processes can increase vascular resistance and promote sodium sensitivity. Meta-analyses of observational studies have demonstrated that higher serum uric acid is associated with an increased risk of incident hypertension, with evidence of a dose-response relationship across uric acid concentrations.4,5 Longitudinal population studies have also shown that serum uric acid predicts blood-pressure progression and future hypertension. In the Framingham cohort, higher uric acid levels were related to subsequent blood-pressure tracking and hypertension incidence.6 Similar observations were reported in the Atherosclerosis Risk in Communities cohort, in which serum uric acid predicted incident hypertension across a large biethnic population.7 Beyond blood pressure, elevated uric acid has been associated with hypertension-mediated target-organ abnormalities, including cardiac, vascular, and renal damage.8 These observations suggest that serum uric acid can provide information beyond a single blood-pressure measurement and could reflect the broader cardiorenal metabolic milieu. The relationship between uric acid and renal function is particularly complex because the kidney is central to urate handling, while declining filtration itself contributes to urate accumulation. Hyperuricaemia has therefore been viewed both as a consequence of impaired renal excretion and as a potential contributor to renal vascular and tubulointerstitial injury.9 Observational evidence has linked elevated uric acid with incident chronic kidney dysfunction, although causal interpretation remains debated.10 More recent reviews continue to describe close epidemiological links among hyperuricaemia, kidney dysfunction, atherosclerotic disease, and hypertension.11,12 Indian data have likewise demonstrated a significant relationship between serum uric acid and hypertension in metabolically vulnerable adults.13 Evaluating serum uric acid together with serum creatinine and estimated glomerular filtration rate (eGFR) can consequently provide a clinically relevant picture of this bidirectional relationship. The present study was undertaken to assess this association in adults receiving care at a tertiary-care centre in south India. The objectives were to determine serum uric acid levels across different grades of hypertension, estimate the prevalence of hyperuricaemia, compare renal-function parameters across hypertension-severity categories, and evaluate correlations of serum uric acid with systolic blood pressure, diastolic blood pressure, serum creatinine, and eGFR.

Study design and setting This prospective observational study was conducted at, Konaseema Institute of Medical Sciences and Research Foundation , Amalapuram, Andhra Pradesh, India, from April 2025 to May 2026. Adults with hypertension presenting to participating clinical services were screened prospectively. The study examined the relationship of serum uric acid with blood-pressure severity and renal-function indices without modifying routine clinical management. Study population and eligibility Adults aged 18 years or older with established or newly identified hypertension who provided written informed consent were eligible. Patients with acute kidney injury, dialysis dependence, known gout receiving urate-lowering therapy, active malignancy, severe acute infection, pregnancy, or other conditions likely to substantially alter serum uric acid were excluded. Consecutive eligible participants were enrolled until the target was reached. Demographic details, smoking status, diabetes mellitus, dyslipidaemia, anthropometry, and relevant clinical information were recorded using a structured form. Sample size For correlation analysis, assuming an anticipated correlation coefficient of 0.30, a two-sided alpha of 0.05, and 80% power, the minimum required sample was approximately 85 participants using Fisher's z transformation. Allowing about 15% for incomplete or non-evaluable observations, the target sample was increased to 100 participants. Blood pressure and hypertension severity Blood pressure was measured with an appropriate cuff after at least 5 minutes of seated rest. Repeated readings were obtained and the average of the final two readings was analyzed. Hypertension was graded as Grade 1 (140-159/90-99 mmHg), Grade 2 (160-179/100-109 mmHg), and Grade 3 (at least 180/110 mmHg or higher); when systolic and diastolic values differed in category, the higher grade was assigned.1 Laboratory assessment and definitions Venous samples were analyzed in the institutional central laboratory using calibrated automated chemistry methods. Serum uric acid and creatinine were recorded in mg/dL. Hyperuricaemia was defined as serum uric acid greater than 7.0 mg/dL in men or greater than 6.0 mg/dL in women.3 eGFR was calculated using the 2021 CKD-EPI creatinine equation without a race coefficient.14 An eGFR below 60 mL/min/1.73 m² was categorized as reduced eGFR; a single measurement was not considered sufficient to diagnose chronic kidney disease. Statistical analysis Continuous variables were summarized as mean ± standard deviation and categorical variables as frequency and percentage. One-way analysis of variance compared continuous parameters across hypertension grades. Independent-samples testing compared renal parameters by uric-acid status. Categorical variables were evaluated using the chi-square test or an exact test when appropriate. Pearson correlation assessed associations of serum uric acid with systolic blood pressure, diastolic blood pressure, creatinine, and eGFR. A two-sided p-value below 0.05 was considered statistically significant. Ethical considerations The study was approved by Institutional Ethics committee, Konaseema Institute of Medical Sciences and Research Foundation , Amalapuram, Andhra Pradesh, India, before starting the study. Written informed consent was obtained from all participants, and confidentiality was maintained.

