Management of Acute-on-Chronic Kidney Injury
In patients with acute-on-chronic kidney injury (AKI on CKD), immediately discontinue all nephrotoxic medications including NSAIDs, avoid ACE inhibitors/ARBs during the acute phase, perform careful fluid resuscitation with balanced crystalloids only if hypovolemic, and arrange nephrology follow-up within 1 week for stage 3-4 CKD regardless of AKI severity. 1
Initial Assessment and Risk Stratification
Determine AKI stage and underlying CKD severity first, as this drives all subsequent management decisions:
- Stage AKI using KDIGO criteria: Stage 1 (Cr increase ≥0.3 mg/dL or 1.5-1.9× baseline), Stage 2 (2.0-2.9× baseline), Stage 3 (≥3× baseline or Cr ≥4.0 mg/dL or RRT initiation) 1
- Classify underlying CKD stage by baseline eGFR: Stage 3 (30-59 mL/min/1.73m²), Stage 4 (15-29 mL/min/1.73m²), Stage 5 (<15 mL/min/1.73m²) 1
- Patients with CKD G4 require nephrology consultation within 1 week regardless of AKI severity 1
The combination of pre-existing CKD and AKI creates particularly high risk—decreased GFR and proteinuria are both strong independent risk factors for developing AKI, and AKI accelerates CKD progression 2. Diabetes and hypertension as underlying causes further amplify this risk 1.
Immediate Medication Management
Stop all nephrotoxic agents immediately 1, 3:
- Discontinue NSAIDs completely—they cause both tubular injury and hemodynamic dysfunction, particularly dangerous when combined with diuretics and ACE inhibitors/ARBs (the "triple whammy") 1, 4
- Hold ACE inhibitors and ARBs during acute AKI episodes 1, 3, 4. The VA NEPHRON-D trial demonstrated that dual RAS blockade (losartan + lisinopril) increased acute kidney injury and hyperkalemia without additional benefit 4
- Withdraw diuretics before fluid assessment 5
- Adjust all renally-excreted medication doses based on current eGFR 1, 3
Critical pitfall: In elderly patients on diuretics with compromised renal function, NSAIDs combined with ARBs/ACE inhibitors cause rapid deterioration of renal function including acute renal failure 4.
Fluid Management Strategy
Fluid administration must be guided by volume status assessment, not given reflexively:
If Hypovolemic (tachycardia, hypotension, clear temporal relationship to volume loss):
- Administer balanced crystalloids (lactated Ringer's) as 500-1000 mL bolus over 30-60 minutes 5
- Avoid 0.9% saline—causes metabolic acidosis and hyperchloremia that worsens kidney injury 5
- Reassess hemodynamics after each bolus using dynamic indices 5
- Stop fluid administration once euvolemia is achieved—continuing beyond this point causes harm 5
If Euvolemic or Hypervolemic:
- Do NOT administer fluids 5. Volume overload >10-15% body weight is associated with adverse outcomes and delayed renal recovery 5
- Signs against fluid administration: peripheral edema, pulmonary edema, elevated JVP, established oliguric AKI without hemodynamic instability 5
Special Consideration for Diabetic Nephropathy:
- In diabetic patients with proteinuria (albumin-to-creatinine ratio ≥300 mg/g) and elevated creatinine, avoid aggressive fluid resuscitation unless clear hypovolemia 1, 4
- These patients are particularly vulnerable to fluid overload complications 1
Critical pitfall: The most common error is interpreting all AKI as "hypovolemic" requiring aggressive fluid resuscitation—clinical context and timing of insult are critical 5.
Monitoring During Acute Phase
Check daily until stabilized 3:
- Serum creatinine and electrolytes (sodium, potassium, bicarbonate) daily 1, 3
- Urine output monitoring 1
- Weight assessment 1
- Blood pressure monitoring 1
Monitor for hyperkalemia closely—patients with CKD on ACE inhibitors/ARBs who develop AKI are at extremely high risk 4.
Renal Replacement Therapy Indications
Initiate RRT for absolute indications 1, 6:
- Refractory hyperkalemia
- Volume overload unresponsive to diuretics
- Intractable metabolic acidosis
- Uremic encephalopathy, pericarditis, or pleuritis
- Certain toxin removal
For hemodynamically unstable patients, use continuous RRT rather than intermittent hemodialysis 1. When using continuous RRT, deliver effluent volume of 20-25 mL/kg/h 1.
Follow-Up and Recovery Assessment
Structured follow-up is mandatory 1:
- Within 3-7 days after hospital discharge: Check creatinine, electrolytes, assess for sustained RRT independence 1
- Weekly assessment if discharged on RRT: Serial pre-dialysis creatinine values, 24-hour urine collection for volume and creatinine/urea clearance 1
- Nephrology follow-up within 1 week for CKD G4 patients 1
- Monitor for at least 7 days after initial insult; sustained recovery defined as RRT independence >14 days 1, 3
Recovery assessment challenges: Standard creatinine-based eGFR may be inaccurate due to muscle mass loss during critical illness—consider cystatin C or direct GFR measurement in selected cases 1.
Long-Term Implications
AKI on CKD dramatically increases risk of 1, 7, 2:
- Progression to end-stage renal disease (particularly after dialysis-requiring AKI) 2
- Cardiovascular morbidity and mortality 7
- Recurrent AKI episodes 2
The association is amplified by: pre-existing CKD severity, higher AKI stage, and cumulative number of AKI episodes 2. Patients with diabetes and hypertension as underlying causes face particularly poor prognosis 1.