Effects of Oral Adsorbent AST-120 (Kremezin®) on the Progression of Chronic Kidney Disease

Purpose: AST-120 is known to delay progression of chronic kidney disease (CKD) when combined with other proven therapy. AST-120 is an oral adsorbent for uremic toxin, such as indoxyl sulfate from the gastrointestinal tract. There have been a lot of studies to show its effect in other countries, but there are few studies done in Korea yet. Methods: 195 patients were included in the study (mean age, 64±14 years; diabetes mellitus (DM), 104 patients; male, 130 patients). The patients with CKD who started AST-120 and maintained the medication for at least 6 months were enrolled. The patients’ laboratory results for 6 months before and after administrating AST-120 was surveyed. Then the rate of patients’ renal functional deterioration was compared before and after AST-120. In addition, adverse effects during the medication were surveyed. Results: There were no statistically significant differences in laboratory data between before and after AST-120 administration. But, after administrating AST-120, the renal deterioration slope has blunted significantly from -0.0123±0.0318 to -0.0013±0.0184 dL/mg/month (p<0.01) in 1/sCr and from -1.1423± 2.3906 to 0.0639±1.3825 ml/min/1.73m2/month (p<0.01) in estimated glomerular filtration rate (eGFR). There were no differences between DM and non-DM patients in the effect of AST-120, as well as ages over 70 and below 70. There were no serious adverse effects during medication. Conclusion: This study showed that AST-120 had additive effect on retarding the CKD progression when combined with established therapy regardless of DM and ages without serious adverse effects.ope

A Case of Severe Metabolic Acidosis Associated with Sodium Hypochlorite (Bleach) Poisoning Treated by Hemodialysis

Sodium hypochlorite (NaOCl) is commonly used as a disinfectant or bleaching agent. The ingestion of household bleach is often benign, with minimal irritating effect on the mucosa. Occasionally, however, it can be life-threatening. Here, we report an unusual case of acute poisoning involving household bleach with a near-fatal outcome that was treated with intense hemodialysis. A 42-year-old woman presented to the emergency room after ingesting 1 liter of 5% household bleach. Ten hours later, her metabolic acidosis, hypernatremia, hyperchloremia, and renal failure deteriorated gradually, despite aggressive medical treatment. Rapid, effective correction of the metabolic acidosis and electrolytes imbalance was needed and hemodialysis was performed immediately. After 3 days of dialysis, the laboratory imbalance was completely corrected.ope

A Case of Distal Renal Tubular Acidosis and Sjögren’s Syndrome in a Patient with Autoimmune Thyroiditis

A 52-year old woman, who had hypothyroidism associated with autoimmune thyroiditis for 5 years, was hospitalized for tingling sensation and muscle weakness of both lower extremities. Her initial laboratory findings showed severe hypokalemia, metabolic acidosis, and high titer of thyroid autoimmune antibodies. She was diagnosed of distal renal tubular acidosis by bicarbonate loading testope

Serum Adiponectin as a Predictor for Cardiovascular Outcomes in Non-Diabetic End-Stage Renal Disease Patients

Purpose: Adiponectin (ADPN) has been known to protect against cardiovascular disease (CVD) in metabolic syndrome with normal renal function for its anti-inflammatory and anti-atherogenic property. However, it is still unclear whether ADPN is associated with cardiovascular outcomes in end-stage renal disease (ESRD) patients. Methods: This study included 80 non-diabetic ESRD patients [mean age, 52.8±13.7 years; dialysis duration, 67.1±52.0 months; hemodialysis (HD), 35 pts; peritoneal dialysis (PD), 45 pts] who survived for more than 3 months after the start of dialysis, and serum ADPN levels were measured at the beginning of the study. We conducted a longitudinal follow-up to evaluate the association of serum ADPN level with cardiovascular outcomes for 29.3±6.7 months. Results: ADPN was inversely correlated with fasting serum insulin (r=-0.309, p=0.006) and HOMA-IR (r=-0.321, p=0.004) in ESRD patients. In a multiple linear regression analysis adjusted for age, gender, waist to hip ratio (WHR), and HDL-cholesterol, HOMA-IR (β=-0.880, p=0.041) was an independent factor associated with serum ADPN level. Kaplan-Meier analysis revealed that patients with higher ADPN levels (≥15.8 μg/mL) had a significantly higher survival rate compared with lowers (<15.8 μg/ mL) (p=0.032). Cox proportional hazard model adjusted for age, WHR, creatinine, CRP, and previous CVD history revealed that serum ADPN level (HR, 0.899; 95% CI, 0.818-0.987; p=0.026) was an independent determinant of cardiovascular outcomes. Conclusion: These findings suggest that lower ADPN levels independently predict cardiovascular events in non-diabetic ESRD patients.ope

Clinical features and outcomes of IgA nephropathy with nephrotic syndrome.

