Tertiary Lymphoid Structure-Like Lymphocyte Aggregate Generation in Human and Mouse Hypokalaemic Nephropathy:...

Potassium (K⁺) is an essential ion that keeps the cells and organs functioning properly. Systemic K⁺ deficiency occasionally leads to kidney damage, known as hypokalaemic nephropathy (HN). Hypokalaemic nephropathy is commonly treated with K⁺ supplementation; however, the long-term prognosis of HN and the role of inflammation remain poorly understood. Here, we analysed five kidney biopsy samples from patients diagnosed with HN at a single centre. All five HN kidneys displayed T-cell infiltration, and three showed segregated T and B lymphocyte aggregates, suggesting the presence of tertiary lymphoid structures (TLSs). No patient progressed to kidney failure after K⁺ supplementation over 8.4 ± 3.4 years of follow-up. We also analysed a mouse model of experimental post-HN kidneys. After a low-K⁺ diet for six weeks, feeding a six-month recovery diet restored K⁺ levels and the kidney function of HN. Histologically, however, fibrosis and TLS-like aggregates developed in the post-HN kidneys, manifesting a positive correlation between them. Together, we identified TLS-like lymphocyte aggregates in human HN kidneys and mouse post-HN kidneys. Our study indicates that TLSs may reflect the risk of chronic kidney disease progression and contribute to a perpetuating inflammatory microenvironment in HN kidneys.