What is the management approach for a patient with nephritic syndrome, including treatment of underlying causes and management of complications such as hypertension and significant proteinuria?

Management of Nephritic Syndrome

Nephritic syndrome requires immediate supportive care targeting hypertension and proteinuria with RAAS inhibitors, combined with disease-specific immunosuppression based on the underlying glomerular pathology identified by renal biopsy. 1, 2

Initial Diagnostic Evaluation

The diagnostic workup must establish the underlying cause before initiating immunosuppression:

• Obtain renal biopsy as the gold standard for diagnosis when results will alter treatment decisions or prognosis 2
• Evaluate urine sediment for dysmorphic erythrocytes and red blood cell casts, which are pathognomonic for glomerulonephritis 2
• Measure 24-hour urine protein excretion in adults (or spot protein-creatinine ratio in children) to quantify proteinuria 2
• Assess kidney function using eGFR (CKD-EPI equation in adults, modified Schwartz in children) to guide medication dosing 2
• Order complete blood count, serum electrolytes, albumin, complement levels (C3, C4), and serologic studies (ANA, anti-dsDNA, ANCA) based on clinical suspicion 2, 3

General Supportive Management

Blood Pressure and Proteinuria Control

Start ACE inhibitors or ARBs as first-line therapy for all patients with proteinuria or hypertension to reduce proteinuria and slow progression of kidney disease 1, 3, 4:

• Target blood pressure reduction while monitoring for acute kidney injury 1
• Counsel patients to hold ACE inhibitors/ARBs during acute illness with vomiting, diarrhea, or volume depletion to prevent hemodynamic acute kidney injury 1
• Avoid dihydropyridine calcium channel blockers (amlodipine, nifedipine) as they exacerbate edema and may increase proteinuria 1

Volume Management

• Use loop diuretics (furosemide 0.5-2 mg/kg per dose) for fluid overload in patients with preserved kidney function 2
• Avoid diuretics in patients with intravascular volume depletion despite peripheral edema 2
• Monitor for diuretic resistance requiring dose escalation or combination therapy 1

Infection Prevention

Critical given immunosuppression and urinary immunoglobulin losses:

• Screen for latent tuberculosis, hepatitis B/C, HIV, and syphilis before starting immunosuppression 1
• Screen for Strongyloides in at-risk patients with eosinophilia 1
• Administer trimethoprim-sulfamethoxazole prophylaxis when using prednisone ≥20 mg/day to prevent Pneumocystis jirovecii pneumonia 1
• Vaccinate against encapsulated organisms, especially when using complement inhibitors 1

Thromboembolism Prevention

• Monitor for thromboembolism risk, particularly with serum albumin <2.9 g/dL 1, 2
• Consider anticoagulation (unfractionated heparin, low-molecular-weight heparin, or warfarin) in high-risk patients based on bleeding risk assessment 1
• Avoid factor Xa inhibitors and direct thrombin inhibitors as they are lost in nephrotic urine with unpredictable pharmacokinetics 1

Additional Supportive Measures

• Treat hyperlipidemia with statins (target LDL <100 mg/dL) for persistent dyslipidemia 3
• Provide adequate nutrition to prevent malnutrition while restricting dietary sodium 1, 2
• Monitor for and treat hypothyroidism, vitamin D deficiency, and bone disease 1

Disease-Specific Immunosuppression

Post-Infectious Glomerulonephritis

• Provide supportive care only with antibiotics for active infection 5, 6
• Immunosuppression is not indicated unless crescentic disease develops 1

IgA Nephropathy

For persistent proteinuria >1 g/day despite 3-6 months of optimized RAAS blockade:

• Initiate 6-month course of corticosteroids (e.g., methylprednisolone 0.4 mg/kg/day for 2 months, then taper) 1
• For crescentic IgA nephropathy with rapidly progressive kidney failure: treat with corticosteroids plus cyclophosphamide analogous to ANCA vasculitis 1

Lupus Nephritis (Class III/IV)

Initial therapy options (choose one regimen) 1, 3:

• Mycophenolate mofetil 2-3 g/day plus glucocorticoids, OR
• Low-dose IV cyclophosphamide (500 mg every 2 weeks × 6 doses) plus glucocorticoids, OR
• Multitarget therapy: mycophenolate 1-2 g/day plus tacrolimus with glucocorticoids (preferred for nephrotic-range proteinuria) 3

Maintenance therapy after achieving remission 1, 3:

• Mycophenolate 1-2 g/day or azathioprine 2 mg/kg/day plus low-dose prednisone (2.5-5 mg/day) for ≥3-5 years 3
• Add hydroxychloroquine (≤5 mg/kg/day, adjusted for GFR) for all patients unless contraindicated 1, 3

Henoch-Schönlein Purpura Nephritis

• For proteinuria 0.5-1 g/day per 1.73 m²: start ACE inhibitors or ARBs 1
• For proteinuria >1 g/day per 1.73 m² with GFR >50 mL/min per 1.73 m²: treat with 6-month corticosteroid course as for IgA nephropathy 1
• For crescentic disease: treat as crescentic IgA nephropathy 1

ANCA-Associated Vasculitis

For rapidly progressive glomerulonephritis with crescents:

• Initiate corticosteroids plus cyclophosphamide as induction therapy 1
• Consider rituximab as alternative to cyclophosphamide 1

Monitoring and Treatment Goals

Establish clear endpoints to assess response 2, 3:

• Reduction in proteinuria by ≥25% at 3 months and ≥50% at 6 months 3
• Preservation or improvement of kidney function (stable or improving eGFR) 3
• Monitor serum creatinine, eGFR, proteinuria, urinary sediment, and disease-specific serologies regularly 3

Critical Pitfalls to Avoid

• Do not use immunosuppression for genetic forms of glomerular disease identified by genetic testing—they will not respond 2, 7
• Do not use immunosuppression for secondary FSGS (from obesity, drugs, viral infections)—treat the underlying cause 7
• Avoid excessive diuretic dosing causing intravascular volume depletion despite peripheral edema 2
• Do not discontinue RAAS inhibitors prematurely for mild creatinine elevation (up to 30% increase is acceptable) 1
• Perform repeat biopsy if no response after 12 months of maintenance therapy to reassess diagnosis and guide further treatment 1