BACKGROUND AND OBJECTIVES: Nephrotic syndrome (NS) is a rare manifestation of IgA nephropathy (IgAN). Clinical characteristics and long-term outcomes of this condition have not yet been explored. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter observational study was conducted between January 2000 and September 2010 in 1076 patients with biopsy-proven IgAN from four medical centers in Korea. The primary outcome was a doubling of the baseline serum creatinine concentration. RESULTS: Of the 1076 patients, 100 (10.2%) presented with NS; complete remission (CR), partial remission (PR), and no response (NR) occurred in 48 (48%), 32 (32%), and 20 (20%) patients, respectively. During the median follow-up of 45.2 months, 24 patients (24%) in the NS group reached the primary endpoint compared with 63 (7.1%) in the non-NS group (P50% decrease in proteinuria within 3 months after NS onset. None of the patients with SR reached the primary endpoint and they had fewer relapses during follow-up. CONCLUSIONS: This study demonstrated that the prognosis of NS in IgAN was not favorable unless PR or CR was achieved. In addition, SR was more common than expected, particularly in patients with preserved kidney function and spontaneous decrease in proteinuria shortly after NS onset.ope

Leptin/Adiponectin Ratio Is an Independent Predictor of Mortality in Nondiabetic Peritoneal Dialysis Patients

BACKGROUND: The leptin/adiponectin (L/A) ratio has been suggested to be an atherosclerotic index for diabetic patients and a useful marker of insulin resistance in patients with and without diabetes. Even though end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) are well characterized by abnormal adipocytokine metabolism, the significance of alterations in the L/A ratio is largely unexplored in these patients. In this prospective study, we investigated the associations of leptin, adiponectin, and the L/A ratio with clinical outcomes in nondiabetic PD patients. METHODS: The study included 131 stable nondiabetic ESRD patients who had been on PD for more than 3 months. Serum leptin and adiponectin levels were determined at baseline. Mortality was evaluated over a 5-year follow-up period. RESULTS: During the follow-up period, 22 patients died (16.8%), including 10 (45.5%) as a result of cardiovascular disease. The L/A ratio showed a significant positive correlation with body mass index [BMI (r = 0.47, p < 0.001)], high-sensitivity C-reactive protein (r = 0.32, p < 0.001), and triglycerides (r = 0.43, p < 0.001). In addition, we observed significant inverse correlations between the L/A ratio and percentage lean body mass (r = -0.30, p = 0.001) and high-density lipoprotein cholesterol (r = -0.31, p = 0.001). In contrast to individual leptin and adiponectin levels, the L/A ratio was found to be independently associated with an increased mortality risk (relative risk: 1.15; 95% confidence interval: 1.05 to 1.27; p = 0.003) even after adjustments for age and BMI. CONCLUSIONS: The L/A ratio might be better related to patient outcomes than adipocytokines are individually in nondiabetic patients undergoing PD.ope

