• Toxicological Research
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• 제34권2호
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• Journal of Chest Surgery
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• 제49권6호
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• pp.427-434
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• 2016

Background: Recent studies have demonstrated the benefits of off-pump coronary bypass grafting over the on-pump technique in patients with chronic kidney disease (CKD). To further reduce the risk of acute kidney injury and the need for renal replacement therapy, even in patients undergoing off-pump coronary artery bypass grafting, we adopted protocol-based perioperative management for patients with CKD. Methods: From December 2012 to March 2015, 265 patients underwent isolated off-pump coronary artery bypass grafting. To analyze renal function in a stable condition, we excluded 12 dialysis-dependent end stage renal failure and 10 emergency or urgent cases. Among the remaining 243 patients, 208 patients had normal kidney function (normal group), and 35 patients had CKD (CKD group). Minimizing contrast exposure, ensuring adequate hydration, using strict drug dosage adjustment, and optimizing hemodynamic status were key elements of the protocol for the CKD group. Results: The risk of acute kidney injury was about ${\times}3$ higher in the CKD group than in the normal group (p=0.01). Estimated glomerular filtration rates and serum creatinine levels deteriorated until the third postoperative day in the CKD group. However, by adopting protocol-based perioperative management, this transient renal dysfunction recovered to preoperative levels by the fifth postoperative day without requiring renal replacement therapy in all cases. Conclusion: Off-pump coronary bypass surgery combined with this protocol-based perioperative management strategy in patients with non-dialysis-dependent CKD could mostly be performed without renal replacement therapy.

• 한국임상수의학회지
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• 제26권3호
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• pp.200-204
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• 2009

This study was performed to evaluate the effects of reduced L-glutathione on the oxidant/antioxidant status(superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GPx), protein carbonyl and lipid hydroperoxide(LPO) concentration), renal function(blood urea nitrogen(BUN) and serum creatinine levels), and microscopy of renal tissues in pigs undergoing unilateral renal ischemia-reperfusion(I/R). Sixteen Landrace and Yorkshire mixed-breed pigs were divided randomly into two groups: untreated control group and reduced L-glutathione-treated group(4 mg/kg IV). Each group had 8 pigs. Pigs were unilaterally nephrectomized and the kidney was subject to 30 min of renal pedicle occlusion. Blood samples for biochemical assay were collected on days 1, 3, 5, 7, and 14 post nephrectomy. Renal I/R injury were evaluated histopathologically by the microscopic observation of renal tissue sections and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as SOD, GPx, CAT, protein carbonyl and LPO were measured. The elevation of creatine and BUN levels was lower in the treated group, compared with the control group. The activities of antioxidant-enzyme were higher in the treated group, compared with the control group. In histological findings, the severity of damage in the reduced L-glutathione treated group was less when compared to the control group.

• Journal of Medicine and Life Science
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• 제15권2호
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• pp.37-41
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• 2018

Mitochondrial injury in renal tubule has been recognized as a major contributor in acute kidney injury (AKI) pathogenesis. Ischemic insult, nephrotoxin, endotoxin and contrast medium destroy mitochondrial structure and function as well as their biogenesis and dynamics, especially in renal proximal tubule, to elicit ATP depletion. Mitochondrial fatty acid ${\beta}$-oxidation (FAO) is the preferred source of ATP in the kidney, and its impairment is a critical factor in AKI pathogenesis. This review explores current knowledge of mitochondrial dysfunction and energy depletion in AKI and prospective views on developing therapeutic strategies targeting mitochondrial dysfunction in AKI.

• Childhood Kidney Diseases
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• 제15권2호
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• pp.107-115
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• 2011

소아에서 급성 신손상의 흔한 원인들로는 신허혈, 신독성 약물들, 그리고 패혈증 등이 있으며, 신대체요법 시작시의 저혈압, 신대체 요법 동안 승압제의 사용, 그리고 신대체 요법 시작시의 수액 과부하 정도가 환자의 생존(소아 중환자실 퇴원)에 영향을 미치는 요인들로 알려져 있다. 지속적 신대체 요법의 빠른 시작은 급성 신손상을 가진 환자들에게서 사망률과 예후에 나쁜 영향을 미치는 수액 과부하를 감소시키는 것으로 보고되었다. 이에 저자들은 소아 환자에게서 지속적 신대체 요법의 실제 처방과 급성 신손상, 수액 과부하, 그리고 지속적 신대체 요법간의 연관성 및 치료결과를 살펴보고자 한다. 결론적으로, 급성 신손상을 가진 소아의 치료에 있어서 과도한 수액 과부하가 발생하기 전에 빠른 지속적 신대체 요법의 시작이 필요하다고 제시하는 바이다.

