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Microalbuminuria as a Prognostic Marker of Sepsis
Rutika D. Pathakjee, MBBS¹
Janakkumar R. Khambholja, MD, DNB (General Medicine)¹
Jaydev S. Mod, MD¹
Dhwani H. Shah, MD¹
¹Department of General Medicine, Smt. N.H.L. Municipal Medical College and S.V.P.I.M.S.R. Hospital, Ahmedabad – 380006, Gujarat, India
Corresponding Author:
Dr. Rutika D. Pathakjee
Department of General Medicine, Smt. N.H.L. Municipal Medical College and S.V.P.I.M.S.R. Hospital, Ahmedabad – 380006, Gujarat, India
Email: [Please insert]
Funding: None
Conflicts of Interest: None declared
Ethical Approval: Institutional Ethics Committee (as per thesis protocol); informed consent obtained from all participants.
Word count: ~2,800 (excluding tables and references)
Abstract word count: 250
Abstract
Background: Sepsis remains a leading cause of ICU mortality worldwide. Endothelial dysfunction and capillary leak — hallmarks of the septic response — are reflected early in urinary albumin excretion. This study evaluated urinary albumin-creatinine ratio (UACR) measured at 6 and 24 hours of ICU admission as a prognostic marker in sepsis, and compared its discriminatory performance with APACHE II, NEWS, and SOFA scores.
Methods: A prospective observational study enrolled 100 consecutive patients aged >12 years admitted to the medical ICU with sepsis (SOFA ≥2, Sepsis-3 criteria) between January 2023 and July 2024. Patients with anuria, pre-existing chronic kidney disease (CKD), pregnancy, menstruation, or macroscopic hematuria were excluded. Spot urine samples for UACR were collected within 6 hours (UACR1) and at 24 hours (UACR2) of admission. The change in UACR (ΔUACR = UACR2 − UACR1) was calculated. APACHE II and NEWS scores were computed from first-24-hour data. The primary outcome was in-hospital mortality. Statistical analysis used the Mann-Whitney U test, chi-square test, and receiver operating characteristic (ROC) curve analysis (SPSS version 26.0; significance threshold p<0.05).
Results: Mean age was 54.5 ± 18.3 years; 53% were male. In-hospital mortality was 45%. Lower respiratory tract infection was the most common sepsis source (35%). UACR1, UACR2, and ΔUACR were all significantly higher in non-survivors (median UACR1: 155 vs 58; UACR2: 222 vs 88; ΔUACR: 45 vs 20; all p<0.001). APACHE II (median 22 vs 14), NEWS (7 vs 4), and SOFA scores were also significantly higher in non-survivors (p<0.001, p<0.001, and p=0.02, respectively). ROC analysis demonstrated AUC of 0.860 for APACHE II, 0.775 for UACR2, 0.753 for UACR1, 0.703 for ΔUACR, and 0.673 for NEWS.
Conclusion: Serial UACR measurement within 6 and 24 hours of ICU admission is a simple, inexpensive, and reliable early prognostic marker in sepsis, with discriminatory performance comparable to established scoring systems. Serial UACR monitoring may guide risk stratification and therapeutic decision-making, particularly in resource-limited settings.
Keywords: Sepsis; microalbuminuria; urinary albumin-creatinine ratio; APACHE II; NEWS score; prognosis; endothelial dysfunction
1. Introduction
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and continues to be a major driver of ICU mortality globally, despite advances in antimicrobial therapy and critical care.[1] The pathophysiology involves systemic inflammatory activation, endothelial injury, and microvascular leak, culminating in multi-organ dysfunction. Early identification of patients at high risk of deterioration remains a clinical priority, as timely intervention is the principal determinant of outcome.
Conventional prognostic tools — the Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and National Early Warning Score (NEWS) — are validated and widely used. However, they require aggregation of multiple physiological variables over 24 hours, are labour-intensive, and may not be feasible in resource-limited settings.[2,3]
Microalbuminuria, defined as urinary albumin excretion of 30–300 mg/day (or an equivalent spot urinary albumin-creatinine ratio, UACR), is an established surrogate marker of generalised endothelial dysfunction.[4] In sepsis, systemic inflammatory mediators rapidly increase glomerular capillary permeability, causing early and measurable albumin leak into urine — often within hours of the insult, well before clinical deterioration becomes apparent.[5] Spot urine UACR requires only a single urine sample and is inexpensive, making it an attractive candidate for early bedside risk stratification.
Several prior studies have reported elevated microalbuminuria in critically ill patients and its association with adverse outcomes.[6–8] However, data from the Indian subcontinent remain limited. This study was therefore designed to prospectively evaluate serial UACR measurements (at 6 and 24 hours) as prognostic markers in a medical ICU population with sepsis, and to compare their performance with established scoring systems.