Left atrial volume is an independent predictor of mortality in CAPD patients

BACKGROUND: Echocardiography is an established technique to estimate the risk for cardiovascular complications in patients with end-stage renal disease (ESRD). An enlarged left atrium (LA) has recently emerged as a marker of adverse cardiovascular outcomes in various pathologic conditions. However, there have been few studies to evaluate its prognostic value in patients with ESRD, particularly those receiving continuous ambulatory peritoneal dialysis (CAPD). METHODS: We conducted an observational cohort study to investigate whether enlarged LA can predict patient outcome in 216 patients with CAPD. Study outcomes were all-cause and cardiovascular mortality. RESULTS: Increased left atrium volume index (LAVI > 32 mL/m(2)) was observed in 99 (45.8%) of the CAPD patients. During the follow-up (26.3 ± 18.6 months), 20 patients (9.3%) died. Kaplan-Meier analysis revealed that the 5-year survival rate was significantly lower in patients with LAVI > 32 mL/m(2) than those with LAVI ≤ 32 mL/m(2) (69 versus 82%, P = 0.024). In multivariate analyses adjusted for echocardiographic parameters and clinical and laboratory data, increased LAVI was an independent predictor of all-cause mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01-1.10, P = 0.03] and cardiovascular mortality (HR 1.08, 95% CI 1.02-1.14, P = 0.006). Furthermore, increased LAVI provided the highest predictive value for all-cause mortality [area under the receiver operating characteristic curve (AUC) = 0.766, P < 0.001] and cardiovascular mortality (AUC = 0.836, P < 0.001) among the measured echocardiographic parameters. CONCLUSIONS: We showed that increased LAVI predicted adverse outcomes better than other echocardiographic parameters in patients with CAPD.ope

Estimating average glucose levels from glycated albumin in patients with end-stage renal disease

PURPOSE: In patients with diabetic end stage renal disease (ESRD), glycated albumin (GA) reflects recent glycemic control more accurately than glycated hemoglobin (HbA1c). We evaluated the relationship between GA and average blood glucose (AG) level and developed an estimating equation for translating GA values into easier-to-understand AG levels. MATERIALS AND METHODS: A total of 185 ESRD patients, including 154 diabetic and 31 non-diabetic participants, were enrolled (108 hemodialysis, 77 peritoneal dialysis). Patients were asked to perform four-point daily self-monitoring of capillary blood glucose (SMBG) at least three consecutive days each week for four weeks. Serum levels of GA, HbA1c and other biochemical parameters were checked at baseline, as well as at 4 and 8 weeks. RESULTS: Approximately 74.3±7.0 SMBG readings were obtained from each participant and mean AG was 169.1±48.2 mg/dL. The correlation coefficient between serum GA and AG levels (r=0.70, p<0.001) was higher than that of HbA1c and AG (r=0.54, p<0.001). Linear regression analysis yielded the following equation: estimated AG (eAG) (mg/dL)=4.71×GA%+73.35, and with this formula, serum GA levels could be easily translated to eAG levels. Multivariate analysis revealed significant contributions of postprandial hyperglycemia (β=0.25, p=0.03) and serum albumin (β=0.17, p=0.04) in determining serum GA level, independent to other clinical parameters. CONCLUSION: Compared to HbA1c, serum GA levels were better correlated with AG levels. Using the estimating equation, an average blood glucose level of 155-160 mg/dL could be matched to a GA value of 18-19% in patients with ESRD.ope

Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy

PURPOSE: This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 μM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated. RESULTS: Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. CONCLUSION: GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.ope

Renal outcomes in patients with type 2 diabetes with or without coexisting non-diabetic renal disease

AIMS: We sought not only to determine the independent predictors of non-diabetic renal disease (NDRD) but also to investigate the impact of NDRD on renal outcomes in patients with type 2 diabetes who underwent renal biopsy and were followed-up longitudinally. METHODS: The present study was conducted by reviewing the medical records of 119 type 2 diabetic patients who underwent renal biopsy at Yonsei University Health System from January 1988 to December 2008. RESULTS: Renal biopsy findings declared that 43 patients (36.1%) had diabetic nephropathy alone, 12 (10.1%) had NDRD superimposed on diabetic nephropathy, and 64 (53.8%) had only NDRD. On multivariate analysis, the absence of diabetic retinopathy, higher hemoglobin levels, and shorter duration of diabetes were independent predictors of NDRD in these patients. During the follow-up period, end-stage renal disease (ESRD) developed in 33 patients (27.7%). On multivariate Cox regression, higher serum creatinine levels, higher systolic blood pressure, longer duration of diabetes, and the presence of diabetic nephropathy were identified as significant independent predictors of ESRD. When the presence of diabetic retinopathy was included in the multivariate model, higher serum creatinine levels, higher systolic blood pressure, and the presence of retinopathy were shown to be independent predictors of ESRD. CONCLUSIONS: Since diabetic patients with NDRD have significantly better renal outcomes compared to patients with biopsy-proven diabetic nephropathy, it is important to suspect, identify, and manage NDRD as early as possible, especially in type 2 diabetic patients with short duration of diabetes and those without diabetic retinopathy or anemia.ope