title: Overlapping pathways to transplant glomerulopathy: chronic humoral rejection, hepatitis C infection, and thrombotic microangiopathy.
abstract: Transplant glomerulopathy (TG) has received much attention in recent years as a symptom of chronic humoral rejection; however, many cases lack C4d deposition and/or circulating donor-specific antibodies (DSAs). To determine the contribution of other causes, we studied 209 consecutive renal allograft indication biopsies for chronic allograft dysfunction, of which 25 met the pathological criteria of TG. Three partially overlapping etiologies accounted for 21 (84%) cases: C4d-positive (48%), hepatitis C-positive (36%), and thrombotic microangiopathy (TMA)-positive (32%) TG. The majority of patients with confirmed TMA were also hepatitis C positive, and the majority of hepatitis C-positive patients had TMA. DSAs were significantly associated with C4d-positive but not with hepatitis C-positive TG. The prevalence of hepatitis C was significantly higher in the TG group than in 29 control patients. Within the TG cohort, those who were hepatitis C-positive developed allograft failure significantly earlier than hepatitis C-negative patients. Thus, TG is not a specific diagnosis but a pattern of pathological injury involving three major overlapping pathways. It is important to distinguish these mechanisms, as they may have different prognostic and therapeutic implications.
authors.affiliation: Department of Nephrology and Medical Intensive Care, Campus Virchow Clinic, Charite Universitatsmedizin Berlin, Berlin, Germany. seema.baid-agrawal@charite.de
authors.forename: Seema
authors.initials: S
authors.lastname: Baid-Agrawal
authors.forename: Alton B
authors.initials: AB
authors.lastname: Farris
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.forename: Shamila
authors.initials: S
authors.lastname: Mauiyyedi
authors.forename: Mary Lin
authors.initials: ML
authors.lastname: Farrell
authors.forename: Nina
authors.initials: N
authors.lastname: Tolkoff-Rubin
authors.forename: A Bernard
authors.initials: AB
authors.lastname: Collins
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frei
authors.forename: Robert B
authors.initials: RB
authors.lastname: Colvin
mesh_terms: D002908:Chronic Disease; D015935:Complement C4b; D006084:Graft Rejection / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood; D057049:Thrombotic Microangiopathies / Q000150:complications*; D014019:Tissue Donors
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d