Cirrhosis is a major cause of morbidity and mortality worldwide and commonly progresses from compensated disease to clinically overt decompensation [1,2]. Renal dysfunction is among the most consequential complications of decompensated cirrhosis because it affects treatment tolerance, prognostic scores, transplant prioritization, and survival [2-4]. The underlying physiology includes splanchnic vasodilatation, reduced effective arterial blood volume, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, vasopressin release, and progressive renal vasoconstriction [3,4]. These changes produce avid sodium retention before advanced renal failure becomes clinically evident.

Serum creatinine remains central to renal assessment, but its interpretation in cirrhosis is difficult. Reduced hepatic creatine synthesis, sarcopenia, altered tubular handling, expanded extracellular volume, and analytical interference from hyperbilirubinemia may cause creatinine-based estimates to overstate glomerular filtration [5]. Contemporary consensus definitions appropriately emphasize dynamic changes in creatinine and urine output for acute kidney injury; nevertheless, a single admission value remains the most readily available measure in many resource-limited settings [4].

Urinary electrolyte indices provide complementary information about renal sodium handling. The spot urinary sodium-to-potassium ratio is obtained from a single voided sample and avoids the inconvenience and collection error of 24-hour urine measurement. Guidelines and observational studies have mainly evaluated the ratio as a surrogate of 24-hour natriuresis or as an indicator of diuretic response in cirrhotic ascites [6-10]. Other studies have reported associations between a low ratio, renal dysfunction, progression to acute kidney injury, and mortality [11,12]. However, data describing its graded relationship with renal dysfunction among Indian patients with decompensated cirrhosis remain limited.

Aims and Objectives

The primary objective was to determine the association between the spot urinary sodium-to-potassium ratio and serum creatinine in patients with decompensated cirrhosis. Secondary objectives were to compare the ratio across study-defined grades of renal dysfunction and to examine its associations with serum urea and serum sodium.

2.1 Study Design and Setting This hospital-based observational cross-sectional study was conducted in the Department of General Medicine at a tertiary care teaching hospital in Bengaluru, Karnataka, India, from April 2024 to October 2025. 2.2 Participants Adults aged 18 years or older with diagnosed decompensated cirrhosis who attended the outpatient department or were admitted to the medical wards and provided written informed consent were eligible. Patients with chronic kidney disease, sepsis, heart failure, postrenal obstruction, a history of nephrotoxic drug exposure, or diuretic use during the 24 hours preceding assessment were excluded. 2.3 Sample Size and Sampling The thesis protocol specified a sample size of 91 participants based on an expected proportion of 36.5%, 95% confidence, and 10% absolute precision. Eligible participants were enrolled until the required sample was achieved. 2.4 Clinical and Laboratory Assessment Clinical history and examination were completed within 24 hours of admission using a predefined proforma. A spot urine specimen was analyzed for sodium and potassium using an ion-selective electrode method. Serum creatinine and urea and serum sodium were measured using routine automated laboratory methods. Ultrasonography was used to confirm cirrhotic morphology and categorize liver disease as mild, moderate, or severe according to the study protocol. The urinary sodium-to-potassium ratio was the final ratio recorded in the locked thesis dataset. 2.5 Definitions Renal status was categorized a priori using serum creatinine as normal (<1.2 mg/dL), mild dysfunction (1.2-1.9 mg/dL), moderate dysfunction (2.0-2.9 mg/dL), or severe dysfunction (≥3.0 mg/dL). These strata were used to describe cross-sectional renal dysfunction and were not intended to substitute for consensus acute kidney injury criteria, which require a change from baseline and/or urine-output assessment [4,13]. No participant had serum creatinine ≥3.0 mg/dL. 2.6 Statistical Analysis Continuous variables were summarized as mean ± standard deviation and median with interquartile range; categorical variables were summarized as frequencies and percentages. The prespecified primary analysis used Pearson correlation between the urinary sodium-to-potassium ratio and serum creatinine. Spearman rank correlation was added as a sensitivity analysis. Because group variances were unequal (Levene p<0.001), ratios across renal strata were compared using the Kruskal-Wallis test, followed by pairwise Mann-Whitney U tests with Holm correction. An exploratory multivariable linear regression assessed the association of serum creatinine with the ratio after adjustment for age, sex, and ultrasonographic liver-disease severity; HC3 heteroscedasticity-robust standard errors were used. Tests were two-sided, and p<0.05 was considered statistically significant. Analyses were performed in Python 3.12 using SciPy 1.17.0. 2.7 Ethical Considerations Approval was obtained from the Institutional Ethics Committee before study commencement. Written informed consent was obtained from all participants, confidentiality was maintained, and study procedures conformed to the principles of the Declaration of Helsinki.

