Pharmacokinetics of intravenous piperacillin/tazobactam among patients with peritoneal dialysis-associated peritonitis.

Currently, pharmacokinetic information on intravenous (IV) piperacillin/tazobactam in patients with peritoneal dialysis-associated peritonitis (PD peritonitis) is limited. This study employed a prospective single-dose pharmacokinetic design to assess the pharmacokinetics of IV piperacillin/tazobactam in these patients. Four patients with PD peritonitis who received an IV loading dose of 4000 mg/500 mg piperacillin/tazobactam were enrolled in this study. The concentrations of piperacillin and tazobactam in plasma, peritoneal dialysis fluid (PDF) and urine were determined by high-performance liquid chromatography. Non-compartmental methods were used for pharmacokinetic analysis. During a 6-h dwell time for chronic ambulatory peritoneal dialysis (CAPD), 9.23 ± 4.01% of the piperacillin was recovered in the PDF. This result is greater than that observed in patients without peritonitis in prior research. Piperacillin's PD clearance (CLPD), steady-state volume of distribution (Vss) and terminal half-life (t 1/2) were 5.79 ± 2.55 mL/min, 24.35 ± 11.26 L and 5.74 ± 1.53 h, respectively. These values are also higher than those of patients without peritonitis in a prior study. Eight hours following the loading dosage, the plasma and PDF piperacillin concentrations of all patients (98.25 ± 26.03 and 52.70 ± 22.99 mg/L, respectively) surpassed the Pseudomonas aeruginosa and Enterobacterales Clinical and Laboratory Standards Institute susceptible breakpoints. In summary, the CLPD, Vss and t 1/2 for piperacillin were found to be greater in patients with PD peritonitis than in CAPD patients without peritonitis when compared with the results of a previous study. The IV loading dose of 4000 mg/500 mg piperacillin/tazobactam is sufficient to treat peritonitis caused by susceptible P. aeruginosa and Enterobacterales. The multiple-dose pharmacokinetics of IV piperacillin and tazobactam in this specific patient group should be further investigated.

Comparison of immediate-start peritoneal dialysis without break-in period and conventional-start peritoneal dialysis: a two-center retrospective audit.

PURPOSE: Immediate-start peritoneal dialysis (PD) has emerged as a strategy for patients in need of urgent dialysis. However, the ideal timing for initiating this procedure remains uncertain. In this study, we aimed to compare complications and outcomes between immediate-start PD and conventional-start PD. METHODS: We performed a two-center retrospective cohort study between 1 January 2015 and 31 May 2020. Patients who underwent PD were divided into immediate-start PD (without break-in period) and conventional-start PD group (break-in period within at least 14 days). The primary outcomes were the incidence of the mechanical complications and infectious complication. The secondary outcomes were technique failure and patient survival. RESULTS: A total of 209 patients (106 in the immediate-start PD group and 103 in the conventional-start PD group) were included. Immediate-start PD had significantly lower catheter malfunction or migration rate compare with conventional-start PD (2.8% vs. 15.5%, p = 0.003) but comparable rates of dialysate leaks, pleuroperitoneal leaks, and hemoperitoneum. Infectious complications (exit-site infection and peritonitis) were similar between groups. Technique survival was comparable (7.5% vs. 4.8%, p = 0.22), while immediate-start PD exhibited lower mortality rates (0.9% vs. 13.6%, p = 0.001). CONCLUSION: Immediate-start PD appears to be a viable option for patients in need of urgent dialysis, with reduced catheter complications and comparable infectious complications and technique survival when compared to conventional-start PD.

Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand.

Background: Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). Methods: We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. Results: A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). Conclusion: PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

Estimates of Chronic Kidney Diseases Associated with Proton-Pump Inhibitors Using a Retrospective Hospital-Based Cohort in Thailand.

Purpose: Potential adverse outcomes of Proton pump inhibitors (PPIs) have increasingly been reported. The potential risks to PPIs include hypomagnesemia and chronic kidney disease (CKD). Unlike a real-world electronic medical record (RW-EMR) with active-comparator design, claim databases and special population cohort with non-user design, using in previous studies, resulted in a wide range of strength of association with indication bias. This study aimed to measure the total effect of association between PPIs use and CKD incidence using Thai RW-EMR. Patients and Methods: A retrospective hospital-based cohort was applied into this study. Electronic medical records and administrative data of out- and inpatient were retrieved from October 1st, 2010 to September 30th, 2017. On-treatment with grace period as well as propensity score matching was used in data analysis. Cox proportional hazard models were applied to evaluate the PPIs-CKD association. Results: Of all 63,595 participants, a total of 59,477 new PPIs and 4118 Histamine 2-receptor antagonist (H2RA) users were eligible for follow-up. As compared with H2RA, the PPI users were non-elderly and more likely being female. The association of PPIs with CKD was statistically significant (adjusted hazard ratio [HR] = 3.753, 95% CI = 2.385-5.905). The HR were not statistically different by concomitant use PPIs with NSAIDs and by medication possession ratio levels. Conclusion: The association between PPIs and CKD incidence was statistically significant in this hospital-based cohort. However, self-treatment with over-the-counter PPIs, as well as, smoking, drinking alcohol and body mass index could not be fully retrieved, affecting the estimation of treatment effect.

A Rare Case Report of Postoperative Paraneoplastic Glomerulopathy in Kidney Transplant.

