For this reason, we reckon that, prior to a universal recommendation of CNI as first line treatment in LN, these findings have to be corroborated in large, multiethnic randomised trials with a prolonged follow up, as patients from different racial or ethnic backgrounds may respond variably to IS drugs.51 With current knowledge, we consider CNI for patients with proliferative or membranous LN who are refractory to initial treatment after 6 12 months, especially when proteinuria/nephrotic syndrome is the cardinal manifestation. In such cases, we typically add the CNI to MMF, rather than using CNI monotherapy52 (provided a well controlled blood pressure, lack of significant renal fibrosis and a glomerular filtration rate >60 mL/min2). For refractory patients with predominant nephritic features, we favour the use of high dose intravenous CYC or RTX (see also below) over CNI.

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