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

Area of Science:

• Nephrology
• Immunology
• Cell Biology

Background:

• Potassium (K+) is vital for cellular and organ function.
• Systemic K+ deficiency can cause kidney damage, termed hypokalemic nephropathy (HN).
• The long-term outlook for HN and the role of inflammation are not well understood.

Purpose of the Study:

• To investigate the presence of inflammation and tertiary lymphoid structures (TLSs) in human and mouse hypokalemic nephropathy kidneys.
• To explore the correlation between TLSs, fibrosis, and kidney function.
• To understand the potential role of TLSs in chronic kidney disease progression.

Main Methods:

• Analysis of five human kidney biopsy samples from HN patients.
• Examination of a mouse model of experimental post-HN kidneys.
• Histological analysis for T-cell infiltration, lymphocyte aggregates, and fibrosis.
• Long-term follow-up of human patients after K+ supplementation.

Main Results:

• All five HN kidneys showed T-cell infiltration; three had TLSs.
• No patients progressed to kidney failure after K+ supplementation over an average of 8.4 years.
• Mouse models developed fibrosis and TLS-like aggregates after recovery from a low-K+ diet, correlating positively.
• TLS-like lymphocyte aggregates were identified in both human and mouse post-HN kidneys.

Conclusions:

• Tertiary lymphoid structures (TLSs) are present in hypokalemic nephropathy (HN) kidneys.
• TLSs may indicate a risk for chronic kidney disease progression in HN.
• TLSs might contribute to a persistent inflammatory microenvironment in HN kidneys.