2. Aims and Objectives
- To evaluate the correlation between the degree of microalbuminuria and the severity of sepsis.
- To assess the ability of microalbuminuria to predict in-hospital mortality in sepsis.
- To compare the prognostic value of UACR with APACHE II, NEWS, and SOFA scores.
3. Materials and Methods
3.1 Study Design and Setting
This was a prospective observational study conducted in the Medical ICU of Smt. N.H.L. Municipal Medical College and S.V.P.I.M.S.R. Hospital, Ahmedabad — a tertiary care government centre. The study period was January 2023 to July 2024.
3.2 Participants
Inclusion criteria: Patients aged >12 years admitted to the medical ICU with sepsis, defined per Sepsis-3 as suspected or documented infection with acute SOFA score increase ≥2 points.[1]
Exclusion criteria: Anuria; pre-existing CKD (currently on renal replacement therapy, estimated GFR <30 mL/min/1.73 m², or ultrasound features of chronic parenchymal damage); active menstruation or pregnancy; macroscopic hematuria due to renal or post-renal causes.
A consecutive sample of 100 patients meeting criteria was enrolled.
3.3 Data Collection
On admission, demographic data (age, sex), presenting complaints, comorbidities (hypertension, diabetes mellitus, etc.), substance use history, source of sepsis, and requirement for organ support (mechanical ventilation, vasopressors) were recorded.
3.4 UACR Measurement
Spot urine samples were collected at two time points: within 6 hours of ICU admission (UACR1) and at 24 hours (UACR2). Urinary microalbumin was assayed by the immunoturbidimetric method and urinary creatinine by the modified kinetic Jaffe reaction. Results were expressed as mg/g creatinine. The change in UACR (ΔUACR = UACR2 − UACR1) was calculated as a surrogate of temporal trend.
3.5 Severity Scores
APACHE II and NEWS scores were computed from data collected in the first 24 hours of admission by the attending clinical team, blinded to UACR results. SOFA score at admission was used for enrolment confirmation and outcome comparison.
3.6 Outcome
The primary outcome was in-hospital mortality (death vs. recovery to discharge). All patients were followed until hospital outcome.
3.7 Statistical Analysis
Data were analysed using IBM SPSS Statistics version 26.0. Continuous variables with non-normal distribution are reported as median (interquartile range, IQR). Between-group comparisons used the Mann-Whitney U test for continuous data and the chi-square test for categorical data. Receiver operating characteristic (ROC) curves were constructed for each parameter; areas under the curve (AUC) with 95% confidence intervals were computed. A two-tailed p-value <0.05 was considered statistically significant.
4. Results
4.1 Demographic and Clinical Profile
One hundred patients were enrolled. Mean age was 54.5 ± 18.3 years, with the 51–60-year age group most frequently represented. Males constituted 53% of the cohort. Fifty percent of patients had no pre-existing comorbidity; hypertension was the most common comorbidity (35%), and 12% had multiple comorbidities. Regarding substance use, 76% reported none; bidi smoking was reported in 10%, tobacco use in 7%, and alcohol in 6%.
The most frequent sepsis source was lower respiratory tract infection (35%), followed by soft tissue infection (15%), acute gastroenteritis (12%), and meningitis (11%). Mechanical ventilation was required in 41% and vasopressor/inotropic support in 38% of patients. Overall in-hospital mortality was 45% (n=45 deaths; n=55 recovered).
4.2 UACR and Clinical Outcome
UACR1, UACR2, and ΔUACR were all significantly elevated in non-survivors compared with survivors (Table 1).
Table 1. UACR parameters by outcome
| Parameter | Survivors (n=55) Median (IQR) | Non-survivors (n=45) Median (IQR) | Mean difference | p-value |
|---|---|---|---|---|
| UACR1 (mg/g) | 58 (30–110) | 155 (72–230) | 126.53 | <0.001 |
| UACR2 (mg/g) | 88 (55–118) | 222 (106.5–325.5) | 175.65 | <0.001 |
| ΔUACR (mg/g) | 20 (4–35) | 45 (17–96) | 59.75 | <0.001 |
UACR1 = UACR within 6 hours; UACR2 = UACR at 24 hours; ΔUACR = UACR2 − UACR1.
4.3 Severity Scores and Outcome
APACHE II score was significantly higher in non-survivors (median 22 vs 14; p<0.001), as was NEWS score (median 7 vs 4; p<0.001). SOFA score also differed significantly (p=0.02). Need for inotropic support was associated with significantly higher mortality (p=0.04).
