Emergency Nephrology Management
Learning Objectives: Learners will recognize the clinical presentation and urgency of rapidly progressive glomerulonephritis, implement immediate diagnostic and therapeutic interventions, understand the role of kidney biopsy in diagnosis and management, and demonstrate appropriate use of immunosuppressive therapy and plasmapheresis.
Case Presentation – Emergency Department:
Dr. Patricia Williams, a 45-year-old African American female physician, presents to the emergency department with a two-week history of progressive fatigue, decreased urine output, and lower extremity swelling. She initially attributed her symptoms to work stress and long hours, but became concerned when she noticed dark, tea-colored urine and significant facial swelling upon awakening this morning.
The patient has no significant past medical history and takes no regular medications except occasional ibuprofen for headaches. She denies recent illnesses, though she recalls having a “cold” with sore throat approximately three weeks ago that resolved without treatment. She has no family history of kidney disease but reports that her grandmother had “kidney problems” of unknown etiology.
Rapid Assessment and Triage:
Given the patient’s medical background, she provides a detailed history of her symptoms. She reports that her urine output has decreased from normal to approximately 400 mL over the past 24 hours, and she has gained approximately 8 pounds over the past week. She has developed progressive dyspnea on exertion and orthopnea, requiring two pillows to sleep comfortably.
Physical examination reveals an ill-appearing woman with blood pressure of 180/110 mmHg, heart rate of 105 beats per minute, respiratory rate of 24 breaths per minute, and oxygen saturation of 94% on room air. She has significant periorbital and facial edema, jugular venous distension to the angle of the jaw, and bilateral lower extremity pitting edema to the knees.
Interactive Decision Point 1: Recognition and Urgency
Question for Medical Students: What clinical features suggest rapidly progressive glomerulonephritis, and why is this considered a nephrology emergency?
Question for Residents: What immediate diagnostic studies would you order, and what therapeutic interventions should be considered while awaiting results?
Question for Nephrologists: What are the differential diagnoses for RPGN, and how would you approach immediate management?
Emergency Laboratory Results:
Stat laboratory studies reveal severe acute kidney injury with serum creatinine of 6.8 mg/dL and blood urea nitrogen of 95 mg/dL. Estimated glomerular filtration rate is 8 mL/min/1.73m², representing severe kidney dysfunction. Electrolyte abnormalities include potassium of 6.2 mEq/L, bicarbonate of 16 mEq/L, and anion gap of 18.
Urinalysis shows 4+ proteinuria, 3+ blood, and numerous red blood cell casts on microscopic examination. Quantitative proteinuria measurement reveals protein excretion of 3.2 grams per 24 hours. Complete blood count shows hemoglobin of 8.9 g/dL, hematocrit of 26.8%, and platelet count of 180,000/μL.
Immediate Serological Studies:
Given the clinical presentation suggestive of rapidly progressive glomerulonephritis, comprehensive serological studies are ordered emergently. Anti-neutrophil cytoplasmic antibodies (ANCA) are sent with both cytoplasmic (c-ANCA) and perinuclear (p-ANCA) patterns. Anti-glomerular basement membrane (anti-GBM) antibodies are ordered to evaluate for Goodpasture’s syndrome.
Complement levels including C3 and C4 are measured to assess for complement-mediated glomerulonephritis. Antinuclear antibodies (ANA) and anti-double-stranded DNA antibodies are sent to evaluate for systemic lupus erythematosus. Blood cultures are obtained to rule out infectious endocarditis, and hepatitis B and C serologies are sent.
Interactive Decision Point 2: Immediate Management
Question for Medical Students: What are the immediate life-threatening complications of RPGN that require urgent intervention?
Question for Residents: How would you manage the hyperkalemia and fluid overload in this patient?
Question for Nephrologists: What are the indications for emergency dialysis in RPGN, and when should immunosuppressive therapy be initiated?
Emergency Interventions:
The patient’s hyperkalemia requires immediate treatment with calcium gluconate 1 gram intravenously for cardiac protection, followed by insulin 10 units with dextrose 25 grams to shift potassium intracellularly. Sodium bicarbonate 50 mEq is administered to address metabolic acidosis and provide additional potassium-lowering effect.
Given the severe fluid overload with pulmonary edema, furosemide 80 mg intravenously is administered with minimal response. The patient’s oxygen saturation decreases to 90% on room air, requiring supplemental oxygen at 4 liters per minute via nasal cannula.
Urgent Nephrology Consultation:
The nephrology consultant evaluates the patient within one hour of presentation and determines that this represents rapidly progressive glomerulonephritis requiring immediate intervention. Given the severity of presentation and high likelihood of crescentic glomerulonephritis, the decision is made to initiate empirical immunosuppressive therapy while awaiting serological results and kidney biopsy.