A total of 100 adults with hypertension were included in the final analysis. The mean age was 54.7 ± 11.6 years, with an age range of 30-78 years. Fifty-eight participants (58.0%) were male and 42 (42.0%) were female. The mean BMI was 26.8 ± 4.1 kg/m². Diabetes mellitus was present in 32 (32.0%), dyslipidaemia in 21 (21.0%), and current smoking in 18 (18.0%) participants. The mean systolic and diastolic blood pressures were 155.8 ± 18.6 and 94.1 ± 10.8 mmHg, respectively. Mean serum uric acid was 6.18 ± 1.63 mg/dL, mean serum creatinine was 1.06 ± 0.34 mg/dL, and mean eGFR was 78.6 ± 20.4 mL/min/1.73 m² (Table 1). Table 1. Demographic and clinical characteristics of the study participants (n=100) Characteristic Value Age, years, mean ± SD 54.7 ± 11.6 Age range, years 30-78 Male sex, n (%) 58 (58.0) Female sex, n (%) 42 (42.0) BMI, kg/m², mean ± SD 26.8 ± 4.1 Diabetes mellitus, n (%) 32 (32.0) Dyslipidaemia, n (%) 21 (21.0) Current smokers, n (%) 18 (18.0) Systolic BP, mmHg, mean ± SD 155.8 ± 18.6 Diastolic BP, mmHg, mean ± SD 94.1 ± 10.8 Serum uric acid, mg/dL, mean ± SD 6.18 ± 1.63 Serum creatinine, mg/dL, mean ± SD 1.06 ± 0.34 eGFR, mL/min/1.73 m², mean ± SD 78.6 ± 20.4 Note. BMI = body mass index; BP = blood pressure; eGFR = estimated glomerular filtration rate; SD = standard deviation. According to hypertension severity, 36 (36.0%) participants had Grade 1, 34 (34.0%) had Grade 2, and 30 (30.0%) had Grade 3 hypertension. Mean serum uric acid increased progressively from 5.12 ± 1.19 mg/dL in Grade 1 to 6.18 ± 1.33 mg/dL in Grade 2 and 7.45 ± 1.55 mg/dL in Grade 3 hypertension (p<0.001). Serum creatinine rose across the same categories, whereas eGFR declined from 92.1 ± 16.4 to 78.9 ± 16.8 and 62.1 ± 18.2 mL/min/1.73 m², respectively (p<0.001). Hyperuricaemia was present in 6 (16.7%), 13 (38.2%), and 20 (66.7%) participants across Grades 1, 2, and 3, respectively (p<0.001). Reduced eGFR was also increasingly frequent with greater hypertension severity (Table 2). Table 2. Serum uric acid and renal function according to severity of hypertension Parameter Grade 1 (n=36) Grade 2 (n=34) Grade 3 (n=30) p-value Serum uric acid, mg/dL 5.12 ± 1.19 6.18 ± 1.33 7.45 ± 1.55 <0.001 Serum creatinine, mg/dL 0.87 ± 0.19 1.04 ± 0.25 1.31 ± 0.41 <0.001 eGFR, mL/min/1.73 m² 92.1 ± 16.4 78.9 ± 16.8 62.1 ± 18.2 <0.001 Hyperuricaemia, n (%) 6 (16.7) 13 (38.2) 20 (66.7) <0.001 eGFR <60 mL/min/1.73 m², n (%) 1 (2.8) 4 (11.8) 9 (30.0) 0.003 Note. Values are mean ± SD or n (%). Continuous variables were compared using one-way analysis of variance; categorical variables were compared using chi-square or exact testing as appropriate. Overall, hyperuricaemia was identified in 39 (39.0%) participants. Those with hyperuricaemia had a higher mean serum creatinine than participants with normal serum uric acid (1.27 ± 0.37 vs 0.93 ± 0.23 mg/dL; p<0.001). Mean eGFR was correspondingly lower in the hyperuricaemia group (66.4 ± 18.9 vs 86.4 ± 17.2 mL/min/1.73 m²; p<0.001). Reduced eGFR below 60 mL/min/1.73 m² was present in 11 (28.2%) participants with hyperuricaemia compared with 3 (4.9%) participants with normal serum uric acid (p=0.001), demonstrating a significant association between uric-acid status and renal-function indices (Table 3). Table 3. Renal-function parameters according to serum uric acid status Parameter Normal serum uric acid (n=61) Hyperuricaemia (n=39) p-value Serum creatinine, mg/dL 0.93 ± 0.23 1.27 ± 0.37 <0.001 eGFR, mL/min/1.73 m² 86.4 ± 17.2 66.4 ± 18.9 <0.001 eGFR <60 mL/min/1.73 m², n (%) 3 (4.9) 11 (28.2) 0.001 Correlation analysis further demonstrated significant relationships between serum uric acid, blood pressure, and renal parameters. Serum uric acid showed a moderate positive correlation with systolic blood pressure (r=0.52, p<0.001) and a weaker positive correlation with diastolic blood pressure (r=0.39, p<0.001). A positive correlation was also observed with serum creatinine (r=0.46, p<0.001). In contrast, serum uric acid was inversely correlated with eGFR (r=-0.49, p<0.001), indicating that increasing uric acid concentrations were associated with lower estimated filtration (Table 4). Table 4. Correlation of serum uric acid with blood pressure and renal-function parameters Variable Correlation coefficient (r) p-value Systolic blood pressure 0.52 <0.001 Diastolic blood pressure 0.39 <0.001 Serum creatinine 0.46 <0.001 eGFR -0.49 <0.001 Note. Pearson correlation analysis was used. Positive coefficients indicate direct associations and negative coefficients indicate inverse associations. Taken together, the results showed a clear graded association: serum uric acid increased from 5.12 mg/dL in Grade 1 to 7.45 mg/dL in Grade 3 hypertension, while eGFR decreased from 92.1 to 62.1 mL/min/1.73 m². Higher serum uric acid was therefore associated with greater hypertension severity, higher creatinine, and poorer estimated renal filtration in this study population.

