1908

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

1UCL; 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.

Histological pattern of ICKD / No.(%) / Interpretation
Membranous / 17 (19) / Considerable overlap in glomerular morphology and location of deposits seen between these three groups
Considered together for analysis as 'Core ICKD'
Mesangio-capillary / 5 (6)
Not Otherwise Specified (NOS) / 34 (39)
IgA Nephropathy / 26 (30) / These two groups were histologically or clinically (SLE) distinct and excluded from present analyses
Lupus nephritis (ie clinical SLE) / 6 (7)
Core ICKD / HIVAN / P value
Ethnicity (% black) / 54 / 97 / <0.001
HIV duration (median yrs) / 6.2 / 0.1 / <0.001
Nadir CD4 (cells/ mm3) / 155 / 56 / <0.001
Biopsy CD4
(cells/ mm3) / 382 / 122 / <0.001
eGFR at biopsy / 53 / 23 / <0.001
% on ART at biopsy / 67 / 35 / 0.02
% HIV RNA <200 c/ml / 53 / 19 / 0.04
ESKD 1yr post biopsy % / 4 / 32 / <0.0001
ESKD 5 yrs post biopsy % / 21 / 54 / <0.0001
Incidence rate ratios (IRR) / Core ICKD (n=44) / HIVAN
(n=32)
Black ethnicity / 2.23 [1.13, 4.40] / 9.94 [3.69, 26.75]
HIV viraemia / 1.48 [1.17, 1.86] / 1.35 [1.02, 1.79]
CD4 count / ns / 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.