3.1  Participant Characteristics

All 91 participants had complete data for the variables included in this analysis. The mean age was 58.2 ± 8.4 years; 61 (67.0%) were men. Severe ultrasonographic liver disease was present in 66 (72.5%), moderate disease in 20 (22.0%), and mild disease in 5 (5.5%). The mean serum creatinine was 1.84 ± 0.56 mg/dL, and the mean urinary sodium-to-potassium ratio was 3.23 ± 0.91 (Table 1).

Table 1: Baseline Demographic, Clinical, and Laboratory Characteristics (N=91)

Data are presented as mean ± standard deviation or n (%).

3.2  Renal Dysfunction Categories

Thirteen participants (14.3%) had serum creatinine <1.2 mg/dL, 37 (40.7%) had mild dysfunction, and 41 (45.1%) had moderate dysfunction. The mean urinary sodium-to-potassium ratio decreased from 4.27 ± 1.16 in the normal group to 3.50 ± 0.69 in mild dysfunction and 2.66 ± 0.53 in moderate dysfunction (Table 2; Figure 2). The distributions differed significantly (Kruskal-Wallis H=33.99, p<0.001). Holm-adjusted pairwise p values were 0.041 for normal versus mild, <0.001 for normal versus moderate, and <0.001 for mild versus moderate.

Table 2: Spot Urinary Sodium-to-Potassium Ratio Across Renal Dysfunction Categories

Kruskal-Wallis H=33.99, p<0.001. Holm-adjusted pairwise p values: normal versus mild, p=0.041; normal versus moderate, p<0.001; mild versus moderate, p<0.001. IQR, interquartile range; SD, standard deviation.

3.3  Correlation Analyses

The urinary sodium-to-potassium ratio showed a strong inverse linear correlation with serum creatinine (r=-0.776, p<0.001; Figure 1) and a similar rank correlation (ρ=-0.815, p<0.001). It also correlated inversely with serum urea (r=-0.607, p<0.001). The Pearson correlation with serum sodium was weak and not significant (r=0.115, p=0.279), although the Spearman association was weakly positive (ρ=0.273, p=0.009) (Table 3).

Table 3: Correlations of the Spot Urinary Sodium-to-Potassium Ratio With Renal Function Tests

Figure 1: Association between the spot urinary sodium-to-potassium ratio and serum creatinine. Points represent individual participants; the solid line is the ordinary least-squares regression line and the shaded area is the 95% confidence band.

Figure 2: Distribution of the spot urinary sodium-to-potassium ratio across study-defined renal dysfunction categories. Boxes show the interquartile range, central lines show medians, whiskers show 1.5 times the interquartile range, and points represent individual participants.

3.4  Adjusted Analysis

In multivariable analysis, serum creatinine remained independently associated with the urinary sodium-to-potassium ratio after adjustment for age, sex, and ultrasonographic liver severity. Each 1 mg/dL increase in serum creatinine corresponded to a 1.175-unit lower ratio (95% confidence interval, -1.439 to -0.912; p<0.001). Age, sex, and ultrasonographic severity were not independently associated with the ratio. The model explained 62.6% of observed variance (adjusted R²=0.604) (Table 4).

Table 4: Multivariable Linear Regression for the Spot Urinary Sodium-to-Potassium Ratio

Dependent variable: spot urinary sodium-to-potassium ratio. Reference categories: female sex and mild ultrasonographic liver severity. HC3 heteroscedasticity-robust standard errors were used. R²=0.626; adjusted R²=0.604. CI, confidence interval; SE, standard error.