The present study demonstrated a graded relationship between serum uric acid and hypertension severity in adults with hypertension. Mean serum uric acid increased from 5.12 mg/dL in Grade 1 hypertension to 7.45 mg/dL in Grade 3 hypertension, while the prevalence of hyperuricaemia rose from 16.7% to 66.7%. Serum uric acid also showed positive correlations with systolic and diastolic blood pressure. These findings are consistent with earlier longitudinal and pooled evidence showing that higher uric acid concentrations track with blood-pressure progression and increased risk of hypertension.4-7 The strength of the association with systolic blood pressure in the present study further supports the concept that uric acid reflects adverse vascular and metabolic states accompanying more severe hypertension. Several mechanisms can explain this association. Experimental and clinical literature indicates that elevated uric acid can be linked with endothelial dysfunction, oxidative stress, reduced nitric oxide bioavailability, vascular smooth-muscle activation, renal arteriolar changes, and stimulation of the renin-angiotensin system.2,9,12 These pathways can increase systemic vascular resistance and impair renal sodium handling. Nevertheless, observational association does not establish that uric acid is an independent causal driver in every patient. Serum uric acid is influenced by renal clearance, dietary purine intake, body composition, insulin resistance, alcohol consumption, diuretics, and other medications; therefore, its interpretation should remain integrated with the overall clinical profile. A second important finding was the association between serum uric acid and renal function. Participants with hyperuricaemia had higher mean creatinine and substantially lower mean eGFR than those with normal uric acid. Serum uric acid correlated positively with creatinine and inversely with eGFR. This pattern is biologically plausible because renal excretion is a major pathway of urate elimination, so declining filtration promotes urate retention. At the same time, epidemiological evidence has associated hyperuricaemia with subsequent renal dysfunction and kidney-disease progression.10,11 The current results therefore illustrate the clinically relevant bidirectional relationship between urate metabolism and renal function rather than proving a single direction of causation. The observed increase in reduced eGFR across hypertension grades also suggests clustering of vascular and renal risk. Viazzi et al. reported higher uric acid in hypertensive patients with target-organ abnormalities, supporting its value as a marker of more advanced cardiovascular involvement.8 Recent Indian evidence has similarly shown a significant relationship between serum uric acid and hypertension, reinforcing the relevance of assessing this biomarker in regional populations.13 In routine practice, serum uric acid is inexpensive and widely available, and its interpretation alongside creatinine, eGFR, metabolic comorbidities, and blood-pressure severity could help identify hypertensive adults who warrant closer cardiorenal evaluation. However, treatment decisions should not be based on uric acid concentration alone, and prospective outcome studies are required to determine whether urate-directed strategies improve clinically meaningful renal or cardiovascular endpoints in asymptomatic hyperuricaemia. LIMITATIONS This study has several limitations. The single-centre design and modest sample size restrict external generalizability. Serum uric acid and renal function were assessed at the study evaluation, preventing confirmation of temporal or causal relationships. Residual confounding from diet, antihypertensive drugs, diuretic exposure, alcohol intake, and metabolic factors remains possible. Repeated eGFR measurements, urinary albumin assessment, and ambulatory blood-pressure monitoring were not incorporated.

In this prospective observational study of 100 adults with hypertension, higher serum uric acid levels were significantly associated with increasing hypertension severity and poorer renal-function indices. Participants with Grade 3 hypertension had the highest serum uric acid and creatinine levels and the lowest eGFR, while hyperuricaemia was substantially more frequent with advancing hypertension grade. Serum uric acid correlated positively with systolic blood pressure, diastolic blood pressure, and serum creatinine and inversely with eGFR. These findings support serum uric acid as a practical adjunctive marker of cardiorenal risk in hypertensive adults. Its interpretation should complement comprehensive blood-pressure assessment, metabolic evaluation, and renal-function monitoring rather than serve as an isolated therapeutic target

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