Table 2.
Research studies on biomarkers of renal tubular lesions and main outcomes in CKD patients.
| Year | Study Type | Study Population | Biomarker (s) | Study Outcomes | Reference |
|---|---|---|---|---|---|
| 2015 | Prospective cohort | 1245 women aged ≥ 70 from the general population | plasma NGAL | NGAL is of modest clinical utility in predicting renal function decline and acute or chronic renal disease-related events in individuals with mild-to-moderate CKD | [71] |
| 2015 | Cross-sectional | 276 type 2 diabetic patients with CKD at stage 1 and 2 | urinary L-FABP | Urinary L-FABP was significantly correlated with UACR in the early stages of CKD | [66] |
| 2015 | Prospective cohort | 138 patients with CHF | urinary KIM-1, NGAL, NAG | In patients with CKD progression, KIM-1 and NAG were elevated in contrast to NGAL; KIM-1 and NAG were negatively correlated with ejection fraction and eGFR | [58] |
| 2016 | Cross-sectional | 355 patients with CKD at stages 1–5 and 71 patients without CKD | plasma and urinary UMOD | UMOD allowed the identification of patients without CKD and patients at any stage of CKD; Plasma UMOD appears to outperform urinary uromodulin as a CKD marker |
[69] |
| 2016 | Prospective cohort | 244 adult patients with CKD | urinary NAG, L-FABP |
Elevated urinary L-FABP and low eGFR were associated with the development of ESRD and CVD, irrespective of diabetes | [65] |
| 2016 | Cross-sectional | 170 patients with CKD at stages 1 to 5 and 30 healthy individuals | serum UMOD | Serum UMOD concentrations in CKD patients were lower than in healthy subjects, and the lower concentrations were associated with more advanced stages | [68] |
| 2017 | Case–control | 74 adult CKD patients (stages 3–5) and 25 healthy subjects | urinary L-FABP | L-FABP shows a negative correlation with GFR and a positive correlation with UAC; in patients without albuminuria, L-FABP was associated with renal function decline | [64] |
| 2017 | Prospective cohort | 250 patients with CKD at stages 1–5, including 111 on hemodialysis | urinary KIM-1, NGAL, NAG | NGAL was moderately correlated with the 5 stages of CKD, while KIM-1 and NAG were also correlated, but weakly | [59] |
| 2018 | Cross-sectional | 80 patients with T2D without significant decrease in eGFR and albuminuria | urinary NGAL, KIM-1, UMOD | Urinary NGAL and KIM-1 correlated positively with albuminuria; all markers differed significantly between patients with moderately increased albuminuria compared to those with normal to mildly increased albuminuria | [55] |
| 2018 | Prospective cohort | 2813 patients from C-STRIDE study | serum UMOD | Higher incidence rates of ESRD, CVD and death were associated with decreased UMOD levels | [72] |
| 2018 | Cross-sectional | 132 patients with CKD at stages 1–5 and 33 patients without CKD | serum UMOD | UMOD levels inversely correlated with creatinine and creatinine/cystatin C-based eGFR | [70] |
| 2018 | Case–control | 324 participants from the SPRINT trial (162 who developed CKD during the follow-up and 162 matched controls) | urinary KIM-1, NGAL, UMOD | Only baseline concentrations of KIM-1 were associated with the development of incident CKD during the follow-up | [54] |
| 2018 | Prospective cohort | 527 adults with type 1 diabetes from the CACTI study | plasma KIM-1, NGAL, UMOD | NGAL and UMOD were associated with UACR and incident impaired GFR over the 12-year follow-up period | [56] |
| 2018 | Prospective cohort | 143 patients with stable CKD with diverse etiologies | urinary NGAL, KIM-1 | Neither NGAL nor KIM-1 provided robust prognostic information on the loss or renal function in a heterogeneous CKD population | [73] |
| 2018 | Cross-sectional | 109 biopsy-proven lupus nephritis patients and 50 healthy individuals | urinary NGAL, KIM-1 | Patients with active lupus nephritis exhibited elevated urinary levels of KIM-1 and NGAL compared with patients in remission and controls; KIM-1 levels correlated with tubular atrophy and interstitial inflammatory lesions | [74] |
| 2019 | Prospective cohort | 230 CKD patients stages 1 to 5 | urinary UMOD | UMOD concentrations were positively associated with eGFR and inversely associated with proteinuria; UMOD levels were independently associated with ESRD or rapid loss of eGFR | [75] |
| 2019 | Prospective cohort | 933 individuals aged ≥65 years from the CHS study | serum UMOD | Lower UMOD was associated with the development of ESRD independently of eGFR, UACR, and cardiovascular and CKD risk factors | [76] |
| 2019 | Cross-sectional | 39 children with kidney cysts, including 20 subjects with ADPKD, and 20 controls | urinary and serum L-FABP | Higher concentration of L-FABP in serum and urine indicated early damage to the renal parenchyma, detectable before the onset of hypertension and other organ damage | [77] |
| 2019 | Cross-sectional | 165 biopsy-proven CKD patients and 64 healthy controls | urinary NAG, KIM-1, NGAL | All biomarkers were significantly increased in patients, but their values were similar for patients with moderate and severe tubular injury | [78] |
| 2019 | Systematic review and meta-analysis | 22 studies involving 683 healthy individuals and 3249 diabetic patients | serum and urinary NGAL | Both urinary and serum NGAL showed an increasing trend, in parallel with albuminuria and progression of the disease, estimated by eGFR; the highest concentrations were achieved in patients with the highest severity of diabetic nephropathy | [52] |
| 2019 | Cross-sectional | 209 T2D normoalbuminuric patients with or without CKD | urinary NGAL | Levels of urinary NGAL were elevated in patients with renal insufficiency and negatively related to eGFR in T2D patients with normoalbuminuria | [79] |
| 2019 | Prospective cohort | 2377 participants from SPRINT trial with non-diabetic CKD | urinary UMOD | Lower uromodulin levels were associated with higher risk of CVD events and mortality, independently of eGFR, UACR, and other risk factors | [80] |
| 2019 | Cross-sectional | 287 T2D patients and 42 healthy controls | urinary NGAL | Urinary NGAL was significantly correlated with the UACR in patients with T2D | [81] |
| 2020 | Cross-sectional | 133 patients with diabetes and 39 healthy controls | urinary NGAL | Patients with severely increased albuminuria had higher levels of NGAL compared to patients with normal albuminuria and controls | [51] |
| 2020 | Prospective cohort | 4739 participants of the population-based Malmö Diet and Cancer Study | plasma KIM-1 | Plasma KIM-1 was able to predict the future decline of eGFR and the risk of CKD in healthy participants | [82] |
Abbreviations: ADPKD, autosomal dominant polycystic kidney disease; CACTI, Coronary Artery Calcification in Type 1 Diabetes study; CHF, congestive heart failure; CHS, Cardiovascular Health Study; CKD, chronic kidney disease; C-STRIDE, Chinese Cohort Study of Chronic Kidney Disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; KIM-1, kidney injury molecule-1; L-FABP, liver-type fatty acid binding protein; NAG, N-acetyl-β-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; SPRINT, Systolic Blood Pressure Intervention Trial; T2D, type 2 diabetes; UACR, urine albumin-to-creatinine ratio; UMOD, uromodulin.