Clinical outcomes and prognostic factors of mortality in liver cirrhosis patients on continuous renal replacement therapy in two tertiary hospitals in Korea

Background@#Data on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite the dismal prognosis. We therefore evaluated clinical characteristics and predictive factors related to mortality in LC patients undergoing CRRT. @*Methods@#We performed a retrospective observational study at two tertiary hospitals in Korea. A total of 229 LC patients who underwent CRRT were analyzed. Patients were classified into survivor and non-survivor groups. We used multivariable Cox regression analyses to identify factors predictive of in-hospital mortality. @*Results@#During a median follow-up of 5 days (interquartile range, 1–19 days), in-hospital mortality rate was 66.4%. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01–1.06; p = 0.02), Model for End-Stage Liver Disease (MELD) score (HR, 1.08; 95% CI, 1.04–1.11; p 35 mL/kg/hr (HR, 3.13; 95% CI, 1.62–6.05; p = 0.001). Subgroup analysis revealed that a CRRT delivered dose < 25 mL/kg/hr was a significant risk factor for in-hospital mortality among LC patients with a MELD score ≥ 30. @*Conclusion@#High APACHE II score, high MELD score, and low delivered CRRT dose were significant risk factors for in-hospital mortality. CRRT delivered dose impacted mortality significantly, especially in patients with a MELD score ≥ 30.

Fabry nephropathy before and after enzyme replacement therapy: important role of renal biopsy in patients with Fabry disease

Background@#In Fabry disease, the presence of globotriaosylceramide (GL3) deposits in various kidney cells leads to progressive renal dysfunction. However, kidney biopsy studies in patients with Fabry disease are limited. In the present study, the pathologic findings of patients with Fabry nephropathy receiving enzyme replacement therapy (ERT) and untreated patients without albuminuria were investigated. @*Methods@#The present study included 15 patients with Fabry disease who underwent renal biopsy while receiving ERT (group 1: n = 9, age 19–58 years, two males and seven females) or before ERT initiation (group 2: n = 6, age 11–66 years, one male and five females). All patients in group 2 were normoalbuminuric. @*Results@#Group 1 showed improved clinical symptoms, such as acroparesthesia. The ERT duration was 1.2 to 8 years and seven of the nine patients showed GL3 deposits in various kidney cells and segmental foot process effacement (FPE) of podocytes. GL3 deposits and FPE were not observed in the two remaining patients in group 1. Group 2 showed segmental FPE and podocyte GL3 deposits. Most patients in group 2 also showed GL3 deposits in the mesangium, endothelium, or tubular epithelium. @*Conclusion@#The study results showed that segmental FPE and GL3 deposits can persist in Fabry nephropathy despite ERT. In addition, segmental FPE and GL3 deposits were observed in various kidney cells in normoalbuminuric patients with Fabry disease. These findings indicated that kidney biopsies at baseline and follow-up evaluation of Fabry nephropathy are essential for timely ERT initiation and ERT response assessment.

Role of Akt1 in renal fibrosis and tubular dedifferentiation during the progression of acute kidney injury to chronic kidney disease

Background/Aims@#Acute kidney injury (AKI) is an underestimated yet important risk factor for the development of chronic kidney disease (CKD), characterized by tubulointerstitial fibrosis and tubular dedifferentiation. Tubular dedifferentiation, which is associated with the loss of epithelial markers and the gain of mesenchymal features, is thought to be involved in tubulointerstitial fibrosis. As protein kinase B/Akt is involved in the development of CKD, we investigated the role of Akt1, one of the three Akt isoforms, in a murine model of AKI-to-CKD progression. @*Methods@#We subjected C57BL/6 male mice to unilateral ischemia-reperfusion injury (UIRI) and harvested their kidneys after 6 weeks. Mice were divided into four groups, namely, wild-type (WT) UIRI, Akt1−/− UIRI, WT sham, and Akt1−/− sham. @*Results@#Akt1 (but not Akt2 or Akt3) was markedly activated in WT UIRI mice than in WT sham mice. Tubulointerstitial fibrosis and tubular dedifferentiation significantly increased in WT UIRI mice, but were attenuated in Akt1−/− UIRI mice. Both WT UIRI and Akt1−/− UIRI mice showed markedly upregulated transforming growth factor-β1 (TGF-β1)/Smad signaling compared with WT sham mice. However, TGF-β1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3β, β-catenin, and Snail were attenuated in Akt1−/− UIRI mice compared with those in WT UIRI mice. @*Conclusions@#Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-β1/Smad signaling, during AKI-to-CKD progression in a UIRI without contralateral nephrectomy model. Thus, Akt1 may serve as a therapeutic target in AKI-to-CKD progression.

