Aliskiren add-on therapy effectively reduces proteinuria in chronic kidney disease: an open-label prospective trial.

INTRODUCTION: The combination therapy of aliskiren and renin-angiotensin-aldosterone system (RAAS) blocker in chronic kidney disease (CKD) is controversial. Whether such dual blockade can effectively apply to patients with CKD irrespective of stage and amount of proteinuria remains uncertain. METHODS: We added aliskiren at a dosage of 150 mg/day for six months in 103 Chinese CKD patients who had been treated with angiotensin converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) and still had significant proteinuria or uncontrolled hypertension. Blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), potassium, and spot urine protein-to-creatinine ratio (UPCR) were measured at three and six months after aliskiren add-on therapy and compared with baseline. RESULTS: The combination of aliskiren and ACEi or ARB significantly reduced UPCR by 23% (p=0.001) and mean arterial pressure by 7.9 ± 13.8 mmHg (p<0.001) at six months. Twenty-five percent of subjects had a greater than 50% reduction in UPCR. No significant changes in eGFR and serum potassium level were noted at six months. CONCLUSIONS: Adding aliskiren on ACEi or ARB in CKD patients, both in diabetes and non-diabetes, has a favorable effect on reducing residual proteinuria and inadequately controlled blood pressure.

Ultrasound localization of the femoral vein facilitates successful cannulation for hemodialysis.

BACKGROUND: Real-time ultrasound-guided techniques allow for improved cannulation of the internal jugular vein and femoral vein for hemodialysis; however, these techniques require extra sterilization procedures, specialized probes, or needle guides. A simpler ultrasound vessel localization method was performed to investigate whether this alternative approach would aid in the cannulation of the femoral vein for patients in whom temporary angioaccess was required for hemodialysis. METHODS: Patients requiring temporary femoral vein catheters for hemodialysis were divided into 2 groups on alternating days of the week during a 6-month period. One group underwent ultrasound localization of the femoral vein before cannulation and the second group received conventional landmark localization. Data regarding the strength of the femoral arterial pulse, number of attempts, failures, and complications were recorded. RESULTS: Ultrasound localization resulted in significantly improved first-attempt success rates, reduced attempts, and reduced failure and complication rates overall (p < 0.001, p < 0.001, p = 0.002 and p = 0.004 respectively) as well as in the group of patients with a clearly discernible arterial pulse (p < 0.001, p = 0.001, p = 0.004 and p = 0.011 respectively). The same trend was observed among patients with faintly palpable or non-palpable femoral arterial pulses, although the differences were not statistically significant. CONCLUSION: Cannulation of the femoral vein for hemodialysis should be performed with the aid of ultrasound. If real-time ultrasound-guided cannulation is not available, the vessel localization method is a good alternative, given its known limitations and the fact that it is simpler. It remains to be determined whether 1 - dimensional localization or localization including vessel depth information can improve outcomes in patients with faintly palpable or non-palpable femoral arterial pulses.

Free p-cresol sulfate is associated with survival and function of vascular access in chronic hemodialysis patients.

BACKGROUND: Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresol sulfate (p-CS) have been implicated as an important factor in uremic syndrome. Recent evidence indicates that both IS and p-CS are predictors of cardiovascular as well as all-cause mortality among chronic dialysis patients. We conducted a study to analyze the relationship between IS and p-CS and vascular access (VA) outcome in chronic hemodialysis (HD) patients. METHODS: A total of 91 chronic stable HD patients were divided into groups according to survival of VA and frequency of VA dysfunction. Demographic and biochemical data were reviewed and recorded. Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, and the total and free forms of IS and p-CS were determined. RESULTS: Patients with a history of frequent VA failure and dysfunction had lower albumin and higher levels of ICAM-1, free IS, free and total p-CS. Diabetes was associated with higher IS and p-CS. Logistic regression revealed that diabetes and free p-CS were independent factors associated with poor outcome of VA. CONCLUSION: Endothelial dysfunction and uremic toxins were associated with survival and function of VA. Diabetes and free p-CS were significantly related to the outcome of VA among chronic HD patients.

Albuminuria, proteinuria, and urinary albumin to protein ratio in chronic kidney disease.

BACKGROUND: Both albuminuria and proteinuria are important disease markers of chronic kidney disease (CKD). Their relationship and the ratio between urinary albumin and protein in patients with CKD have not been investigated. Whether clinical features can affect these measurements is not clear. METHODS: We conducted a cross-sectional study in 602 CKD patients. Demographic data, including age, gender, and co-morbidity such as diabetes, hypertension, hyperuricemia, and hyperlipidemia, were reviewed and recorded. Their urinary albumin, total protein, and creatinine were determined and urinary albumin to creatinine ratio (UACR), total protein to creatinine ratio (UPCR), and albumin to total protein ratio (UAPR) were calculated. Their estimated glomerular filtration rate (eGFR) was calculated according to serum creatinine. The correlation between UACR and UPCR was thus analyzed. We also investigated factors associated with these urinary measurements. RESULTS: UACR and UPCR increased progressively as renal function deteriorated, while UAPR increased to a plateau in CKD stage 4. There was direct relationship between UACR and UPCR. UAPR rose exponentially with the increase of both UACR and UPCR when UACR <500 mg/g or UPCR <1,000 mg/g. Multivariate regression analysis revealed diabetes and hyperuricemia were associated with increased UACR and UPCR, while both urinary parameters were inversely related to male gender and eGFR. Diabetes and hyperuricemia were associated with increased UAPR and UAPR was negatively correlated with age and eGFR. CONCLUSION: There was a significant association between UACR and UPCR in patients with CKD. Characteristics of patients, renal function, and co-morbidities all affected UACR, UPCR, and UAPR.

Development of cephradine-induced acquired factor V inhibitors: a case report.

OBJECTIVE: To report a case of cephalosporin-induced factor V inhibitor development, an uncommon but potentially fatal condition characterized by severe hemorrhage. CASE SUMMARY: A 71-year-old Chinese man presented with factor V inhibitors after a 7-day cephradine course for a urinary tract infection, characterized by abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT), gross hematuria, upper gastrointestinal bleeding, and left groin hematoma. Systemic corticosteroid administration restored his factor V activity levels, PT, and aPTT to within normal limits, and hemorrhagic symptoms resolved. Three weeks after successful treatment of bleeding diathesis, he received another 8-day cephradine course for cellulitis. After another 4 weeks, he suffered from recurrent factor V inhibitors presented with abnormal PT, aPTT, and upper gastrointestinal bleeding. The patient eventually died due to hemorrhagic shock despite a second course of corticosteroids. DISCUSSION: Cephalosporins are known to cause coagulopathy via hypoprothrombinemia. Another pathway seldom mentioned in the literature is factor V inhibitor induction, which may result in factor V deficiency. In our patient, factor V deficiency due to inhibitors developed each time that the patient received repeated cephradine treatment. According to the Naranjo probability scale, the relation between the formation of factor V inhibitors and cephradine treatment was probable. CONCLUSIONS: Because cephalosporins are commonly used for their wide therapeutic index and few adverse effects, iatrogenic complications associated with these drugs may be neglected or underdiagnosed. On the basis of our patient's report, careful review of medical records to avoid reexposure to the offending drug cannot be overemphasized.