The predominant phenotype of DGKEnephropathy is early-onset relapsing HUS with chronic proteinuria and long-term progression to CKD. Most patients with DGKE-HUS are diagnosed within the first year of life, although later presentations also occur. Relapsing HUS is common, and viral infections are frequently reported as triggers.
A second presentation is a more chronic proteinuric glomerulopathy with an MPGN-like biopsy pattern and no overt HUS. These patients are often older at diagnosis and may have nephrotic-range proteinuria that persists long term. Overlap phenotypes with features of both HUS and MPGN/TMA have also been described. The long-term outcome is variable. Many patients continue to have proteinuria and hypertension, and some progress to end-stage kidney disease. Complement levels are typically normal, but they are often abnormal since DGKE-related diseases are almost invariably triggered by infections. As with all forms of kidney TMA, complement biomarkers are unhelpful for diagnosis.
Figure 2. Clinical phenotypes and progression of DGKE-associated nephropathy.
This schematic illustrates two major clinical trajectories observed in patients with DGKE-related disease. In both groups, proteinuria increases progressively over time and may lead to chronic kidney disease and eventual kidney failure. In a minority of patients (approximately 5–10%), disease presents primarily as progressive proteinuric nephropathy without early thrombotic events. In contrast, most patients (approximately 90–95%) present in early childhood with recurrent TMA episodes (red peaks), often triggered by intercurrent illness, followed by persistent proteinuria and progressive renal impairment. Despite differences in early presentation, similar pathogenic DGKEgenotypes are observed across both phenotypic groups.
