Pharmacokinetics of single‐dose rosiglitazone in chronic ambulatory peritoneal dialysis patients

Background: End‐stage renal disease (ESRD) is associated with marked alterations in the pharmacokinetics of many drugs, not only from reduction in renal clearance but also from changes in metabolic activity, bioavailability, volume of distribution and plasma protein binding. Objective: To study the pharmacokinetics of a single 8‐mg oral dose of rosiglitazone in patients with ESRD and requiring long‐term chronic ambulatory peritoneal dialysis (CAPD). Method: The medication was administered just before the first exchange of peritoneal dialysis fluid on the day that blood and peritoneal dialysate collection was performed. Results: In our CAPD patients the mean (±SD) T_max and T_1/2 of rosiglitazone were 1·20 ± 0·26 and 21·38 ± 21·96 h respectively. These values were different to those reported for healthy volunteers reported in previous studies. The mean area under the concentration–time curve (AUC_(0–∞)) and an average maximum observed plasma concentration (C_max) of rosiglitazone in our CAPD patients were 4203·56 ± 2916·97 ng h/mL and 409·67 ± 148·89 ng/mL respectively. These appear no different from those reported in healthy volunteers . Conclusion: The apparently significant difference in T_1/2 of rosiglitazone in CAPD patients compared with healthy volunteers suggest that dose adjustment may be necessary in order to avoid toxicity.     

Normalized protein nitrogen appearance is correlated with hospitalization and mortality in hemodialysis patients with Kt/V greater than 1.20.

OBJECTIVES: Normalized protein nitrogen appearance (nPNA), also known as protein catabolic rate (nPCR), reflects the daily protein intake in maintenance hemodialysis (MHD) patients. Several studies indicate that nPNA and Kt/V correlate with clinical outcome and also with each other. Thus, the relationship between low nPNA and poor outcome could be due to uremia, low Kt/V or due to reported mathematical coupling between nPNA and Kt/V. We therefore investigated whether nPNA is associated with outcome in patients who have adequate or high Kt/V. DESIGN: Prospective cohort. SETTINGS: Outpatient dialysis unit affiliated with a tertiary-care community medical center. PATIENTS: From a pool of 135 MHD outpatients in one dialysis unit, 122 patients with a delivered, Kt/V(sp)>1.20, independent of their residual renal function, were evaluated. Patients (61 women, 61 men), aged from 23 to 89 years (53.4+/-14.0 years)(+/-SD), had been undergoing MHD for one month to 17 years. INTERVENTION: Review of laboratory values and clinical outcome. MAIN OUTCOME MEASURES: Twelve-month mortality and hospitalization. RESULTS: Delivered Kt/V(sp) ranged from 1.23 to 2.71 (1.77+/-0.34), nPNA from 0.5 to 2.15 (1.13+/-0.29 g/kg/day), and serum albumin, from 1.9 to 4.6 (3.76+/-0.37 g/dL). During the 12-month follow-up, 55 patients were hospitalized overnight at least once; 12 patients died; 5 patients underwent renal transplantation, and 6 patients left the study. The nPNA and Kt/V(sp) did not correlate significantly (r=.09) except when analysis was limited to Kt/V values < 1.5 (r=.54). Serum nPNA and albumin were the only variables with statistically significant correlations with both mortality and 3 measures of hospitalization (H): total days of H (H(D)), total number of H (H(F)), and time to first H (H(T)). The case-mix adjusted correlations for serum albumin and nPNA versus total days (r(HD)) and frequency of H (r(HF)) were significant, and Cox analysis based on H(T) and time to death resulted in significant odds ratios for each standard deviation decrement for both serum albumin and nPNA. Serum total iron binding capacity (TIBC) and creatinine concentrations also correlated with some but not all outcome measures: lower serum concentrations of these values were each significantly associated with poor clinical outcomes. CONCLUSIONS: Both nPNA and serum albumin predict prospective hospitalization and mortality in MHD patients with Kt/V > 1.20. Serum TIBC and creatinine concentrations appear to have association with some outcome measures as well. These data are consistent with the possibility that protein intake affects the clinical course even in the setting of an adequate to high hemodialysis dose. Studies based on randomized assignments to different protein intakes would be helpful to confirm these conclusions.     

Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study

BackgroundNovel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).MethodsA prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.Main findingsThe composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38–6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40– 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.ConclusionsPatients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.     

Pseudallescheria boydii brain abscess in a renal transplant recipient: first case report in Southeast Asia

Pseudallescheria boydii and its asexual form, Scedosporium apiospermum, are ubiquitous filamentous fungi that rarely cause central nervous system (CNS) infection. Brain abscess caused by P. boydii is a highly lethal infection, usually seen in organ transplant recipients who receive a number of immunosuppressive agents. We have presented a case of a 48-year-old man 6 years after renal transplantation who received methylprednisolone followed by antithymocyte globulin for treatment of acute cellular rejection. Eight weeks later, he developed fever, headache, and left-sided hemiparesis. Further investigation with magnetic resonance imaging of the brain showed multiple ring-enhancing hypodense lesions with marked edema which were compatible with brain abscesses. Following surgical drainage, multiple fungal elements were initially described as Aspergillus species. The patient failed to improve and died from rapidly progressive infection despite treatment with amphotericin B. Later a diagnosis was finally made by the isolation of P. boydii in pus culture. The specific diagnosis is difficult to rapidly make, because P. boydii mimics other fungi morphologically in tissue sections and may produce infections clinically similar to other mycoses. Culture of the organism is required for definitive diagnosis. P. boydii infections are important complications of transplantation. They are difficult to treat due to resistance to amphotericin B. Physicians should consider P. boydii a possible cause of brain abscess in organ transplant recipients, especially with heavy immunosuppressive agents. This is the first case report of CNS infection due to P. boydii in a renal transplant patient in Southeast Asia.