Role of Akt1 in renal fibrosis and tubular dedifferentiation during the progression of acute kidney injury to chronic kidney disease

Background/Aims@#Acute kidney injury (AKI) is an underestimated yet important risk factor for the development of chronic kidney disease (CKD), characterized by tubulointerstitial fibrosis and tubular dedifferentiation. Tubular dedifferentiation, which is associated with the loss of epithelial markers and the gain of mesenchymal features, is thought to be involved in tubulointerstitial fibrosis. As protein kinase B/Akt is involved in the development of CKD, we investigated the role of Akt1, one of the three Akt isoforms, in a murine model of AKI-to-CKD progression. @*Methods@#We subjected C57BL/6 male mice to unilateral ischemia-reperfusion injury (UIRI) and harvested their kidneys after 6 weeks. Mice were divided into four groups, namely, wild-type (WT) UIRI, Akt1−/− UIRI, WT sham, and Akt1−/− sham. @*Results@#Akt1 (but not Akt2 or Akt3) was markedly activated in WT UIRI mice than in WT sham mice. Tubulointerstitial fibrosis and tubular dedifferentiation significantly increased in WT UIRI mice, but were attenuated in Akt1−/− UIRI mice. Both WT UIRI and Akt1−/− UIRI mice showed markedly upregulated transforming growth factor-β1 (TGF-β1)/Smad signaling compared with WT sham mice. However, TGF-β1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3β, β-catenin, and Snail were attenuated in Akt1−/− UIRI mice compared with those in WT UIRI mice. @*Conclusions@#Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-β1/Smad signaling, during AKI-to-CKD progression in a UIRI without contralateral nephrectomy model. Thus, Akt1 may serve as a therapeutic target in AKI-to-CKD progression.

Percutaneous peritoneal dialysis catheter implantation with no break-in period: a viable option for patients requiring unplanned urgent-start peritoneal dialysis

Background@#Urgent-start peritoneal dialysis (PD) is applied to patients who need PD within two weeks but are able to wait for more than 48 hours before starting PD. To evaluate the usefulness of percutaneous PD catheter insertion in urgent-start PD, we reviewed the clinical outcomes of percutaneous catheter insertion with immediate start PD and surgical insertion with longer break-in time in Pusan National University Hospital. @*Methods@#This study included 177 patients who underwent urgent-start PD. Based on the PD catheter insertion techniques, the patients with urgent-start PD were divided into percutaneous (n = 103) and surgical (n = 74) groups. For the percutaneous group, a modified Seldinger percutaneous catheter insertion with immediate initiation of continuous ambulatory PD was performed by nephrologists. @*Results@#The percutaneous group showed higher serum urea nitrogen, creatinine, and lower serum albumin compared with the surgical group (P < 0.05). Ninety-day infectious and mechanical complications showed no significant differences between the two groups. Ninety-day peritonitis in the percutaneous group was 9.7% compared to 5.4% in the surgical group (P = not significant [NS]). Major leakage was 3.9% in the percutaneous group compared to 1.4% in the surgical group (P = NS). Overall infectious and mechanical complication-free survival was not significantly different between the two groups. The percutaneous group and surgical group showed no statistical difference with respect to catheter survival over the entire observation period (P = NS). @*Conclusion@#This study suggests that urgent-start PD can be applied safely with percutaneous catheter insertion by nephrologists with no break-in period.