Kidney transplant recipients are more likely to develop posttransplant renal cell carcinoma than the general population. Symptoms of renal cell carcinoma are often nonspecific, such as nausea, vomiting, and weight loss, and tend to occur syndrome caused by the release of peptides and hormones by the cancer itself. However, there have been rare case reports of postoperative paraneoplastic glomerulopathy associated with renal cell carcinoma in kidney transplant recipients. Here, we report the case of a 54-year-old male who presented with subnephrotic range proteinuria with a urine protein-to-creatinine ratio of 1.0 within 1 year after a deceased donor kidney transplant without kidney function decline. The transplant team decided to perform a biopsy of the transplanted kidney, and the ultrasonography before intervention revealed a right- side native renal mass. The result of the kidney biopsy revealed focal segmental glomerulosclerosis. At the same time, computed tomography was done to find the cause of the renal mass, and we found that the right native kidney mass had features highly suspicious for renal cell carcinoma. The urologist subsequently performed a right radical nephrectomy. The pathology diagnosis of the kidney mass was renal cell carcinoma. After the cancer had been eliminated, clinical improvement of proteinuria was achieved. Hence, we diagnosed a rare secondary focal segmental glomerulosclerosis from renal cell carcinoma (paraneoplastic glomerulopathy) about which, to our knowledge, there are no previous reports. To date, there is no consensus recommendation for screening postoperative renal cell carcinoma in organ transplant recipients. The potential postoperative diagnosis of paraneoplastic glomerulopathy-associated renal cell carcinoma in kidney transplant recipients must be recognized.

Glomerular filtration rate correlation and agreement between common predictive equations and standard 24-hour urinary creatinine clearance in medical critically ill patients.

Background: Determining kidney function in critically ill patients is paramount for the dose adjustment of several medications. When assessing kidney function, the glomerular filtration rate (GFR) is generally estimated either by calculating urine creatinine clearance (UCrCl) or using a predictive equation. Unfortunately, all predictive equations have been derived for medical outpatients. Therefore, the validity of predictive equations is of concern when compared with that of the UCrCl method, particularly in medical critically ill patients. Therefore, we conducted this study to assess the agreement of the estimated GFR (eGFR) using common predictive equations and UCrCl in medical critical care setting. Methods: This was the secondary analysis of a nutrition therapy study. Urine was collected from participating patients over 24 h for urine creatinine, urine nitrogen, urine volume, and serum creatinine measurements on days 1, 3, 5, and 14 of the study. Subsequently, we calculated UCrCl and eGFR using four predictive equations, the Cockcroft-Gault (CG) formula, the four and six-variable Modification of Diet in Renal Disease Study (MDRD-4 and MDRD-6) equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The correlation and agreement between eGFR and UCrCl were determined using the Spearman rank correlation coefficient and Bland-Altman plot with multiple measurements per subject, respectively. The performance of each predictive equation for estimating GFR was reported as bias, precision, and absolute percentage error (APE). Results: A total of 49 patients with 170 urine samples were included in the final analysis. Of 49 patients, the median age was 74 (21-92) years-old and 49% was male. All patients were hemodynamically stable with mean arterial blood pressure of 82 (65-108) mmHg. Baseline serum creatinine was 0.93 (0.3-4.84) mg/dL and baseline UCrCl was 46.69 (3.40-165.53) mL/min. The eGFR from all the predictive equations showed modest correlation with UCrCl (r: 0.692 to 0.759). However, the performance of all the predictive equations in estimating GFR compared to that of UCrCl was poor, demonstrating bias ranged from -8.36 to -31.95 mL/min, precision ranged from 92.02 to 166.43 mL/min, and an unacceptable APE (23.01% to 47.18%). Nevertheless, the CG formula showed the best performance in estimating GFR, with a small bias (-2.30 (-9.46 to 4.86) mL/min) and an acceptable APE (14.72% (10.87% to 23.80%)), especially in patients with normal UCrCl. Conclusion: From our finding, CG formula was the best eGFR formula in the medical critically ill patients, which demonstrated the least bias and acceptable APE, especially in normal UCrCl patients. However, the predictive equation commonly used to estimate GFR in critically ill patients must be cautiously applied due to its large bias, wide precision, and unacceptable error, particularly in renal function impairment.

High collagen I gene expression as an independent predictor of adverse renal outcomes in lupus nephritis patients with preserved renal function.

CONTEXT: The deposition of extracellular matrix is a major pathogenic mechanism leading to fibrosis and progressive decline in renal function in patients with lupus nephritis (LN). Currently, available clinicopathologic features cannot predict renal outcome consistently. OBJECTIVE: To test that the expression of renal fibrogenic genes correlates with renal fibrosis at the time of biopsy and is predictive of renal outcomes. DESIGN: Renal gene expression levels of transforming growth factor ß-1 (TGFB1), and collagen I (COL1) were studied by real-time multiplex quantitative polymerase chain reaction in a prospective cohort of patients with LN (n = 39). Extracellular matrix index (ECMI) and collagen I/III matrix index were measured from Picro-Sirius Red-stained slides under normal and polarized light, respectively. RESULTS: After follow-up (median, 43.9 months), renal failure (50% reduction in glomerular filtration rate [GFR] or dialysis) had developed in 13 subjects. The expression levels of renal fibrogenic genes were increased as compared to controls without LN. COL1 correlated with collagen I/III matrix index at baseline. Both high expression of TGFB1 or COL1 tended to predict renal failure by univariate analysis. By multivariate analysis, high ECMI and low GFR were predictive of renal failure. In patients with baseline GFR of 60 mL/min/1.73 m(2) or greater, high renal COL1 expression was an independent (hazard ratio = 4.4, P = .04) predictor of renal failure. CONCLUSIONS: High renal COL1 expression is a strong predictor of adverse renal outcome in patients with LN and preserved baseline GFR. These findings support larger prospective studies to confirm the benefits of COL1 in identifying patients at high risk of progression to renal disease.