drug dosing in renal disease

PURPOSE: Infectious disease pharmacists and physicians overseeing antimicrobial stewardship programs possess expertise and often advanced certification in management of antiretrovirals to treat HIV. Stewardship programs are responsible for managing facility formularies and must stay up to date with the latest antiretrovirals, including once daily formulations and depot injectables. Furthermore, stewardship program members need to understand drug-interactions, short-, and long-term toxicities of these regimens, including dyslipidemia and cardiovascular effects...

BACKGROUND: Adult nephrotic syndrome is a well-known kidney disease that causes heavy proteinuria, hypoalbuminemia, hypercholesterolemia, edema, and hypertension. The treatment varies according to its underlying cause but often faces medication resistance or adverse drug effects. CASE PRESENTATION: A Japanese woman in her 80s presented with nephrotic syndrome after a 3 year latent period of urinary protein and occult blood. She did not have any secondary causes of nephrotic syndrome...

Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types...

ETHNOPHARMACOLOGICAL RELEVANCE: Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field...

Hemophagocytic syndrome/macrophage activation syndrome (HPS/MAS) is a serious clinical condition that frequently leads to multiple organ failure, including acute kidney injury (AKI). Although the pathogenesis of AKI is not yet fully understood, it is believed to result from uncontrolled activation of the immune system involving macrophages and cytotoxic lymphocytes. Renal histology in HPS/MAS often presents with characteristic foamy glomerular lesions (glomerular lipidosis) with massive macrophage infiltration, known as histiocytic glomerulopathy...

Amantadine, despite being on the market for 55 years, has several unknown aspects of its pharmacokinetics especially related to the influence of covariates such as age, disease, or interactions linked to amantadine's renal elimination. As amantadine is used in Parkinson's disease and is considered a potential candidate in COVID treatment and other diseases, there is an unmet need for thorough understanding of its pharmacokinetic in special populations, such as the elderly. We aimed to mechanistically describe amantadine pharmacokinetics in healthy subjects and shed some light on the differences in drug behavior between healthy volunteers (18-65 years) and an elderly/geriatric population (65-98 years) using PBPK modeling and simulation...

Diabetic kidney disease (DKD) is one of the most serious complications of diabetes and has become the leading cause of end-stage kidney disease, causing serious health damage and a huge economic burden. Tubulointerstitial fibrosis play important role in the development of DKD. Itaconate, a macrophage-specific metabolite, has been reported to have anti-oxidant, anti-inflammatory effects. However, it is unknown whether it perform anti-fibrotic effect in renal tubular epithelial cells. In this current study, we observed that in human renal tubular epithelial cells (HK2), high glucose induced an increase in transforming growth factor β (TGF-β) production, and upregulated the expressions of fibronectin and collagen I through the TGF-β receptor as verified by administration of TGF-β receptor blocker LY2109761...

INTRODUCTION: One of the most significant clinical features of chronic  kidney disease is renal interstitial fibrosis (RIF). This study aimed  to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral  ureteral obstruction (UUO) surgery on rat or stimulating human  kidney-2 (HK-2) cell with transforming growth factor β1 (TGFβ1).  After modeling, the rats in the SQP low dose group (SQP-L), SQP  middle dose group (SQP-M) and SQP high dose group (SQP-H)  were treated with SQP at 1...

PURPOSE: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. PATIENTS AND METHODS: Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly...

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed the suitability of a fixed-dose regimen of tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients with asthma or healthy participants enrolled in 8 clinical studies (phases 1-3). Tezepelumab exposure-efficacy relationships were analyzed in the phase 3 NAVIGATOR study (NCT03347279), using asthma exacerbation rates over 52 weeks and changes in pre-bronchodilator forced expiratory volume in 1 s at week 52...

INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks...

BACKGROUND: Primary membranous nephropathy (PMN) is an autoimmune glomerular disease. IL-6 is a potential therapeutic target for PMN. Previous clinical studies have demonstrated the effectiveness of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in treating membranous nephropathy. However, the mechanism of action of MFSD remains unclear. METHODS: Serum IL-6 levels were measured in patients with PMN and healthy subjects. The passive Heymann nephritis (PHN) rat model was established, and high and low doses of MFSD were used for intervention to observe the repair effect of MFSD on renal pathological changes and podocyte injury...

Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure-response (ER) analysis, were performed...

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets...

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group...

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set...

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events...

Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm...

Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, and placebo-controlled trials that assessed specific issues of safety related to the continuous use of colchicine in a range of clinical settings to inform physicians, pharmacists, and patients of the absolute risks of continuous use of low-dose colchicine, including among individuals taking statin therapy...

When sarcoidosis needs treatment, pharmacotherapy is usually required. Although glucocorticoids work reliably and relatively quickly for sarcoidosis, these drugs are associated with numerous significant side effects. Such side effects are common in sarcoidosis patients, as the disease frequently has a chronic course and glucocorticoid treatment courses are often prolonged. For these reasons, corticosteroid-sparing and corticosteroid-replacing therapies are often required for sarcoidosis. Unfortunately, many healthcare providers who care for sarcoidosis patients are not familiar with the use of these agents...