O2
HIV-IMMUNE COMPLEX KIDNEY DISEASE: RISK FACTORS AND
PROGRESSION TO END-STAGE KIDNEY DISEASE
Booth JW1, Hamzah L2, Jose S1, McAdoo SP3, Turner-Stokes T1, Horsfield C2, O'Donnell PJ2,
Baharani J4, Kingdon E5, Hendry BM2, Hilton R2, Levy J3, Sabin C1, Post FA2, Connolly JO1
1
UCL; 2King's Health Partners; 3Imperial College; 4Birmingham, 5Brighton, UK
PROBLEM: Immune complex kidney disease (ICKD) has become the dominant pathology in
renal biopsy series of HIV+ patients. Despite this, the spectrum of ICKD in HIV remains poorly
described and optimal treatment unclear. In particular, the benefit of anti-retroviral therapy
(ART) is uncertain.
PURPOSE: 1) To define the spectrum of biopsy-proven ICKD in a large contemporary HIV+
cohort, 2) To examine renal outcomes in ICKD in comparison to patients with HIV-associated
nephropathy (HIVAN) and 3) To examine risk factors associated with ICKD and HIVAN in the
UK Collaborative HIV Cohort (CHIC) study cohort.
DESIGN: We reviewed consecutive renal biopsies (1998-2012) of HIV+ patients attending
eight clinics in the UK. ICKD was defined by the unequivocal presence of glomerular
immunoglobulin deposits and corroborated, where available, by the presence of electron dense
deposits on electron microscopy. We compared patients with ICKD to those with HIVAN and
patients without renal biopsies in the UK CHIC cohort. Kaplan-Meier analysis was used to
estimate progression to end-stage kidney disease (ESKD), and Poisson regression analysis to
examine factors associated with ICKD and HIVAN in the UK CHIC cohort.
RESULTS: Of 250 diagnostic biopsies, 88 (35%) showed ICKD and 67 (27%) HIVAN.
Table 1: Spectrum of ICKD in the biopsy cohort
Histological pattern of ICKD
Membranous
Mesangio-capillary
Not Otherwise Specified (NOS)
IgA Nephropathy
Lupus nephritis (ie clinical SLE)
No.(%)
17 (19)
5 (6)
34 (39)
26 (30)
6 (7)
Interpretation
Considerable overlap in glomerular morphology and
location of deposits seen between these three groups
Considered together for analysis as 'Core ICKD'
These two groups were histologically or clinically (SLE)
distinct and excluded from present analyses
Table 2: Clinical characteristics and outcomes
Ethnicity (% black)
HIV duration (median yrs)
Nadir CD4 (cells/ mm3)
Biopsy CD4
(cells/ mm3)
eGFR at biopsy
% on ART at biopsy
% HIV RNA <200 c/ml
ESKD 1yr post biopsy %
ESKD 5 yrs post biopsy %
Core
ICKD
54
6.2
155
382
HIVAN
P value
97
0.1
56
122
<0.001
<0.001
<0.001
<0.001
53
67
53
4
21
23
35
19
32
54
<0.001
0.02
0.04
<0.0001
<0.0001
Table 3: Multivariable analysis of
risk factors in the UK CHIC
cohort (31,483 patients)
Incidence
rate ratios
(IRR)
Black
ethnicity
HIV
viraemia
CD4
count
Core
ICKD
(n=44)
2.23 [1.13,
4.40]
1.48 [1.17,
1.86]
ns
HIVAN
(n=32)
9.94 [3.69,
26.75]
1.35 [1.02,
1.79]
0.78 [0.68,
0.88]
CONCLUSIONS: Black ethnicity and HIV viraemia were risk factors for both 'core' ICKD and
HIVAN. Compared to HIVAN, ICKD was associated with less advanced immunodeficiency
and a lower rate of progression to ESKD.
IMPACT: This focussed study of ICKD in HIV has identified a 'core' group of nephropathies
with common clinical and histological features. The observed association with HIV viraemia
provides the first objective evidence that the risk of developing 'core' ICKD in HIV may be
reduced by viral suppression with ART.