• Childhood Kidney Diseases
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• v.24 no.1
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• pp.19-26
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• 2020

Acute kidney injury (AKI) is common in critically ill children, and is associated with increased mortality and long-term renal sequelae. The definition of pediatric AKI was standardized based on elevation in serum creatinine levels or decrease in urine output; accordingly, epidemiological studies have ensued. Although new biomarkers appear to detect AKI earlier and predict prognosis more accurately than traditional markers, they are not frequently used in clinical setting. There is no validated pharmacological intervention for AKI, so prevention and early detection are the mainstays of treatment. For high risk or early stage AKI patients, optimization of volume status and blood pressure, avoidance of nephrotoxins, and sufficient nutritional support are necessary, and have been demonstrated to be effective in preventing the occurrence of AKI and improving prognosis. Nevertheless, renal replacement therapy is needed when conservative care fails.

• The Journal of Internal Korean Medicine
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• v.44 no.5
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• pp.1017-1024
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• 2023

Objectives: The aim of this study is to report the effectiveness and safety of herbal medicine treatment for abdominal pain with acute kidney injury. Methods: A 80-year-old female patient presented with abdominal pain. Blood test results showed increased blood urea nitrogen, serum creatinine, amylase, and lipase. The patient was treated with acupuncture and herbal medicine, specifically Hyangsayukgunja-tang-gahwangryeon for 4 days and Gagam-gunbi-tang for 11 days. Gastrointestinal symptoms were assessed using the Numerical Rating Scale, Gastrointestinal Symptom Rating Scale, and abdominal examination. Results: Gastrointestinal symptoms improved after taking Korean herbal medicine. Additionally, blood urea nitrogen, serum creatinine, amylase, and lipase levels showed improvement compared to values before treatment. Conclusions: Korean medicine treatment can improve clinical symptoms without damaging the kidneys of patients with acute kidney injuries.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.213-221
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• 2020

Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a non-receptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.599-610
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• 2023

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

• Korean Journal of Clinical Pharmacy
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• v.29 no.2
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• pp.115-124
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• 2019

The purpose of this systematic review and meta-analysis was to assess the preventive effect of theophylline on acute kidney injury and the ameliorative effect of theophylline on renal function in asphyxiated neonates. A literature search of the PubMed/Medline, Embase, and Cochrane Library databases for information published up to February 2019 was conducted. All studies that reported the incidence rate of acute kidney injury, serum creatinine level, and glomerular filtration rate after the randomized administration of theophylline or placebo were included. In total, eight studies involving 498 neonates were eligible. The incidence rate of acute kidney injury was significantly lower in the theophylline group than in the placebo group (risk ratio [RR]: 0.42, 95% confidence interval [CI]: 0.32-0.55, p < 0.001). The changes in serum creatinine level in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 and 5 days of age (weighted mean difference [WMD]: -0.51, 95% CI: -0.62 to -0.40, p < 0.001, and WMD: -0.26, 95% CI: -0.34 to -0.18, p < 0.001, respectively). The changes in glomerular filtration rate in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 days of age and the last day of follow-up (WMD: 12.30, 95% CI: 9.39-15.21, p < 0.001, and WMD: 9.35, 95% CI: 6.43-12.27, p < 0.001, respectively). These results suggested that theophylline has a beneficial effect on the prevention of acute kidney injury in neonates with perinatal asphyxia.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1015-1025
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• 2018

Kidney diseases including acute kidney injury and chronic kidney disease are among the largest health issues worldwide. Dialysis and kidney transplantation can replace a significant portion of renal function, however these treatments still have limitations. To overcome these shortcomings, a variety of innovative efforts have been introduced, including cell-based therapies. During the past decades, advances have been made in the stem cell and developmental biology, and tissue engineering. As part of such efforts, studies on renal cell therapy and artificial kidney developments have been conducted, and multiple therapeutic interventions have shown promise in the pre-clinical and clinical settings. More recently, therapeutic cell-secreting secretomes have emerged as a potential alternative to cell-based approaches. This approach involves the use of renotropic factors, such as growth factors and cytokines, that are produced by cells and these factors have shown effectiveness in facilitating kidney function recovery. This review focuses on the renotropic functions of bioactive compounds that provide protective and regenerative effects for kidney tissue repair, based on the available data in the literature.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.89-97
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• 2015

