What is the likely diagnosis and management for a 40-year-old male with no prior co-morbidities and a non-alcoholic history, presenting with recurrent vomiting, pallor, leukocytosis (Total Leukocyte Count (TLC) of 13,500), hyperbilirubinemia (total bilirubin of 15, direct of 6.35), and acute kidney injury (serum creatinine of 8.5)?

Likely Diagnosis: Hepatorenal Syndrome (HRS) or Acute Kidney Injury with Cholestatic Hepatitis

This 40-year-old male with recurrent vomiting, pallor, leukocytosis (TLC 13,500), mixed hyperbilirubinemia (total bilirubin 15 mg/dL, direct 6.35 mg/dL), and severe acute kidney injury (creatinine 8.5 mg/dL) most likely has acute kidney injury secondary to severe dehydration from protracted vomiting, with concurrent hepatic dysfunction, requiring immediate hospitalization, aggressive fluid resuscitation, and urgent evaluation for sepsis and hepatorenal syndrome. 1, 2

Immediate Clinical Assessment

Sepsis evaluation is the first priority given the combination of leukocytosis, vomiting, and multi-organ dysfunction (liver and kidney). 1

• Check for sepsis criteria immediately: heart rate ≥90 bpm, respiratory rate ≥20 bpm, temperature <36°C or ≥38°C, and signs of malaise/apathy are sufficient for sepsis diagnosis in resource-limited settings 1
• Assess for severe sepsis signs: decreased capillary refill, skin mottling, peripheral cyanosis, arterial hypotension (systolic BP ≤90 mmHg), SpO2 ≤90%, oliguria (<0.5 mL/kg/h for 2 hours), jaundice, petechiae, or absent bowel sounds 1
• Evaluate hydration status: orthostatic symptoms, urine output, ability to tolerate oral fluids, and signs of severe dehydration 3

Diagnostic Workup

Immediate Laboratory Tests

Complete hepatobiliary evaluation is mandatory given the mixed hyperbilirubinemia (42% direct bilirubin) indicating conjugated hyperbilirubinemia requiring urgent investigation. 2

• Liver function tests: AST, ALT, alkaline phosphatase, GGT, albumin, and prothrombin time/INR to assess hepatocellular injury, cholestasis, and synthetic function 1, 2
• Renal function: calculate eGFR using creatinine 8.5 mg/dL, age, gender, and race 2
• Urinalysis with microscopy: examine for bilirubinuria (confirms conjugated hyperbilirubinemia), proteinuria, red cell casts, and dysmorphic RBCs 2
• Albumin-to-creatinine ratio (ACR): quantify proteinuria if present on dipstick 2
• Blood cultures: obtain before antibiotics if sepsis suspected 1
• Lactate and blood gas: assess for tissue hypoperfusion and metabolic acidosis 1

Imaging Studies

• Abdominal ultrasound immediately: evaluate liver parenchyma, biliary tree dilation, gallbladder, and kidney size to exclude biliary obstruction 1, 2
• Consider MRCP or ERCP if biliary obstruction suspected on ultrasound 2

Additional Testing Based on Clinical Context

• Viral hepatitis serologies: HAV-IgM, HBsAg, HBc-IgM, HCV antibody if hepatocellular pattern (ALT/AST elevation predominates) 1
• Leptospirosis serology: if history of fresh-water exposure, given the combination of jaundice, renal failure, and leukocytosis (Weil's disease) 1
• Malaria blood smear: if any travel to endemic areas, as malaria can present with fever, vomiting, jaundice, and renal failure 1

Immediate Management

Fluid Resuscitation

Aggressive intravenous crystalloid resuscitation is the cornerstone of initial management for suspected dehydration-induced acute kidney injury. 1

• Administer rapid IV crystalloid bolus of at least 20 mL/kg (approximately 1400 mL for a 70 kg patient) over 30-60 minutes 1
• Assess response to fluid loading: ≥10% increase in systolic/mean arterial BP, ≥10% reduction in heart rate, improvement in mental state, peripheral perfusion, and/or urine output 1
• Continue fluid resuscitation if positive response; some patients may require several liters during the first 24-48 hours 1
• Stop or interrupt fluids if no improvement in tissue perfusion or if crepitations develop (indicating fluid overload or impaired cardiac function) 1

Antibiotic Therapy

If sepsis is confirmed, start empiric broad-spectrum antibiotics immediately after obtaining blood cultures. 1

• For suspected leptospirosis (if Weil's disease suspected): start penicillin or tetracycline antibiotics immediately despite non-specific initial investigations 1

Monitoring

• Serial neurological assessments to monitor for deterioration 4
• Monitor urine output hourly: oliguria (<0.5 mL/kg/h for 2 hours) indicates severe sepsis or acute tubular necrosis 1
• Serial liver function tests: recheck in 2-3 weeks if viral hepatitis suspected, or more frequently if worsening 3
• Daily monitoring: full blood count, hepatic, kidney, and metabolic exams (glycemia and blood gas analysis) 1

Differential Diagnosis

Most Likely Diagnoses

1. Acute kidney injury from severe dehydration secondary to protracted vomiting with concurrent hepatic dysfunction 5
2. Hepatorenal syndrome: serum sodium, creatinine, and bilirubin are important predictors; this patient has elevated creatinine and bilirubin 6
3. Bile cast nephropathy: suspected in setting of liver disease and hyperbilirubinemia, characterized by tubular bile casts and acute tubular injury 7
4. Leptospirosis (Weil's disease): combination of jaundice, renal failure, leukocytosis, and vomiting 1
5. Viral hepatitis with acute renal failure: hepatitis A can cause liver failure, acute renal failure, and hyperbilirubinemia 8

Less Likely but Important to Exclude

• Sepsis with multi-organ dysfunction: leukocytosis, vomiting, and organ dysfunction 1
• Drug-induced liver injury with acute kidney injury: most common cause of liver disease in case series 1
• Malaria: if travel history present 1

Nephrology and Hepatology Referral

Urgent nephrology referral is indicated given creatinine 8.5 mg/dL (eGFR likely <10 mL/min/1.73 m²). 2

• Nephrology consultation criteria met: eGFR <30 mL/min/1.73 m² requires urgent evaluation 2
• Consider hepatology consultation if liver enzymes worsen or fail to improve after 4-6 weeks 3
• Dialysis may be required if oliguria persists, severe metabolic acidosis develops, or uremic symptoms appear 5, 8

Critical Pitfalls to Avoid

• Do not assume protracted vomiting is benign: latent renal insufficiency and dehydration can induce rapid and recurrent deterioration of renal function 5
• Do not delay evaluation of conjugated hyperbilirubinemia: bilirubinuria indicates conjugated hyperbilirubinemia requiring immediate hepatobiliary workup 2
• Do not miss sepsis: this patient has leukocytosis and multi-organ dysfunction requiring immediate sepsis evaluation 1
• Do not overlook leptospirosis: combination of jaundice, renal failure, and leukocytosis is classic for Weil's disease 1
• Do not assume all hyperbilirubinemia with renal failure is hepatorenal syndrome: bile cast nephropathy, acute tubular necrosis from dehydration, and viral hepatitis with renal involvement are important differentials 7, 8

Prognosis

• Higher initial serum creatinine is independently associated with dialysis requirement or death in bile cast nephropathy (adjusted OR 1.291 per 1 mg/dL increase) 7
• Serum sodium, creatinine, and bilirubin are important predictors of hepatorenal syndrome in alcoholic liver disease, though this patient is non-alcoholic 6
• Control of vomiting is the cardinal measure to prevent recurrent deterioration of renal function 5