• Journal of Ginseng Research
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• 제41권3호
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• pp.233-239
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• 2017

Background: Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. Methods: An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed Panax ginseng). Cytotoxicity was induced by treatment of $20{\mu}M$ cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination. Results: The in vitro assay demonstrated that KG-KH ($50{\mu}g/mL$) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, per os) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold). Conclusion: Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.11-19
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• 2024

Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.

• Childhood Kidney Diseases
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• 제20권2호
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• pp.37-44
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• 2016

Although asymptomatic bacteriuria, cystitis, and acute pyelonephritis (APN) have been categorized as urinary tract infections (UTIs), the immunopathogenesis of each disease is different. APN shows an age predilection; the majority of children (over 70-80%) with APN are under 1-2 years of age, with a male predominance. After 1-2 years of age, female predominance has been reported. This finding suggests that the immature immune state of infancy may be associated with the pathogenesis of APN. Escherichia coli is the most common etiologic agent; other uropathogens associated with UTIs originate from the host and comprise normal flora that are continuously altered by environmental factors. Therefore, uropathogens may have characteristics different from those of extraneous bacterial pathogens. Although antibiotic-resistant uropathogens, including extended-spectrum beta-lactamase-producing strains, are increasing in Korea and worldwide, treatment failure is rare in immune-competent children. The immunopathogenesis of APN remains unknown. Intact bacteria may not be the causative substances in renal cell injury; rather, smaller substances produced during bacterial replication may be responsible for renal cell injury and scarring. Moreover, substances from host cells such as proinflammatory cytokines may be involved in renal cell injury. A dimercaptosuccinic acid scan is used to detect the site of bacterial replication in the renal parenchyma, and may be influenced by the size of the focus and the stage of APN. Traditional aggressive studies used to identify vesicoureteral reflux after the first episode of APN have been modified because of rare cases of chronic kidney disease in patients with recurrent UTI.

• Journal of Acupuncture Research
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• 제18권2호
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• pp.101-110
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• 2001

Objective : This study was undertaken to determine if Scutellaria baicalensis Georgi (SbG) extract exerts protective effect against oxidant-induced cell injury in renal proximal tubular cells. Methods : The cell injury was evaluated by lactate dehydrogenase (LDH) release in rabbit renal cortical slices and lipid peroxidation was estimated by measuring malondialdehyde (MDA). t-Butylhydroperoxide (tBHP) was used as a model of oxidant. Results : tBHP at 1 mM increased LDH release and lipid peroxidation, which were prevented by SbG in a dose dependent manner over concentration range of 0.001-0.1%. SbG provided the protective effect against oxidant-induced reduction in PAH uptake by renal cortical slices and microsomal Na+-K+-ATPase activity. SbG attenuated tBHP-induced depletion of reduced glutathione. 0.2 mM $HgCl_2$ increased LDH release and lipid peroxidation, which were completely prevented by 0.05% SbG. Conclusion : SbG prevents oxidant-induced impairment in membrane transport function.

• Childhood Kidney Diseases
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• 제23권2호
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• pp.116-120
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• 2019

Bilateral renal obstruction is a rare critical condition, requiring a prompt diagnostic approach and treatment to restore the renal function. The most commonly observed obstructive uropathy in children is congenital malformation, such as posterior urethral valves and bilateral ureteropelvic junction obstruction. Malignant pelvic masses obstructing the ureter are widely reported in adults but are rarely observed in children. The treatment of ureteral obstruction related to pelvic malignancy is a therapeutic challenge with a median survival duration of 3-7 months in adults; however, pediatric patients with pelvic malignancy leading to ureteral obstruction had better outcomes, with a reported 5-year mortality rate of 20%, than the adult patients. Here, we report a rare case of bilateral ureteral obstruction associated with pelvic rhabdomyosarcoma presenting with acute kidney injury treated by ureteral diversion with double J stent, and concommittent emergency hemodialysis, leading to restoration of good renal function. We suggest that bilateral ureteral obstruction should be released as soon as possible using surgical or interventional approach to minimize the obstruction period, and subsequential chemotherapy may contribute to improvement of survival and recovery of renal function.