• ACE inhibitor
• AT1 receptor blocker
• Diabetes
• Diabetic nephropathy
• Oxidative stress
• Trace elements

• Rats
• Animals
• Angiotensin-Converting Enzyme Inhibitors/pharmacology
• Angiotensin-Converting Enzyme Inhibitors/therapeutic use
• Angiotensin-Converting Enzyme Inhibitors/metabolism
• Irbesartan/metabolism
• Irbesartan/pharmacology
• Irbesartan/therapeutic use
• Angiotensin Receptor Antagonists/metabolism
• Angiotensin Receptor Antagonists/pharmacology
• Angiotensin Receptor Antagonists/therapeutic use
• Perindopril/metabolism
• Perindopril/pharmacology
• Perindopril/therapeutic use
• Streptozocin/metabolism
• Streptozocin/pharmacology
• Streptozocin/therapeutic use
• Rats, Wistar
• Diabetes Mellitus, Experimental/metabolism
• Trace Elements/metabolism
• Trace Elements/pharmacology
• Trace Elements/therapeutic use
• Kidney/pathology
• Diabetic Nephropathies/metabolism
• Angiotensin II Type 1 Receptor Blockers/pharmacology
• Angiotensin II Type 1 Receptor Blockers/therapeutic use
• Angiotensin II Type 1 Receptor Blockers/metabolism
• Oxidative Stress
• Superoxide Dismutase/metabolism

• Chronic kidney disease
• Extracellular matrix
• Proximal tubule
• Tubulointerstitial fibrosis

• Rats
• Humans
• Animals
• Podocytes/pathology
• Glomerulosclerosis, Focal Segmental/pathology
• Nephrosclerosis/complications
• Capillaries/pathology
• Glomerular Basement Membrane/pathology
• Hypertension, Renal/complications

• Cameroon
• Chronic kidney disease
• Douala
• Human immune deficiency virus

• Adult
• Cameroon
• Female
• HIV Infections/complications
• Humans
• Male
• Middle Aged
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/epidemiology
• Renal Insufficiency, Chronic/therapy
• Retrospective Studies
• Treatment Outcome

• 5/6 nephrectomy
• Chronic kidney disease
• Epoxyeicosatrienoic acids
• Hypertension
• Renin-angiotensin system
• Soluble epoxide hydrolase

• chronic kidney disease
• developing countries
• screening

Previous studies have shown that a higher resistive index (RI) on renal duplex ultrasonography was related with renal progression and acute kidney injury, especially in patients with chronic kidney disease (CKD) using an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB). We evaluated whether a RI value is a predictive factor for renal progression regardless of ACEI or ARB medication in patients with moderate renal dysfunction.

We retrospectively analyzed 119 patients with moderate renal dysfunction that had been evaluated with renal duplex ultrasonography from February 2011 to April 2015. Moderate renal dysfunction was defined as a stage 3 to 4 CKD. Renal progression was defined as a doubling of the baseline serum creatinine (sCr), a decrease of baseline glomerular filtration rate by > 50%, or initiation of renal replacement therapy.

The mean age was 64.7 ± 11.0 years and sCr level was 2.1 ± 1.2 mg/dL. The RI ≥ 0.79 group showed a higher incidence of renal progression (P = 0.004, log-rank test) compared with the RI < 0.79 group, irrespective of ACEI or ARB usage. In the Cox proportional hazard model, RI ≥ 0.79 was an independent prognostic factor after adjusting for age, sex, diabetes mellitus, sCr, proteinuria, and use of ACEI or ARB (hazard ratio, 4.88; 95% confidence interval, 1.06–22.53; P = 0.043).

RI ≥ 0.79 on the renal duplex ultrasonography can be a helpful predictor for renal progression in patients with moderate renal dysfunction, regardless of their ACEI or ARB usage.

