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.

Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis

Background@#Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. @*Methods@#Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. @*Results@#Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. @*Conclusion@#These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.

Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis

Background@#Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. @*Methods@#Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. @*Results@#Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. @*Conclusion@#These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.

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.

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

No abstract available.

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.

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.

Risk Factors and Reversibility of Renal Failure in Patients with Newly Diagnosed Multiple Myeloma / 대한내과학회지

BACKGROUND/AIMS: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. METHODS: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. RESULTS: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high beta2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher eGFR (OR, 1.084; p < 0.01) were associated with renal function recovery. CONCLUSIONS: Levels of hemoglobin and beta2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and eGFR at diagnosis significantly influenced recovery of renal function.

Risk Factors and Reversibility of Renal Failure in Patients with Newly Diagnosed Multiple Myeloma / 대한내과학회지

BACKGROUND/AIMS: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. METHODS: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. RESULTS: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high beta2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher eGFR (OR, 1.084; p < 0.01) were associated with renal function recovery. CONCLUSIONS: Levels of hemoglobin and beta2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and eGFR at diagnosis significantly influenced recovery of renal function.

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.

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.

Percutaneous renal biopsy should be considered as a daycare procedure in select patients

No abstract available.

What is the Optimal Period of Observation after Percutaneous Renal Biopsy? / 대한신장학회지

No abstract available.

Renal Infarction Concurrent with Multiple Venous Thrombosis in Association with Inherited Antithrombin Deficiency / 대한신장학회지

Antithrombin deficiency is a rare condition among the numerous conditions that can lead to a hypercoagulable state, and can manifest as deep vein thrombosis, portal or mesenteric venous thrombosis, pulmonary thromboembolism and cerebrovascular accidents. In this report, we present a case of acute renal infarction and multiple venous thrombosis in a 36-year-old man with a family history of thromboembolism. He presented with a sudden onset of pain in the right flank and was admitted to the emergency room for evaluation. On computed tomography and renal angiography, the diagnosis of acute renal infarction concurrent with portal, splenic and superior mesenteric venous thrombosis was made. Laboratory data revealed parallel decreases in activity and antigen concentration of antithrombin despite normal liver and renal functions. He was treated with intravenous heparin and fresh frozen plasma followed by concomitant warfarin therapy. Taken together, the etiology of acute renal infarction and multiple venous thrombosis was considered to be associated with type I inherited antithrombin deficiency.

A Synonymous Genetic Alteration of LMX1B in a Family with Nail-Patella Syndrome

The gene responsible for nail-patella syndrome, LMX1B, has recently been identified on chromosome 9q. Here we present a patient with nail-patella syndrome and an autosomal dominant pattern of inheritance. A 17-year-old girl visited our clinic for the evaluation and treatment of proteinuria. She had dystrophic nails, palpable iliac horns, and hypoplastic patellae. Electron microscopy of a renal biopsy showed irregular thickening of the glomerular basement membrane. A family history over three generations revealed five affected family members. Genetic analysis found a change of TCG to TCC, resulting in a synonymous alteration at codon 219 in exon 4 of the LMX1B gene in two affected family members. The same alteration was not detected in an unaffected family member. This is the first report of familial nail-patella syndrome associated with an LMX1B in Korea mutation, However, we can not completely rule out the possibility that the G-to-C change may be a single nucleotide polymorphism as this genetic mutation cause no alteration in amino acid sequence of LMX1B.