Is There Any Prognostic Value of Serum Uromodulin in Sepsis Induced AKI.

Sepsis remains a leading cause of morbidity and mortality worldwide, with risk rising as organs failure accumulate, particularly when acute kidney injury (AKI) develops. AKI complicates nearly half of all septic episodes in ICU and is independently associated with poorer short- and long-term outcomes. Current prognostic tools as SOFA score , serum creatinine, urine output, NGAL and KIM-1have limited prognostic value. They often detect injury only after significant damage has occurred.

Uromodulin, the most abundant urinary protein produced by the renal thick ascending limb, is present in small amounts in the circulation. Experimental models reveal that uromodulin deficiency worsens sepsis outcomes, while administration of exogenous uromodulin can reduce mortality . In clinical studies of septic patients, early rises in circulating uromodulin are observed, yet those who go on to develop AKI or die tend to have lower levels at presentation. Genetic analyses, however, have not definitively proven a causal protective role for baseline uromodulin.

It has roles in tubular protection, immune modulation, and infection control, These important physiological functions may translate into valuable prognostic tools that may aid in predicting clinical outcomes. Serum uromodulin may serve as an early indicator of both renal tubular integrity and host defence capacity-qualities not captured by existing markers. Assessing serum uromodulin at time of diagnosis(day 0), day 7 and at time of discharge may predict recovery or progression of AKI. Establishing the prognostic value of uromodulin could enable early risk stratification, guide tailored interventions, and inform clinical decision-making, potentially improving outcomes in sepsis-induced AKI.

Inclusion criteria

• Age ≥ 18 years
• Septic patients with AKI: Diagnosis of sepsis is based on combination of variables including Sepsis-3 criteria within 24 hours of ICU admission(suspected or confirmed infection on clinical , lab and imaging evidence , acute increase in SOFA score =>2 points( or presence of septic shock). The latter is defined by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia (Singer et al 2016).
• Diagnosis of AKI according to KDIGO-criteria ( increase creatinine by =>0.3 mg/dl ( =>26.5 micmol/l ) within 48 hrs or increase cr =>1.5 × baseline within 7days or urine output < 0.5 ml / kg / hr for => 6hrs)
• Informed consent obtained and in case patient is unable to sign the consent his next of kin or has power

Exclusion criteria

• Patients diagnosed with ESRD or kidney transplantation
• Other causes of AKI
• Pregnancy related causes of AKI
• Active immunosuppressive therapy (e.g., high-dose steroids, chemotherapy)
• Patients with background of adult polycystic kidney disease
• Patients with cardiac failure
• Patients with solitary kidney because of small renal mass that could affect uromodulin level.