Clinical Characteristics of Rapid Progression in Asia-Pacific Patients With ADPKD.

Introduction: This study aimed to determine the utility of different methods to predict rapid progressors (RPs) and their clinical characteristics in Asia-Pacific patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: This was a multinational retrospective observational cohort study of patients with ADPKD in the Asia-Pacific region. Five hospitals from Australia, China, South Korea, Taiwan, and Turkey participated in this study. RP was defined by European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) guidelines and compared to slow progressors (SPs). Results: Among 768 patients, 426 patients were RPs. Three hundred six patients met only 1 criterion and 120 patients satisfied multiple criteria for RP. Historical estimated glomerular filtration rate (eGFR) decline fulfilled the criteria for RP in 210 patients. Five patients met the criteria for a historical increase in height-adjusted total kidney volume (TKV). The 210 patients satisfied the criteria for based on kidney volume. During the follow-up period, cyst infections, cyst hemorrhage, and proteinuria occurred more frequently in RP; and 13.9% and 2.1% of RPs and SPs, respectively, progressed to end-stage kidney disease (ESKD). RP criteria based on historical eGFR decline had the strongest correlation with eGFR change over a 2-year follow-up. Conclusion: Various assessment strategies should be used for identifying RPs among Asian-Pacific patients with ADPKD in real-world clinical practice during the follow-up period, cyst infections, cyst hemorrhage, and proteinuria occurred more frequently; and more patients progressed to ESKD in RPs compared with SPs.

Formulation Development of Doxycycline-Loaded Lipid Nanocarriers using Microfluidics by QbD Approach.

Liposomes have been used to improve therapeutic efficacy of drugs by increasing their bioavailability and altering biodistribution. The loading capacity of small molecules in liposomes remains a critical issue. Besides, the manufacturing process of liposomes requires multi-step procedures which hinders the clinical development. In this study, we developed a promising lipid-based nanocarriers (LN) delivery system for hydrophilic charged compounds using doxycycline (Doxy) as a model drug. This Doxy-loaded lipid nanocarrier (LN-Doxy) was fabricated by microfluidic technology. Design of experiments (DoE) was constructed to outline the interactions among the critical attributes of formulation, the parameters of microfluidic systems and excipient compositions. Response surface methodology (RSM) was furthered used for the optimization of LN-Doxy formulation. The LN-Doxy developed in this study showed high drug to lipid ratio and uniform distribution of particle size. Compared to Doxy solution, this LN-Doxy has reduced in vitro cellular toxicity and significant therapeutic efficacy which was verified in a peritonitis animal model. These results show the feasibility of using microfluidic technology combined with QbD approach to develop the LN formulation with high loading efficiency for ionizable hydrophilic drugs.

Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests.

BACKGROUND: To assess whether angiotensin-II receptor blockers (ARBs) offer any additional advantage in confirming the diagnosis of primary aldosteronism (PA) and their use in the differentiation of PA subtypes. METHODS: A prospective, cohort, head-to-head study was conducted between July 2003 and July 2006. A total of 135 patients received captopril and losartan tests to confirm the diagnosis of PA in the TAIPAI (Taiwan Primary Aldosteronism Investigation) intervention. RESULTS: In total, 71 patients were diagnosed with PA. The area under the receiver-operating characteristic (ROC) curve of the postcaptopril plasma aldosterone concentration (PAC) was significantly less than that of the postlosartan PAC (0.744 vs. 0.829, P = 0.038). Using an aldosterone-renin ratio (ARR, ng/dl per ng/ml/h) >35 with a PAC >10 ng/dl, the specificity was 89.1% vs. 93.8% and the sensitivity was 66.2% vs. 84.5 % for the captopril test vs. the losartan test, respectively. With respect to the losartan test, the accuracy was 88.9%, the agreement was good (k = 0.778), and there was no disagreement with the McNemar test (P = 0.118). Losartan had the advantage of a better negative predictive value to exclude PA when patients were referred with a serum potassium (SK) level <3.8 mmol/l. When a postlosartan ARR >60 was the cutoff value, the positive predictive value was 82% with a negative predictive value of 57% in distinguishing aldosterone-producing adenomas (APAs) from idiopathic hyperaldosteronism (IHA). CONCLUSIONS: The postlosartan ARR and PAC were shown to have better accuracy for the diagnosis of PA than the captopril test. With a postlosartan ARR >60, APAs can be adequately differentiated from IHA.

Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis.

AIM: Patients with end-stage renal disease (ESRD) often start long-term haemodialysis (HD) thrice weekly, regardless of the level of residual renal function (RRF). In this study, we investigated whether ESRD patients having sufficient RRF can be maintained on twice-weekly HD, and how they fare compared to patients without RRF on thrice-weekly HD. METHODS: We analyzed 74 patients who had undergone long-term HD and maintained on the same dialysis frequency from February 1998 to July 2005, and followed until December 2005. We compared the clinical variables between twice-weekly and thrice-weekly HD patients and a second analysis testing the residual urine output as an independent predictor for twice-weekly HD. RESULTS: After a mean follow up of 18 months, twice-weekly HD patients (n = 23) had lower serum beta2-microglobulin than thrice-weekly HD patients (n = 51). Moreover, the twice-weekly group had a slower decline of RRF, as indicated by their higher urine output and creatinine clearance, fewer intradialytic hypotensive episodes, and required less frequent hospitalization. There was no difference between the two groups in cardiothoracic ratio or indices of nutrition and inflammation. Multivariable logistic regression identified age (odds ratio (OR), 1.866; 95% CI, 1.093-3.183), dry body mass index (OR, 0.790; 95% CI, 0.625-0.999), and urine output (OR, 1.093; 95% CI, 1.026-1.164) as predictors for maintaining twice-weekly HD. CONCLUSION: Our data suggest that when patients who have sufficient urine output are given twice-weekly HD, they maintain dialysis adequacy and exhibit better preservation of RRF than patients on thrice-weekly HD.

Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: focus on identifying the best cut-off point.

BACKGROUND: Malnutrition-inflammation score (MIS) is a comprehensive and quantitative system to assess malnutrition-inflammation complex syndrome, and a strong correlation between MIS and morbidity/mortality in maintenance hemodialysis (MHD) patients had been demonstrated. However, there is no cut-off value of MIS to categorize patients into high risk or low risk patients. METHODS: A total of 257 chronic stable and ambulatory adult MHD patients from Far Eastern Memorial Hospital were enrolled for the study. The MIS of each patient was recorded at the initiation of study and the study population was followed up as a 12-month prospective cohort to evaluate mortality as the primary outcome. RESULTS: Twelve patients died in the 12-month observational period. Both multiple logistic regression analyses and Cox proportional hazards model denoted MIS, alkaline phosphatase, transferrin saturation, ferritin, and total iron binding capacity as significant predictors of 1-year mortality. The conditional effect plot of MIS on 1-year mortality revealed that when fixing the alkaline phosphatase, transferrin saturation, ferritin, and total iron binding capacity at a mean value, the probability of death for an MHD patient whose MIS was 3, 4, and 5 is 10, 40, and 80%, respectively. CONCLUSIONS: Our study shows that MHD patients with MIS score of more than 4-5 had a significant risk of 1-year mortality. Additional risk factors associated with short-term mortality besides malnutrition-inflammation complex syndrome were anemia and renal osteodystrophy. This study proves that MIS is a useful tool to risk-stratify Asian MHD patients and to identify those at risk of short-term death. Nutritional interventions that can improve the MIS may also improve survival, but this hypothesis needs to be verified in interventional studies.