• Biomolecules & Therapeutics
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• 제26권4호
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• pp.389-398
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• 2018

p-Cresol, found at high concentrations in the serum of chronic kidney failure patients, is known to cause cell senescence and other complications in different parts of the body. p-Cresol is thought to mediate cytotoxic effects through the induction of autophagy response. However, toxic effects of p-cresol on mesenchymal stem cells have not been elucidated. Thus, we aimed to investigate whether p-cresol induces senescence of mesenchymal stem cells, and whether melatonin can ameliorate abnormal autophagy response caused by p-cresol. We found that p-cresol concentration-dependently reduced proliferation of mesenchymal stem cells. Pretreatment with melatonin prevented pro-senescence effects of p-cresol on mesenchymal stem cells. We found that by inducing phosphorylation of Akt and activating the Akt signaling pathway, melatonin enhanced catalase activity and thereby inhibited the accumulation of reactive oxygen species induced by p-cresol in mesenchymal stem cells, ultimately preventing abnormal activation of autophagy. Furthermore, preincubation with melatonin counteracted other pro-senescence changes caused by p-cresol, such as the increase in total 5'-AMP-activated protein kinase expression and decrease in the level of phosphorylated mechanistic target of rapamycin. Ultimately, we discovered that melatonin restored the expression of senescence marker protein 30, which is normally suppressed because of the induction of the autophagy pathway in chronic kidney failure patients by p-cresol. Our findings suggest that stem cell senescence in patients with chronic kidney failure could be potentially rescued by the administration of melatonin, which grants this hormone a novel therapeutic role.

• BMB Reports
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• 제56권3호
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• pp.196-201
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• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.365-372
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• 2021

Type 2 diabetes mellitus (T2DM) leads to many health problems like diabetic nephropathy (DN). One of the key factors for chronic kidney disease and end-stage renal disease (ESRD) is T2DM. Extensive work is being done to delineate the pathogenesis of DN and to extend possible remedies. This review is intended to understand the nature of DN risk factors, progression, effects of glycemic levels, and stages of DN. We also explored the novel diagnostic and therapeutic approaches for DN such as gene therapy and stem cell treatments.

• Kidney Research and Clinical Practice
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• 제37권4호
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• pp.384-392
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• 2018

Background: A very low protein diet (VLPD) with ketoacid analogs of essential amino acids (KA/EAA) administration can remarkably influence protein synthesis and metabolic disturbances of patients with advanced chronic kidney disease (CKD), and may also slow the decline in renal function. Methods: A retrospective cohort study was carried out to monitor renal progression and metabolic and nutritional status among 140 patients with CKD stage III or IV. One group (n = 70) was on a low protein diet (LPD) with 0.6 g of protein intake, and another group (n = 70) was on a VLPD with 0.3 g of protein and KA/EAA supplementation of 100 mg/kg/day for 12 months. Results: At 12-month follow-up, estimated glomerular filtration rate (GFR) significantly decreased from $41.6{\pm}10.2$ to $36.4{\pm}8.8mL/min/1.73m^2$ (P < 0.001) and urine protein increased from $0.6{\pm}0.5$ to $0.9{\pm}1.1g/day$ (P = 0.017) in the LPD group, but no significant changes in estimated GFR and urine protein were found in the VLPD plus KA/EAA group. A significant mean difference in rate of change in estimated GFR ($-5.2{\pm}3.6mL/min/1.73m^2$ per year; P < 0.001) was observed between the two groups. After Cox regression analysis, treatment with VLPD plus KA/EAA significantly protected against the incidence of declining GFR > 10% annually (adjusted hazard ratio, 0.42; 95% confidence interval, 0.23-0.79; P = 0.006) and significant correlations were found between using VLPD plus KA/EEA and increased GFR. Conclusion: VLPD supplementation with KA/EAA is associated with delayed renal progression while preserving the nutritional status in the patients with CKD. Co-administration of VLPD and KA/EAA may prove an effective alternative to conservative management of CKD.

• 대한족부족관절학회지
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• 제13권1호
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• pp.109-112
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• 2009

Calciphylaxis is a rare disease that appear in patients with secondary hyper-parathyroidism or chronic renal failure or that show defect in calcium phosphate metabolism which is characterized by fibrin deposit or calcification of medial wall of vessels causing gradual ischemic skin necrosis. Calciphylaxis is a disease with poor prognosis as skin necrosis can progress rapidly. If left untreated, calciphylaxis will progress to sepsis with high mortality. The treatment is controversial but kidney transplantation or parathyroidectomy is suggested to recover calcium-phosphate metabolism. The authors have experienced calciphylaxis in a patient with chronic renal failure caused by DM nephropathy with characteristic skin lesion and rapid skin necrosis. We describe this case with documentary reviews.

• Journal of Yeungnam Medical Science
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• 제33권2호
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• pp.150-154
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• 2016

Hepatitis C virus (HCV) infection is present in a high proportion of patients with kidney transplantation. Compared with uninfected kidney transplant recipients, HCV infected kidney recipient have higher prevalence of liver disease and worse allograft survival after transplantation. Interferon monotherapy before transplantation is standard therapy for HCV-infected kidney transplant candidates. If HCV infection is discovered after transplantation, interferon monotherapy is considered due to the limited critical situation. However, in this patient, who was a kidney recipient, HCV infection was treated after kidney transplantation with peginterferon-${\alpha}$ and rivabirin. As a result, the patient achieved sustained virologic response.

