Renal Arterial Resistive Index Versus Novel Biomarkers for Early Prediction of Sepsis Associated-acute Kidney Injury

Populations at high risk of Sepsis-Associated Acute Kidney Injury (SA-AKI) have been identified. Sources of sepsis, in particular, bloodstream infection, abdominal and genitourinary sepsis, and infective endocarditis, are associated with a higher likelihood of developing AKI. Similar to the poor outcome of patients with sepsis, delayed administration of appropriate antimicrobial therapy was shown to be an independent predictor of the development of AKI. Incremental delays in antimicrobial delivery after the onset of hypotension showed a direct relationship with the development of AKI. The need for sensitive, simple and time-applicable biomarker to predict AKI development after renal insult is urgent.

Serum creatinine (sCr) and urea are used routinely for the diagnosis of AKI. However, these parameters are not accurate for the diagnosis of AKI. Cystatin C. (CysC) is suggested to be a good biomarker because of its constant rate of production, almost filtered by glomeruli (99%), has no significant protein binding and not secreted by renal tubule. Neutrophil gelatinase-associated lipocalin (NGAL) is recently identified and extensively investigated as a most promising early marker of AKI. Urinary NGAL is not only effective in detection of AKI but also its degree of expression might distinguish among AKI, prerenal azotemia and chronic kidney disease, and it is detectable before the accumulation of serum creatinine.

Ultrasonography (US) is used routinely to assess renal morphology. Renal Resistive Index (RRI) is a non-invasive Doppler-measured parameter that is directly correlated with intra-renal arterial resistance. RRI is defined as \[(peak systolic velocity - end diastolic velocity)/ peak systolic velocity\]. It theoretically ranges from 0 to 1 and it is normally lower than 0.7 with age differences. RRI calculation was found to be useful as an early indicator of the vascular resistance changes and in the determination of the optimal systemic hemodynamics required for renal perfusion.

The aim of this study is to compare the ability of arterial renal resistive index (RRI), serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (CysC) in early diagnosis and predicting the persistence of acute kidney injury in septic patients.

All included patients in this study will be assessed for the following:

1. Data Collection

   * Complete history taking (age, sex, illness, medications, etc.).
   * Complete physical examination (Glasgow coma scale (GCS), temperature, blood pressure, urine output, heart rate, respiratory rate and chest auscultation).
   * SOFA score, APACHE II score, and Quick SOFA (qSOFA).
   * Routine laboratory investigations and Coagulation profile.
   * C-reactive protein (CRP), and Serum lactate.
   * Complete sepsis workup (chest x-ray, urine analysis, abdomen and pelvis ultrasound, microbiological cultures) to identify the source of sepsis.
2. Renal Biomarkers

   - Serum and urinary samples will be collected directly at time of enrollment (within 2 hours from admission). It will be assayed for serum creatinine, serum neutrophil gelatinase-associated lipocalin (NGAL), urinary NGAL and serum Cystatin C (CysC). Then, it will be repeated at day 3.
3. Ultrasound evaluation of kidneys and renal Doppler

   * In each patient, both kidneys will be examined with real-time ultrasound (US) with a 3.75-MHz transducer (ACUSON X 300). Pulsed Doppler US evaluation of the intrarenal arteries will be obtained at the same respective scanning frequencies. The color Doppler functions are set for a study focused on interlobar arteries, that is, the highest gains possible, the use of the lowest filters and a low pulse repetition frequency (PRF) of 1-1.5 kHz that must be preferred while always limiting the aliasing phenomenon.
   * The renal resistance index (RRI, \[peak systolic frequency shift-minimum diastolic frequency shift\]/ peak systolic frequency shift) will be calculated from calibrated software. (26) All measurements will be performed by the same examiner.
   * The renal resistive index (RRI) will be measured at time of enrollment (within 2 hours from admission) and 24 hours after admission.
4. Treatment All patients will receive the standard treatment for management of sepsis on the guidelines of SCC (sepsis-3). The protocol of treatment will not be changed during the study time.
5. Follow up - All patients will be followed up using urine output (UOP), serum creatinine, KDIGO (Kidney Disease Improving Global Outcomes) classification, the use of vasopressors and need for renal replacement therapy (RRT).

Eligibility Criteria:
Inclusion Criteria:

* Adult patients (aged above 18 years) recently admitted with sepsis

Exclusion Criteria:

* Pregnant Females
* Patients with renal transplant.
* Patients with End Stage Renal Disease (ESRD).
* Patients with Chronic Kidney Disease (CKD) known with history, laboratory or ultrasonographic evaluation with chronic nephropathic changes.
* Patients with renal artery stenosis.
* Patients with obstructive uropathy.