Table 3.
Human studies of soluble Klotho in AKI
| Study | Clinical Setting | AKI Definition | Methods | Results/Observations |
|---|---|---|---|---|
| Hu et al. (50) | 17 adults with AKI (inpatient consults) and 14 HV | ↑ SCr≥50% or ≥2 mg/dl | Urine immunoblot | Mean urine Klotho/Cr levels were significantly lower in AKI versus HV (4.85±1.69 versus 25.38±4.08 fmol/mg of Cr; P=0.01) |
| Liu et al. (120) | 35 adults undergoing cardiac surgery (19 AKI) | AKIN ≥ stage 1 (SCr only) | Serum ELISA | Serum Klotho levels were lower in patients with AKI versus patients without AKI immediately after CS: mean ± SD, 102±17 versus 124±21 U/L; P=0.05. Klotho levels increased as early as day 1 post-CS such that levels were no longer different in patients with AKI versus patients without AKI |
| Torregrosa et al. (121) | 60 adults undergoing cardiac surgery or coronary angiography (30 AKI) | ↑ SCr≥50% | Urine IBL and SSBT ELISA | Urine samples were collected 12 h post-CS or post-CA (single time point). Urine Klotho/Cr was not different in patients with AKI versus no AKI (mean ± SD, 2.45±0.26 versus 2.04±0.20 ng/mg of Cr; P=>0.05 by SSBT and 1.60±0.30 versus 1.24±0.30; P>0.05 by IBL). No correlation between the two Klotho assays was found |
| Kim et al. (122) | 61 adults in the ICU or floor (42 prerenal and 19 intrinsic AKI) | AKIN ≥ stage 1 | Serum and urine IBL ELISA | Patients with prerenal and intrinsic AKI had similar SCr levels. Urine Klotho/Cr levels were lower in prerenal versus intrinsic AKI (mean ± SD, 174±292 versus 381±630 ng/g of Cr; P=0.001). There was no difference between groups in serum Klotho levels |
| Castellano et al. (118) | 30 adults undergoing kidney transplant (15 developed DGF) | DGF | Serum IBL ELISA | Patients with versus without DGF had lower levels of serum Klotho at 2 yr post-transplantation |
| Seibert et al. (123) | 46 hospitalized adults (30 AKI; 16 controls) | AKIN ≥ stage 1 | Serum IBL ELISA | Serum Klotho levels were higher in AKI (assessed at the time of nephrology consultation) versus control patients (mean ± SD, 567.6±294.4 versus 403.5±152.5 pg/ml; P=0.01). AKI and controls were not matched |
| Neyra et al. (116) | 106 adults in the ICU (54 AKI; 52 controls) | KDIGO ≥ stage 2 | Urine immunoblot | Urine Klotho/Cr levels assessed at a single time point (at time of AKI diagnosis [patients] or within 24 h of ICU admission [controls]) were significantly lower in AKI versus controls: median (IQR), 9.2 (3.0–33.6) versus 25.0 (6.0–92.8) fmol/mg of Cr; P<0.001. Each one-fold higher urine Klotho/Cr level was associated with an 83% (95% CI, 60% to 93%) lower risk of major adverse kidney events at 90 d (composite of death, KRT dependence, or decrease in eGFR≥50% from baseline). ICU controls were matched to patients by age, sex, and baseline eGFR |
HV, healthy volunteer; SCr, serum creatinine; Cr, creatinine; AKIN, Acute Kidney Injury Network; CS, cardiac surgery; IBL, Immuno-Biologic Laboratories Co., Ltd.; SSBT, Shangai Sunred Biologic Technology Co., Ltd.; CA, coronary angiography; ICU, intensive care unit; DGF, delayed graft function (defined as need for KRT within 7 days post-transplantation); KDIGO, Kidney Disease Improving Global Outcomes; IQR, interquartile range; 95% CI, 95% confidence interval.