Klotho: A multifaceted protector in sepsis-induced organ damage and a potential therapeutic target

Table 3 Summary of clinical data showing the change in klotho expression in septic patients

Sepsis model	Mechanism	Effect	Ref.
Sepsis patients. Collection of warm postmortem biopsies from patients who died of sepsis and renal failure in the ICU	Reduction in renal klotho level. Increased mRNA levels of kidney damage markers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1	Correlated to renal damage	Jou-Valencia et al[38]
Sepsis patients	Reduced serum klotho level	An early predictor of AKI to allow immediate interventions	Pei et al[69]
A prospective cohort of ICU patients with sepsis and previously normal renal function	Low klotho and high erythropoietin plasma levels are cofactors for activating FGF-23	The klotho level is an early predictor of the development of AKI, mortality, and long-term CKD progression in sepsis patients	Toro et al[37]
Patients with CKD are admitted to the ICU with acute inflammation/sepsis	At the peak of infection, suppressing the active form of FGF-23 and activating α-klotho	Counter-regulatory response to acute inflammation	Dounousi et al[62]
Patients admitted to the ICU with septic shock within the previous 72 hours	Increasing serum level of α-klotho	Higher mortality rate	Abdelmalik et al[40]

AKI: Acute kidney injury; CKD: Chronic kidney disease; FGF: Fibroblast growth factor; ICU: Intensive care unit.