What is the appropriate management plan for a patient with sepsis secondary to UTI and acute-on-chronic kidney injury, considering her history of septic shock and chronic kidney disease?

Management of Sepsis Secondary to UTI with Acute-on-Chronic Kidney Injury

This patient requires immediate aggressive fluid resuscitation with at least 30 mL/kg isotonic crystalloids within 3 hours, broad-spectrum antibiotics within 1 hour, vasopressor support targeting MAP ≥65 mmHg if hypotensive, avoidance of all nephrotoxic agents, and close monitoring for renal replacement therapy indications—while recognizing that her kidney injury likely began before presentation and prevention is no longer an option. 1, 2

Immediate Resuscitation (First 3 Hours)

Fluid Management

• Administer at least 30 mL/kg of isotonic crystalloids (approximately 2.3 liters for a 76 kg patient) within the first 3 hours targeting MAP ≥65 mmHg 1, 2
• Use isotonic crystalloids rather than colloids (albumin or starches) for initial volume expansion, as starches are associated with higher AKI incidence 2
• Avoid overzealous fluid administration once hemodynamically stable, as volume overload worsens outcomes in AKI 1
• Monitor for fluid responsiveness using clinical parameters (mental status, urine output, lactate clearance) rather than continuing aggressive fluids if already euvolemic 3

Vasopressor Therapy (If Hypotensive)

• Initiate vasopressors in conjunction with fluids if MAP <65 mmHg despite initial fluid resuscitation 3, 1
• Norepinephrine is the first-line vasopressor targeting MAP ≥65 mmHg 3, 1
• Add vasopressin (up to 0.03 U/min) as adjunctive therapy if additional agent needed to maintain MAP or to reduce norepinephrine dosage 3
• Recognize that vasopressor use, while necessary for systemic perfusion, paradoxically increases renal vascular resistance and contributes to AKI progression 4

Antimicrobial Therapy (Within 1 Hour)

Immediate Actions

• Obtain blood cultures and urine culture before antibiotics, but do not delay antibiotic administration beyond 1 hour of septic shock recognition 3, 1
• Initiate empiric broad-spectrum therapy covering all likely uropathogens including resistant gram-negative bacilli and potentially MRSA if risk factors present 3
• For complicated UTI with sepsis in a patient with single functioning kidney and CKD 3B, consider: piperacillin-tazobactam OR ceftriaxone PLUS vancomycin if MRSA risk factors exist (recent hospitalization, indwelling catheter, prior MRSA) 3

Antibiotic Considerations in Renal Dysfunction

• Adjust all renally-cleared antibiotics for her estimated GFR (CKD 3B = GFR 30-44 mL/min) 1, 2
• If vancomycin is indicated, initiate immediately despite AKI, as survival benefit outweighs nephrotoxicity risk—ensure adequate resuscitation before attributing worsening renal function to vancomycin 1
• Narrow therapy once pathogen identification and sensitivities are established 3

Acute-on-Chronic Kidney Injury Management

Critical Recognition

• Most patients presenting with septic shock and developing AKI have evidence of kidney damage at the time of or within 24 hours of admission—prevention is not viable as injury has already occurred 5
• Her declining GFR represents acute-on-chronic injury that began before presentation 5, 6

Medication Review and Nephrotoxin Avoidance

• Hold all nephrotoxic medications immediately: NSAIDs, aminoglycosides (unless no alternative), ACE inhibitors/ARBs, and any contrast agents 1, 2
• Each additional nephrotoxin increases AKI odds by 53%; combining 3+ nephrotoxins doubles AKI risk 1
• Review and adjust all renally-cleared medications for decreased GFR 1, 2
• Do not use low-dose dopamine to prevent or treat AKI—it is ineffective 2

Diuretic Use

• Do not use diuretics to prevent AKI 2
• Consider diuretics only for managing volume overload once hemodynamically stable 2

Renal Replacement Therapy Indications

• Use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis for hemodynamically unstable septic patients to facilitate fluid balance management 3, 1, 2
• Initiate RRT for definitive indications: severe acidosis (pH <7.15), hyperkalemia, uremic complications (pericarditis, encephalopathy, bleeding), or refractory volume overload 1, 2
• Do not initiate RRT solely for creatinine elevation or oliguria without other definitive indications 1, 2
• Timing should be individualized based on clinical trajectory, but do not delay in rapidly developing oliguric AKI with complications 3

