Yu-Che Tsai

Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis

Background: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear. Methods: Male Sprague-Dawley rats were fed with water containing 0.14 M NH4Cl to induce metabolic acidosis for 1 and 8 weeks, respectively. They were compared with animals fed with deionized water (control) and equimolar sodium chloride water (NaCl). Gene expression analysis of RAS components included renin, renin/prorenin receptor, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 and 2 receptors (AT1R and AT2R). Histological examination was also performed to detect morphological change. Results: Acidosis was found in 1-week NH4Cl-treated rats but not in the 8-week group. More than twofold proteinuria and a significant decline of glomerular filtration rate (GFR) were observed in acid-loaded rats. Compared to the control and NaCl groups, angiotensinogen, ACE, AT1R and AT2R were significantly increased in the 1-week acidosis group (all p < 0.05). Sustained increase of AT1R expression was found as NH4Cl was continued for 8 weeks. There was no significant change in transforming growth factor-β and nuclear factor-ĸB. The architecture of tubular epithelial cells was affected during our experiment. Conclusion: Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.

FACTORS ASSOCIATED WITH BLOOD CONCENTRATIONS OF INDOXYL SULFATE AND p-CRESOL IN PATIENTS UNDERGOING PERITONEAL DIALYSIS

♦ Background: Accumulating evidence supports the important role of protein-bound uremic toxins such as indoxyl sulfate and p-cresol in uremic syndrome. They exert direct deleterious effects on a variety of cells and could link to clinical outcome. Factors relevant to indoxyl sulfate and p-cresol levels in peritoneal dialysis (PD) patients have rarely been investigated. We conducted a cross-sectional study to analyze the factors that correlate with both total and free indoxyl sulfate and p-cresol. ♦ Methods: 182 stable PD patients with mean PD therapy duration 38.5 ± 33.3 months were enrolled. Their mean age was 48.9 ± 13.5 years; 62.6% (114/182) were female patients. Demographic data, including age, gender, and PD therapy duration, were reviewed and recorded. PD-associated features such as residual kidney function (RKF), peritoneal transport property, and dialysis modality were also recorded. Hemoglobin, blood urea nitrogen (BUN), serum creatinine, C-reactive protein, interleukin (IL)-6, and IL-10 were measured. Levels of total and free indoxyl sulfate and p-cresol were determined. ♦ Results: Patients without RKF had lower Kt/V and weekly creatinine clearance and higher serum creatinine and IL-6 levels. These patients also had higher total and free indoxyl sulfate levels. There was no difference in indoxyl sulfate or p-cresol levels compared to patients with different peritoneal transport properties or with different treatment modalities. Multivariate regression analysis revealed that weekly creatinine clearance and serum creatinine were independent associates of total indoxyl sulfate level; IL-6, total indoxyl sulfate, and free p-cresol were associated with free indoxyl sulfate level. Weekly creatinine clearance and free p-cresol level independently correlated with total p-cresol; while gender, total p-cresol, and free indoxyl sulfate were associated with free p-cresol level. ♦ Conclusion: The free forms of indoxyl sulfate and p-cresol constituted a small portion of their total forms. The presence of RKF affected levels of free and total indoxyl sulfate. IL-6 level was significantly associated with free indoxyl sulfate level. There was a close relationship between indoxyl sulfate and p-cresol levels in their free forms in PD patients.

Biomarkers associated with vascular and valvular calcification in chronic hemodialysis patients

Background: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients. Methods: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared. Results: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC. Conclusions: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients.

Proinflammatory Cytokines, Hepatocyte Growth Factor and Adipokines in Peritoneal Dialysis Patients

Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) but not with IL-10 and IL-18. IL-6 correlated with TNF-alpha, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-alpha, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients.

Inflammatory Marker but Not Adipokine Predicts Mortality among Long-Term Hemodialysis Patients

Aims: chronic inflammation contributes significantly to the morbidity and mortality of chronic hemodialysis patients. A recent research has shown that adipokines were associated with inflammation in these patients. We aim to investigate whether biomarkers of inflammation, adipokines, and clinical features can predict the outcome of hemodialysis patients. Materials and methods: we enrolled 181 hemodialysis patients (men: 97, mean age: 56.3±13.6) and analyzed predictors of long-term outcomes. Results: during the 3-year followup period, 41 patients died; the main causes of death were infection and cardiovascular disease. Elevated serum levels of hsCRP and albumin and advanced age were highly associated with death (all P<.001). Leptin and adiponectin levels were not significantly different between deceased patients and survivors. Cox-regression analysis indicated that age, diabetes, albumin level, and hsCRP were independent factors predicting mortality. Conclusion: the presence of underlying disease, advanced age, and markers of chronic inflammation is strongly related to survival rate in long-term hemodialysis patients.

