Eun Sil Koh

Oleanolic acid attenuates renal fibrosis in mice with unilateral ureteral obstruction via facilitating nuclear translocation of Nrf2

BackgroundRenal interstitial fibrosis is a common final pathological process in the progression of kidney disease. This is primarily due to oxidative stress, which contributes to renal inflammation and fibrosis. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is known to coordinate induction of genes that encode antioxidant enzymes. We investigated the effects of oleanolic acid, a known Nrf2 activator, on oxidative stress-induced renal inflammation and fibrosis.MethodsOne day before unilateral ureteral obstruction (UUO) performed in C57BL/6 mice, oleanolic acid treatment was initiated and was continued until 3 and 7 days after UUO. Renal inflammation and fibrosis, markers of oxidative stress, and changes in Nrf2 expression were subsequently evaluated.ResultsIn the obstructed kidneys of UUO mice, oleanolic acid significantly attenuated UUO-induced collagen deposition and fibrosis on day 7. Additionally, significantly less inflammatory cell infiltration, a lower ratio of Bax to Bcl-2 expression, and fewer apoptotic cells on TUNEL staining were observed in the obstructed kidneys of oleanolic acid-treated mice. Oleanolic acid increased the expression of nuclear Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and heat shock protein 70, and decreased lipid peroxidation in the obstructed kidney of UUO mice. There were no changes in the expression of total Nrf2 and Kelch-like ECH-associated protein 1, indicating that oleanolic acid enhanced nuclear translocation of Nrf2.ConclusionsThese results suggest that oleanolic acid may exert beneficial effects on renal fibrosis by increasing nuclear translocation of Nrf2 and subsequently reducing renal oxidative stress.

Safety and tissue yield for percutaneous native kidney biopsy according to practitioner and ultrasound technique

BackgroundAlthough percutaneous renal biopsy remains an essential tool in the diagnosis and treatment of renal diseases, in recent times the traditional procedure of nephrologists has been performed by non-nephrologists rather than nephrologists at many institutions. The present study assessed the safety and adequacy of tissue yield during percutaneous renal biopsy according to practitioners and techniques based on ultrasound.MethodsThis study included 658 native renal biopsies performed from 2005 to 2010 at a single centre. The biopsies were performed by nephrologists or expert ultrasound radiologists using the ultrasound-marked blind or real-time ultrasound-guided techniques.ResultsA total of 271 ultrasound-marked blind biopsies were performed by nephrologists, 170 real-time ultrasound-guided biopsies were performed by nephrologists, and 217 real-time ultrasound-guided biopsies were performed by radiologists during the study period. No differences in post-biopsy complications such as haematoma, need for transfusion and intervention, gross haematuria, pain, or infection were observed among groups. Glomerular numbers of renal specimens from biopsies performed by nephrologists without reference to any technique were higher than those obtained from real-time ultrasound-guided biopsies performed by expert ultrasound radiologists.ConclusionsPercutaneous renal biopsy performed by nephrologists was not inferior to that performed by expert ultrasound radiologists as related to specimen yield and post-biopsy complications.

Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

Objective: In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Method: Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m2, eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m2 (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. Results: baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) Conclusions: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

Decisive Indicator for Gastrointestinal Workup in Anemic Patients with Nondialysis Chronic Kidney Disease

Background: Anemia and iron deficiency are universal problems in patients with chronic kidney disease (CKD). However, decisive indicator to guide the further gastrointestinal (GI) workup has not been determined. Methods: We included 104 anemic patients with nondialysis-dependent CKD stages 3-5 (38 patients at stage 3, 26 patients at stage 4, and 40 patients at stage 5). Hemoglobin, serum ferritin, transferrin saturation (TSAT), mean corpuscular volume (MCV), and corrected reticulocyte count data were assessed to evaluate diagnostic utility for bleeding-related GI lesions, which were identified by esophagogastroduodenoscopy and colonoscopy. Results: Bleeding-related GI lesions were found in 55 (52.9%) patients, and patients with stage 5 CKD had a higher prevalence of gastric lesions than patients with CKD stage 3 or 4 (all p < 0.05). The areas under the receiver operating characteristic curves used to predict bleeding-related lesions were 0.69 for TSAT (p = 0.002) and 0.61 for serum ferritin (p = 0.085). The sensitivity and specificity of a cutoff value for TSAT < 20% were 0.59 and 0.74, respectively. Hemoglobin, MCV, and corrected reticulocyte levels had no significant diagnostic utility. On multivariable logistic regression, the chance of GI lesions increased by 6% for each 1% reduction in TSAT and increased 4.1-fold for patients with CKD stage 5 (all p < 0.05). Conclusions: TSAT is a useful indicator for determining the GI workup in anemic patients with nondialysis-dependent CKD stages 3-5. Stage 5 CKD is independently associated with bleeding-related lesions and TSAT should be used cautiously in these patients.