Metabolic Management

Acid-Base Status

• Do not use sodium bicarbonate therapy to improve hemodynamics or reduce vasopressor requirements if pH ≥7.15 3, 1, 2
• Bicarbonate therapy has not been shown to improve outcomes in septic shock with lactic acidosis 3

Glucose Control

• Target blood glucose ≤180 mg/dL using protocolized insulin therapy 3, 1, 2
• Avoid tight glycemic control (≤110 mg/dL) as it increases hypoglycemia risk without mortality benefit 3, 1
• Monitor blood glucose every 1-2 hours until stable, then every 4 hours 3

Supportive Care Measures

Venous Thromboembolism Prophylaxis

• Administer pharmacologic VTE prophylaxis with low-molecular-weight heparin (LMWH) unless contraindicated 3, 1
• If creatinine clearance <30 mL/min (likely in this patient with CKD 3B and acute injury), use dalteparin or unfractionated heparin rather than other LMWHs with higher renal metabolism 3
• Combine with intermittent pneumatic compression devices whenever possible 3

Stress Ulcer Prophylaxis

• Provide stress ulcer prophylaxis with proton pump inhibitor (preferred) or H2-receptor antagonist for patients with GI bleeding risk factors 3, 1
• Risk factors include mechanical ventilation, coagulopathy, and septic shock 3

Nutritional Support

• Initiate early enteral nutrition within 48 hours if tolerated, preferentially over parenteral nutrition 3, 1, 2
• Target total energy intake of 20-30 kcal/kg/day 1, 2
• Provide 0.8-1.0 g/kg/day protein in non-catabolic AKI without dialysis; increase to 1.0-1.5 g/kg/day if on RRT 1, 2
• Do not restrict protein intake to prevent or delay RRT initiation 2

Monitoring Parameters

Serial Assessments

• Monitor creatinine, urine output, and fluid balance every 4-6 hours 1, 2
• Lactate clearance as marker of adequate resuscitation 3, 1
• Mental status, skin perfusion, and urine output to assess regional perfusion 3
• Blood glucose monitoring every 1-2 hours until stable 3

Troponin Elevation

• Elevated troponin in sepsis represents myocardial injury from sepsis-induced stress and microvascular dysfunction, not necessarily acute coronary syndrome 3
• Continue hemodynamic optimization and avoid additional cardiac workup unless clinical suspicion for ACS exists 3

Long-Term Considerations and Follow-Up

Risk of Chronic Kidney Disease Progression

• This patient is at high risk for CKD progression given her age, female sex, pre-existing CKD 3B, single functioning kidney, and septic AKI 6, 7
• Even stage 1 AKI can lead to CKD development in 10% of patients at one year 6
• Old age, female sex, diabetes, low hemoglobin, and high creatinine at discharge are independent risk factors for CKD development 6

Post-Discharge Management

• Arrange nephrology follow-up within 2-4 weeks of discharge, prioritizing early follow-up given her severe AKI (stage 3 if meeting KDIGO criteria) and persistent renal dysfunction 2
• Monitor for recovery of renal function versus progression to CKD or end-stage renal disease 2, 6
• Avoid nephrotoxins indefinitely and ensure all future medications are renally dosed 2

Common Pitfalls to Avoid

• Do not delay antibiotics while waiting for cultures—survival depends on administration within 1 hour 3, 1
• Do not continue aggressive fluid resuscitation once euvolemic—volume overload worsens AKI outcomes 1, 2
• Do not withhold necessary antibiotics (including vancomycin) due to AKI concerns—survival benefit outweighs nephrotoxicity risk with adequate resuscitation 1
• Do not use dopamine as first-line vasopressor—norepinephrine is superior 3
• Do not initiate RRT prematurely for creatinine elevation alone—wait for definitive indications 1, 2
• Do not assume kidney injury can be prevented at this stage—injury has already occurred and focus should be on limiting further damage and supporting recovery 5