The combined clinical impact of red blood cell distribution width and vascular calcification on cardiovascular events and mortality in patients with endstage kidney disease

Little is known about how the interaction between red blood cell distribution width (RDW) and vascular calcification (VC) affects cardiovascular (CV) events and mortality in end-stage kidney disease (ESKD) patients. This study investigated the combined prognostic effect of RDW and VC in ESKD patients starting dialysis. Methods: A retrospective single-center study of 582 ESKD patients was conducted. VC was assessed by calculating the aortic calcification index (ACI) using computed tomography. Patients were divided into low ACI-low RDW, low ACI-high RDW, high ACI-low RDW, and high ACI-high RDW groups based on median ACI (17.12) and RDW (14.3) values. The association between RDW and VC and the composite endpoint of CV events and death was analyzed. Results: During a median follow-up of 3.1 years (range, 1.5–5.5 years), 165 CV events (28.4%) and 124 deaths (21.4%) occurred. Cox regression showed that the low ACI-high RDW (adjusted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.04–2.66; p = 0.03) and high ACI-low RDW (adjusted HR, 1.95; 95% CI, 1.21–3.14; p = 0.006) groups had a greater risk of CV events and death than the low ACI-low RDW group. The high ACI-high RDW group had the greatest risk (adjusted HR, 2.23; 95% CI, 1.42–3.52; p = 0.001). The effect of the interaction between ACI and RDW on CV events and mortality was statistically significant (p = 0.005). Conclusion: High RDW and VC interact to increase the risk of CV events and death in ESKD patients.

Development of donepezil-induced hypokalemia following treatment of cognitive impairment / 영남의대학술지

Donepezil is a cholinesterase inhibitor used extensively to treat Alzheimer disease. The increased cholinergic activity is associated with adverse effects, therefore gastrointestinal symptoms, including nausea, vomiting, and diarrhea, are common. Hypokalemia is a rare adverse event that occurs in less than 1% of donepezil-treated patients. Although hypokalemia of mild and moderate grade does not present serious signs and symptoms, severe hypokalemia often results in prolonged hospitalization and mortality. Herein, we report a case of hypokalemia developed after the initiation of donepezil therapy for cognitive impairment.

Sex-specific relationship between vascular calcification and incident fracture in patients with end-stage renal disease

Background@#Vascular calcification (VC) is a major component of mineral bone disorders in patients with end-stage renal disease (ESRD). Bone metabolism is affected by various factors, including sex hormones. This study investigated whether there was a sex-specific relationship between VC and incident fracture in patients with ESRD. @*Methods@#This was a retrospective cohort study of dialysis patients from a single center. VC was assessed by the aortic calcification index (ACI) using abdominal computed tomography. Patients were grouped by sex and stratified into low or high ACI groups, according to the median ACI value. The association between ACI and incident fracture was analyzed. @*Results@#Data from 593 patients (male: n = 328, median ACI, 14.57; female: n = 265, median ACI, 19.44) were included. During a median follow-up of 36.7 months, 71 patients (12.0%) developed fractures. The fracture-free survival rate was significantly lower in the high ACI group versus the low ACI group, both in males (P = 0.021) and females (P = 0.001). In males, multivariate analysis showed that the high ACI group and ACI per se were not significant risks for fracture. However, in females, both the high ACI group (adjusted hazard ratio, 2.720; P = 0.003) and ACI per se (adjusted hazard ratio, 1.768; P = 0.035) were independently associated with fracture after adjustment for confounding variables. @*Conclusion@#VC was independently associated with incident fracture in female patients with ESRD. There may be a sex-specific relationship between VC and fracture in patients with ESRD.

Korean clinical practice guidelines for preventing transmission of coronavirus disease 2019 (COVID-19) in hemodialysis facilities

Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease that is caused by the novel virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). COVID-19 has become pandemic since December 2019, when the first case developed in Wuhan, China. Patients receiving hemodialysis are more vulnerable to viral transmission because their immune functions are impaired and they receive treatment within a narrow space. Calling on previous experience with Middle East Respiratory Syndrome during the 2015 outbreak, the joint committee of the Korean Society of Nephrology and the Korean Society of Dialysis Therapy quickly formed a COVID-19 task force team to develop a manual before the first index case was diagnosed in the hemodialysis unit. This special article introduces clinical practice guidelines to prevent secondary transmission of COVID-19 within hemodialysis facilities, which were developed to protect patients, healthcare workers, and caregivers from this highly transmissible virus. The areas of infection control covered by these guidelines include standard precautions, performing dialysis therapy for confirmed or suspected cases, performing cohort isolation for contact patients, and disease monitoring and contact surveillance. We hope these guidelines help healthcare workers and hemodialysis patients around the world cope with the COVID-19 pandemic.

