• Korean Journal of Radiology
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• 제24권10호
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• pp.1017-1027
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• 2023

Objective: The assessment of cortical integrity following renal injuries with planar Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy depends on measuring relatively decreased cortical uptake (i.e., split renal function [SRF]). We analyzed the additive values of the volumetric and quantitative analyses of the residual cortical integrity using single-photon emission computed tomography (SPECT) compared to the planar scintigraphy. Materials and Methods: This prospective study included 47 patients (male:female, 32:15; age, 47 ± 22 years) who had non-operatively managed renal injuries and underwent DMSA planar and SPECT imaging 3-6 months after the index injury. In addition to planar SRF, SPECT SRF, cortical volume, and absolute cortical uptake were measured for the injured kidney and both kidneys together. The correlations of planar SRF with SPECT SRF and those of SRF with volumetric/quantitative parameters obtained with SPECT were analyzed. The association of SPECT parameters with renal function, grades of renal injuries, and the risk of renal failure was also analyzed. Results: SPECT SRF was significantly lower than planar SRF, with particularly higher biases in severe renal injuries. Planar and SPECT SRF (dichotomized with a cutoff of 45%) showed 19%-36% of discrepancies with volumetric and quantitative DMSA indices (when dichotomized as either high or low). Absolute cortical uptake of the injured kidney best correlated with glomerular filtration rate (GFR) at follow-up (ρ = 0.687, P < 0.001) with significant stepwise decreases by GFR strata (90 and 60 mL/min/1.73 m²). Total renal cortical uptake was significantly lower in patients with moderate-to-high risk of renal failure than those with low risk. However, SRF did not reflect GFR decrease below 60 mL/min/1.73 m² or the risk of renal failure, regardless of planar or SPECT (count- or volume-based SRF) imaging. Conclusion: Quantitative measurements of renal cortical integrity assessed with DMSA SPECT can provide more clinically relevant and comprehensive information than planar imaging or SRF alone.

• 한국임상수의학회지
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• 제26권1호
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• pp.29-35
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• 2009

본 연구의 목적은 돼지의 신장 자가이식에서 항산화제에 의한 허혈 및 재관류 손상의 감소에 대하여 ascorbic acid와 alpha-tocopherol이 미치는 영향을 평가하는 데 있다. 6두의 어린 돼지에 자가 신장 이식을 실시하였으며, 처치군에서는 수술 2일전 비타민 C와 E를 이틀 동안 전처치 하고, 그 뒤에 수술 중 비타민 C와 heparin이 첨가된 생리식염수를 절제되어 자가 이식할 신장에 관주하였다. 대조군에서는 수술 중 heparin이 첨가된 생리 식염수만을 절제되어 자가 이식할 신장에 관주하였다. 신장 기능을 평가하기 위하여 혈액 샘플을 채취하였으며, 수술 전, 수술 후 1, 3, 7, 14일에 혈청 creatinine과 BUN을 측정하였다. 그리고 병리조직 검사를 위해 14일 후 신장을 적출 보관하였다. 신장의 기능 검사에서 대조군과 처치군 사이에서 전체적인 유의성은 없었지만, 1일째, 3일째 또는 5일째에 두 그룹간의 유의적인 차이가 인정되었다 (p<0.05). 병리조직 검사 결과 처치군이 대조군 보다 더 적은 조직 손상의 정도를 보였다. 이러한 결과는, 비타민 C와 heparin을 이용한 신장의 관주 및 흡인의 과정이 신장의 허혈 및 재관류 손상을 감소시키는 데에 효과가 있었음을 시사하며, 이는 돼지의 신장 자가 이식에서 허혈 및 재관류의 손상을 감소시키며 신기능의 회복에 효과가 있음을 시사하는 바이다.

• BMB Reports
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• 제55권1호
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• pp.3-10
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• 2022

Extracellular vesicles (EVs) released from different types of kidney cells under physiologic conditions contribute to homeostasis maintenance, immune-modulation, and cell-to-cell communications. EVs can also negatively affect the progression of renal diseases through their pro-inflammatory, pro-fibrotic, and tumorigenic potential. Inhibiting EVs by blocking their production, release, and uptake has been suggested as a potential therapeutic mechanism based on the significant implication of exosomes in various renal diseases. On the other hand, stem cell-derived EVs can ameliorate tissue injury and mediate tissue repair by ameliorating apoptosis, inflammation, and fibrosis while promoting angiogenesis and tubular cell proliferation. Recent advancement in biomedical engineering technique has made it feasible to modulate the composition of exosomes with diverse biologic functions, making EV one of the most popular drug delivery tools. The objective of this review was to provide updates of recent clinical and experimental findings on the therapeutic potential of EVs in renal diseases and discuss the clinical applicability of EVs in various renal diseases.

• Childhood Kidney Diseases
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• 제25권1호
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• pp.44-48
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• 2021

Idiopathic renal hypouricemia (iRHUC) is a rare hereditary disease caused by a defect in urate handling of renal tubules. Type 1 renal hypouricemia (RHUC1) is diagnosed with confirmation of a mutation in SLC22A12 gene which encodes a renal urate-anion exchanger (URAT1). The majority of iRHUC patients are asymptomatic, especially during childhood, and thus many cases go undiagnosed or they are diagnosed late in older age with complications of hematuria, renal stones, or acute kidney injury (AKI). We report a case of a 7-year-old boy with subtle symptoms such as general weakness and dizziness and revealed hypouricemia and incidental nephrolithiasis. Homozygous mutations were detected in the SLC22A12 (c.774G>A) by molecular analysis. The present case suggests that fractional excretion of uric acid (FEUA) screening could be better followed by the coincidental discovery of hypouricemia, to prevent conflicting complications of iRHUC, even with normal urine uric acid to creatinine ratio (U_UA/U_Cr), and sequential genetic analysis if needed.

