Urine phthalate metabolites are associated with urothelial cancer in chronic kidney disease patients.

BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population. METHODS: In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs. RESULTS: We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21-1.68). CONCLUSION: Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC.

Development and validation of a nomogram for urothelial cancer in patients with chronic kidney disease.

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24-10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67-2.35). A nomogram based on patients' age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86-0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history.

Long-Term Follow-Up of a Homozygous Familial Hypercholesterolemic Patient Receiving Regular Double Filtration Plasmapheresis - Case Report and Literature Review.

Homozygous familial hypercholesterolemia (HoFH) is a very rare condition (1 case per 1 million people) with a dismal outcome due to inevitable coronary artery disease that occurs when left untreated. Lipoprotein apheresis (LA), previously known as low-density lipoprotein (LDL) apheresis, is very effective in reducing LDL-cholesterol (LDL-C) if HoFH is refractory to aggressive drug therapy and diet control. In this study, we report a case with HoFH, who presented with xanthomata over the 4 limbs when she was 3 years old. When she was 11 years old, she began treatment with semi-selective LA with double filtration plasmapheresis (DFPP) once per week because HoFH was refractory to high-dose statin and diet control. LDL-C was reduced from 8.2 ± 0.9 to 2.69 ± 0.75 mmol/l (reduction rate = 67.3 ± 6.1%). The xanthomata over the 4 limbs were nearly completely resolved after 2 years of DFPP. Two years later, after the initiation of DFPP, we performed coronary angiography and echocardiography for regular checkup in the absence of chest pain, and the result was negative. To date (11 years after initiation of DFPP), she has not complained of any chest pain, shown intolerance to exercise, or exhibited ST-T change on electrocardiography. At the age of 20, multidetector computed tomography showed no significant stenosis over the coronary arteries. At the most recent follow-up visit, she was found to have good heart function and no xanthomata. LA is effective in the treatment of HoFH when drug therapy and diet control fail. With this treatment, pre-existing xanthomata can regress and coronary artery disease can be prevented.

Long-term effects of an oral iron chelator, deferasirox, in hemodialysis patients with iron overload.

Background/Purpose Retention of excess iron from transfused blood in organs in patients with renal anemia may lead to various systemic complications. Iron chelating agents such as deferasirox (DFX) decrease such iron overload. This study assessed the efficacy, safety, and tolerability of DFX in hemodialysis (HD) patients with iron overload. Methods We retrospectively (February 2008 to June 2012) reviewed data for eight HD patients with end-stage renal disease who were prescribed DFX (15 mg/kg/day) for transfusion-induced iron overload. Baseline and post-treatment levels of hematocrit, ferritin, erythropoietin (EPO), transferrin saturation (TSAT), total and unsaturated iron-binding capacity (TIBC and UIBC, respectively), and blood transfusion volumes were measured. Treatment efficacy was evaluated by observing changes in ferritin and TSAT during the study period; monthly EPO doses and blood transfusions were also recorded. Safety was evaluated in the form of adverse events. Results DFX administration caused statistically significant reductions in TSAT (68.2-49.2%; P = 0.036) and ferritin (3133.1-1215.6 ng/ml; P = 0.017). Significant post-treatment increases in UIBC (63.3-196.6 µg/dl; P = 0.018) and TIBC (210.0-422.4 µg/dl; P = 0.012) were also observed. While there were no significant differences in hematocrit values or EPO requirements after treatment, significant reductions in average monthly transfusion volumes (P = 0.026) were recorded. DFX was generally well tolerated; common adverse effects included nausea, vomiting, diarrhea, and abdominal pain. Conclusion DFX significantly improved iron metabolism in HD patients with iron overload and had an acceptable frequency of adverse effects.

Effect of oral ferric citrate on serum phosphorus in hemodialysis patients: multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Hyperphosphatemia is a common complication in dialysis patients that can be treated by oral phosphate binders. We investigated the efficacy and safety of oral ferric citrate as a phosphate binder for Taiwanese patients with end stage renal disease and with hyperphosphatemia who were undergoing hemodialysis. METHODS: This was a prospective, double-blind, placebo-controlled, randomized trial carried out in 5 hospitals in Taiwan. Ferric citrate (4 or 6 g/day) or placebo was administered for 56 days. Serum calcium, phosphorous levels, calcium × phosphorus product, serum ferritin level, transferrin saturation, and adverse events were recorded. RESULTS: A total of 166 patients completed the trial. The placebo group had relatively constant serum data. Serum phosphorus declined significantly in the 6 g/day group (p < 0.05 for 4 and 8 weeks) and the 4 g/day group (p < 0.05 for 4 and 8 weeks). There were similar changes in the calcium × phosphorus product. The serum ferritin level increased significantly in the 6 g/day group (p < 0.05) and the 4 g/day group (p < 0.05). There were similar changes in transferrin saturation. Most adverse events were mild to moderate and were comparable among the three groups. CONCLUSIONS: A 56-day treatment with ferric citrate effectively controlled hyperphosphatemia and was well tolerated in maintenance hemodialysis patients. There were also moderate increases in serum ferritin and transferrin saturation.

Mycelia glycoproteins from Cordyceps sobolifera ameliorate cyclosporine-induced renal tubule dysfunction in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sorbolifera has been used in Traditional Chinese Medicine for improving the renal function. Cyclosporine A (CsA) is an important immunosuppressive agent in the prevention of renal allograft rejection, but long-term usage of CsA could lead to chronic nephrotoxicity and renal graft failure. The study was aimed to investigate whether the mycelia glycoproteins of Cordyceps sobolifera (CSP) exert prevention effects on CsA-induced nephrotoxicity. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly assigned into four groups (n=6 per group): normal saline (control group), CSP group, CsA group, and CSP-CsA group (CsA combined treatment with CSP). Glomerular and tubular functions were assessed and histological studies were performed. RESULTS: CSP, prepared by hot water extraction, ethanol precipitation and membrane dialysis, was found to be composed of three glycoproteins with average molecular weights of 543, 31, and 6.3 kDa, respectively. CsA impaired urea clearance and creatinine clearance were significantly improved by concomitant administration of CSP. TUNEL histochemical stain revealed that CSP significantly decreased CsA-induced apoptosis in renal tubular cells. The reducing effect of caspase-3 activation by CSP was suggested through the over-expression of the anti-apoptosis protein Bcl-2 in renal tubule cells. In assessment of CSP protection of renal tubule function, we found that CSP restored CsA induced magnesium wasting by increasing the magnesium reabsorption channels TRMP6 and TRMP7. CONCLUSION: The results suggested that CSP had a significant suppressive activity on CsA-induced apoptosis and protective activity against nephron loss possibly via its restoring activity by increasing the magnesium reabsorption channels TRMP6 and TRMP7 on CsA induced magnesium wasting.