Clinical outcomes and effects of treatment in older patients with idiopathic membranous nephropathy

BACKGROUND/AIMS@#Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN.@*METHODS@#The outcomes of 135 patients with histologically proven MN were analyzed. ‘Older’ was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients.@*RESULTS@#The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients.@*CONCLUSIONS@#Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids.

Erratum: Age-related Changes in the Sirtuin1-NFE2-related Factor 2 Signaling System in the Kidney / 대한내과학회지

The authors apologize for any inconvenience that this may have caused.

Age-related Changes in the Sirtuin1-NFE2-related Factor 2 Signaling System in the Kidney / 대한내과학회지

BACKGROUND/AIMS: Renal aging-related changes are characterized by oxidative stress. SIRT1 regulates cellular conditions by activating Nrf2. The present study investigated the processes of renal changes by antioxidant enzymes and the relationship between SIRT1 and Nrf2. METHODS: We used male 2-, 12-, and 24-month-old C57BL/6 mice. We measured renal function, histological changes, oxidative stress, and expression of SIRT1–Nrf2 signaling in the kidneys. RESULTS: 24-month-old mice exhibited increased albuminuria and serum creatinine. Creatinine clearance was decreased in 24-month-old mice compared with 12-month-old mice. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. Moreover, oxidative stress marker, 3-Nitrotyrosine, expression and apoptosis were increased in 24-month-old mice. The 24 h urinary 8-isoprostane and 8-hydroxy-deoxyguanosine excretion increased with aging. The levels of expression of SIRT1 and nuclear Nrf2 were decreased in 24-month-old mice. The antioxidant enzymes HO-1 and NQO-1 were down-regulated in 24-month-old mice. Another antioxidant enzyme, SOD2, was decreased in 24-month-old mice. CONCLUSIONS: Our results demonstrated that SIRT1 was down-regulated with aging, and this may be related to changes in the expression of target molecules including Nrf2. As a result, oxidative stress was induced. The pharmacological targeting of these signaling molecules may reduce the pathological changes associated with aging in the kidney.

Identification of Compound Heterozygous Mutations in the BBS7 Gene in a Korean Family with Bardet-Biedl Syndrome

No abstract available.

Effects on G2/M Phase Cell Cycle Distribution and Aneuploidy Formation of Exposure to a 60 Hz Electromagnetic Field in Combination with Ionizing Radiation or Hydrogen Peroxide in L132 Nontumorigenic Human Lung Epithelial Cells

The aim of the present study was to assess whether exposure to the combination of an extremely low frequency magnetic field (ELF-MF; 60 Hz, 1 mT or 2 mT) with a stress factor, such as ionizing radiation (IR) or H2O2, results in genomic instability in non-tumorigenic human lung epithelial L132 cells. To this end, the percentages of G2/M-arrested cells and aneuploid cells were examined. Exposure to 0.5 Gy IR or 0.05 mM H2O2 for 9 h resulted in the highest levels of aneuploidy; however, no cells were observed in the subG1 phase, which indicated the absence of apoptotic cell death. Exposure to an ELF-MF alone (1 mT or 2 mT) did not affect the percentages of G2/M-arrested cells, aneuploid cells, or the populations of cells in the subG1 phase. Moreover, when cells were exposed to a 1 mT or 2 mT ELF-MF in combination with IR (0.5 Gy) or H2O2 (0.05 mM), the ELF-MF did not further increase the percentages of G2/M-arrested cells or aneuploid cells. These results suggest that ELF-MFs alone do not induce either G2/M arrest or aneuploidy, even when administered in combination with different stressors.

