Diagnosis and assessment of flares as well as treatment response in LN remains an area of unmet need in patients with LN. Kidney biopsy is the gold standard for diagnosis and assessment of LN flares to guide treatment despite its invasiveness and associated complications.[6, 7] Furthermore, kidney biopsy as a diagnostic test is not readily available in all centres, especially in developing countries and some conventional clinical and laboratory parameters used for making decisions on timing of kidney biopsy may lack specificity and sensitivity. There is therefore need to use more accurate and less invasive techniques other than kidney biopsy, serum creatinine, complements, urine protein and sediment in assessing disease activity and treatment response in LN. Although some studies have shown the usefulness of urinary biomarkers in diagnosis of disease activity in patients with LN,[11, 24, 25] we are unaware of any studies from Africa and whether these biomarkers could be useful in our population.
The main finding of this study is the correlation between both biomarkers and disease activity in patients with LN in our population. This suggests that these biomarkers could be useful for monitoring disease activity in patients with LN and for assessing response to induction treatment to determine if use of immunosuppression should be continued, tapered or stopped. It also suggests that these biomarkers can be useful for disease stratification and prognosis in patients. This is of relevance in resource poor countries where access to kidney biopsy is often unavailable. As kidney biopsy remains the most reliable way of “nailing down” the diagnosis of LN, easily available and non-invasive methods that are equally reliable needs to be sourced for such populations.
The pathogenesis of LN is known to involve a complex process, leading to glomerular autoantibody deposition, activation of complement and macrophages and production of pro-inflammatory cytokines and chemokines. Several studies have assessed for non-invasive ways of making a diagnosis or predicting increased disease activity in patients with LN.[11, 25, 27, 28] Most of these studies have relied on the activated inflammatory milieu in the kidney during an active state of the disease for production of cytokines or increased loss of epithelial cells into the urine. TWEAK belongs to the TNF superfamily of structurally related cytokines and its gene is expressed in multiple kidney cells including mesangial, glomerular and tubular cells of the kidney. During active inflammation, TWEAK binds to its receptor Fn14 (fibroblast growth factor-inducible 14) on cell surfaces signalling through the NF-κB pathway to stimulate a wide array of other cytokines, chemokines and cell adhesion molecules including MCP-1. This explains the rise in both uTWEAK and uMCP-1 during intra-renal inflammation.
Observations of increased levels of uTWEAK and uMCP-1 have been documented in other studies with some showing correlation with histological features on the kidney biopsy. One study from China reported a higher concentration of both biomarkers in the urine of patients with active LN compared to those with non-active disease (P < 0.01) and also showed significant correlation between both biomarkers and kidney biopsy activity index (P < 0.01) but not with chronicity index of the biopsies (P > 0.05)  Similar findings have been reported by other studies. 
Although our study did not demonstrate correlation between the biomarkers and renal activity scores, we think this may be related to the low sample size of our study given that other clinical and biochemical markers of activity were elevated at baseline and declined following treatment. This could suggest that these biomarkers can be useful for monitoring renal disease flares which are more aggressive and often more frequent in non-Caucasian populations. The usefulness of these biomarkers for monitoring flare of LN have been demonstrated in some studies [31, 32] while others have also shown their benefit with monitoring response to treatment. A study has suggested that combining both uMCP-1 and uTWEAK might be useful as potential predictors for proteinuria in LN. In a prospective multicentre study, uTWEAK was used, at month 3 of induction therapy, to predict complete response to treatment with a sensitivity of 70% and specificity of 63%. When they combined uTWEAK and level of urine protein excretion at month 3, this significantly improved the predictive performance for complete response at 6 months (ROC-AUC 0.83, p < 0.001).
The strength of this study is the ability to demonstrate that non-invasive methods can be used to detect disease activity in patients with LN in an African setting. If this can be further developed for routine clinical use, it will be of benefit in determining the treatment needs and prognosis of patients with LN. Limitations of our study include the size of our sample as well as our study design in which a repeat biopsy was not performed to clearly demonstrate reduced inflammation / activity of disease in the kidney. A repeat kidney biopsy could not be done due to the invasiveness of the procedure in the face of reducing amounts of daily urine protein excretion. Also, our study was not designed to assess the specificity and sensitivity of these biomarkers in predicting disease activity or treatment response which could be useful in making a preferred choice between both. Despite these limitations, we believe our study results demonstrate the usefulness of using non-invasive techniques in evaluating patients with LN in resource limited countries.