Thanks to Naina for presenting an interesting case of a young woman presenting with fever, nausea/vomiting, and R flank pain found to have pyelonephritis and lupus nephritis!

Clinical Pearls

• Renal involvement is noted in ~50% of patients with SLE and can present as nephrotic or nephritic syndromes.
• The most common and severe form is diffuse proliferative lupus nephritis (class IV)
• It is important to distinguish SLE flare from an infection. When infection is present, it must be treated first before starting immunosuppression.
  • SLE flare is associated with a normal WBC, low CRP (because CRP production by hepatocytes is down-regulated by type 1 IFN release in lupus flare), and absence of fever
• Lab findings suggestive of flare include elevated anti-dsDNA (correlates with disease activity), low complement levels (predominantly C3 decline), worsening proteinuria, and elevated creatinine.

* Membranoproliferative GN can present with mixed nephrotic/nephritic picture.

SLE and renal disease:

• Renal involvement is common and eventually occurs in ~50% of SLE patients
• 10% progress to ESRD
• High mortality compared to SLE w/o nephritis
• More common and severe in African Americans, Hispanics, Asians and can be the only manifestation of lupus on presentation!
• Classifications of GN:
  • Can evolve from one to another
  • Minimal mesangial lupus nephritis (class I)
    • Earliest and mildest form
    • Rarely diagnosed b/c pts have a normal U/A, no or minimal proteinuria, and normal Cr
  • Mesangial proliferative lupus nephritis (class II)
    • Microscopic hematuria and/or proteinuria
    • Light microscopy would show mesangial hypercellularity or mesangial matrix expansion
  • Focal lupus nephritis (class III)
    • Hematuria, proteinuria, some HTN, decreased GFR
    • Less than 50% glomeruli affected by light microscopy
    • Segmental glomerulonephritis
  • Diffuse lupus nephritis (class IV)
    • Most common and most severe
    • Hematuria, proteinuria, nephrotic syndrome, HTN, reduced GFR
    • Hypocomplementemia (esp C3) and elevated anti-dsDNA during active disease
    • >50% of glomeruli are affected
  • Lupus membranous nephropathy (class V)
    • nephrotic syndrome, Cr normal or slightly elevated
    • Diffuse thickening of the glomerular capillary wall and subepithelial deposits
    • Can present without any other clinical or serologic manifestations of SLE
  • Advanced sclerosing lupus nephritis (class VI)
    • Slow, progressive renal dysfunction with proteinuria and relatively bland urine sediment
    • Global sclerosis >90% of glomeruli
    • Active GN no longer observed
• Treatment:

  • Best to initiate early but AFTER treatment of active infection:

    • Cyclophosphamide or Mycophenolate PLUS solumedrol 250-1 g/day x 3 days (former takes 10-14 days to have an effect so the latter is much faster) or prednisone 60 mg/day
    • Mycophenolate is the preferred choice to preserve fertility in women of reproductive age
  • Goals of therapy:
    • substantial reduction in urine protein excretion  to <0.33 g/day
    • improvement or stabilization of serum creatinine
    • improvement of urinary sediment