Background: We conducted this experimental study to examine whether human adipose-derived stem cells (ADSCs) are effective in achieving a recovery of damaged renal tubular epithelial cells in an animal model of cisplatin-induced acute kidney injury using rats. Methods: To examine the in vitro effects of ADSCs in improving nephrotoxicity, we treated mouse renal tubular epithelial cells with both ADSCs and cisplatin mouse renal tubular epithelial cells. And we equally divided 30 male white Sprague-Dawley (SD) rats into the three groups: the control group (intraperitoneal injection of a sterile saline), the cisplatin group (intraperitoneal injection of cisplatin) and the ADSC group (intraperitoneal injection of cisplatin and the hADSC via the caudal vein). At five days after the treatment with cisplatin, serum levels of blood urine nitrogen (BUN) and creatinine were measured from each SD rat. We performed histopathologic examinations of tissue samples obtained from the kidney. Results: The degree of the expression of TNF-${\alpha}$ and that of Bcl-2 were significantly higher and lower respectively, in cisplatin group (P<0.05). Serum levels of BUN (P=0.027) and creatinine (P=0.02) were significantly higher in cisplatin group. On histopathologic examinations, there was a significant difference in the ratio of the renal injury between cisplatin group and ADSC group (P=0.002). Conclusion: The ADSCs might have a beneficial effect in regenerating the damaged renal tubular epithelial cells.

• Childhood Kidney Diseases
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• v.22 no.2
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• pp.52-57
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• 2018

Purpose: Rhabdomyolysis is a metabolic disorder in which the content of damaged muscle cells is released into plasma. Its manifestations include asymptomatic, myalgia, gross hematuria, and complications of acute kidney injury. Because of limited data on rhabdomyolysis in children, we performed this study to determine clinical characteristics of rhabdomyolysis in children. Methods: We retrospectively reviewed the records of patients with rhabdomyolysis who were treated at the Pusan National University Children's hospital from January 2011 to July 2016. The diagnostic criteria were serum myoglobin level of ${\geq}80ng/mL$, exclusive of acute myocardial injury, cardiac arrest, and brain damage. Results: Forty-five patients were enrolled; mean age, $116{\pm}68$ months. Of these, 35 were boys and 10 were girls. Twenty-six patients experienced myalgia and 12 patients showed gross hematuria. Among these, seven patients initially had both myalgia and gross hematuria. The most common causes of rhabdomyolysis were infection, physical exertion, prolonged seizures, metabolic abnormalities, and drug addiction. Acute kidney injury (AKI) was the most common complication, followed by disseminated intravascular coagulation. Thirty-seven patients improved with sufficient fluid supply but two patients underwent hemodialysis due to deterioration of kidney function. Gross hematuria, positive occult blood test, and positive urine protein were more common in patients with AKI than in those without AKI. Conclusions: In children, infection was the most common cause of rhabdomyolysis. Most patients recovered by sufficient fluid therapy. However, in severe cases, especially in patients with underlying kidney disease, hemodialysis may be necessary in the present study.

• Journal of Ginseng Research
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• v.41 no.3
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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.

• Nutrition Research and Practice
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• v.15 no.1
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• pp.26-37
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• 2021

BACKGROUND/OBJECTIVES: Hyperuricemic nephropathy is a common cause of acute kidney injury. Resveratrol can ameliorate kidney injury, but the explicit mechanism remains unclear. We investigated the effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats. MATERIALS/METHODS: A rat model of hyperuricemic nephropathy was established by the oral administration of a mixture of adenine and potassium oxinate. Biochemical analysis and hematoxylin and eosin staining were performed to assess the rat kidney function. Enzyme-linked immunosorbent assays were performed to evaluate the immune and oxidative responses. RESULTS: The expression levels of urine albumin and β2-microglobulin were significantly decreased after resveratrol treatment. In addition, the levels of serum creatinine and uric acid were significantly decreased in the resveratrol groups, compared with the control group. The levels of proinflammatory factors, such as interleukin-1β and tumor necrosis factor-α, in kidney tissue and serum were also increased in the hyperuricemic rats, and resveratrol treatment inhibited their expression. Moreover, the total antioxidant capacity in kidney tissue as well as the superoxide dismutase and xanthine oxidase levels in serum were all decreased by resveratrol treatment. CONCLUSIONS: Resveratrol may protect against hyperuricemic nephropathy through regulating the inflammatory response.