Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM-1) as Predictors of Incident CKD Stage 3: The Atherosclerosis Risk in Communities (ARIC) Study
ABSTRACT Identifying individuals at risk of chronic kidney disease (CKD) is critical for timely treatment initiation to slow progression of the disease. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are known biomarkers of acute kidney injury, but it is unknown whether these markers are associated with incident CKD stage 3 in the general population.
Matched case-control study.
African American and white participants from the Atherosclerosis Risk in Communities (ARIC) Study who at baseline had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and urinary albumin-creatinine ratio ≤30 mg/g. 143 controls were matched for age, sex, and race to 143 cases of incident CKD stage 3 after 8.6 years of follow-up.
Quartile of NGAL and KIM-1.
Incident CKD stage 3 (eGFR <60 mL/min/1.73 m(2) at follow-up and a decrease in eGFR from baseline to follow-up ≥25%).
Both NGAL (P = 0.05) and KIM-1 levels (P < 0.001) were correlated positively with baseline urinary albumin-creatinine ratio; neither was associated with baseline eGFR. Participants with NGAL concentrations in the fourth quartile had more than 2-fold higher odds (adjusted OR, 2.11; 95% CI, 0.96-4.64) of incident CKD stage 3 compared with participants in the first quartile after multivariable adjustment (P-trend = 0.03). Adjustment for urinary creatinine and albumin levels resulted in a nonsignificant association (highest quartile adjusted OR, 1.52; 95% CI, 0.64-3.58; P = 0.2). No significant association between KIM-1 level and incident CKD was observed in crude or adjusted models.
The relatively small sample size of the study limits precision and power to detect weak associations.
Higher NGAL, but not KIM-1, levels were associated with incident CKD stage 3. Adjustment for urinary creatinine and albumin concentration attenuated this association. Additional studies are needed to confirm these findings and assess the utility of urinary NGAL as a marker of CKD risk.
- SourceAvailable from: Jimin Gao[Show abstract] [Hide abstract]
ABSTRACT: A revised classification of chronic kidney disease (CKD) was proposed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2012. Neutrophil gelatinase-associated lipocalin (NGAL) was considered as one of the most promising biomarkers in clinical nephrology. The aim of this study was to examine the level of NGAL in patients with different impairment of GFR based on the new classification, and to evaluate whether NGAL in serum or urine was associated with different risk categories in CKD patients.
- [Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVE:: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. METHODS:: In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. RESULTS:: Compared with the lowest tertiles, the highest tertiles of ACR (-0.15ml/min/1.73m2, p<0.0001), IL-18 (-0.09ml/min/1.73m2, p<0.0001) and KIM-1 (-0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87). CONCLUSIONS:: Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2012; 61(5). DOI:10.1097/QAI.0b013e3182737706 · 4.39 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The prevalence of diabetic nephropathy has tremendously increased with the relentless rise in the incidence of diabetes over the last couple decades. Diabetic nephropathy is a leading cause of morbidity and mortality, and it invariably leads to an end-stage renal disease (ESRD). In an effort to delay the onset of ESRD systematic screening and appropriate management are needed to evaluate the progression of renal damage in diabetic nephropathy. The reliability of current tests in predicting the onset, progression and response to various regimens for diabetic nephropathy is still under debate; and it has engendered a search for more sensitive and specific urinary biomarkers, especially those reflective of tubular dysfunctions. It is well-known that there is a good correlation between the degree of damage to the tubulo-interstitial compartment and the deterioration of renal functions. In view of this, the utility of urinary biomarkers, reflective of tubular injury, reported in the literature is discussed in this brief review.Endocrine 10/2012; 43(3). DOI:10.1007/s12020-012-9820-y · 3.53 Impact Factor