Background/Purpose: Complement activation is one of the important pathogenic features of lupus nephritis and low serum complements are conventionally used to monitor disease activity in lupus  Earlier we have shown that urinary C3d correlates with renal disease activity in a cross sectional study(1).  In this study we sought to explore whether urine C3d correates with renal disease activity after 3 months of immunosuppressive therapy.

Methods:  37 consecutive patients of SLE who fulfilled  SLE SLICC 2012 classification criteria seen between – through – month and year  were included in the study of which 18 (M:F-1:17) patients were biopsy proven active nephritis (AN) (defined if there was urinary protein 1 g/day or 0.5g/day and sediment abnormalities (urine RBC or WBC count >5/hpf ) or increased serum creatinine), 4(M:F-1:3) were inactive nephritis(IN), 5(All females) were non nephritis(NN) and 10(all females) were age and sex matched healthy controls . Plasma and urine samples were collected for all the patients and stored at -80. Repeat samples were taken for active nephritis patients on 3 months follow up. Clinical parameters were noted and serum C3,C4 and antiDsdna was obtained. SLEDAI and renal SLEDAI was calculated. Urine C3d was analysed using commercially available ELISA Kit and the values were normalized to creatinine excretion(pg/mg).

All statistical analysis was done using SPSS ver 23.

Results: Twelve patients achieved remission or low disease activity at 3 months.  In these 12 patients the median Urinary C3d significantly decreased from 800.43 pg/mg(IQR- 115.32-1517.52) to                                                                        50.34 pg/mg, (28.43-756.17) after 3 months of treatment(p-0.01). This could be due to increase in C3d values on follow up in 6 patients in whom proteinuria was persistent and there was no response to treatment. The Area under curve(AUC) for differentiating active nephritis from inactive nephritis was 0.926 ( SE- SE-0.064, 95%CI- O.8012-0.99, p- 0.009). The AUC for differentiating active nephritis from extra renal lupus was 0.647 (SE-0.117 95%CI-0.419-0.875, p -0.009) and from healthy controls was 0.906 (SE-0.061, 95%CI- 0.7872-0.99, p-0.001). There was a significant correlation of Urine C3d values with Urine protein to creatinine ratio( r-0.458, p-0.002) but no correlation was seen with serum C3, C4, antidsdna , SLEDAI and rSLEDAI.

Conclusion: Urinary C3d levels can be used to differentiate active renal from inactive renal disease and extra renal involvement. Decrease in urinary levels on follow up makes it a useful biomarker to monitor treatment. Lack of correlation with serum C3 points towards renal generation of C3d and hence an added biomarker in our current repertoire.
References: 
1. Negi VS, Aggarwal AM, Dayal RA, Naik SI, Misra RA. Complement degradation product C3d in urine: marker of lupus nephritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-c3d-is-a-good-marker-for-monitoring-treatment-response-after-3-months-of-induction-treatment-in-patients-with-biopsy-proven-lupus-nephritis/