A Case of Metastatic Papillary Renal Cell Carcinoma Mimicking a Renal Abscess / 대한내과학회지

Papillary renal cell carcinoma (PRCC), a histological subtype of renal cell carcinoma (RCC), accounts for approximately 10% of all RCC. Here, we report a case of metastatic RCC diagnosed unexpectedly in a 31-year-old female patient. Computed tomography revealed a renal abscess in the left kidney and the urine culture confirmed Escherichia coli producing extended-spectrum beta-lactamase. Despite appropriate antibiotic treatment for 2 months, the patient's symptoms and radiological findings worsened and she underwent nephrectomy. Pathological examination confirmed type 2 PRCC and a further staging study found stage 4 (T3N1M1). Our findings indicate that malignancy should be considered in young patients with a bacteriologically confirmed urinary tract infection.

Tempol Attenuates Renal Fibrosis in Mice with Unilateral Ureteral Obstruction: The Role of PI3K-Akt-FoxO3a Signaling

This study investigated whether tempol, an anti-oxidant, protects against renal injury by modulating phosphatidylinositol 3-kinase (PI3K)-Akt-Forkhead homeobox O (FoxO) signaling. Mice received unilateral ureteral obstruction (UUO) surgery with or without administration of tempol. We evaluated renal damage, oxidative stress and the expression of PI3K, Akt, FoxO3a and their target molecules including manganese superoxide dismutase (MnSOD), catalase, Bax, and Bcl-2 on day 3 and day 7 after UUO. Tubulointerstitial fibrosis, collagen deposition, alpha-smooth muscle actin-positive area, and F4/80-positive macrophage infiltration were significantly lower in tempol-treated mice compared with control mice. The expression of PI3K, phosphorylated Akt, and phosphorylated FoxO3a markedly decreased in tempol-treated mice compared with control mice. Tempol prominently increased the expressions of MnSOD and catalase, and decreased the production of hydrogen peroxide and lipid peroxidation in the obstructed kidneys. Significantly less apoptosis, a lower ratio of Bax to Bcl-2 expression and fewer apoptotic cells in TUNEL staining, and decreased expression of transforming growth factor-beta1 were observed in the obstructed kidneys from tempol-treated mice compared with those from control mice. Tempol attenuates oxidative stress, inflammation, and fibrosis in the obstructed kidneys of UUO mice, and the modulation of PI3K-Akt-FoxO3a signaling may be involved in this pathogenesis.

The renin-angiotensin system and aging in the kidney

Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and functional changes in the aging kidney and age-related renal injury, and describes the underlying mechanisms of RAS-related renal aging. An improved understanding of the renal aging process may lead to better individualized care of the elderly and improved renal survival in age-related diseases.

Cat-induced Pasteurella multocida peritonitis in continuous ambulatory peritoneal dialysis

Pasteurella multocida is a zoonotic pathogen found in the oral cavities of both domestic and wild animals. Although P. multocida has been involved in a wide range of human diseases, only a limited number of studies on P. multocida peritonitis in patients undergoing peritoneal dialysis (PD) had been carried out. We herein present the case of P. multocida peritonitis in a patient undergoing continuous ambulatory PD, which is believed to have resulted from contact with cats. We suggest that patients undergoing PD and having domestic animals at home should be educated about the possible transmission of the infection from the animals; in addition, these patients should also maintain a high level of personal hygiene.

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Delta1.2+/-2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Delta363.6+/-543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Delta0.5+/-2.7 mL/min/1.73 m2, P=0.266; -Delta108.6+/-543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, beta2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549]

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Delta1.2+/-2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Delta363.6+/-543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Delta0.5+/-2.7 mL/min/1.73 m2, P=0.266; -Delta108.6+/-543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, beta2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549]

Hypermagnesemia Accompanied with Colonic Perforation in a Hemodialysis Patient

We report a case of a chronic hemodialysis patient who developed hypermagnesemia due to an overdose of magnesium-containing laxative and paralytic ileus resulting in colonic perforation. Despite intravenous calcium infusion and daily hemodialysis, the patient developed ischemic colitis and intestinal perforation. Colonic perforation accompanied with hypermagnesemia in hemodialysis patients has rarely been reported. This case suggests that hypermagnesemia should be considered in renal failure patients as this can result in life-threatening events despite prompt treatment.

