(A) Complications of CKD. Kidney disease is associated with disruption of peripheral and central circadian rhythms. The molecular clock modulates the levels or activity of serum phosphate, parathyroid hormone, erythropoietin (EPO), and other hormones that are known to exhibit diurnal rhythms. (B) Schema of progression of SLE to end-organ renal disease (lupus nephritis [LN]) and potential contribution from disturbed circadian clock. Genetically susceptible individuals develop SLE. During disease progression there is a complex crosstalk between multiple cell types involving both innate and adaptive immune systems. The antigen-presenting cells (APCs) present self-antigens from various sources to T lymphocytes, which results in generation of autoreactive T cells. These CD4⁺ T lymphocytes in turn instruct B cells to produce autoantibodies of different specificities that deposit as immune complexes (ICs) in the glomeruli. This leads to progressive glomerular pathology and local production of chemoattractants and matrix proteins, resulting in immune cell infiltration and tissue damage. Loss of glomerular permeability also leads to tubulointerstitial injury, which is perpetuated by intrinsic tubular cell inflammatory phenotype and infiltrating immune cells and eventually leads to renal failure. Sleep fragmentation or genetic mutations in key clock proteins in SLE patients can potentially accentuate immune cell effector function. Furthermore, mutations in the renal intrinsic cells’ clock genes can render them susceptible to injury, as local injurious events unfold during the progression of LN.