scholarly journals Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ling Wang ◽  
Jia-Fen Cheng ◽  
Li-Ping Sun ◽  
Ya-Xiang Song ◽  
Le-Hang Guo ◽  
...  

Purpose.To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method.Materials and Methods.79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis.Results.Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P<0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P<0.05).Conclusion.Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

2020 ◽  
Author(s):  
Ning Ma ◽  
Ning Xu ◽  
Dong Yin ◽  
Ping Zheng ◽  
Weiwei Liu ◽  
...  

Abstract Background: The kidney has a rich endoplasmic reticulum system. A close relationship exists between endoplasmic reticulum stress (ERS) and diabetic kidney disease (DKD). The current study aimed to investigate serum glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer binding protein homologous protein (CHOP) concentrations in type 2 diabetes mellitus (T2DM) Chinese patients, especially those with microalbuminuria. Methods: We evaluated the relationships between serum GRP78 or CHOP levels and DKD. We recruited 67 patients with T2DM and 63 control subjects. We determined serum GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Results: Compared with control groups, Chinese T2DM patients showed decreased serum levels of GRP78 [0.21 (0.16–0.24) vs. 0.16 (0.16–0.19) ng/mL, p < 0.01] and CHOP [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Reduction in GRP78 and CHOP serum levels was more pronounced in patients with more severe categories of microalbuminuria. Amounts of serum GRP78 correlated directly with serum fasting c-peptide, cystatin-c (cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Serum CHOP level was positively correlated with age, Cr, BUN, cys-c, urinary microalbumin/creatinine (UmALB/Cr), and eGFR. Serum GRP78 was predicted independently by Cr, BUN, serum uric acid, eGFR, and cys-c, while CHOP depended on age, Cr, BUN, serum uric acid, eGFR, UmALB/Cr, and cys-c. After controlling for confounding factors, GRP78 and CHOP expression was significantly associated with DKD (binary logistic regression, p < 0.01). Conclusions: T2DM patients showed increased serum GRP78 and CHOP concentrations. Receiver operating characteristic (ROC) areas under the curve for predicting DKD based on GRP78 and CHOP were 0.686 [95% CI: 0.558–0.813] and 0.670[0.524–0.816], respectively.


2019 ◽  
Vol 12 (2) ◽  
pp. 169-178
Author(s):  
Lili Liu ◽  
Bixia Gao ◽  
Jinwei Wang ◽  
Chao Yang ◽  
Shouling Wu ◽  
...  

2020 ◽  
Author(s):  
Ning Ma ◽  
Ning Xu ◽  
Dong Yin ◽  
Ping Zheng ◽  
Weiwei Liu ◽  
...  

Abstract Background The kidney has a rich endoplasmic reticulum system. A close relationship exists between endoplasmic reticulum stress (ERS) and diabetic kidney disease (DKD). The current study aimed to investigate serum glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer binding protein homologous protein (CHOP) concentrations in type 2 diabetes mellitus (T2DM) Chinese patients, especially those with microalbuminuria. Methods We evaluated the relationships between serum GRP78 or CHOP levels and DKD. We recruited 67 patients with T2DM and 63 control subjects. We determined serum GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Results Compared with control groups, Chinese T2DM patients showed decreased serum levels of GRP78 [0.21 (0.16–0.24) vs. 0.16 (0.16–0.19) ng/mL, p < 0.01] and CHOP [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Reduction in GRP78 and CHOP serum levels was more pronounced in patients with more severe categories of microalbuminuria. Amounts of serum GRP78 correlated directly with serum fasting c-peptide, cystatin-c (cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Serum CHOP level was positively correlated with age, Cr, BUN, cys-c, urinary microalbumin/creatinine (UmALB/Cr), and eGFR. Serum GRP78 was predicted independently by Cr, BUN, serum uric acid, eGFR, and cys-c, while CHOP depended on age, Cr, BUN, serum uric acid, eGFR, UmALB/Cr, and cys-c. After controlling for confounding factors, GRP78 and CHOP expression was significantly associated with DKD (binary logistic regression, p < 0.01). Conclusions T2DM patients showed increased serum GRP78 and CHOP concentrations. Receiver operating characteristic (ROC) areas under the curve for predicting DKD based on GRP78 and CHOP were 0.686 [95% CI: 0.558–0.813] and 0.670[0.524–0.816], respectively.


2012 ◽  
Vol 27 (7) ◽  
pp. 2891-2898 ◽  
Author(s):  
Fang Ma ◽  
Yanqin Cang ◽  
Baozhen Zhao ◽  
Yuanyuan Liu ◽  
Chaoqing Wang ◽  
...  

