Hoon Young Choi

Sclerosing encapsulating peritonitis as a complication of long-term continuous ambulatory peritoneal dialysis in Korea

SUMMARY:  Sclerosing encapsulating peritonitis (SEP) is a rare yet serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD). Incidence and prevalence of this syndrome have been defined in some large populations and a few single‐centre experiences, but there is no satisfactory estimate of the comparative incidence of dialysis related SEP. The pathogenesis of SEP still remains uncertain, but there could be various causative factors. The diagnosis of SEP remains based on clinical suspicion confirmed with radiologic and/or pathologic findings. The possible variable etiologies and probable distinct pathways leading to this syndrome may make a uniform therapeutic approach unlikely.

Clinical characteristics of dialysis related sclerosing encapsulating peritonitis: multi-center experience in Korea.

Sclerosing encapsulating peritonitis (SEP) is a rare but serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD), and is characterized by a progressive, intra-abdominal, inflammatory process resulting in the formation of sheets of new fibrous tissue, which cover, bind, and constrict the viscera, thereby compromising the motility of the bowel. No satisfactory estimate is available on the comparative incidence of dialysis related SEP and the pathogenesis of SEP still remains uncertain. Although recent therapeutic approaches have reported varying degrees of success, an efficient measure to detect, at an early stage, patients at risk for SEP would be beneficial and a standardized treatment regimen to prevent the illness is urgently needed. This study aimed to evaluate the clinical features of SEP and to identify the possible risk factors for the development of SEP in CAPD patients. We retrospectively reviewed by questionnaire SEP cases among CAPD patients from 7 university hospital dialysis centers in Korea, including Yonsei University, Ajou University, Catholic University, Inha University, Kyungpook University, Seoul National University and Soonchunhyang University, from January 1981 to December 2002. Out of a total of 4,290 CAPD patients in these centers, 34 cases developed SEP with an overall prevalence of 0.79%. The male to female ratio was 17:17. The median age of these patients was 44.5 years (range 19 - 66). The median duration of CAPD before SEP was 64 months (9 - 144) and 68% of patients (23/34) had been on CAPD for more than 4 years. Peritonitis (including two fungal cases) was the main cause of catheter removal in SEP (27 cases, 79%). Seventy-five percent of the cases (15/20) were administered β-blocker for a mean duration of 85 months (26 - 130). Among 10 cases with available peritoneal equilibration test (PET) data, 8 showed high transporter characteristics, and the remaining 2 were high average. Eighteen cases were diagnosed by clinical and radiologic methods, and 16 were surgically diagnosed. Eleven cases were surgically treated and the others were treated conservatively with intermittent total parenteral nutrition (TPN). The overall mortality rate was 24%. SEP is a serious, life threatening complication of CAPD. Most cases had a PD duration of more than 4 years, a history of severe peritonitis, and high transporter characteristics in PET. Therefore, to reduce the incidence of SEP, careful monitoring and treatment, including early catheter removal in patients with severe peritonitis, should be considered for long-term CAPD patients with the above characteristics.

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics.

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1β and interferon-γ levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.

Association of inflammation and protein-energy wasting with endothelial dysfunction in peritoneal dialysis patients

