369 research outputs found
Pharmacokinetic relevance of glomerular hyperfiltration for drug dosing
No full textIn chronic kidney disease (CKD) patients, hypofiltration may lead to the accumulation of drugs that are cleared mainly by the kidney and, vice versa, hyperfiltration may cause augmented renal excretion of the same drugs. In this review we mainly focus on the issue of whether hyperfiltration significantly impacts the renal clearance of drugs and whether the same alteration may demand an up-titration of the doses applied in clinical practice. About half of severely ill, septic patients and patients with burns show glomerular hyperfiltration and this may lead to enhanced removal of drugs such as hydrophilic antibiotics and a higher risk of antibiotic treatment failure. In general, hyperfiltering obese individuals show higher absolute drug clearances than non-obese control subjects, but this depends on the body size descriptor adopted to adjust for fat excess. Several mechanisms influence pharmacokinetics in type 2 diabetes, including renal hyperfiltration, reduced tubular reabsorption and augmented tubular excretion. However, no consistent pharmacokinetic alteration has been identified in hyperfiltering obese subjects and type 2 diabetics. Non-vitamin K antagonist oral anticoagulants (NOACs) have exhibited lower plasma concentrations in hyperfiltering patients in some studies in patients with atrial fibrillation, but a recent systematic review failed to document any excess risk for stroke and systemic embolism in these patients. Hyperfiltration is common among severely ill patients in intensive care units and drug levels should be measured whenever possible in these high-risk patients to prevent underdosing and treatment failure. Hyperfiltration is also common in patients with obesity or type 2 diabetes, but no consistent pharmacokinetic alteration has been described in these patients. No NOAC dose adjustment is indicated in patients with atrial fibrillation being treated with these drugs
New trials in resistant hypertension: mixed blessing stories
No full textResistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive drug combinations, including diuretics. Renal denervation is another option for treatment-resistant hypertension. New compounds targeting different pathways involved in RH-including inhibitors of aminopeptidase A, endothelin antagonists and selective aldosterone synthase inhibitors-have been tested in clinical trials in this condition. The centrally acting drug firibastat, targeting the brain renin-angiotensin system, failed to demonstrate significant effectiveness in reducing blood pressure (BP) in patients with difficult-to-treat and RH in the Firibistat in Resistant Hypertension (FRESH) trial. Aprocitentan, a dual endothelin A and B receptor antagonist, showed a moderate but statistically significant decrease in BP in patients with RH in the Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension (PRECISION) trial. However, concerns remain about potential adverse events, such as fluid retention. The use of baxdrostat, a selective aldosterone synthase inhibitor, showed promising results in reducing BP in patients with treatment-resistant hypertension in the Baxdrostat in Resistant Hypertension (BrigHTN) trial. However, a subsequent trial, HALO, failed to meet its primary endpoint. The unexpected results may be influenced by factors such as patient adherence and white-coat hypertension. Despite the disappointing results from HALO, the potential benefits of inhibiting aldosterone synthesis remain to be fully understood. In conclusion, managing RH remains challenging, and new compounds like firibastat, aprocitentan and baxdrostat have shown varied effectiveness. Further research is needed to improve our understanding and treatment of this condition
Thiazide diuretics are back in CKD: the case of chlorthalidone
No full textSodium and volume excess is the fundamental risk factor underlying hypertension in chronic kidney disease (CKD) patients, who represent the prototypical population characterized by salt-sensitive hypertension. Low salt diets and diuretics constitute the centrepiece for blood pressure control in CKD. In patients with CKD stage 4, loop diuretics are generally preferred to thiazides. Furthermore, thiazide diuretics have long been held as being of limited efficacy in this population. In this review, by systematically appraising published randomized trials of thiazides in CKD, we show that this class of drugs may be useful even among people with advanced CKD. Thiazides cause a negative sodium balance and reduce body fluids by 1–2 l within the first 2–4 weeks and these effects go along with improvement in hypertension control. The recent CLICK trial has documented the antihypertensive efficacy of chlorthalidone, a long-acting thiazide-like diuretic, in stage 4 CKD patients with poorly controlled hypertension. Overall, chlorthalidone use could be considered in patients with treatment-resistant hypertension when spironolactone cannot be administered or must be withdrawn due to side effects. Hyponatremia, hypokalaemia, volume depletion and acute kidney injury are side effects that demand a vigilant attitude by physicians prescribing these drugs. Well-powered randomized trials assessing hard outcomes are still necessary to more confidently recommend the use of these drugs in advanced CKD