In Vivo and In Vitro Quantification of Glucose Kinetics: From Bedside to Bench

Like other substrates, plasma glucose is in a dynamic state of constant turnover (i.e., rates of glucose appearance [Ra glucose] into and disappearance [Rd glucose] from the plasma) while staying within a narrow range of normal concentrations, a physiological priority. Persistent imbalance of glucose turnover leads to elevations (i.e., hyperglycemia, Ra>Rd) or falls (i.e., hypoglycemia, Ra

In Vivo and In Vitro Quantification of Glucose Kinetics: From Bedside to Bench

Like other substrates, plasma glucose is in a dynamic state of constant turnover (i.e., rates of glucose appearance [Ra glucose] into and disappearance [Rd glucose] from the plasma) while staying within a narrow range of normal concentrations, a physiological priority. Persistent imbalance of glucose turnover leads to elevations (i.e., hyperglycemia, Ra>Rd) or falls (i.e., hypoglycemia, Ra

Quantifications of Lipid Kinetics In Vivo Using Stable Isotope Tracer Methodology

Like other bodily materials, lipids such as plasma triacylglycerol, cholesterols, and free fatty acids are in a dynamic state of constant turnover (i.e., synthesis, breakdown, oxidation, and/or conversion to other compounds) as essential processes for achieving dynamic homeostasis in the body. However, dysregulation of lipid turnover can lead to clinical conditions such as obesity, fatty liver disease, and dyslipidemia. Assessment of “snap-shot” information on lipid metabolism (e.g., tissue contents of lipids, abundance of mRNA and protein and/or signaling molecules) are often used in clinical and research settings, and can help to understand one's health and disease status. However, such “snapshots” do not provide critical information on dynamic nature of lipid metabolism, and therefore may miss “true” origin of the dysregulation implicated in related diseases. In this regard, stable isotope tracer methodology can provide the in vivo kinetic information of lipid metabolism. Combining with “static” information, knowledge of lipid kinetics can enable the acquisition of in depth understanding of lipid metabolism in relation to various health and disease status. This in turn facilitates the development of effective therapeutic approaches (e.g., exercise, nutrition, and/or drugs). In this review we will discuss 1) the importance of obtaining kinetic information for a better understanding of lipid metabolism, 2) basic principles of stable isotope tracer methodologies that enable exploration of “lipid kinetics” in vivo, and 3) quantification of some aspects of lipid kinetics in vivo with numerical examples.

Epidemiology of Legionella and Climatic Variables in Seoul, Korea

Legionella species are abundant in the built environment and are increasingly recognized as a cause of Legionnaires' disease (LD). As the number of cases of Legionnaires' disease acquired by local communities in the Seoul metropolitan area in Korea has been increased, there was concern that changes in environmental factors could affect disease outbreaks. We described the association between climatic variables and occurrence of legionellosis in Korea and Legionella detection rate in Seoul area. A total of 418 cases of legionellosis were reported between 2014 and 2017. There was a seasonal peak in summer. LD continuously occurred from early spring to winter every year and rapidly increased in summer. In the regression analysis, the primary variables of interest- PM2.5 (µg/m³), NO₂ (ppb), and a number of the date of issue O₃ warning were not significant except for average temperature (R²=0.8075). The Legionella detection rate in Seoul, Korea showed a trend similar to precipitation (P=0.708, ANOVA). A relatively high proportion of Legionella detection rate was shown, especially cooling tower (17.7%) and public bath (19.3%). This finding is in line with current understanding of the ecological profile of this pathogen and supports the assertion that legionellosis occurs through contamination of water sources.

Blood pressure measurement in patients with chronic kidney disease: from clinical trial to clinical practice

No abstract available.

Molecular Characterization of Enterotoxigenic Escherichia coli in Foodborne Outbreak

Diarrheagenic Escherichia coli (E. coli) is a main cause of diarrhea worldwide. This study reports the investigation on the occurrence of enterotoxigenic E. coli (ETEC) serotype O27:H7-associated foodborne gastrointestinal disease that occurred at two schools, one middle school and one high school, in Seoul, Korea in June 2015. The immediate government investigation in 1,216 students and 19 food handlers in these two schools revealed that 116 students, 32 students in the middle school and 84 students in the high school, and 2 food handlers, one from middle school and the other from high school, developed gastrointestinal illness symptoms including diarrhea. Following lab investigation identified 29 ETEC serotype O27:H7 strains, 27 from 116 students and 2 from 19 food handlers. Pattern of pulsed-field gel electrophoresis analysis of ETEC isolates suggested that ETEC serotype O27:H7 caused the diarrheal outbreak in June 2015 in Seoul, Korea was a specific clone. In addition, these ETEC serotype O27:H7 isolates were highly resistance to the several antibiotics. The results from the present study provide the evidence that ETEC serotype O27:H7 can be an important cause of domestic foodborne outbreak in Korea.