• The Korean Journal of Pain
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• 제24권3호
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• pp.154-157
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• 2011

Background: Postherpetic neuralgia (PHN) is usually managed pharmacologically. It is not uncommon for patients with chronic kidney disease (CKD) to suffer from PHN. It is difficult to prescribe a sufficient dose of anticonvulsants for intractable pain because of the decreased glomerular filtration rate. If the neural blockade and pulsed radiofrequency ablation provide only short-term amelioration of pain, spinal cord stimulation (SCS) with a low level of evidence may be used only as a last resort. This study was done to evaluate the efficacy of spinal cord stimulation in the treatment of PHN in patients with CKD. Methods: PHN patients with CKD who needed hemo-dialysis who received insufficient relief of pain over a VAS of 8 regardless of the neuropathic medications were eligible for SCS trial. The follow-up period was at least 2 years after permanent implantation. Results: Eleven patients received percutaneous SCS test trial from Jan 2003 to Dec 2007. Four patients had successfully received a permanent SCS implant with their pain being tolerable at a VAS score of less than 3 along with small doses of neuropathic medications. Conclusions: SCS was helpful in managing tolerable pain levels in some PHN patients with CKD along with tolerable neuropathic medications for over 2 years.

• 대한한방내과학회지
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• 제42권5호
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• pp.727-737
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• 2021

Objectives: This study investigated the effect of Korean medicine on an elderly patient with posterior circulation cerebral infarction, chronic kidney disease (CKD), and early neurological deterioration (END). Methods: The patient, who already had CKD, was treated with Korean medicine, comprising herbal medicine, acupuncture, moxa, and cupping combined with Western medicine (antiplatelet, diabetes) and physical therapy. A manual muscle test (MMT) and a modified Barthel index (MBI) were used to observe the treatment effects, and blood tests were performed to check estimated glomerular filtration rate (eGFR), creatinine and blood urea nitrogen (BUN), which represent renal function. Results: After the treatment, MMT, MBI, and renal function scores had increased. Conclusions: This study suggests that Korean medicine can effectively treat posterior circulation cerebral infarction with END in CKD, but further studies should be conducted.

• 대한핵의학회지
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• 제3권1호
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• pp.19-32
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• 1969

Radioisotope renography was carried out in 564 cases consisting of 150 normal controls, 140 hypertensives, 102 hypertensive nephropathys, 62 chronic renal diseases, non-functioning kidneys. It was aimed to study which parameter of the renogram is most applicable to any definite disease of the kidney. The analytical methods adopted were; Tobe, Spencer, Krueger, Matchida and Takeuchi. In the non-functioning kidney groups, the hemograms and serum nitrogen series were also studied to evaluate the relationships between the renograms and renal anemia. The parameters were; time of maximum amplitude (Tmax), half-time of maximum amplitude ($T\frac{1}{2}$), Kac value calculated from these two parameters in Tobe's method, slopes of Band C phase, B/A and B/C values in Spencer's method, total concentration (T.C.), minute concentration (M.C.) and minute excretion (M.E.) in Krueger's method, Matchida's K value and Takeuchi's renal function Index (R.F.I.). Following were the results: 1. In general, marked differences in the patterns of the renogram were observed between the normal controls and nephropathys. In Tobe's method, each parameter showed statistically significant delay or decrease in patients with hypertensive nephropathys and chronic renal diseases. In Spencer's method, slopes of B and C phase and B/C, also showed the statistically significant decrease in patients with hypertension, hypertensive nephropathys and chronic renal diseases. In Krueger's method, M.C. and ME showed the statistically significant differences between the control and patients with hypertension, hypertensive nephropathys and chronic renal diseases, In Matchida's method, K value showed the statistically significant differences between the control and patients with hypertensive nephropathys and chronic renal diseases. 2. It appeared, therefore, that Tobe's $T\frac{1}{2}$, Kac value, Spencer's slopes of Band C phase, B/A, B/C values, Krueger's T.C., M.C., and M.E. values, Matchida's K value are useful for the differentiation of various renal diseases, however, qualitative analysis of the renogram with one or two parameters is not accurate. 3. In bilateral non-functioning kidney groups, a positive correlation between anemia and nitrogen retention was observed, although the quantitative assessment of the degree of non-functioning was impossible.

• Journal of Korean Medical Science
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• 제33권43호
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• pp.277.1-277.10
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• 2018

Background: To examine survival rates and renal function after partial nephrectomy (PN) and radical nephrectomy (RN) in patients with chronic kidney disease (CKD). Methods: We studied 4,332 patients who underwent PN or RN for pathological T1a-T2N0M0 renal cell carcinoma from 1988 to 2014. Patients were divided into two subgroups of CKD stage I-II and stage III. Kidney function, and survival outcomes were compared between groups. Results: We included 1,756 patients with CKD I-II and 276 patients with CKD III in the final pair-matched analysis. Kidney function was significantly better preserved in the PN than in the RN group among all patients. However, the beneficial effect of PN on kidney function gradually disappeared over time in CKD III patients. The 5-year overall survival (OS) rates after PN and RN differed in patients with CKD I-II disease (99.4% vs. 96.5%, respectively, P = 0.015). The 5-year OS rates after surgery were not affected by mode of nephrectomy in CKD III patients (97.8% vs. 93.5%, P = 0.103). The 5-year cancer-specific survival rates did not differ between treatment groups in all CKD stage. Cox hazard analysis showed that the operative method was a significant factor for OS in CKD I-II patients (hazard ratio [HR], 0.320; confidence interval [CI], 0.122-0.840; P = 0.021). However, PN was not beneficial in terms of OS in CKD III patients (HR, 0.395; CI, 0.086-1.172; P = 0.117). Conclusion: PN is associated with a higher OS rate and better kidney function in patients with preoperative CKD stage I and II, but not in those with CKD stage III.