The prognosis and pathogenesis of severe lupus glomerulonephritis.
BACKGROUND
The International Society of Nephrology/ Renal Pathology Society classification (ISN/RPS) of lupus glomerulonephritis (GN) divides diffuse GN (>/=50% involvement) into diffuse segmental (IV-S) and diffuse global GN (IV-G). This division tests whether the pathogenesis and clinical outcomes are the same as when similar patients are classified using the World Health Organization (WHO) classification into severe segmental (WHO III >/=50%) and diffuse global (WHO-IV) GN.


METHODS
Thirty-nine renal biopsies with WHO class IV and 44 with WHO III >/= 50% were reclassified using the ISN/RPS and were correlated with pathogenesis and outcome.


RESULTS
There were 22 biopsies with ISN/RPS class IV-S. ISN/RPS class IV-G comprises two morphologically discrete classes of renal biopsies: 39 biopsies originally classified as WHO class IV (WHO-IV) and 22 that switched from WHO III >/=50% to ISN/RPS class IV-G (IV-Q). We will analyze IV-S, IV-Q and WHO-IV separately. WHO-IV had significantly more immune aggregate deposition than IV-S and IV-Q. WHO-IV had lower serum complements C3 (P = 0.05) and C4 (P = 0.05) than patients with IV-Q. Patients with WHO-IV had more remissions (56%) than IV-Q (23%) (P = 0.01), and stable renal function at the last follow-up was less frequent in patients with IV-Q (18%) than IV-S (50%, P = 0.05) and WHO-IV (62%, P = 0.001). Renal survival and renal survival without end-stage renal disease were different when the patients were diagnosed as WHO classes III >/=50% and IV, but the outcomes for ISN/RPS class IV-S and IV-G (WHO-IV plus IV-Q) were not different.


CONCLUSIONS
WHO III >/=50% and WHO-IV lupus GN are not congruent with ISN/RPS IV-S and IV-G. The ISN/RPS minimizes pathological and outcome differences between classes IV-S and IV-G which results in the loss of informational content from the renal biopsies. ISN/RPS does not detect pathogenetic or clinical differences among patients with severe lupus GN.
Department of Pathology, Rush University Medical College, 1753 W. Congress Parkway, Chicago, IL 60612, USA. Melvin_Schwartz@rush.edu
Melvin M
MM
Schwartz
Stephen M
SM
Korbet
Edmund J
EJ
Lewis
D000284:Administration, Oral; D000328:Adult; D001706:Biopsy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007678:Kidney Glomerulus / Q000473:pathology*; D008181:Lupus Nephritis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D010956:Plasmapheresis / Q000379:methods; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011241:Prednisone