Low Dosage Ingestion of Chlorpyrifos Methyl Exposes to Acute Pancreatitis and Multiple Organ Failure: Role of Alpha Amylase
No full textThe Chlorpyrifos-methyl belongs to the organophosphorus pesticides, widely used in agriculture and for domestic gardening in several European countries. Its toxic action is associated with the inhibition of the enzyme acetylcholinesterase, which controls the levels of acetylcholine. Acute pancreatitis and hyperamylasemia are both possible consequence to a severe intoxication by Chlorpyrifos-methyl, however few cases are reported in the literature and they reported intoxication by high dosage of pesticide. \nIn this case report, we suggest that even a slight dosage of pure Chlorpyrifos-methyl can cause pancreatic damage with the concrete risk of pump failure condition and multi-organs failure related to the processes of cytopathic hypoxia and of cellular oxidative stress. Finally, a prognostic role is proposed to the alpha-amylase, to evaluate the effectiveness of the pharmacological therap
The legacy effect of a home walking exercise programme in kidney failure patients on dialysis
No full textBackground: The EXerCise Introduction To Enhance performance (EXCITE) trial (J Am Soc Nephrol 28: 1259-1268, 2017) in dialysis patients showed that a 6-month home walking exercise programme improves physical function and two dimensions of the Kidney Disease Quality of Life Short Form (KDQOLSF-SFTM) questionnaire. Whether improvements in physical function achieved by exercise interventions are maintained in the long term has never been tested in the dialysis population. Methods: In this post-trial study embedded in the EXCITE trial, we tested the response to the 6 min walking test (6MWT) and the 5-time Sit-To-Stand (5STS) tests and the KDQOLSF-SFTM from the 6th month (end of the trial) to the 36th month. Results: Among the 227 patients of the EXCITE trial cohort, 162 underwent at least three out of four testing visits (baseline, 6, 18 and/or 36 months) contemplated by the study protocol and 89 during all four testing visits. In the primary analysis by the linear mixed model, the gain in walking distance achieved in the 6th month in the exercise group [between-arms difference: +36 m, 95% confidence interval (CI): 22-51, P < .001] was maintained at the 18th month (between-arms difference: +37 m, 95% CI: 19-57, P < .001) and reduced to 23 m (95% CI: -4 to 49 meters, P = .10) at the 36th month. Overall, the post-trial difference in walking distance trajectories between the two study arms was highly significant (P = .004). Furthermore, the walking distance changes at the 6th (r = 0.34, P = .018) and 18th month (r = 0.30, P = .043) were directly related to the number of structured exercise sessions completed during the trial (i.e. the first 6 month). No such effect was registered in the response to the 5STS or in quality of life as measured by the KDQOLSF-SFTM. Conclusions: In dialysis patients, the benefits of a 6-month structured walking programme outlast the duration of the intervention and postpone the loss of walking performance which naturally occurs in this population, but does not affect the quality of life (QoL) and the response to the STS test
Advanced chronic kidney disease coexisting with heart failure: navigating patients' management
No full textChronic kidney disease (CKD) and heart failure (HF) are interrelated, mutually exacerbating conditions. HF in patients with moderate to severe CKD poses unique clinical problems. Indeed, considerations related to specific concomitant derangements, such as vascular calcification, inflammation, and proteinuria, inform and demand personalized treatment strategies. Pharmacological interventions, including renin–angiotensin system antagonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors and novel mineralocorticoid receptor blockers are valuable in managing these complex conditions, although frequently difficult or impossible to use in advanced kidney disease. Precision medicine, innovative treatments, and the incorporation of digital health tools, artificial intelligence, remote monitoring, and advanced imaging techniques into patient care are redesigning the scenario of HF associated with CKD. AI-driven predictive