Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients

Abstract

Diabetic kidney disease develops in half of genetically predisposed patients with type 2 diabetes (T2DM). Early diagnosis of kidney damage and nephroprotective treatment are the ways of preventing the disease progression. Our aim was to evaluate selected laboratory markers of glomerular and tubular damage in T2DM patients with early stages of chronic kidney disease (G1/G2, A1/A2) for their associations with A2 albuminuria and early decline in the estimated glomerular filtration rate (eGFR). Among 80 T2DM patients with median eGFR of 92.4 ml/min/1.73 m2 and median urinary albumin to creatinine ratio (uACR) of 4.69 mg/g, 19 had uACR > 30 mg/g (A2). Higher serum cystatin C, serum and urine neutrophil gelatinase associated lipocalin (NGAL), urine kidney injury molecule 1 (KIM-1), detectable urine transferrin and IgG, and lower serum uromodulin significantly predicted A2 albuminuria, urine KIM-1/creatinine ratio, and IgG being the best predictors. Albuminuria, urine NGAL/creatinine, and IgG correlated with diabetes duration. Albuminuria, urine NGAL, transferrin, IgG, and uromodulin correlated with diabetes control. In a subgroup of 29 patients, retrospective data were available on changes in eGFR and uACR over one year. Decline in eGFR was observed in 17 patients and increase in uACR in 10 patients. Serum and urine NGAL correlated with eGFR changes. Higher urine NGAL, KIM-1/creatinine ratio, and detectable IgG were significantly associated with the increase in uACR. Widely available markers, serum cystatin C, urine IgG, transferrin, and NGAL, may help in early assessment of kidney disease in T2DM patients; however, large prospective studies are needed to confirm the conclusion.

<p>Evaluation of Urinary Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 as Diagnostic Markers for Early Nephropathy in Patients with Type 2 Diabetes Mellitus</p>

“…Although our diabetic subject had different average age, duration of disease, race and socioeconomic status, the result had high consistency with other studies and also demonstrated that NGAL and KIM-1 appeared earlier in nephropathy. 15,16,27,28,31,[35][36][37][38][39] Sensitivity and specificity of urine NGAL and KIM-1 in early diagnostic diabetic nephropathy of our study were similar to other researches. 39,40 Kapoula et al had showed the pooled sensitivity and specificity among the different settings analyzed ranged from 0.42 (95% CI, 0.22-0.66) to 1.00 (95% CI, 0.99-1.00) and 0.72 (95% CI, 0.62-0.80) to 0.98 (95% CI, 0.50-1.00) in T2DM patients, respectively.…”

“…40 Zylka et al had found sensitivity of NGAL and KIM-1 were 80%, 79%, respectively, and specificity of NGAL, KIM −1 was 61%, 51%, respectively. 39 Based on these values, urinary NGAL and KIM-1 could be used as independent markers for diagnostic and prediction for diabetic nephropathy.…”

A panel of urinary biochemical markers for the non-invasive detection of kidney dysfunction in HIV-patients

“…In addition, it is a sensitive and early indicator of pathological changes in the kidneys exposed to nephrotoxic xenobiotics. 23 The increased release of lysosomal enzymes from renal tubular epithelial cells that we observed in our study may indicate an ongoing inflammatory process in the kidneys, as the rising number of lysosomes in tubular cells reflects defense mechanisms of kidney cells.…”

Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules

“…Proteinuria and albuminuria induce proximal tubular injury, leading to interstitial fibrosis, and are seen as independent risk factors for reducing renal function. The other markers that indicate the early progression of kidney diseases are neutrophil gelatinase associated lipocalin and angiopoietin-2 [25][26][27]. Although we could not measure urinary albumin levels and these early indicators, both groups showed overt proteinuria suggesting kidney injury in our model had already progressed to some degree.…”