Novel biomarkers of acute kidney injury: Evaluation and evidence in urologic surgery

Table 1 Baseline reference values of novel biomarkers of acute kidney injury obtained from different studies

Biomarker	Injury	Source	Test	Unit	Healthy controls (range)
Cystatin C	Proximal tubule injury	Serum	Nephelometric immunoassay/ELISA	mg/L	0.53-0.95[38]
					0. 85 ± 0.21[39]
		Urine	Nephelometric immunoassay/ELISA	mg/L	0.051-0.28[37]
					0.02-0.11[96]
NGAL	Ischemia and nephrotoxins	Serum	ELISA	ng/mL	86.3 ± 43.0 (men)[54]
					88.9 ± 38.2 (women)[54]
					56.71 ± 17.57[39]
					1.7 ± 0.5[55]
					0.4-100[56]
		Urine	ELISA	ng/mL	5.7-17.7[55]
					11.94 ± 8.09[39]
					0.8-28.9 (men)[96]
					1.9-316.7 (women)[96]
KIM-1	Ischemia and nephrotoxins	Urine	ELISA	pg/mL	59-2146[70]
					395.1 ± 398.8[39]
					31.0-1000.0[56]
					31.0-1736.5[96]
IL-18	Toxic, delayed graft function	Urine	ELISA	pg/mL	1.4-1.8[80]
					3.0-108.6[96]
					6.2-311.1[96]
L-FABP	Ischemia and nephrotoxins	Urine	ELISA	ng/mL	3-400[83]
				μg/gCr	5.67 (2.74-8.21)[87]
NAG	Tubule injury	Urine	Colorimetry	U/g	0.75-0.90 U/g[95]
					1.06 ± 0.1 U/g (children)[90]

¹Lower reference values are not presented due to the detection limit of 0.05 mg/L. NGAL: Neutrophil gelatinase-associated lipocalin; KIM-1: Kidney injury molecule-1; IL-18: Interleukin-18; L-FABP: Liver-type fatty acid binding protein; NAG: N-acetyl-β-D-glucosaminidase; ELISA: Enzyme-linked immunosorbent assay; U: Unit.

Table 2 Biomarkers of acute kidney injury evaluated within urologic surgery settings

Ref.	Biomarker	Source	Cohort	Surgical setting	Outcome	Comparison	Time
Langetepe et al[65]	CysC, NGAL, KIM-1 Cr	Urine Serum	31 RCC patients	PN, RN	Increased values of CysC, NGAL, KIM-1 NGAL significant correlation to Cr No advantage for earlier detection of renal injury	Pre-/postoperative	24 h after surgery
Sprenkle et al[63]	NGAL	Urine	PN: 88 patients, RN: 32 patients, thoracic surgery: 42 patients	PN, RN (warm or cold ischemia)	No association between postoperative NGAL and any AKI AKI was not significantly associated with increased NGAL in PN patients No correlation with ischemia time Patients with eGFR < 60 mL/min per 1.73 m2 had higher NGAL postoperatively than those with an eGFR > 60 mL/min per 1.73 m2	PN/RN /thoracic surgery patients	4, 8, 12, 24 h post surgery
Parekh et al[62]	Cr, NGAL, CysC NGAL, LFABP, NAG, KIM-1, IL-18	Serum Urine, (renal biopsy)	20 patients with renal mass	PN (warm or cold ischemia)	Cr was significantly increased at 24 h CysC was not significantly changed at 2 or 24 h Significant increases serum NGAL at 2 and 24 h, increase of NGAL with increased ischemia time, no relation to peak Cr or morphology-score Early increases of L-FABP Early increase of NAG Increased NGAL at all times KIM-1maximally increased at 24 h IL-18 was increased at all time points	Correlation to renal biopsies (pre-, intra. postoperative)	2 or 24 h after surgery
Schmid et al[50]	Cr, CysC	Serum	31 RCC patients	PN, RN	Postoperative Cysc and Cr elevations similarly predict renal function deterioration CysC-based GFR appears superior to eGFR in “Cr-blind” area	Pre-/postoperative, 1 yr follow up	24 h, 1 yr after surgery
Xue et al[76]	Cr NGAL, KIM-1	Serum Urine	90 patients with obstructive uropathy	NA	KIM-1 and NGAL good accuracy for detecting AKI KIM-1 predicts the renal outcome 72 h postoperatively	Pre-/postoperative	4, 8, 12, 24, 48, 72 h after surgery
Cost et al[66]	NGAL	Urine (bladder and renal pelvis)	61 pediatric patients with ureteropelvic junction obstruction	Pyeloplasty	Significantly increased bladder NGAL Inverse correlation of bladder and renal pelvic NGAL levels with the differential renal function of the affected kidney	Healthy children	Intraoperative
Zekey et al[64]	Cr NGAL	Serum Urine	40 patients with kidney stones	SWL	No statistical Cr and urine NGAL levels	Before/after intervention	day 1, 2, 7 after intervention
Fahmy et al[74]	KIM-1, NAG	Urine	60 patients with kidney stones (50 SWL, 10 URS)	SWL, URS	KIM-1 values were increased in patients with kidney stones when compared with volunteers KIM-1 and NAG levels significantly increased post-SWL Poor kidney function was significantly associated with increased KIM-1 and NAG baseline and post-SWL No significant change in urinary KIM-1 and NAG concentrations before and after URS	Volunteers without kidney stones	2-3 h after intervention
Ng et al[82]	IL-18, NAG	Urine	206 patinets with renal stones	SWL	Increased IL-18 and NAG I slower shock wave delivery group	60 vs 120 shock waves/min	After intervention
Hatipoğlu et al[75]	KIM-1 (free radical production)	Urine	30 patients with kidney stones	SWL	Significant increase of KIM-1	Pre-/postoperative	2 h after intervention

PN: Partial nephrectomy; RN: Radical nephrectomy; NGAL: Neutrophil gelatinase-associated lipocalin; KIM-1: Kidney injury molecule-1; URS: Ureterorenoscopy; SWL: Shockwave lithotripsy; Cr: Creatinine; CysC: Cystatin C; LFABP: Liver fatty acid–binding protein; NAG: Nacetyl-b-D-glucosaminidase; eGFR: Estimated glomerular filtration rate; RCC: Renal cell carcinoma; NA: Not available.