4.1 Principal Findings This study found a strong inverse association between the spot urinary sodium-to-potassium ratio and renal dysfunction in decompensated cirrhosis. The result was consistent across Pearson and Spearman methods, followed a graded pattern across renal-function strata, and remained robust after adjustment for age, sex, and ultrasonographic liver severity. The parallel inverse association with serum urea and the absence of a comparable linear association with serum sodium support the interpretation that the ratio reflects renal sodium-handling physiology rather than merely circulating sodium concentration. 4.2 Comparison With Previous Evidence Cholongitas et al. reported that a random urinary sodium-to-potassium ratio below 1 was associated with impaired renal function and short-term mortality in decompensated cirrhosis [11]. Morais Rateke et al. subsequently found that a lower admission ratio was associated with progression to acute kidney injury and 30-day mortality [12]. The present study extends this evidence by demonstrating a continuous and graded cross-sectional association across serum-creatinine strata. However, its observed ratio range was 1.62-6.14, so it cannot validate the previously proposed threshold below 1 or establish an outcome-prediction cutoff. 4.3 Relation to Natriuresis Studies The spot ratio has also been studied as a practical substitute for 24-hour urinary sodium measurement. Park et al. found that a random ratio above 1.25 could identify adequate natriuresis in cirrhotic ascites [8], while Lee et al. confirmed that the ratio reflects 24-hour urinary sodium but noted more modest diagnostic discrimination than some earlier studies [9]. Contemporary ascites guidance recognizes the practical value of random urinary sodium-to-potassium assessment while acknowledging variable specificity [6,7]. Our analysis addressed a different clinical question: its association with concurrent renal dysfunction rather than dietary adherence or diuretic response. 4.4 Pathophysiological Interpretation Progressive portal hypertension and splanchnic vasodilatation reduce effective arterial filling and activate sodium-retaining neurohumoral pathways [3,4]. Increased proximal and distal sodium reabsorption lowers urinary sodium relative to potassium, while worsening circulatory and renal dysfunction raises serum creatinine and urea. A declining urinary sodium-to-potassium ratio is therefore biologically coherent as renal dysfunction advances. Potassium in the denominator may partially contextualize urinary concentration and aldosterone-mediated distal exchange, but dietary intake, sampling time, acid-base status, and medications can still influence the ratio. 4.5 Clinical Implications The ratio requires only a spot urine sodium and potassium measurement and is therefore attractive where cystatin C, measured glomerular filtration rate, or novel injury biomarkers are unavailable. In practice, it could serve as an adjunctive signal prompting closer review of volume status, nephrotoxin exposure, infection, urine output, creatinine trajectory, and structural kidney injury. It should not be interpreted as a replacement for serial creatinine measurements or current consensus criteria for acute kidney injury and hepatorenal syndrome [4,13]. 4.6 Strengths and Limitations Strengths include a complete dataset of 91 participants, urine sampling early in admission, exclusion of recent diuretic and nephrotoxic exposure, and concordant parametric, rank-based, group-wise, and adjusted analyses. Several limitations require emphasis. The cross-sectional design cannot establish temporal direction, predict acute kidney injury, or assess mortality. Serum-creatinine strata were study-defined rather than consensus acute kidney injury stages, and creatinine itself is imperfect in cirrhosis [5]. There was no baseline creatinine trajectory, timed urinary sodium, measured glomerular filtration rate, cystatin C, albuminuria, urinary sediment, or tubular-injury biomarker. Liver severity was based on ultrasonography rather than Child-Pugh or Model for End-Stage Liver Disease scores. Etiology, dietary sodium, and outcome data were unavailable for adjusted modeling. The mild liver-disease group was small, no participant had creatinine ≥3.0 mg/dL, and the single-center design limits generalizability. Residual confounding and within-day variation in spot urine electrolytes remain possible.

Among adults with decompensated cirrhosis, a lower spot urinary sodium-to-potassium ratio was strongly associated with higher serum creatinine, higher serum urea, and greater cross-sectional renal dysfunction. The ratio is inexpensive and readily obtainable and may complement conventional renal assessment in resource-constrained settings. Prospective studies incorporating serial creatinine, urine output, validated liver-severity scores, and clinical outcomes are needed before prognostic thresholds or treatment decisions can be based on this index.

Acknowledgments

The authors thank the participants and the clinical and laboratory staff who supported data collection.

Author Contributions

M.R.K.: conception and design, data acquisition, data curation, analysis and interpretation, and drafting of the manuscript. S.R.: supervision, methodology, interpretation of findings, and critical revision of the manuscript. Both authors approved the final manuscript and accept accountability for the work.

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

The authors declare no funding for this research.

Data Availability

De-identified data supporting the findings are available from the corresponding author on reasonable request, subject to institutional and ethical requirements.