Serum β2-Microglobulin Predicts Mortality in Peritoneal Dialysis Patients: A Prospective Cohort Study

Background/Aims: β2-Microglobulin (β2-M) is a surrogate marker of middle-molecule uremic toxins and is associated with mortality in chronic hemodialysis patients. However, the impact of serum β2-M levels on mortality in peritoneal dialysis (PD) patients is uncertain. The purpose of this study was to examine the association of serum β2-M levels with all-cause mortality in PD patients. Methods: A total of 771 PD patients were selected from the Clinical Research Center registry for end-stage renal disease cohort in Korea. Patients were categorized into 3 groups by tertiles of serum β2-M levels. The primary outcome was all-cause mortality. Results: The median value of serum β2-M was 23.6 mg/l (interquartile range 14.8-33.4 mg/l), and the median follow-up period was 39 months. The Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of serum β2-M in PD patients (p = 0.03, log-rank). Multivariate Cox proportional analysis showed that the hazards ratio for all-cause mortality was 1.02 (95% CI 1.01-1.04, p = 0.006) per 1 mg/l increase in β2-M after adjustment for multiple confounding factors that relate to malnutrition and inflammation marker. However, serum β2-M was not associated with all-cause mortality after adjustment for residual renal clearance. Conclusions: These results are supportive of the potential role of the serum β2-M level as a predictor of mortality in PD patients.

Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients.

Background Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients. Methods A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization. Results During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55–3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.07–4.26, P = 0.031) and infection-related mortality (HR 3.07, 95% CI, 1.30–7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00–1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06–1.92, P = 0.028). Conclusions Our data demonstrate that high serum GGT levels were an independent risk factor for all-cause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients.

Incidental renal artery pseudoaneurysm after percutaneous native renal biopsy

Renal artery pseudoaneurysm (RAP) is an uncommon but potentially life-threatening condition that is often difficult to diagnose. Rarely, it can occur as a complication associated with a percutaneous renal biopsy procedure. The clinical manifestations vary from asymptomatic lesions found incidentally on imaging studies to a mass causing high blood pressure, pain, haematuria and rupture. Although the risk of rupture is considered low, RAP is associated with a high death rate if ruptured. Currently, with the aid of high-quality interventional radiology, this challenging pathology can be effectively treated. In this report, we describe a case of RAP that was incidentally discovered 4 years after percutaneous renal biopsy which was successfully treated with selective angiographic embolisation.

Spontaneous spinal epidural hematoma

A 32-year-old woman was referred to our hospital with the sudden onset of low back and cervical pain during a hemodialysis session at a local hospital. She had been on hemodialysis because of progressive renal failure due to lupus nephritis. There were no external signs of trauma on physical examination. A few hours after admission …

Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin

The aim of this study was to assess any potential additive effects of a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually with aliskiren and/or paricalcitol until 7 days after initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO mice, monotherapy with aliskiren or paricalcitol significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells. The combination treatment showed additive efficacy in inhibition of these parameters. Renal NADPH oxidase (Nox)1 and Nox2 were significantly decreased by aliskiren or paricalcitol alone or in combination, while renal Nox4 expression was significantly reduced by paricalcitol mono- or combination treatment. Increased levels of p-Erk and p-p38 MAPK, and NF-κB in UUO kidneys were also significantly reduced by either aliskiren or paricalcitol treatment alone or in combination. Aliskiren or paricalcitol monotherapy significantly reduced the expression of (pro)renin receptor in UUO kidneys. In addition, aliskiren tended to augment renin expression in UUO kidneys, but paricalcitol reduced its expression level. The combination treatment effectively blocked both (pro)renin receptor and renin expression induced by aliskiren, and resulted in a further reduction of the renal expression of angiotensin II AT1 receptor. Aliskiren failed to increase the expression of vitamin D receptor in UUO kidneys, but the combination treatment restored its expression level. Taken together, a treatment combining aliskiren with paricalcitol better inhibits UUO-induced renal injury. The mechanism of this synergy may involve more profound inhibition of the intrarenal renin-angiotensin system.

Sarcoidosis as a cause of unappreciated hypercalcaemia in a patient with end-stage renal disease on peritoneal dialysis

The differential diagnosis of hypercalcaemia in patients with end-stage renal disease undergoing dialysis should be considered for causes related or unrelated to renal failure itself or therapies for renal failure. In particular, peritoneal dialysis may hinder awareness of a clinical problem due to its own peculiarities and effects on homeostasis of the body, thus creating misconceptions in interpreting laboratory data and diagnosing a disease. We describe here a case of systemic sarcoidosis which was delayed due to failure to recognise underestimated hypercalcaemia in a patient undergoing peritoneal dialysis. Clinicians need to remain aware of the change of minerals that may arise from peritoneal dialysis and should perform an extensive investigation for the cause of hypercalcaemia.