Successful Treatment of Bilateral Emphysematous Pyelonephritis in a Uremic Patient without Nephrectomy

Emphysematous pyelonephritis (EPN) is a severe and complicated renal infection characterized by gas formation within the infected kidney and its surrounding tissues. Early diagnosis with a high index of suspicion and aggressive treatment are important for improving outcome. Bilateral involvement is rare, and surgical intervention is usually required because of its high mortality rate. A literature review found that EPN has rarely been noted in chronic dialysis patients, and those who show bilateral EPN have demonstrated no survival at all until now. Herein, we presented a 51-year-old diabetic uremic woman who developed right emphysematous pyelitis initially and then progressed to bilateral EPN when hospitalized. Percutaneous drainage (PCD) with simultaneous antibiotic therapy successfully eradicated her renal infection. In this study, all reported cases of EPN in chronic dialysis patients were also reviewed.

Association between interleukin-10 gene polymorphism -592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis.

Aim:  The aim of this analysis was to know whether these three cytokine polymorphisms, including interleukin‐6 (IL‐6; −572 G/C), tumour necrosis factor‐α (TNF‐α; −308 G/A), and IL‐10 (–592 A/C) have an effect on baseline peritoneal transport property and longitudinal evolution of peritoneal function.

Clinical Interpretation of Reticulocyte Hemoglobin Content, RET-Y, in Chronic Hemodialysis Patients

Background: Iron deficiency is the most common factor associated with erythropoietin (EPO) hyporesponsiveness. Current iron indices are inadequate to demonstrate the status or utility of iron in erythropoiesis. The aims of this study are to investigate the value of the reticulocyte hemoglobin content, RET-Y, in hemodialysis (HD) patients and compare the levels with conventional iron indices. Methods: HD patients (n = 289) were divided into 4 groups according to serum ferritin (cutoff value 100 ng/ml) and transferrin saturation (TSAT, cutoff value 20%). The RET-Y value, hemogram and biochemical data were determined and compared between groups. Factors associated with RET-Y were examined. Results: The mean RET-Y value was 1,716 ± 125 AU. Patients with absolute iron deficiency had lower RET-Y levels and mean corpuscular volume (MCV). Patients with functional iron deficiency had a lower reticulocyte production index and serum albumin levels. MCV, mean corpuscular hemoglobin concentration (MCHC) and albumin were independently correlated with the RET-Y level (all p < 0.001). EPO-independent patients had low iron indices and low RET-Y levels, but a higher reticulocyte production index and albumin levels were noted. Conclusion: RET-Y levels in HD patients were close to that of the normal population. Low RET-Y levels were observed in patients with absolute iron deficiency and also in EPO-independent patients with low ferritin and low TSAT. There was a strong association between the serum albumin and RET-Y levels in chronic HD patients.

Preserved Residual Kidney Function after Twelve Years' Hemodialysis

Residual kidney function (RKF) contributes significantly to solute clearance and fluid removal for dialysis patients, and the presence of RKF is associated with less morbidity and better long-term outcome. Most studies demonstrate that peritoneal dialysis preserves RKF better than hemodialysis (HD). Herein, we report a 55-year-old man with end stage renal failure who had been on chronic HD for 12 years. His RKF is preserved with very slow decline during the past years. Without specific intervention, delicate fluid management, minimal ultrafiltration, and stable hemodynamics during HD may help maintain his RKF. He is currently normotensive with good nutritional status. Although unexpected, we report this HD patient can preserve his RKF for at least 12 years.

Splenic infarction as a cause of acute abdominal pain in nephrotic syndrome.

A 49-year-old man was referred to emergency department with sudden onset severe abdominal dull pain. The pain presented initially around umbilical area, then progressed to left upper quadrant of abdomen. Medical history was significant for mesangial proliferative glomerulonephritis with nephritic range proteinuria for about 1 year. Laboratory data showed white blood cell count of 22 ¥ 10/mL, haemoglobin of 16.8 g/dL and platelet count of 408 ¥ 10/mL. Serum albumin was 1.8 g/dL, creatinine and blood urea nitrogen were within normal limit. Coagulation study showed low serum anti-thrombin III of 34.8% (75~125%) and a high fibrinogen of 635 mg/dL (190~380 mg/dL). Computed tomography disclosed two focal wedge-shaped hypodensity over the spleen (Fig. 1), which indicated splenic infarction. Low molecular weight heparin (enoxaparin, 80 mg) subcutaneous injection per 12 h was prescribed and was replaced by coumadin 3 days later. After 1 week of anticoagulation therapy, he was discharged with complete resolution of abdominal pain. Six weeks later, a follow-up abdominal magnetic resonance imaging showed a patent splenic artery marked splenomegaly with uneven area of signal intensity. Arterial thrombosis is less common than venous involvement in nephrotic syndrome. Single vascular event, such as splenic infarction, has not been reported yet. Our patient was successfully treated by immediate anticoagulant therapy and infarction did not progress further.