BACKGROUND Cardiovascular disease is the main cause of mortality in end-stage renal disease (ESRD) patients. Recent studies have indicated that non-traditional risk factors such as endothelial dysfunction (ED), chronic inflammation and protein-energy wasting (PEW) may contribute significantly to the increased cardiovascular mortality among dialysis patients. To further ascertain this association, we carried out a cross-sectional assessment of nutritional status, inflammatory markers and endothelial dysfunction in peritoneal dialysis (PD) patients. METHODS We measured ED functionally by flow-mediated vasodilatation (FMD) using doppler ultrasonography and biochemically by soluble intercellular adhesion molecule-1 (sICAM-1) in 105 stable PD patients and 32 age- and sex-matched healthy controls. We also simultaneously measured inflammatory markers and performed a subjective global assessment (SGA) of their nutritional status using a seven-point scoring scale. Subjects were subgrouped according to their nutritional and inflammatory status. RESULTS In PD patients, FMD was markedly lower (9.9 +/- 4.8% vs. 16.4 +/- 4.8%, P < 0.05), and sICAM-1 was significantly higher than those in controls. The malnourished patients had significantly lower FMD (8.4+/-4.6% vs. 10.8+/-4.7%, P <0.05) and higher sICAM-1 than the nourished patients. The inflamed group had significantly lower FMD (7.1 +/- 3.8 vs.11.1 +/- 4.6%, P < 0.05) and higher sICAM-1 than the non-inflamed group. In all PD patients, lean body mass/body weight %, albumin and SGA correlated positively with FMD (r = +0.207, r = +0.224, r = +0.285, P < 0.05). However, age, log high sensitivity C-reactive protein (hsCRP), log IL-6 and sICAM-1 were negatively correlated with FMD (r = -0.275, r = -0.361, r = -0.360, r = -0.271, P < 0.05). A multiple regression analysis showed that log hsCRP was an independent factor affecting FMD. Endothelial function, demonstrated as FMD and sICAM-1 in the nourished PD patients without inflammation, was well preserved compared to other subgroups. CONCLUSION Our data suggest that chronic inflammation and PEW are closely linked to ED in PD patients.

Microparticles from Kidney-Derived Mesenchymal Stem Cells Act as Carriers of Proangiogenic Signals and Contribute to Recovery from Acute Kidney Injury

We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

Usefulness of 23S rRNA amplification by PCR in the detection of bacteria in CAPD peritonitis.

Background: Peritonitis is the most common complication of continuous ambulatory peritoneal dialysis (CAPD), and the spectrum of organisms causing CAPD peritonitis is broad. Polymerase chain reaction (PCR) has recently broadened its diagnostic capabilities in infectious diseases. PCR can provide a sensitive method for identifying causative infectious organisms. Methods: To evaluate the usefulness of 23S bacterial ribosomal RNA amplification and direct sequencing for the detection of infectious organisms, we compared PCR with bacteriological culture for the analysis of dialysates from CAPD peritonitis patients. Thirty-two samples from CAPD peritonitis patients with current antibiotic use and control samples from 30 CAPD patients without peritonitis were examined by PCR with sequencing analysis and by conventional bacteriological culture. In addition, 95 culture-positive samples and 39 culture-negative samples from CAPD peritonitis patients before antibiotic treatment were analyzed by PCR assay. Results: In the control samples from patients without CAPD peritonitis, false-positive rates were relatively rare: 3 of 30 in the PCR study and 2 of 30 in the culture study. Of the 134 CAPD peritonitis samples collected before antibiotic therapy, positive cultures were obtained in 70.9% (95/134) of them. In 75 of the culture-positive samples, the same microorganisms were confirmed by PCR assay, and the others showed discrepant results as compared with culture study. In 30 of the 39 culture-negative samples, microbial organisms were detected by PCR assay. Of the 32 samples from patients who developed CAPD peritonitis during antibiotic treatment, 17 (53.1%) were positive by PCR assay, and 5 (15.6%) were positive by culture. Conclusion: Our study suggests that broad-spectrum PCR with RNA sequencing can complement culture methods in the diagnosis of CAPD peritonitis, especially in patients with previous or current antibiotic use.

Metabolic syndrome predicts mortality in non-diabetic patients on continuous ambulatory peritoneal dialysis

BACKGROUND Metabolic syndrome is associated with higher morbidity and mortality in the general population, but the corresponding effects in patients on dialysis have not been clearly defined. In this study, we prospectively investigated the effect of metabolic syndrome and its individual components on outcome in non-diabetic peritoneal dialysis (PD) patients. Method. The study subjects included 106 stable non-diabetic PD patients who had been on PD for >3 months. We measured baseline characteristics, blood pressure, fasting blood glucose, lipid profiles and high-sensitivity CRP (hsCRP), and defined metabolic syndrome using the modified National Cholesterol Education Program (Adult Treatment Panel III) criteria. Mortality, technical failure and hospitalization were evaluated during the follow-up period. RESULTS Metabolic syndrome was present in 50 patients (47.2%), and these showed higher baseline hsCRP levels (0.67; 95% CI: 0.50-0.94 versus 1.78 mg/dl; 95% CI: 1.21-2.57; P < 0.001). Patients with metabolic syndrome experienced significantly lower 5-year survival rates than patients without (90% versus 67%, P = 0.02), although these groups did not differ in peritonitis rates, technical failure or hospitalization. A Cox proportional hazards analysis identified the following as predictors of mortality: metabolic syndrome (RR: 3.39; 95% CI: 1.16-9.94; P = 0.02), baseline albumin (RR: 0.06; 95% CI: 0.01-0.30; P = 0.001) and baseline hsCRP levels (RR: 1.14; 95% CI: 1.07-1.22; P < 0.001). CONCLUSION Metabolic syndrome is prevalent and is a risk factor influencing long-term survival in non-diabetic PD patients.

