On-line Hemodiafiltration in Southeast Asia: A Three-year Prospective Study of a Single Center

Abstract: Growing evidence suggests the superiority of on-line hemodiafiltration (HDF) compared with the conventional hemodialysis technique in many aspects; however, on-line HDF is still not used worldwide, including in Southeast Asia. The purpose of this study is to compare various clinical outcomes between on-line HDF and high-flux hemodialysis (HFHD). This was a single-center three-year prospective observational study that demonstrated the clinical parameters after switching from HFHD to on-line HDF in 22 HDF patients, whose average age was 58.1 ± 13.3 years. The incidence of intradialytic undesired events, including hypotension, decreased and an apparent increase in appetite and an improvement in overall well-being were recorded by most patients after switching to on-line HDF. The data for dry weight, body mass index, and normalized protein nitrogen appearance, which represent nutritional status, showed a significant improvement while still maintaining a satisfactory albumin level. The adequacy in terms of urea reduction ratio significantly increased. The serum predialysis β₂-microglobulin levels were reduced by 25.7% from 31.1 ± 3.1 to 23.1 ± 4.8 mg/L (P < 0.05) at six months and remained constant during the three years of follow-up. The patients' lipid profile was well controlled, and the mean C-reactive protein value was still maintained in the normal range. In conclusion, our three-year experience showed that on-line HDF is a well-tolerated treatment with a lower incidence of intradialytic undesired events. The potential benefits may include the effective removal of higher molecular weight uremic toxins and an improved nutritional status, along with a low inflammatory state.     

High glucose blunts vascular endothelial growth factor response to hypoxia via the oxidative stress-regulated hypoxia-inducible factor/hypoxia-responsible element pathway

Vascular endothelial growth factor (VEGF) is an important survival factor for endothelial cells in hypoxic environments. High glucose regulates certain aspects of VEGF expression in various cell types, including proximal tubular cells. Thus, ambient glucose levels may modulate the progression of chronic kidney disease, especially diabetic nephropathy. Immortalized rat proximal tubular cells (IRPTC) were cultured for 24 h under hypoxic conditions (1% O(2)), with or without high d-glucose (25 mM), or with or without high l-glucose (25 mM). Controls included culture in normoxic conditions and normal d-glucose (5.5 mM). VEGF mRNA expression was assessed by real-time quantitative PCR, and VEGF protein in the supernatant was assessed by ELISA. Hypoxia increased VEGF expression. This response was significantly blunted by high d-glucose (1.98 +/- 0.11- versus 2.65 +/- 0.27-fold increase for VEGF mRNA expression, 252.8 +/- 14.7 versus 324.0 +/- 11.5 pg/10(5) cells for VEGF protein; P < 0.05 both) but not by high l-glucose. It is interesting that hydrogen peroxide also blunted this response, whereas alpha-tocopherol restored the VEGF response to hypoxia in the presence of high d-glucose. For determination of involvement of the hypoxia-inducible factor (HIF)/hypoxia-responsible element (HRE) pathway, IRPTC that were stably transfected with HRE-luciferase were cultured under the previous conditions. High d-glucose also reduced luciferase activity under hypoxia, whereas alpha-tocopherol restored activity. In vivo experiments using streptozotocin-induced diabetic rats confirmed that hyperglycemia blunted HIF-HRE pathway activation. Insulin treatment restored activation of the HIF-HRE pathway in streptozotocin-induced diabetic rats. In conclusion, high glucose blunts VEGF response to hypoxia in IRPTC. This effect is mediated by the oxidative stress-regulated HIF-HRE pathway.     

Ear length and kidney function decline after kidney donation

The preservation of kidney function after kidney donation depends on the kidney reserve – the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post‐donation visits. Pre‐donation serum creatinine and post‐donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD‐EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 cm increase in ear length, it was associated with 5.7% less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, P = 0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre‐donation eGFR did not significantly associate with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation.     

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.     

Comparison of Different Types of Static Computer-Guided Implant Surgery in Varying Bone Inclinations

This research aimed to compare the accuracy of dental implant placement among three types of surgical guide: metal sleeve with key handle (Nobel guide, Nobel Biocare, Göteborg, Sweden), metal sleeve without key handle, and non-sleeve without key handle (Dentium full guide kit, Dentium Co., Seoul, Korea) when placing the implant in different bone inclinations. A total of 72 polyurethane bone models were fabricated in different inclinations (0°, 45°, and 60°). The dental implants were placed in bone models following the company’s recommendations. After dental implants were installed, the digital scans were done by an extraoral scanner. The deviations of the dental implant position were evaluated by superimposition between post-implant placement and reference model by using GOM inspect software. The deviation measurement was shown in 5 parameters: angular deviation, 3D deviation at the crest, 3D deviation at the apex, lateral linear deviation, and vertical linear deviation. The data were analyzed using One-way ANOVA and post-hoc tests at a significance level of 0.05. The accuracy of the dental implant position was not significantly influenced by the difference in the surgical guide system (p > 0.05). There were significant differences between placed and planned implant positions in the different inclinations of the bone. A significant difference was found in all parameters of 0° and 60° bone inclinations (p < 0.05). At 0° and 45°, angulated bone showed significant differences except in 3D deviation at the apex. Between 45° and 60° were significant differences only in angular deviation. Within the limitations of this study, the accuracy of implant placement among three types of surgical guides (Non-sleeve without key handle, Metal sleeve without key handle, and Metal sleeve with key handle) from two companies (Dentium and Nobel Biocare) was similar. Hence, the operators can choose the surgical guide system according to their preference. The inclination of bone can influence the angulation of dental implants.     

Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes

Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type 1 DN project were analyzed for associations across 21 MMP genes in 1705 individual with type 1 diabetes, including 885 normoalbuminuric control subjects and 820 advanced DN case subjects. In total, we investigated the role of 1283 SNPs (198 genotyped SNPs and 1085 imputed SNPs) mapping to the MMP genes. We identified associations at several correlated SNPs across a 29.2kb interval on chromosome 11q at the MMP-3/MMP-12 locus. The strongest associations occurred at 2 highly-correlated SNPs, rs610950 (OR=0.50, P=1.6×10(-5)) and rs1277718 (OR=0.50, P=2.1×10(-5)). Further examination of this locus identified 17 SNPs (2 genotyped SNPs and 15 imputed SNPs) in complete linkage disequilibrium associated with DN (P-values<2.5×10(-4)), including a non-synonymous SNP (rs652438, Asn357Ser) located in exon 8 of MMP-12 that significantly reduced the risk of DN among carriers of the serine substitution relative to homozygous carriers of asparagine (OR=0.51; 95% CI=0.37-0.71, P=6.2×10(-5)). Taken together, our study suggests that genetic variations within the MMP-3/MMP-12 locus influence susceptibility of DN in type 1 diabetes.     

Efficacy of separated system continuous venovenous hemofiltration in critical acute kidney injury

Integrated system continuous venovenous hemofiltration (CVVH), the most popularly utilized mode for continuous renal replacement therapy (CRRT), needs a sophisticated and expensive machine that is available only in limited critical care units. Separated system CVVH, which can be simply set up, might be an effectively alternative to CRRT. A one-year prospective observational study regarding the efficacy of separated system CVVH was conducted with 192 critically ill patients with acute kidney injury. All patients underwent separated system CVVH with the pre-dilution mode and a mean CVVH dose of 34.9±2.7mL/kg/h. The APACHEII score was 23.2±8.4 and the Sequential Organ Failure Assessment score was 12.0±4.3. No complications, including air-embolism or circuit clotting, were observed and the survival rate was 32.3%. Separated system CVVH is simple, safe, and efficient and could provide cheaper treatments than the integrated system. It could thus be an effective, alternative treatment for critical acute kidney injury patients when the integrated mode is unavailable.     

Reliability of Blood Pressure Parameters for Dry Weight Estimation in Hemodialysis Patients

Chronic volume overload resulting from interdialytic weight gain and inadequate fluid removal plays a significant role in poorly controlled high blood pressure. Although bioimpedance has been introduced as an accurate method for assessing hydration status, the instrument is not available in general hemodialysis (HEMO) centers. This study was conducted to explore the correlation between hydration status measured by bioimpedance and blood pressure parameters in chronic HEMO patients. Multifrequency bioimpedance analysis was used to determine pre‐ and post‐dialysis hydration status in 32 stable HEMO patients. Extracellular water/total body water (ECW/TBW) determined by sum of segments from bioimpedance analysis was used as an index of hydration status. The mean age was 57.9 ± 16.4 years. The mean dry weight and body mass index were 57.7 ± 14.5 kg and 22.3 ± 4.7 kg/m², respectively. Pre‐dialysis ECW/TBW was significantly correlated with only pulse pressure (r = 0.5, P = 0.003) whereas post‐dialysis ECW/TBW had significant correlations with pulse pressure, systolic blood pressure, and diastolic blood pressure (r = 0.6, P = 0.001, r = 0.4, P = 0.04, r = ?0.4, and P = 0.02, respectively). After dialysis, the mean values of ECW/TBW, systolic blood pressure, mean arterial pressure, and pulse pressure were significantly decreased. ECW/TBW was used to classify the patients into normohydration (≤0.4) and overhydration (>0.4) groups. Systolic blood pressure, mean arterial pressure, and pulse pressure significantly reduced after dialysis in the normohydration group but did not significantly change in the overhydration group. Pre‐dialysis pulse pressure, post‐dialysis pulse pressure, and post‐dialysis systolic blood pressure in the overhydration group were significantly higher than normohydration group. Due to the simplicity and cost, blood pressure parameters, especially pulse pressure, might be a simple reference for clinicians to determine hydration status in HEMO patients.     

Hypokalemia in peritoneal dialysis patients in Thailand: the pivotal role of low potassium intake

International Urology and Nephrology - Hypokalemia is highly prevalent in chronic peritoneal dialysis (PD) patients worldwide, particularly in Thailand. This study aims to investigate the major...