• Angiotensin receptor antagonists
• Angiotensin-converting enzyme inhibitors
• Chronic kidney disease
• Doppler duplex ultrasonography

• Aboriginal people
• Albumin creatinine ratio
• Albuminuria
• Cohort study
• End stage renal disease
• Risk
• Rural and remote health

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Albuminuria/ethnology
• Albuminuria/urine
• Australia/epidemiology
• Cardiovascular Diseases/ethnology
• Creatinine/urine
• Diabetes Mellitus/ethnology
• Disease Progression
• Female
• Humans
• Kidney Failure, Chronic/ethnology
• Kidney Failure, Chronic/mortality
• Kidney Failure, Chronic/therapy
• Longitudinal Studies
• Male
• Middle Aged
• Obesity/ethnology
• Predictive Value of Tests
• Proportional Hazards Models
• Renal Dialysis
• Retrospective Studies
• Risk Factors
• Urinalysis
• Waist-Hip Ratio
• Young Adult

• Cardiac catheterisation
• Contrast-induced nephropathy
• Renin–angiotensin–aldosterone system

• Cholesterol/blood
• Cholesterol, HDL/blood
• Dyslipidemias/complications
• Female
• Humans
• Male
• Renal Insufficiency, Chronic/etiology

• Albuminuria
• Antiretroviral therapy
• Cystatin C
• Diabetes mellitus
• Human immunodeficiency virus-associated nephropathy
• Hypertension
• Renal tubular biomarkers
• Tenofovir

1. The aim of the present study was to test the hypothesis that increasing kidney tissue concentrations of epoxyeicosatrienoic acids (EETs) by preventing their degradation to the biologically inactive dihydroxyeicosatrienoic acids (DHETEs) using blockade of soluble epoxide hydrolase (sEH) would attenuate the progression of chronic kidney disease (CKD).

2. Ren-2 transgenic rats (TGR) after 5/6 renal mass reduction (5/6 NX) served as a model of CKD associated with angiotensin (Ang) II-dependent hypertension. Soluble epoxide hydrolase was inhibited using cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB; 3 mg/L drinking water) for 20 weeks after 5/6 NX. Sham-operated normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls.

3. When applied in TGR subjected to 5/6 NX, c-AUCB treatment improved survival rate, prevented the increase in blood pressure, retarded the progression of cardiac hypertrophy, reduced proteinuria and the degree of glomerular and tubulointerstitial injury and reduced glomerular volume. All these organ-protective actions were associated with normalization of the intrarenal EETs : DHETEs ratio, an index of the availability of biologically active EETs, to levels observed in sham-operated HanSD rats. There were no significant concurrent changes of increased intrarenal AngII content.

4. Together, these results show that 5/6 NX TGR exhibit a profound deficiency of intrarenal availability of active epoxygenase metabolites (EETs), which probably contributes to the progression of CKD in this model of AngII-dependent hypertension, and that restoration of intrarenal availability of EETs using long-term c-AUCB treatment exhibits substantial renoprotective actions.

• 5/6 nephrectomy
• chronic kidney disease
• cytochrome P450 enzymes
• end-organ damage
• epoxyeicosatrienoic acids
• hypertension
• renin-angiotensin system
• soluble epoxide hydrolase

• bFGF
• chronic kidney disease
• renal recovery

Angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) may induce acute kidney injury (AKI). The aim of this study was to evaluate the role of the resistive index (RI), which reflects renal artery resistance on renal duplex ultrasonography, as a predictor of AKI in chronic kidney disease (CKD) patients who are prescribed an ACE inhibitor or ARB.

We screened 105 CKD patients evaluated with renal duplex ultrasonography from 2008 to 2012. We excluded patients not treated with ACE inhibitor or ARB and diagnosed with renal artery stenosis. Finally, we retrospectively analyzed the medical records of 54 patients. AKI was defined as increased serum creatinine by >30% compared with baseline after starting ACE inhibitor or ARB treatment.

The mean age of the patients was 60.5±13.0 years, serum creatinine level was 1.85±0.85 mg/dL and 22.2% of the patients had AKI after the use of an ACE inhibitor or ARB. The RI (P=0.006) and the percentages of patients with diabetes (P=0.008) and using diuretics (P=0.046) were higher in the AKI group. The area under the receiver operating characteristics curve for the prediction of AKI was 0.736 (95% confidence interval=0.587–0.885, P=0.013), and RI≥0.80 predicted AKI with 83.3% sensitivity and 61.9% specificity. In the multivariate analysis, RI≥0.80 was an independent prognostic factor [Exp (B)=8.03, 95% confidence interval=1.14–56.74, P=0.037] for AKI.