Comparison of hydration and nutritional status between young and elderly hemodialysis patients through bioimpedance analysis.

Background The number of elderly people on dialysis is increasing rapidly. Fluid overload and malnutrition status are serious problems in elderly dialysis patients. We aimed to compare the hydration and nutritional status through bioimpedance analysis (BIA) between young and elderly hemodialysis (HD) patients and to analyze risk factors related to fluid overload and malnutrition status in these patients. Method We conducted a cross-sectional study, in which 82 HD (males 42, mean age 58.7±12.9 years) patients were enrolled. We collected different types of data: laboratory data, such as serum creatinine, albumin, total iron-binding capacity, hemoglobin, total cholesterol; anthropometric data, such as hand grip strength (HGS); BIA data, such as intracellular water, skeletal muscle mass, body cell mass, bone mineral content, phase angle (PhA), extra cellular water (ECW)/total body water (TBW) ratio; and malnutrition-inflammation score (MIS), which is a traditional nutritional parameter for dialysis patients. All patients were stratified into two groups according to their age: young (<65 years [n=54]) and elderly (≥65 years [n=28]). Results Total iron-binding capacity and HGS were significantly lower in elderly HD patients than in young HD patients (198.9±35.6 vs 221.4±52.1 mcg/dL; and 22.4±10.3 vs 36.4±23.2 kg, respectively) (P<0.05). Also, intracellular water and PhA measured by BIA were significantly lower (18.3±4.0 vs 20.3±4.2 L [P=0.043]; and 4.0±1.0 vs 4.9±1.2° [P=0.002], respectively), and ECW/TBW were higher in elderly HD patients (0.40±0.01 vs 0.39±0.01 [P=0.001]). ECW/TBW was positively associated with age (P<0.001) and the presence of diabetes (P<0.001) and was negatively associated with sex (P=0.001), albumin (P<0.001), urine volume (P=0.042), HGS (P<0.001), and PhA by BIA (P<0.001). MIS was negatively related to sex (P=0.001), albumin (P<0.001), HGS (P=0.001), and PhA (P<0.001) in HD patients. On multivariate analysis, older age (P=0.031), the presence of diabetes (P=0.035), and decreased PhA (P<0.001) were independent risk factors for increased ECW/TBW, representative of fluid overload status, whereas only decreased PhA (P=0.008) was a significant factor for MIS, representative of malnutrition status in these HD patients. Conclusion We found that fluid overload and malnutrition status were more common in elderly HD patients compared with young HD patients. PhA was a significant independent factor in fluid overload status and malnutrition in these HD patients. Thus, our results indicated that PhA assessed by BIA might be a clinically useful method for assessing nutritional and hydration status in elderly HD patients.

Endocan as a potential diagnostic or prognostic biomarker for chronic kidney disease.

Developing specific markers for early detection of adverse events such as kidney failure, cardiovascular events, and all-cause mortality in chronic kidney disease (CKD) patients remains a major challenge. Cardiovascular events are the main cause of morbidity and mortality in CKD patients. Recent research supposes endocan as a biomarker for evaluating cardiovascular events, inflammatory diseases, and cancers. Yilmaz et al. propose serum endocan levels as a novel prediction marker of all-cause mortality and cardiovascular events in CKD patients.

Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction

IntroductionMicroparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo.MethodsMPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson’s trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining.ResultsKMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson’s trichrome staining, respectively.ConclusionsOur results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.