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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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-relevance-of-urinary-podocyte-number-and-urinary-podocalyxin-level-with-response-to-treatment-and-1-year-renal-prognosis-in-systemic-lupus-erythematosus/