RI≥0.80 on the renal duplex ultrasonography may be a helpful predictor for AKI in CKD patients who are prescribed an ACE inhibitor or ARB.

• Acute kidney injury
• Angiotensin II receptor blockers
• Angiotensin converting enzyme inhibitors
• Diuretics
• Duplex Doppler ultrasonography

Activated proximal tubular cells play an important role in renal fibrosis. We investigated whether sunitinib and a kidney-targeted conjugate of sunitinib were capable of attenuating fibrogenic events in tubulointerstitial fibrosis.

A kidney-targeted conjugate was prepared by linkage of a sunitinib analog (named 17864) via a platinum-based linker to the kidney-specific carrier lysozyme. Pharmacological activity of 17864-lysozyme was evaluated in human kidney proximal tubular cells (HK-2); the capability of the kidney-directed conjugate to accumulate in the kidneys was studied in mice. Potential antifibrotic effects of a single-dose treatment were evaluated in the unilateral ureteral obstruction (UUO) model in mice.

The 17864-lysozyme conjugate and its metabolites strongly inhibited tyrosine kinase activity. Upon intravenous injection, 17864-lysozyme rapidly accumulated in the kidneys and provided sustained renal drug levels for up to 3 days after a single dose. Renal drug level area under the curve was increased 28-fold versus an equimolar dose of sunitinib malate. Daily treatment of UUO mice with a high dose of sunitinib malate (50 mg/kg) resulted in antifibrotic responses, but also induced drug-related toxicity. A single dose of 17864-lysozyme (equivalent to 1.8 mg/kg sunitinib) was safe but showed no antifibrotic effects.

Multikinase inhibitors like sunitinib can be of benefit in the treatment of fibrotic diseases, provided that their safety can be improved by strategies as presented in this paper, and sustained renal levels can be achieved.

• drug delivery
• fibrosis
• platinum linker
• sunitinib

The combination of Chinese herbs, Astragali Radix and Angelicae Sinensis Radix, could alleviate renal interstitial fibrosis. Astragaloside IV (AS-IV) and ferulic acid (FA) are the two major active constituents in this combination. In this study, we employed rats with unilateral ureteral obstruction to determine whether AS-IV and FA have the same renoprotective effects and investigated the mechanisms of this action.

Renal pathological changes were evaluated after treatment with AS-IV, FA or AS-IV + FA (AF) for 10 days. Meanwhile, the expression of transforming growth factor β₁ (TGF-β₁), fibronectin, α-smooth muscle actin (α-SMA), phosphorylation of c-Jun NH₂-terminal kinase (p-JNK) and nitric oxide (NO) production in kidney were determined. The expressions of fibronectin, α-SMA, mitogen-activated protein kinases [JNK, extracellular signal-regulated kinases (ERK), P38] in TGF-β₁-treated NRK-49F cells or interleukin-1-treated HK-2 cells after AS-IV, FA or AF were assessed.

AF alleviated the infiltration of mononuclear cells, tubular atrophy and interstitial fibrosis; reduced the expression of fibronectin, α-SMA, TGF-β₁ and p-JNK; and dramatically increased the production of NO in obstructed kidneys. Neither AS-IV nor FA alone improved renal damage, but both increased NO production. AF inhibited α-SMA and fibronectin expression in NRK-49F or HK-2 cells. Furthermore, AF significantly inhibited IL-1β-induced JNK phosphorylation, without affecting ERK or P38 phosphorylation. Neither AS-IV nor FA alone had any effect on the cells.

AS-IV synergizes with FA to alleviate renal tubulointerstitial fibrosis; this was associated with inhibition of tubular epithelial–mesenchymal transdifferentiation (EMT) and fibroblast activation, as well as an increase in NO production in the kidney.