4.4 ROC Curve Analysis
ROC analysis for prediction of in-hospital mortality yielded the following AUC values (Table 2):
Table 2. ROC curve analysis — AUC for in-hospital mortality prediction
| Parameter | AUC |
|---|---|
| APACHE II | 0.860 |
| UACR2 (24-hour) | 0.775 |
| UACR1 (6-hour) | 0.753 |
| ΔUACR | 0.703 |
| NEWS | 0.673 |
APACHE II demonstrated the highest discriminatory performance. UACR2 achieved an AUC of 0.775, approaching APACHE II, and outperformed NEWS. Both UACR1 and UACR2 showed good discriminatory power.
5. Discussion
In sepsis, systemic endothelial activation triggers rapid increases in glomerular capillary permeability, causing albumin leak into urine that is measurable within hours of onset — making microalbuminuria a mechanistically rational early biomarker.[4,5] Our study confirms that both UACR1 (measured within 6 hours) and UACR2 (at 24 hours) are significantly elevated in non-survivors, consistent with findings from Gosling et al., Thoreveska et al., and Basu et al.[6–8]
The observed mortality of 45% is consistent with rates reported in comparable Indian ICU cohorts. Lower respiratory tract infection was the predominant sepsis source, reflecting the regional epidemiological pattern.
APACHE II retained the highest AUC (0.860) for mortality prediction. However, UACR2 (AUC 0.775) performed comparably and surpassed NEWS (AUC 0.673) — a clinically important finding, given that UACR requires only a single spot urine sample rather than aggregation of multiple physiological variables over 24 hours. The directional ΔUACR — reflecting a rising or high-and-sustained albuminuria over the first 24 hours — also independently discriminated outcome (AUC 0.703), suggesting that serial monitoring captures prognostic information beyond any single time-point measurement and may serve as a proxy for persistent systemic inflammation and ongoing endothelial injury.
From a practical standpoint, UACR assay is low-cost, widely available in district and secondary care hospitals in India, and does not require specialised laboratory infrastructure. These characteristics make it particularly attractive for risk stratification in resource-limited settings where point-of-care lactate, PCT, or continuous monitoring may not be available.
Limitations: This was a single-centre study with a sample size of 100 patients, limiting generalisability. Patients with primary renal involvement (septic AKI with baseline proteinuria, CKD, pyelonephritis, UTI) were excluded, so findings cannot be extrapolated to these groups. The study did not evaluate 28-day or 90-day mortality. Full reference bibliography and individual patient data (master chart) are available in the parent dissertation.
6. Conclusion
Serial urinary albumin-creatinine ratio measurement at 6 and 24 hours of ICU admission is a reliable, inexpensive, and early prognostic marker in sepsis, with discriminatory performance comparable to APACHE II and superior to NEWS. The absence of significant microalbuminuria at both time points strongly predicts survival. Serial UACR monitoring can meaningfully augment clinical decision-making and risk stratification, particularly in resource-constrained settings. Multicentre studies with larger sample sizes are required for broader validation and optimal cut-off determination.
References
Full bibliography available in dissertation (pages 71–78). Key references include:
- Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810.
- Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–829.
- Royal College of Physicians. National Early Warning Score (NEWS) 2. London: RCP; 2017.
- Gosling P. Microalbuminuria: a marker of systemic disease. Br J Hosp Med. 1995;54(6):285–290.
- Thorevska N, Sabahi R, Upadya A, et al. Microalbuminuria in critically ill medical patients: prevalence, predictors, and prognostic significance. Crit Care Med. 2003;31(4):1075–1081.
- Gosling P, Czyz J, Nightingale P, et al. Microalbuminuria in the intensive care unit: clinical correlates and association with outcomes in 431 patients. Crit Care Med. 2006;34(8):2158–2166.
- Basu G, Chrispal A, Boorugu H, et al. Acute kidney injury in tropical acute febrile illness in a medical ICU — RIFLE criteria validation. Nephrol Dial Transplant. 2011;26(2):524–531.
- (Additional references 36–51 from dissertation to be formatted per target journal style.)
Prepared from the dissertation submitted to Gujarat University for the Degree of Doctor of Medicine, Branch-I (General Medicine), January 2025.
Notes for submission:
- The UACR data table and ROC AUC table above are formatted for inline placement; journal-specific table formatting (numbered, titled, footnoted) should be applied prior to submission.
- Box plots and full statistical tables from the original dissertation (Tables 9–17) should be submitted as separate figure/table files.
- References 1–7 above are placeholders for the key citations; the full 78-page bibliography should be formatted in the target journal's citation style (Vancouver recommended for most medical journals).
- Email of corresponding author needs to be inserted before submission.
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