The expression of two isoforms of matrix metalloproteinase-2 in aged mouse models of diabetes mellitus and chronic kidney disease

BACKGROUND: This study was undertaken to explore the effects of aging on the kidneys in mouse models of diabetes and chronic kidney disease (CKD), and to compare the expression of two isoforms of matrix metalloproteinase-2 (MMP-2)–secretory full-length MMP-2 and intracellular N-terminal truncated MMP-2 (NTT-MMP-2)–in these models. METHODS: Two experimental ICR mouse models were used: a streptozotocin (STZ)-induced type 1 diabetes mellitus model and a 5/6 nephrectomized (5/6Nx) CKD model. The abundance of each isoform of MMP-2 was determined by quantitative polymerase chain reaction (qPCR), and functional analyses were conducted. Moreover, the protein levels of the two MMP-2 isoforms were determined semi-quantitatively by immunohistochemical staining, and their association with tissue damage was assessed. RESULTS: Both isoforms of MMP-2 were upregulated in the kidney tissues of STZ-induced diabetic mice and 5/6Nx mice, irrespective of age. Characteristically, NTT-MMP-2 protein expression was elevated in old control mice, in line with the qPCR results. NTT-MMP-2 expression was limited to the renal cortex, and to the tubulointerstitial area rather than the glomerular area. In terms of tissue damage, tubulointerstitial fibrosis was more severe in old 5/6Nx mice than in their young counterparts, whereas glomerulosclerosis was comparable in old and young 5/6Nx mice. CONCLUSION: The intracellular isoform of MMP-2 was induced by ageing, irrespective of the presence of diabetes or CKD, and its induction may be related to tubulointerstitial fibrosis in chronic kidney disease.

Severe Hypernatremia Caused by Acute Exogenous Salt Intake Combined with Primary Hypothyroidism

This report describes a case of severe hypernatremia with a serum sodium concentration of 188.1mmol/L caused by exogenous salt intake. A 26-year-old man diagnosed with Crohn's disease 5 years previously visited our clinic due to generalized edema and personality changes, with aggressive behavior. He had compulsively consumed salts, ingesting approximately 154 g of salt over the last 4 days. Despite careful fluid management that included not only hypotonic fluid therapy for 8 hours but also hypertonic saline administration, his serum sodium level decreased sharply at 40.6 mmol/L; however, it returned to normal within 72-hour of treatment without any neurological deficits. Primary hypothyroidism was also diagnosed. He was discharged after 9 days from admission, with a stable serum sodium level. We have described the possibility of successful treatment in a patient with hypernatremia caused by acute salt intoxication without sustained hypotonic fluid therapy.

Unmasked chronic renal function deterioration after unilateral adrenalectomy in patients with primary aldosteronism

We report 2 cases of chronic estimated glomerular filtration rate (eGFR) decline after unilateral adrenalectomy due to primary aldosteronism. The patients were diagnosed with unilateral adrenal cortical adenoma releasing aldosterone. Two patients were examined for hypertension and hypokalemia. Unilateral laparoscopic adrenalectomy was performed in both cases, and pathology confirmed adrenal cortical adenoma. After adrenalectomy, hypertension and hypokalemia improved to within normal range. However, the eGFR decreased postoperatively, and abdominal computed tomography scan showed decreased kidney size compared to previous images. Kidney biopsy was performed to delineate the exact cause of renal function deterioration and revealed hypertensive changes with chronic interstitial changes, indicating that glomerular hyperfiltration with aldosterone excess masked renal function damage. Physicians have to consider the probability of postadrenalectomy eGFR decline related to chronic hypertensive change.