Microalbuminuria is Independently Associated with Arterial Stiffness and Vascular Inflammation but not with Carotid Intima-Media Thickness in Patients with Newly Diagnosed Type 2 Diabetes or Essential Hypertension

The association between microalbuminuria (MAU) and the indices of macrovascular complication in patients with newly diagnosed type 2 diabetes (D) or essential hypertension (H) was evaluated. Total 446 patients were classified into four groups according to the urinary albumin-to-creatinine ratio: MAU-D (n = 104), normoalbuminuria (NAU)-D (n = 114), MAU-H (n = 116), and NAU-H (n = 112). The indices of macrovascular complication including arterial stiffness evaluated by pulse-wave-velocity (PWV), carotid intima-media thickness (IMT), and vascular inflammation marked by high-sensitivity C-reactive protein (hsCRP) were assessed. PWV, IMT, and hsCRP were higher in patients with MAU than in those with NAU in both diabetes and hypertension groups. In both MAU-D and MAU-H groups, PWV and hsCRP levels were positively correlated with MAU level (MAU-D: r = 0.47, 0.41, MAU-H: r = 0.36, 0.62, respectively, P < 0.05). Additionally, PWV and hsCRP were independent factors predicting MAU (diabetes group: OR 1.85, 1.54, hypertension group: OR 1.38, 1.51, respectively, P < 0.001), but not IMT. MAU is independently associated with arterial stiffness and vascular inflammation but not with IMT in patients with newly diagnosed type 2 diabetes or essential hypertension, which emphasizes the importance of proactive clinical investigations for atherosclerotic complications in patients with MAU, even in newly diagnosed diabetes or hypertension.

Urine output before the initiation of CRRT and mortality

No abstract available.

Comparison of Early and Late Conversion of Sirolimus in Experimental Model of Chronic Cyclosporine Nephropathy

Sirolimus (SRL) is a promising drug for replacing calcineurin inhibitors. We performed this study to determine the optimal time of conversion from cyclosporine (CsA) to SRL in an experimental model of chronic CsA nephropathy. Three separate studies were performed. In the first study, SRL was given to rats with or without CsA for 4 weeks. In the second study, rats were treated initially with CsA for 1 week, and then switched to SRL (early conversion). In the third study, CsA was given for 4 weeks and then replaced by SRL for 4 weeks treatment of CsA (late conversion). The influence of SRL on CsA-induced renal injury was evaluated by assessing renal function, histopathology (interstitial inflammation and fibrosis), and apoptotic cell death. Combined CsA and SRL treatment significantly impaired renal function, increased apoptosis, and interstitial fibrosis and inflammation compared with CsA or SRL treatment alone. Early conversion to SRL did not change renal function, histopathology, or apoptosis compared with early CsA withdrawal. By contrast, late conversion to SRL significantly aggravated these parameters compared with late CsA withdrawal. In conclusion, early conversion from CsA to SRL is effective in preventing CsA-induced renal injury in a setting of CsA-induced renal injury.

Abdominal Aortic Calcification is Associated with Diastolic Dysfunction, Mortality, and Nonfatal Cardiovascular Events in Maintenance Hemodialysis Patients

This study evaluated the significance of aortic calcification index (ACI), an estimate of abdominal aortic calcification by plain abdominal computed tomography (CT), in terms of left ventricular (LV) diastolic dysfunction, mortality, and nonfatal cardiovascular (CV) events in chronic hemodialysis patients. Hemodialysis patients who took both an abdominal CT and echocardiography were divided into a low-ACI group (n = 64) and a high-ACI group (n = 64). The high-ACI group was significantly older, had a longer dialysis vintage and higher comorbidity indices, and more patients had a previous history of CV disease than the low-ACI group. The ACI was negatively correlated with LV end-diastolic volume or LV stroke volume, and was positively correlated with the ratio of peak early transmitral flow velocity to peak early diastolic mitral annular velocity (E/E' ratio), a marker of LV diastolic function. The E/E' ratio was independently associated with the ACI. The event-free survival rates for mortality and nonfatal CV events were significantly lower in the high-ACI group compared with those in the low-ACI group, and the ACI was an independent predictor for all-cause deaths and nonfatal CV events. In conclusion, ACI is significantly associated with diastolic dysfunction and predicts all-cause mortality and nonfatal CV events in hemodialysis patients.