Background/Purpose: Podocytes, glomerular visceral epithelial cells, function as molecular sieve not to filter high molecular weight proteins such as albumin and globulins. Various immunological insults damage podocyte to cause detachment from capillary wall in lupus nephritis, leading to reduced podocyte number per glomeruli, glomerulosclerosis, and end stage kidney disease, because podocytes are unable to proliferate and regenerate itself. Therefore, we hypothesized that more podocyte loss or more podocyte damage in a certain period relates to poor renal outcome. It was recently reported that urinary podocyte number (U-Pod) and urinary podocalyxin (U-PCX) were related to podocyte injury in lupus nephritis. We conducted the longitudinal study to clarify the association of accumulated U-Pod and U-PCX with long-term 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. All patients were diagnosed as lupus nephritis with fulfilment of 1997 ACR classification of systemic lupus erythematosus and renal biopsy, and recruited between January 2011 and February 2015 (ISN/RPS Classification III: 2 patients, III+V: 3 patients, IV: 12 patients, IV+V: 7 patients, V: 1 patients). U-Pod, U-PCX, and eGFR were obtained around the treatment start, and at 1, 3, 6 and 12 months (mo) after treatment. eGFR was additionally obtained 5 years after treatment. Cumulative U-Pod (c-U-Pod) and (c-U-PCX) were generated by the summations of values measured at all 5 time points as above. U-Pod and U-PCX were compared between eGFR decliner and non-decliner (eGFR after 5 years – eGFR after 6 months). Correlation of c-U-Pod and c-U-PCX with the change of eGFR was analyzed. Statistical analysis was done with Mann-Whitney U test and Spearman correlation. p< 0.05 was defined as statistical significance. Each value was described as median and interquartile range.

Results: In this study, 10 eGFR decliner and 15 eGFR non-decliner were obtained. Both of c-U-Pod and c-U-PCX were not significantly different between eGFR decliner and eGFR non-decliner (c-U-Pod cells/mgCr, decliner: 3.18, 0.69-7.43, non-decliner: 5.93, 1.73-13.78, p=0.40, c-U-PCX mg/gCr, decliner: 911.1, 561.2-1401.0, non-decliner: 985.6, 396.6-1785.0, p=0.76). There was no significant correlation of c-U-Pod and c-U-PCX with long-term (4 years and 6 months) eGFR change (c-U-Pod: r 0.32, p=0.14, c-U-PCX: r 0.18, p=0.39).

Conclusion: c-U-Pod and c-U-PCX were not significantly associated with long-term eGFR change. Podocyte loss could not solely explain long-term renal prognosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-cumulative-urinary-podocyte-number-and-urinary-podocalyxin-with-long-term-renal-prognosis-in-lupus-nephritis/