What is the best course of treatment for a 40-year-old male with a history of hypertension, presenting with vomiting, generalized body swelling, decreased urine output, and reddish discoloration of urine, diagnosed with Rapidly Progressive Glomerulonephritis (RPGN) and severe impaired renal function, with lab results showing hyperkalemia, hyponatremia, hyperphosphatemia, and hypocalcemia?

Management of Rapidly Progressive Glomerulonephritis with Severe Acute Kidney Injury

This patient requires immediate initiation of high-dose corticosteroids and cyclophosphamide, along with urgent continuation of hemodialysis, while awaiting results of ANCA, anti-GBM antibodies, ANA, C3, and C4 to determine the specific RPGN subtype. 1, 2

Immediate Treatment Priorities

Urgent Immunosuppression

• Start high-dose methylprednisolone pulse therapy (500-1000 mg IV daily for 3 days) followed by oral prednisone 1 mg/kg/day (maximum 80 mg) immediately, even before biopsy confirmation or serologic results return. 1, 3
• Initiate cyclophosphamide as the preferred immunosuppressive agent given the severe presentation with creatinine 18.11 mg/dL and dialysis requirement. 1, 2
• Cyclophosphamide is specifically preferred over rituximab when serum creatinine >4 mg/dl (354 μmol/L), as there are limited data for rituximab in severely impaired kidney function. 1

Critical Dialysis Management

• Continue urgent hemodialysis for severe hyperkalemia (K+ 7.12 mmol/L), uremia (BUN >396 mg/dL), and metabolic acidosis. 1
• Plan for daily or every-other-day dialysis initially given the severity of uremia and electrolyte derangements. 1
• Use dialysis solutions containing potassium, phosphate, and magnesium to prevent electrolyte disorders during kidney replacement therapy. 4

Electrolyte and Metabolic Emergencies

Severe Hyperkalemia Management

• The current potassium of 7.12 mmol/L requires immediate treatment beyond dialysis: 5
  • Calcium gluconate 50-100 mg/kg IV to stabilize cardiac membrane 1
  • Insulin 0.1 units/kg with 25% dextrose 2 mL/kg 1
  • Sodium bicarbonate to correct acidosis 1
  • Continuous ECG monitoring is mandatory 5
• Target potassium range of 4.0-5.0 mmol/L to prevent cardiac arrhythmias. 6, 5

Other Electrolyte Corrections

• Hyponatremia (125 mmol/L): Correct slowly with fluid restriction and dialysis; avoid rapid correction to prevent osmotic demyelination. 4
• Hyperphosphatemia (3.75 mmol/L): Aluminum hydroxide 50-100 mg/kg/day divided in 4 doses. 1
• Hypocalcemia (1.89 mmol/L): Only treat if symptomatic (tetany, seizures) with calcium gluconate 50-100 mg/kg. 1
• Monitor magnesium closely as hypomagnesemia occurs in up to 60-65% of critically ill patients and must be corrected to allow potassium correction. 6, 4

Critical Medication Adjustments

Discontinue Nephrotoxic and Contraindicated Medications

• STOP trimethoprim-sulfamethoxazole (CPT 960 mg) immediately - this drug acts like amiloride and causes hyperkalemia, especially dangerous in renal failure. 7
• STOP or use extreme caution with metoclopramide (Plasil) - causes QTc prolongation, particularly dangerous with severe hyperkalemia and hyponatremia. 6
• Consider ondansetron as a safer antiemetic alternative for uremic gastropathy. 6

Infection Prophylaxis

• Pneumocystis jirovecii prophylaxis is mandatory with high-dose corticosteroids and cyclophosphamide, but NOT with trimethoprim-sulfamethoxazole given the hyperkalemia. 1
• Consider alternative prophylaxis such as atovaquone or inhaled pentamidine. 1
• The current broad-spectrum antibiotics (cefepime, vancomycin, metronidazole) should be continued only if there is documented infection, as infection must be excluded before significant immunosuppression. 1

Diagnostic Workup to Guide Specific Therapy

Essential Serologies (Already Ordered - Expedite Results)

• ANCA (MPO and PR3): Most common cause of RPGN; if positive, confirms pauci-immune glomerulonephritis. 1, 2
• Anti-GBM antibodies: If positive, add plasma exchange immediately to the regimen. 1
• ANA, C3, C4: To evaluate for lupus nephritis or immune complex disease. 1, 2
• If "double-positive" (ANCA + anti-GBM), treat as anti-GBM disease with plasma exchange. 1

Plasma Exchange Considerations

• Do NOT use plasma exchange routinely for ANCA-associated vasculitis - the PEXIVAS trial showed no benefit. 1
• DO use plasma exchange if anti-GBM antibodies are positive: 14 daily exchanges or until antibody undetectable. 1
• Plasma exchange may be considered if there is massive pulmonary hemorrhage regardless of antibody status. 1, 3

Supportive Care Modifications

Blood Pressure Management

• Target systolic BP <120 mm Hg using standardized office measurement. 1
• Hold ACE inhibitors and ARBs during acute kidney injury with severe hyperkalemia and volume depletion risk. 1
• Continue amlodipine and adjust furosemide dose based on volume status and dialysis schedule. 1

Monitoring Requirements

• Check serum potassium every 6-12 hours until stable below 5.5 mmol/L. 5
• Monitor electrolytes 24 hours post-dialysis to assess for rebound abnormalities. 4
• Obtain ECG immediately given potassium >6.0 mmol/L. 5
• Strict input/output monitoring with daily weights. 1

Prognosis and Treatment Duration

Factors Affecting Outcome

• The extremely elevated creatinine (18.11 mg/dL) and dialysis requirement indicate poor prognosis for renal recovery, but early aggressive treatment may still prevent permanent dialysis dependence. 3
• The presence of normal kidney size on ultrasound is favorable and suggests acute rather than chronic process. 2
• Urinalysis showing RBCs "full field" with +2 protein and +2 blood confirms active glomerulonephritis. 1, 8

Treatment Timeline

• Continue high-dose corticosteroids for minimum 4 weeks, up to maximum 16 weeks or until remission. 1
• Cyclophosphamide typically given for 3 months. 1
• No maintenance immunosuppression is needed if this is anti-GBM disease. 1
• If ANCA-associated vasculitis, transition to maintenance therapy with rituximab or azathioprine plus low-dose glucocorticoids after induction. 1

Common Pitfalls to Avoid

• Do not delay immunosuppression waiting for kidney biopsy results - the clinical presentation and positive serologies are sufficient to start treatment. 1
• Do not use trimethoprim-sulfamethoxazole for PCP prophylaxis in patients with hyperkalemia and renal failure. 7
• Do not add plasma exchange routinely for ANCA vasculitis - only if anti-GBM positive or life-threatening pulmonary hemorrhage. 1
• Do not use metoclopramide in patients with severe hyperkalemia and electrolyte disturbances - risk of fatal arrhythmias. 6
• Avoid aggressive correction of post-dialysis electrolyte abnormalities as this causes dangerous fluctuations. 4