Author(s):  
Nabanita Kundu ◽  
Seshagiri R. Nandula ◽  
Laureano D. Asico ◽  
Mona Fakhri ◽  
Jaideep Banerjee ◽  
...  

Background Diabetic kidney disease is associated with glomerulosclerosis and poor renal perfusion. Increased capillary formation and improved perfusion may help to halt or reverse the injury. Transplanting apoptosis‐resistant p53‐silenced endothelial progenitor cells (p53sh‐EPCs) may help improve vascularization and renal perfusion and could be more beneficial than another stem cell such as the mouse mesenchymal stromal cell (mMSC). Methods and Results Hyperglycemia and proteinuria were confirmed at 8 to 10 weeks in streptozotocin‐induced type1 diabetic C57Bl/6 mice, followed by transplantation of 0.3 million p53sh‐EPCs, Null‐EPCs (control), or mMSC under each kidney capsule. Urine was collected weekly for creatinine and protein levels. Blood pressure was measured by direct arterial cannulation and renal perfusion was measured by renal ultrasound. The kidneys were harvested for histology and mRNA expression. Reduction of protein/creatinine (AUC) was observed in p53sh‐EPC‐transplanted mice more than null‐EPC (1.8‐fold, P =0.03) or null‐mMSC (1.6‐fold, P =0.04, n=4) transplanted mice. Markers for angiogenesis, such as endothelial nitric oxide synthase (1.7‐fold, P =0.06), were upregulated post p53sh‐EPC transplantation compared with null EPC. However, vascular endothelial growth factor‐A expression was reduced (7‐fold, P =0.0004) in mMSC‐transplanted mice, compared with p53sh‐EPC‐transplanted mice. Isolectin‐B4 staining of kidney section showed improvement of glomerular sclerosis when p53sh‐EPC was transplanted, compared with null‐EPC or mMSC. In addition, mean and peak renal blood velocity (1.3‐fold, P =0.01, 1.4‐fold, P =0.001, respectively) were increased in p53sh‐EPC‐transplanted mice, relative to null‐EPC transplanted mice. Conclusions Apoptosis‐resistant p53sh EPC transplantation could be beneficial in the treatment of diabetic kidney disease by decreasing proteinuria, and improving renal perfusion and glomerular architecture.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Marques Vidas ◽  
Alba Maroto ◽  
Ignacio Sanz ◽  
Paula López ◽  
Jose' M Portoles

Abstract Background and Aims The use of sodium glucose co-transporter 2 inhibitors (SGLT2i) is consistently associated with decrease of serum uric acid levels due to increase uricosuria coupled to glucosuria by mechanisms that are still incompletely understood. In diabetic kidney disease these drugs had shown only modest effects on HbA1c control allegedly due insufficient glucosuric effect. However, renal patients also benefit from hypouricemic effect of SGLT2 inhibitors. The aim of this study was to evaluate glucosuria and uricosuria in DKD patients treated with SGLT2i Method We prospectively analyzed glucose and urate fractional excretions of patients that were to initiate treatment with an SGLT2i, using fractional excretion classical formulas. Patients on GLP1ar or any uricosuric agent including losartan were excluded. All participants gave written consent. Results 37 patients (75.7% male) diagnosed from DKD were included, median age 69.6 years IQR [65.6-73.4], median CKD-EPI eGFR 54,10 ml/min/1,72 m2 [ 41,12- 69,68 IQR] and UACR 137 [49-443] mg/g. SGLT2i used was 53.3% dapagliflozin, 24.4% empagliflozin or 22.2% canagliflozin and mean follow- up was 1.5 years.Serum uric acid levels didn’t show any significative difference along time in this group of patients (6.8 vs 6.3; p 0.4) and %HbA1C was only slightly decreased by month 12 (7.1 vs 6.7; p0.03). Urinary uric acid fractional excretion increased by month 3 and was stabilized till month 12 when this effect seemed to decrease (figure and table) Glucosuria exhibit a similar effect: Urinary glucose fractional excretion increased immediately after the addition of the drug and stabilized over time decreasing at the end of the observation period. Spearman rank correlation test indicated dependency glucosuria and uricosuria (Spearman´s rho 0,24, p 0,03). GFR estimated by CKD-EPI kept stable along the study indicating that loss of uricosuric and glucosuric effect are independent of GFR Conclusion We conclude that uric acid renal excretion is significantly increased in patients treated with SGLT2i even in the presence of DKD but tends to diminish over time, feature that was also observed on urinary glucose excretion and that showed no correlation with GFR. Over-expression of SGLT1 after SGLT2 inhibition has been described in animal models of DKD. Whether this extends to human tubule and explains these results need to be further investigated


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