Applications of stable, nonradioactive isotope tracers in in vivo human metabolic research

The human body is in a constant state of turnover, that is, being synthesized, broken down and/or converted to different compounds. The dynamic nature of in vivo kinetics of human metabolism at rest and in stressed conditions such as exercise and pathophysiological conditions such as diabetes and cancer can be quantitatively assessed with stable, nonradioactive isotope tracers in conjunction with gas or liquid chromatography mass spectrometry and modeling. Although measurements of metabolite concentrations have been useful as general indicators of one's health status, critical information on in vivo kinetics of metabolites such as rates of production, appearance or disappearance of metabolites are not provided. Over the past decades, stable, nonradioactive isotope tracers have been used to provide information on dynamics of specific metabolites. Stable isotope tracers can be used in conjunction with molecular and cellular biology tools, thereby providing an in-depth dynamic assessment of metabolic changes, as well as simultaneous investigation of the molecular basis for the observed kinetic responses. In this review, we will introduce basic principles of stable isotope methodology for tracing in vivo kinetics of human or animal metabolism with examples of quantifying certain aspects of in vivo kinetics of carbohydrate, lipid and protein metabolism.

Computed Tomography Findings of Thrombosis and Aneurysm of the Portal Venous System

The portal venous system comprises all of the veins draining the abdominal part of the digestive tract, and tributaries of the portal vein are the splenic, superior mesenteric, left and right gastric vein, paraumbilical and cystic veins. The portal vein could be occluded in various clinical settings that may cause portal venous system thrombosis. And rarely aneurysms of the portal venous system may be presented. Multiphasic contrast enhanced computed tomography is a useful tool for both perfusion abnormalities and morphologic analysis of the portal venous system and the liver and it enables discrimination between bland and neoplastic portal vein thrombi.

High serum and urine neutrophil gelatinaseassociated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin A nephropathy

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.

Pyeloduodenal Fistula Successfully Treated By Endoscopic Ligation without Surgical Nephrectomy: Case Report

A 74-yr-old woman presented with fever and abdominal discomfort. She was in a septic condition caused by urinary tract infection. Her computed tomogram of the abdomen revealed features of hydronephrosis with ureteral stones in both kidneys. During percutaneous nephrostomies, right pyeloduodenal fistula (PDF) was diagnosed. Elective surgery was originally planned but the patient was in a poor condition to undergo surgery. Instead, 2 times endoscopic clipping and ligation by endoloop were applied with parenteral antibiotics for the fistula lesion. On admission day 30, she was discharged from the hospital after confirmation of no more contrast leakage on fistulography. We reviewed the literature and discuss the etiologies, clinical presentations, diagnosis, and treatment of PDF.

Decreased Renal Function Is an Independent Predictor of Severity of Coronary Artery Disease: An Application of Gensini Score

Coronary artery disease (CAD) is the leading cause of death in patients with chronic kidney disease (CKD).Although many studies have shown a higher prevalence of CAD among these patients, the association between the spectrum of renal dysfunction and severity of CAD remains unclear. In this study, we investigate the association between renal function and the severity of CAD. We retrospectively reviewed the medical records of 1,192 patients who underwent elective coronary angiography (CAG). The severity of CAD was evaluated by Gensini score according to the degree of luminal narrowing and location(s) of obstruction in the involved main coronary artery. In all patients, the estimated glomerular filtration rate (eGFR) was independently associated with Gensini score (beta=-0.27, P < 0.001) in addition to diabetes mellitus (beta=0.07, P = 0.02), hypertension (beta=0.12, P < 0.001), low density lipoprotein (LDL)-cholesterol (beta=0.08, P = 0.003), and hemoglobin (beta=-0.07, P = 0.03) after controlling for other confounding factors. The result of this study demonstrates that decreased renal function is associated not only with the prevalence, but also the severity, of CAD.

A Case of Rifampin-Induced Crescentic Glomerulonephritis / 대한내과학회지

A 56-year-old male with pulmonary tuberculosis was admitted to our hospital for evaluation of generalized edema. He began antituberculosis treatment with rifampin, isoniazid, ethambutol, and pyrazinamide. He experienced abnormal increments in weight and serum creatinine after 6 weeks. All serological findings, including anti-neutrophil cytoplasmic antibodies (ANCA), were negative. Rifampin was stopped because it might have caused the increase in creatinine. Renal biopsy was consistent with pauci-immune crescentic glomerulonephritis (CrGN). His renal function was improved by high-dose steroid treatment. Rifampin-induced, ANCA-negative pauci-immune CrGN is very rare; most cases of rifampin-induced acute renal failure are due to acute tubulointerstitial nephritis. We present here a case of rifampin-induced CrGN and pulmonary tuberculosis successfully treated with high-dose steroids and antituberculosis medications, excluding rifampin.