analytics for early detection of decompensation, telemedicine for remote consultations, and electronic health records with decision-support systems. These innovations enhance personalized treatment, improve early intervention, and optimize disease management, ultimately leading to better outcomes for patients with HF and CKD. Collaborative care models are being implemented and evaluated to advance the management of such conditions. Thus, the integration of novel therapeutic approaches and personalized medicine holds promise for improving patient outcomes, while ongoing research is essential to enabling innovation in this area. Here we review the current management of concomitant kidney disease and HF, highlighting areas for proposed future refinements
The effect of a ketogenic diet on weight loss in CKD: a randomized controlled trial in obese stage G1-3a CKD patients
No full text: This study describes a multicentre randomized controlled trial comparing the effects of a ketogenic diet with a low-energy standard diet containing 0.8 g/kg/day on weight loss and metabolic alterations in adult patients with mild-to-moderate non-diabetic chronic kidney disease (CKD) and mild-to-severe obesity. The study is being conducted to understand the impact of the ketogenic diet on weight loss in these patients, as the existing evidence on the ketogenic diet's effect in CKD patients is limited and inconclusive. The study will enrol mild-to moderate adult CKD patients (Stages G1-3a) with albumin to creatinine ratio ≥200 mg/g, without diabetes, with obesity (body mass index ≥30 kg/m2), and stable body weight and estimated glomerular filtration rate from at least 3 months. The primary outcome will be weight loss at 6 months, and secondary outcomes will include adherence to prescribed dietary regimens, body composition changes, changes in standardized blood pressure measurements, metabolic parameters, lipid profile, liver profile, mineral bone disease biomarkers, and changes in renal function and albuminuria. The findings of this study will contribute to a better understanding of the potential benefits and risks of the ketogenic diet in CKD patients with obesity. The results will help guide future research on the ketogenic diet and renal health
Decongestion in patients with advanced chronic kidney disease coexisting with heart failure
No full textHeart failure (HF) and chronic kidney disease (CKD) are closely interconnected conditions. Congestion, a central element in HF and CKD pathophysiology, progresses from haemodynamic changes to pulmonary oedema, with asymptomatic pulmonary congestion and an isolated increase in brain natriuretic peptide (BNP) as an intermediate step. Management strategies include sodium restriction, diuretics and emerging technologies for fluid monitoring. Diuretics, while essential, present challenges such as resistance and side effects, necessitating combination therapies and alternatives, like SGLT-2 inhibitors and, in special cases, ultrafiltration. Personalized approaches are critical to improving clinical outcomes in HF and CKD
The bidirectional link between left ventricular hypertrophy and chronic kidney disease. A cross lagged analysis
No full textBackground:Heart failure (HF) is known to reduce glomerular filtration rate (GFR), while chronic kidney disease (CKD) significantly increases the risk of left ventricular hypertrophy (LVH) and HF. Although these connections have been explored in separate studies, comprehensive research examining the mutual links between CKD and LVH progression is lacking.Methods:Our study investigates the longitudinal relationship between estimated GFR (eGFR) and left ventricular mass index (LVMI) in a cohort of 106 CKD patients across stages G1-5. Using a cross-lagged model, we paired each predictor (eGFR or LVMI) with subsequent outcome measurements, adjusting for previous values to ensure accuracy. Over a three-year follow-up period, we analyzed 257 paired LVMI and eGFR measurements.Results:At baseline, the median eGFR was 54 ml/min/1.73 m2, and the LVMI was 134 ± 48 g/m2, with a 62% prevalence of LVH. Our adjusted models revealed that a decrease in eGFR by 1 ml/min/1.73 m2 predicted an increase in LVMI of 1.12 g/m2 (95% CI: 0.71-1.54, P < 0.001). In contrast, high LVMI did not predict a reduction in eGFR over time. This analysis highlights a significant risk of LVH worsening due to GFR loss, while the reverse risk does not achieve statistical significance.Conclusions:Although these observational analyses cannot establish causality, they suggest that the risk of cardiomyopathy driven by kidney disease in stable CKD patients may be more substantial than the risk of CKD progression driven by heart disease. This insight underscores the importance of monitoring kidney function to manage cardiovascular risk in CKD patients
- …