Interactive Decision Point 3: Diagnostic Strategy
Question for Medical Students: What is the role of kidney biopsy in RPGN, and what findings would you expect?
Question for Residents: How do you balance the urgency of treatment with the need for definitive diagnosis?
Question for Nephrologists: What are the contraindications to kidney biopsy, and how would you proceed if biopsy cannot be performed?
Emergency Kidney Biopsy:
Given the rapid progression and need for definitive diagnosis to guide therapy, an emergency kidney biopsy is performed within 6 hours of presentation. Coagulation studies are normal, and blood pressure is controlled to below 160/90 mmHg with intravenous nicardipine prior to the procedure.
The biopsy is performed under ultrasound guidance without complications. Tissue is sent for light microscopy, immunofluorescence, and electron microscopy. Preliminary light microscopy results available within 4 hours show crescentic glomerulonephritis with crescents in 85% of glomeruli examined.
Serological Results:
ANCA testing returns positive for c-ANCA with anti-PR3 antibodies at high titer (>1:640). Anti-GBM antibodies are negative, and complement levels are normal. ANA and anti-dsDNA are negative, effectively ruling out lupus nephritis. These results, combined with the biopsy findings, confirm the diagnosis of ANCA-associated crescentic glomerulonephritis.
Interactive Decision Point 4: Treatment Initiation
Question for Medical Students: What are the main categories of treatment for ANCA-associated glomerulonephritis?
Question for Residents: What are the risks and benefits of immunosuppressive therapy in this setting?
Question for Nephrologists: How would you design an induction and maintenance immunosuppressive regimen?
Immunosuppressive Therapy Initiation:
Given the severity of presentation with crescentic glomerulonephritis and high ANCA titers, aggressive immunosuppressive therapy is initiated immediately. Pulse methylprednisolone 1 gram daily for three days is administered, followed by oral prednisone 1 mg/kg daily with gradual taper over several months.
Cyclophosphamide induction therapy is initiated with intravenous administration of 15 mg/kg (approximately 1 gram) every two weeks, adjusted for age and kidney function. Pre-medication with ondansetron and aggressive hydration are provided to minimize side effects.
Plasmapheresis Consideration:
Given the severity of kidney dysfunction and high ANCA titers, plasmapheresis is initiated to rapidly remove circulating antibodies and inflammatory mediators. Seven sessions of plasmapheresis are planned over two weeks, with each session removing 1.5 plasma volumes and replacing with albumin and fresh frozen plasma.
Renal Replacement Therapy:
Despite aggressive immunosuppressive therapy and plasmapheresis, the patient’s kidney function does not improve immediately, and she develops uremic symptoms including pericarditis and altered mental status. Hemodialysis is initiated through a temporary central venous catheter placed in the right internal jugular vein.
Interactive Decision Point 5: Monitoring and Complications
Question for Medical Students: What are the potential complications of immunosuppressive therapy that require monitoring?
Question for Residents: How would you monitor treatment response in ANCA-associated glomerulonephritis?
Question for Nephrologists: What are the long-term management considerations and prognosis for this patient?
Treatment Response and Monitoring:
Over the following weeks, the patient shows gradual improvement in kidney function with serum creatinine decreasing to 4.2 mg/dL by week 4 and 2.8 mg/dL by week 8. ANCA titers decrease significantly, and urinalysis shows resolution of red blood cell casts and decreased proteinuria.
The patient is able to discontinue dialysis after 6 weeks, though kidney function remains impaired with eGFR stabilizing around 25 mL/min/1.73m². Repeat kidney biopsy at 6 months shows resolution of active inflammation but significant chronic changes with glomerulosclerosis and interstitial fibrosis.
Long-term Management:
Maintenance immunosuppressive therapy is transitioned from cyclophosphamide to azathioprine 2 mg/kg daily after 6 months of induction therapy. Prednisone is gradually tapered to 5-10 mg daily over 12 months. Regular monitoring includes ANCA titers, complete blood counts, liver function tests, and kidney function assessment.
Expert Commentary:
This case demonstrates the critical importance of early recognition and aggressive treatment of rapidly progressive glomerulonephritis. The combination of clinical presentation, serological studies, and kidney biopsy findings allowed for rapid diagnosis and appropriate therapy. While the patient achieved remission of active disease, the delay in presentation resulted in significant irreversible kidney damage, emphasizing the need for early intervention in RPGN
Case Outcome and Prognosis:
At two-year follow-up, the patient remains in clinical remission with stable kidney function (eGFR 28 mL/min/1.73m²) and negative ANCA titers. She has been able to return to work with some modifications and maintains good quality of life. However, she requires ongoing monitoring for disease relapse and preparation for eventual renal replacement therapy given her reduced kidney function.