Lupus membranous GN

Sites of kidney disease
  • Glomerular
  • Tubular
  • Mesangial
  • Interstitial
Stages of CKD based on GFR and albuminuria
   GFR stages      
    G1    >90    Normal
    G2    60-89    Mildly decreased
    G3a    45-59    Mildly to moderately decreased
    G3b    30-44   
    G4    15-29   
    G5    <15   
    Albuminuria stages      
    A1      
    A2      
    A3      
         

How is kidney function measured?

Accurate measurements of kidney function are too laborious to be used in practice. We substitute a convenient but less accurate way to measure by taking the serum creatinine level and plugging it into an equation that contains patient gender and age. [4]

Glomerulonephritis (GN)

Management of proteinuria in GN

Reduction in proteinuria is important, as it reflects control of the primary disease, reduction of glomerular hypertension, and also reduction of podocyte damage (likely a major factor in glomerular scarring). Most studies suggest that the loss of kidney function in the progressive histologic patterns discussed in this guideline largely can be prevented if proteinuria can be reduced to levels below 0.5 g/d, and progression slowed if reduced to levels below 1–1.5 g/d.[1]

Minimal change GN

MPGN

DFGS

Membranous GN

Characterized by massive proteinuria and usually no or minimal blood in urine. Patients often present with leg swelling or even pulmonary edema. Cause could be cancer or lupus. Anti-PLA2R antibody is a marker for primary disease. Tests for underlying diseases:[1]
  • CXR (sarcoidosis)
  • ANA (lupus)
  • Cancer screening
  • Hep B, Hep C, HIV, treponemes
  • Ultrasound kidneys
  • Drug history (NSAID, Gold, Penicillamine)

Definition of remission

Complete
Protein <300 mg per day + stable serum creatinine + serum albumin >3.5 mg/dL
Partial
Protein 300-3500 mg per day + decrease >50% baseline

KDIGO practice points

  • 3.1 Diagnosis 
    • Practice Point 3.1.1: A kidney biopsy is not required to confirm the diagnosis of membranous nephropathy (MN) in patients with nephrotic syndrome and a positive anti-PLA2R antibody test. 
    • Practice Point 3.1.2: Patients with MN should be evaluated for associated conditions, regardless of whether anti-PLA2R antibodies and/or anti-THSD7A antibodies are present or absent.[1]
  • 3.2 Prognosis
    • 3.2.1 Assess risk
      • Low risk
      • Mod risk
      • High risk
      • Very high risk
    • High risk = GFR <60 and/or proteinuria >8 g/d x >6 mos OR noral GFR and protein >3.5 g/d and no decrease >50% with treatment with ACEI AND at least one of PLAR>50, alb<2.5 mg/dL
  • 3.3 Treatment
    • 3.3.1 For patients with MN and at least one risk factor for disease progression, use rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months, or CNI-based therapy for 6 months, with the choice of treatment depending on the risk estimate. 
    • 3.3.4: Longitudinal monitoring of anti-PLA2R antibody levels at 6 months after start of therapy may be useful for evaluating treatment response in patients with MN, and can be used to guide adjustments to therapy[1]

Treatment of Membranous GN

Rituximab
  •  Rituximab is preferred first-line for high- or very-high-risk patients who have normal or near-normal kidney function and moderate-risk patients. 
  • The optimal dosing regimen for rituximab is uncertain. In the MENTOR trial, 1 g initially followed 14 days later by another 1 g dose but some experts use an alternative regimen, 375 mg/m2 weekly for four weeks or a B cell-driven approach in which a second dose of 375 mg/m2 is given if ≥5 circulating B cells/microL are detected by flow cytometry one week after treatment.
  • No controlled trials have compared the efficacy of the various rituximab regimens. [2]
  • RCTs and cohort studies have shown that rituximab and CNIs increase the rate of complete and partial remissions.[1]
  • 65% complete or partial remission at 6 mos vs 34% non-immunosuppressive antiproteinuric treatment [3]
Cyclophosphamide
  • Combination therapy with a cytotoxic agent (cyclophosphamide or chlorambucil) and glucocorticoids is the preferred initial therapy for patients classified as high or very high risk because of deteriorating kidney function due to MN 
  • for whom immunosuppressive therapy is felt to be appropriate
  • Cytotoxic therapy can be used if rituximab is unavailable.
Prednisone


References

[1] KDIGO Guidelines 2021
[2] A De Vriese. Membranous nephropathy: Treatment and prognosis. Uptodate
[3] K Dahane et al. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up 2016
[4] D Tuot, N Powe. Care of the Patient with Abnormal Kidney Test Results. Ann Int Med May 2023