scholarly journals Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 224
Author(s):  
Jaehyun Bae ◽  
Young Jun Won ◽  
Byung-Wan Lee
Keyword(s):  
Kidney Disease ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Early Stage ◽  
Screening Tools ◽  
Tubular Injury ◽  
Current Standard ◽  
Diabetic Kidney ◽  
Wide Range

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.

Value of Doppler ultrasound in early detection of diabetic kidney disease: A systematic review and meta-analysis

Ultrasound ◽  
2020 ◽  
pp. 1742271X2097705
Author(s):  
Heather Kilgour Venables ◽  
Yaw Amo Wiafe ◽  
Theophilus Kofi Adu-Bredu
Keyword(s):  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Early Detection ◽  
Glomerular Filtration ◽  
Doppler Ultrasound ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Resistive Index ◽  
Diabetic Kidney

The diagnosis of diabetic kidney disease can be delayed by limitations of primary biomarkers, which are microalbuminuria and estimated glomerular filtration rate. A number of Doppler ultrasound studies have associated an increase in intrarenal vascular resistance with the disease, which makes ultrasound a potential adjunct tool for early diagnosis. However, there is inadequate evidence to establish the effectiveness of including Doppler ultrasound in the diagnostic process. This systematic review was therefore conducted to determine the value of using Doppler ultrasound in early detection of diabetic kidney disease. Electronic literature searches were carried out in PubMed, CINAHL, Web of Science and EMBASE. All published prospective studies with records of intrarenal Doppler ultrasound, microalbuminuria and estimated glomerular filtration rate were obtained, and their relationship as parameters for diabetic kidney disease assessed. The meta-analysis of Doppler ultrasound versus albuminuria shows insignificant statistical difference between high resistive index of ≥ 0.7 and albuminuria, with the resistive index being the favoured parameter on the forest plot, making Doppler ultrasound highly comparable with albuminuria for the detection of diabetic kidney disease. Again, there was a significant statistical difference between high intrarenal resistive index of ≥ 0.7 and low estimated glomerular filtration rate of  < 60 mL/min/1.73 m2, with the resistive index being the favoured parameter on the forest plot, making Doppler ultrasound a superior parameter compared with estimated glomerular filtration rate for early detection of diabetic kidney disease.

scholarly journals Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

2018 ◽  
Vol 14 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Maarten A. de Jong ◽  
Sergei I. Petrykiv ◽  
Gozewijn D. Laverman ◽  
Antonius E. van Herwaarden ◽  
Dick de Zeeuw ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Glycosylated Hemoglobin ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Phosphate Homeostasis ◽  
Double Blind ◽  
Diabetic Kidney ◽  
Albumin Excretion

Background and objectivesThe sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear.Design, setting, participants, & measurementsWe performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable renin–angiotensin–aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR≥45 ml/min per 1.73 m2, and glycosylated hemoglobin≥7.2% and <11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels.ResultsThirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH)2D decreased by −12% (−25% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment.ConclusionsDapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.

scholarly journals Sulodexide Protects Renal Tubular Epithelial Cells from Oxidative Stress-Induced Injury via Upregulating Klotho Expression at an Early Stage of Diabetic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yu Ning Liu ◽  
Jingwei Zhou ◽  
Tingting Li ◽  
Jing Wu ◽  
Shu Hua Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Epithelial Cells ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Collaborative Study ◽  
Oxidative Activity ◽  
Dependent Manner ◽  
Diabetic Kidney ◽  
Collaborative Study Group

The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression. However, all of these actions were not observed when SDX was administered only at the late stage of diabetic nephropathy (from week 13 to 24). In vitro, advanced glycation end products (AGEs) dose-dependently enhanced the oxidative activity but lowered the klotho expression in cultured proximal tubule epithelial cells (PTECs). Also, H2O2 could downregulate the expression of klotho in a dose-dependent manner. However, overexpression of klotho reduced the HAVCR1 production and the cellular apoptosis level induced by AGEs or H2O2. Our study suggests that SDX may prevent the progression of DKD at the early stage by upregulating renal klotho expression, which inhibits the tubulointerstitial injury induced by oxidative stress.

Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease

2018 ◽  
Vol 132 (22) ◽  
pp. 2407-2422 ◽  
Author(s):  
Wenxia Yang ◽  
Ying Luo ◽  
Shikun Yang ◽  
Mengru Zeng ◽  
Shumin Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lipid Accumulation ◽  
Diabetic Kidney Disease ◽  
Mononuclear Cells ◽  
Regulatory Element ◽  
Tubular Damage ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Tnf Α ◽  
Significant Difference

Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (classes II–III) and db/db mice compared with the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry (IHC) staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol regulatory element binding protein-1 (SREBP-1) was clearly up-regulated, which was positively correlated with the tubulointerstitial damage score and inflammation. Furthermore, the urine ADRP content significantly increased in DKD patients compared with the control, which positively correlated with abnormal lipid metabolism, serum creatinine, urine N-acetyl-β-glucosaminidase (NAG), albumin excretion (albumin-to-creatinine ratio (ACR)), and tumor necrosis factor-α (TNF-α) expression. However, there was no significant difference observed in plasma ADRP levels. In addition, the expression of SREBP-1 protein was dramatically increased in peripheral blood mononuclear cells (PBMCs) isolated from DKD patients, which was also tightly correlated with urine NAG, ACR, and TNF-α levels. In vitro studies demonstrated increased ADRP and SREBP-1 expression accompanied by lipid accumulation in HK-2 cells cultured in high glucose (HG). HG induced high levels of TNF-α expression, which was partially blocked by transfection of ADRP siRNA or SREBP-1 siRNA. These data indicated that ADRP and SREBP-1 are crucial factors that mediate lipid accumulation with tubular damage and inflammation in DKD, and ectopic lipid accumulation may serve as a novel therapeutic target for amelioration of tubular injury in DKD.

Vascular Calcification in Patients with Early-Stage Chronic Kidney Disease: The Pivotal Role of Estimated Glomerular Filtration Rate

2021 ◽  
Vol 104 (6) ◽  
pp. 989-997
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Vascular Calcification ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Early Stage ◽  
Abdominal Aortic Calcification ◽  
Abdominal Aortic

Background: Vascular calcification in advanced chronic kidney disease (CKD) is correlated with uremic toxins and severely impaired calciumphosphate- parathyroid metabolism. The association factors of vascular calcification in early-stage CKD are still unestablished. Objective: To identify the risk factors for vascular calcification in the early-stage CKD, which was the non-target population, different from other previous studies that explored this association in advanced stage CKD. Materials and Methods: The present study was a longitudinal study conducted to examine the risk factors of vascular calcification in CKD stage G2 and G3 patients who had no previous cardiovascular diseases. All parameters including coronary artery calcification (CAC) and abdominal aortic calcification (AAC) at baseline and after twelve months were evaluated. Results: Twenty-two patients without established cardiovascular diseases were included and completed the follow-up period. Mean baseline LDL was 99 mg/dL and no patient received statin. At 12-month, the median CAC score was significantly increased to 266 (126 to 956) versus 282 (198 to 846), (p=0.024]. By multivariable analysis in generalized estimating equations, only estimated glomerular filtration rate (eGFR) was associated with CAC score greater than 400 (aOR 0.92, p=0.041), and AAC score greater than 5 (aOR 0.90, p=0.023). Conclusion: In early-stage CKD, eGFR was associated with vascular calcification. Further studies should explore the potential benefits of delaying CKD progression on vascular calcification in the early-stage CKD patients. Keywords: Chronic kidney disease; Vascular calcification; Coronary artery calcification; Abdominal aortic calcification; Glomerular filtration rate; Renal function

scholarly journals MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José María Mora-Gutiérrez ◽  
José Antonio Rodríguez ◽  
María A. Fernández-Seara ◽  
Josune Orbe ◽  
Francisco Javier Escalada ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin

AbstractMatrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.

scholarly journals Bardoxolone methyl: drug development for diabetic kidney disease

2020 ◽  
Vol 24 (10) ◽  
pp. 857-864 ◽  
Author(s):  
Hironori Kanda ◽  
Kengo Yamawaki
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Defense Responses ◽  
Priority Review ◽  
Phase 3 ◽  
Diabetic Kidney ◽  
Increased Risk ◽  
Phase 2 Study ◽  
First Time

Abstract Bardoxolone methyl activates the Keap1/Nrf2 system that plays an important role in defense responses against oxidative stress. Importantly, bardoxolone methyl has demonstrated increases in estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease (DKD) in clinical studies. However, an overseas Phase 3 study of bardoxolone methyl in patients with stage G4 DKD was prematurely terminated due to an increased risk for heart failure, which was considered to have been caused by early-onset fluid overload. Subsequently, a Japanese Phase 2 study demonstrated, for the first time, that bardoxolone methyl directly improves GFR, which is a true indicator of kidney function, using the inulin clearance method. In Japan, bardoxolone methyl was designated for the treatment of DKD under the Priority Review and Designation (SAKIGAKE Designation) System established by the Ministry of Health, Labour and Welfare. A Japanese Phase 3 study, with endpoints such as a ≥ 30% decrease in eGFR, is currently ongoing to assess the efficacy and safety of bardoxolone methyl in more than 1,000 patients with stages G3 and G4 DKD who have no identified risk factors.

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