Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Renal disease in scleroderma (SSc), including
scleroderma renal crisis (SRC), remains a major clinical challenge. Previous
studies showed up to 50% of SSc patients have renal
involvement. We sought to gain insight into the pathogenesis of SSc kidney disease by examining markers of disease in
serum, urine and renal biopsy specimens.
We collected urine and serum from 80 SSc patients,
with or without renal involvement, for comparison with patients with kidney
disease of other causes (n=10) and healthy controls (n=12). We performed
multiplex analysis of candidate markers of disease activity or severity in SSc and renal injury: MCP-1, MCP-3, IL-6, IL-18, TNFalpha, and VEGF. In a further experiment we examined
biopsies of patients with SRC using immunostaining
40 SSC patients were in the subgroup with renal involvement (“SSc-CKD”) defined by eGFR,
urinalysis or a history of SRC. Serum MCP-1 was increased in SSc compared with controls, with SSc-CKD
significantly lower than SSc without renal
involvement. Mean serum MCP-1 was 132 pg/ml (95% CI
105-162) for SSc with normal renal function compared
with 65 pg/ml in SSc-CKD
(49-81, p<0.001 for this comparison). MCP-1 was not increased in renal
disease of other causes (mean 47 pg/ml, 23-85)
compared with controls (mean 53 pg/ml, 25-85,
p=0.848). Conversely, urine MCP-1:creatinine ratio was
higher in SSc-CKD (mean 64, 32-111) than in SSc with normal renal function (mean 23, 18-28, p=0.046).
20 SRC cases
confirmed on histology were stained with IgG antibodies for MCP-1 (see figure).
Expression was highest in the tubules, interstitium and vasculature. The number
of typical “onion skin” arterial lesions seen was positively correlated with
the level of MCP-1 expression in the vasculature overall (p=0.048).
This is the first study to measure MCP-1 in the urine of SSc
patients. Elevated urine MCP-1 in SSc with renal
involvement was corroborated by immunohistochemistry demonstrating marked expression
of the chemokine in the kidneys of affected patients. The identification of
urine MCP-1 as a marker for local expression in the kidney may help define
organ-specific effects of this chemokine, which has previously been reported to
be increased in serum in association with pulmonary complications. Our findings
support further investigation of urine concentrations of MCP-1 as a marker or
mediator of renal disease in SSc.
To cite this abstract in AMA style:Stern E, Hong C, Ong VH, Burns A, Unwin R, Denton CP. Monocyte Chemoattractant Protein-1 (MCP-1, CCL2) Is a Potential Local Marker of Renal Involvement in Scleroderma [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/monocyte-chemoattractant-protein-1-mcp-1-ccl2-is-a-potential-local-marker-of-renal-involvement-in-scleroderma/. Accessed March 3, 2021.
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