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Abstract Number: 1666

The Relevance of Urinary Podocyte Number and Urinary Podocalyxin Level with Response to Treatment and 1 Year Renal Prognosis in Systemic Lupus Erythematosus

Hiroshi Kajiyama1, Keiju Hiromura2, Daisuke Ikuma1, Hidekazu Ikeuchi2, Hiroyuki Kurosawa3, Yoshiaki Hirayama3, Fumio Gondaira3, Masanori Hara4, Yoshihisa Nojima2 and Toshihide Mimura5, 1Department of Rheumatology and Applied Immunology, Saitama Medical University, Saitama, Japan, 2Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan, 3Department of reagent research and development, Denka Seiken Co. Ltd., Niigata, Japan, 4Department of Pediatrics, Yoshida Hospital, Niigata, Japan, 5Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biomarkers, Lupus nephritis, prognostic factors, systemic lupus erythematosus (SLE) and treatment

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Session Information

Session Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment: Biomarker, Translational and Nephritis Studies

Session Type: Abstract Submissions (ACR)

Background/Purpose

Podocytes are glomerular visceral epithelial cells, whose number decrease due to death and/or detachment from capillary wall leads to severe proteinuria and end stage kidney disease. Podocalyxin (PCX) is one of the podocyte markers, and we reported in ACR meeting last year that two different urine PCX-related biomarkers, urine numbers of PCX-positive cells (podocytes, U-Pod) and urine levels of PCX (U-PCX) were higher in systemic lupus erythematosus (SLE) patients with kidney disease (KD) than those without KD. Purpose of this longitudinal study is to clarify the relevance of U-Pod and U-PCX with the response to treatment and renal prognosis.

Methods

U-Pod were determined by counting PCX-positive cells in sediments from urine samples. U-PCX were measured by sandwich ELISA, normalized to urine creatinine levels. Patients with proteinuria (defined as more than 0.2 urine protein/creatinine ratio, U-PCR) and/or renal failure (defined as estimated glomerular filtration rate, eGFR, less than 60 mL/min/1.73m2) were defined as KD(+), and other patients were defined as KD(-). Patients were recruited between October 2010 and March 2013, 18 SLE-KD(+) patients (ISN/RPS Classification, IV: 5 patients, IV+V: 2 patients, V: 2 patients, biopsy was not performed in 9 patients), and 11 SLE-KD(-) patients. U-Pod, U-PCX, U-PCR and eGFR were obtained around the treatment start, and at 1, 3, 6 and 12 months (mo) after treatment. Correlation of cumulative U-Pods generated by the summations of U-Pods in first 6 months with one year change of eGFR was determined. Statistical analysis was done with Wilcoxon signed-rank test and Spearman correlation. p<0.05 was defined as statistical significance. Each value was described as median and interquartile range.

Results

In KD(-), U-Pod, U-PCX, and U-PCR were not significantly changed all through the year. In KD(+), U-PCR was significantly improved from 6 mo after treatment (before treatment 2.86 (0.91, 5.16), vs 1 mo 1.15 (0.42, 3.99) p=0.2366, vs 3 mo 0.41 (0.21, 3.80) p=0.0894, vs 6 mo 0.31 (0.11, 0.95) p=0.0004, vs 12 mo 0.22 (0.08, 0.72) p=0.0061). U-Pod significantly improved at 1 mo after treatment (before treatment 1.65 (0, 6.07), vs 1 mo 0.30 (0, 1.48) p=0.0084, vs 3 mo 0.30 (0, 0.60) p=0.0046, vs 6 mo 0 (0, 0.45) p=0.0037, vs 12 mo 0 (0, 0.25) cells/mL p=0.0039). Interestingly, U-PCX improvement delayed significantly, and was observed from 6 mo (before treatment 360.0 (160.0, 586.8), vs 1 mo 363.5 (185.5, 540.8) p=0.4204, vs 3 mo 294.0 (114.0, 422.5) p=0.072, vs 6 mo 154.9 (65.5, 251.5) p=0.0039, vs 12 mo 66.6 (41.5, 178.3) μg/gCr p=0.0008). One year changes of eGFR (subtracting 12 mo eGFR from pre-treatment eGFR) were -2.067 (-10.59, 16.00) mL/min./1.73m2 in KD(+) and -20.61 (-35.75, 1.002) mL/min./1.73m2in KD(-). There was no significant correlation of cumulative U-Pods with one year change of eGFR both in KD(+) and KD(-) (p=0.7228, and p=0.3831).

Conclusion

U-Pod significantly improves one month after treatment much faster than U-PCR and U-PCX, suggesting that U-Pod reflects acute inflammation, and that U-PCX is more relevant to filter dysfunction of podocyte. Cumulative podocyte loss may not affect decline of eGFR in one year in SLE.


Disclosure:

H. Kajiyama,
None;

K. Hiromura,
None;

D. Ikuma,
None;

H. Ikeuchi,
None;

H. Kurosawa,
None;

Y. Hirayama,
None;

F. Gondaira,
None;

M. Hara,
None;

Y. Nojima,
None;

T. Mimura,
None.

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