• Journal of Chest Surgery
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• 제12권4호
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• pp.418-423
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• 1979

Chest injuries due to blunt trauma often result in severe derangements that lead to death. And we have to diagnose and treat the patients who have blunt chest trauma immediately and appropriately. A clinical analysis was made on 324 cases of chest injury due to blunt trauma experienced at department of Thoracic and Cardiovascular Surgery, College of Medicine, Kyung Hee University during 8-year period from 1972 to 1979. Of 324 patients of blunt chest injuries, there were 189 cases of rib fracture, 121 of hemothorax or/and pneumothorax, 108 of soft tissue injury of the chest wall only, 41 of lung contusion, 24 of flail chest, 13 of scapular fracture, 7 of diaphragmatic rupture and others. The majority of blunt chest injury patients were traffic accident victims and falls accounted for the next largest group of accidents. Chest injuries were frequently encountered in the age group between 3rd decade and 4th decade [60%] and 238 patients were male comparing to 86 of female [Male: Female = 3:1 ]. In the patients who have the more number of fractured ribs, the more incidence of intrathoracic injury and intraabdominal organ damage were found. The principal associated injuries were head injury on 58 cases, long bone fractures on 37, skull fractures on 12, pelvic fractures on 10, renal injuries on 6 and intraabdominal organ injuries on 5 patients. The principle of early treatment of chest injury due to blunt trauma were rapid reexpansion of the lung by closed thoracotomy which was indicated on 96 cases, but open thoractomy was necessary on 14 cases because massive bleeding, intrapleural hematoma and/or fibrothorax, or diaphragmatic laceration-On 15 cases who were young and have multiple rib fracture with severe dislocation delayed elective open reduction of the fractured ribs with wire was done on the purpose of preserving normal active life. The over all mortality was 2.8% [9 of 324 cases] due to head injury on 3 cases, massive bleeding on 2,wet lung syndrome, acute renal failure on 1 and septicemia on 1 patient.

• 한국임상수의학회지
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• 제26권5호
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• pp.441-444
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• 2009

허혈/재관류 손상은 장기이식 분야에서 해결해야 할 주요 문제점으로 알려져 있다. 본 연구에서는 대퇴 동,정맥 부위에서 기존의 혈관 문합법 대신 맥관 connector를 이용하여 간단하면서 효과적인 체외 재관류 모델을 개발하였기에 소개하고자 한다. 개발된 모델이 허혈/재관류 손상연구에 효과적인지 알아보기 위해 혈액 동력학적 평가와 신장의 재관류 후 손상 양상을 분석하였다. 기존의 재관류 모델에서 사용되는 문합 부위인 복강 대동맥의 혈압과 본 연구에서 재관류 부위로 활용된 대퇴동맥의 혈압은 유의적 차이가 없었다. 허혈 손상 후 재관류 효과를 알아보기 위해 미니돼지에서 적출한 신장을 HTK 용액에 24, 48시간 동안 각각 저온보관 후 대퇴부에 이식하여 재관류 한 결과, 신장의 재관류까지 수술시간은 평균 $7.0{\pm}1.1$분 소요되었으며, 3시간 재관류 후 재관류 손상 정도는 저온보관시간에 따라 증가되는 것이 확인되었다. 이는 개발된 모델이 맥관 문합 없이 간단한 관류방법이면서도 기존의 복잡한 수술에 의한 재관류 방법과 유사한 손상 모델을 만들 수 있는 효과적인 허혈/재관류 동물모델이라는 것을 의미한다. 따라서 본 연구에서 개발한 신장 재관류 모델은 초기 허혈/재관류 손상 연구와 장기이식에서 이식면역연구에 효과적인 모델이라 사료된다.

• Molecules and Cells
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• 제37권3호
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• pp.234-240
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• 2014

Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

• Biomolecules & Therapeutics
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• 제29권1호
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• pp.41-51
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• 2021

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson's trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

• Journal of Ginseng Research
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• 제48권2호
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• pp.190-201
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• 2024

Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.

• Childhood Kidney Diseases
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• 제18권1호
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• pp.13-17
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• 2014

지속적 신 대체 요법(CRRT)은 급성 신손상이 있는 중증 소아의 치료로 점차 사용이 늘어나고 있으며 CRRT의 기술과 실제 사용법이 발달하면서 작은 영아나 신생아에서도 그 사용이 조금씩 늘어나고 있다. 고암모니아혈증이나 체외막산소화 장치(ECMO) 치료 중에 발생한 급성 신손상 등의 경우 CRRT가 안전하고 효과적인 치료가 될 수 있으나, 혈관 접근이나 출혈 그리고 신생아 전용 CRRT device의 부재로 인한 여러 가지 제한점이 있다. 이 종설에서는 기본적인 CRRT의 원리를 알아보고 신생아와 영아에서 특별히 고려해야 할 사항들에 대해 알아보고자 한다.