Advancing kidney transplant outcomes: the role of urinary proteomics in graft function monitoring and rejection detection.

INTRODUCTION: Kidney transplantation significantly improves the lives of those with end-stage kidney disease, offering best alternative to dialysis. However, transplant success is threatened by the acute and chronic rejection mechanisms due to complex immune responses against the new organ. AREAS COVERED: The ongoing research into biomarkers holds promise for revolutionizing the early detection and monitoring of the graft health. Liquid biopsy techniques offer a new avenue, with several diagnostic, predictive, and prognostic biomarkers showing promise in detecting and monitoring kidney diseases and an early and chronic allograft rejection. EXPERT OPINION: Evaluating the protein composition related to kidney transplant results could lead to identifying biomarkers that provide insights into the graft functionality. Non-invasive proteomic biomarkers can drastically enhance clinical outcomes and change the way how kidney transplants are evaluated for patients and physicians if they succeed in this transition. Hence, the advancement in proteomic technologies, leads toward a significant improvement in understanding of the protein markers and molecular mechanisms linked to the outcomes of kidney transplants. However, the road from discovery to the use of such proteins in clinical practice is long, with a need for continuous validation and beyond the singular research team with comprehensive infrastructure and across research groups collaboration.

Hyponatremia - Treatment standard 2024.

Hyponatremia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as 100 mL IV bolus or continuous infusion depends on the severity and persistence of the symptoms, and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatremia. In asymptomatic mild hyponatremia, an adequate solute intake with an initial fluid restriction (FR) of 500 mL/d adjusted according to the serum sodium levels is preferred. Almost half of the syndrome of inappropriate diuresis hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered as most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatremia is lacking. Oral urea is considered as very effective and safe treatment. Mild and asymptomatic hyponatremia is treated with adequate solute intake (salt and protein) and an initial FR with adjustments based on serum sodium levels. Specific treatment with vaptans may be considered in either euvolemic or hypervolemic patients with high ADH activity. In order to ensure optimal patient outcome, a close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in decision making process for specific treatment and eventual overcorrection consequences. According to the guidelines, a gradual correction and clinical evaluation is preferable over the rapid normalization of serum sodium towards the laboratory reference ranges.

Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a substantial complication of type 2 diabetes (T2D), presenting challenges in chronic kidney disease (CKD) management. In addition to traditional and recent therapies, including angiotensin, converting enzyme (ACE) inhibitors, angiotensin receptor blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, the evolution of antihyperglycemic treatments has introduced a promising agent, glucagon-like peptide-1 receptor agonist (GLP-1RA) for the management of DKD. GLP-1RAs enhance insulin release and reduce glucagon release, offering a novel approach to DKD management. This review analyzes the molecular pathways through which GLP1-RAs confer renal protection in T2D and DKD, which are complex and multifaceted. They include modulation of renal hemodynamics, antioxidative and anti-inflammatory actions, metabolic regulation, and direct cellular effects. These mechanisms highlight GLP1-RA's potential as a therapeutic option for glycemic control and direct or indirect renal function protection in diabetic patients, emphasizing the potentiality of GLP-1RAs for dual therapy, with cardiovascular and renal protection as a holistic approach. Clinical evidence supports GLP-1RAs in reducing albuminuria and enhancing kidney outcomes, highlighting their value in a comprehensive DKD management strategy.

Sodium and water dynamics in the progression of chronic kidney disease: mechanisms and clinical significance.

AIM: Lifestyle modifications can postpone the progression of chronic kidney disease toward its terminal stage. This mini-review aims to explore the impact of salt and water intake on the progression of chronic kidney disease (CKD) and provide insights into the optimal consumption levels to preserve the glomerular filtration rate. METHODS: We reviewed relevant literature to examine the association between salt and water consumption and CKD progression. Our analysis includes discussions on the pathophysiology, findings from clinical trials, and recommended intake guidelines. RESULTS: Sodium intake, often linked to cardiovascular risk and CKD progression, has shown a complex J-shaped association in some studies, leading to uncertainty about the ideal salt intake level. Sodium and fluid retention are key factors contributing to hypertension, a well-established risk factor for CKD progression. Low-sodium diets have demonstrated promise in reducing blood pressure and enhancing the effects of renin-angiotensin-aldosterone system inhibitors in non-dialysis CKD patients. However, a debate persists regarding the independent effect of salt restriction on CKD progression. Despite medical recommendations, salt consumption remains high among CKD patients. Additionally, the role of water consumption in CKD remains controversial despite its established benefits for CKD prevention in the general population. CONCLUSION: Lifestyle modifications involving salt and water intake can influence the progression of CKD. While low-sodium diets have shown potential for mitigating hypertension and proteinuria in non-dialysis CKD patients, their independent impact on CKD progression warrants further investigation. The role of water consumption in CKD remains uncertain, and there is a need for additional research in this area. Clinicians should consider individualized dietary recommendations for CKD patients to help preserve the glomerular filtration rate and improve overall outcomes.

A New Hope on the Horizon for Kidney and Cardiovascular Protection with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Mineralocorticoid Receptor Antagonists in Type 2 Diabetic and Chronic Kidney Disease Patients.

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). In addition, the cardiovascular prevalence in diabetic patients is around 32.2%, with a two-fold increased mortality risk compared to those without diabetes. Recent investigations have shed light on the promising cardioprotective and nephroprotective benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) for individuals with T2D. The evidence robustly indicates that SGLT2i and GLP-1RA significantly reduce the risk of CKD and cardiovascular disease (CVD), all while effectively managing blood glucose levels. Furthermore, combining SGLT2i with nsMRAs amplifies the benefits, potentially offering a more profound reduction in cardiovascular and renal outcomes. The data analysis strongly supports the integration of these pharmacological agents in the management strategies for CKD and CVD prevention among T2D patients, highlighting the importance of awareness among nephrologists, especially in regions with limited healthcare resources.

Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease.

The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood-brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain-gut-kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain-gut-kidney axis.

The Current State of Nuclear Nephrology in Modern Medicine.

Glomerular filtration rate (GFR) is the most reliable parameter of renal function. Regarding the complexity of the gold standard inulin clearance, different estimating equations have been developed with CKD-EPI creatinine equation recommended as the most reliable one. In some clinical situations where creatinine based equations might not be valid, alternative methods are needed. Nuclear medicine methods for measuring GFR with 51Cr EDTA and 99mTc DTPA have been widely used for decades. There are different methodologies for the measurement of kidney function with radiopharmaceuticals: urinary clearance, plasma clearance, multiple plasma sampling, slope intercept, single sample plasma equation, slope only, and the gamma camera-based method. Greater precision of measuring GFR is needed in certain clinical situations. The most common are diagnosis and follow up of chronic kidney disease and definition of the beginning of replacement therapy. The assessment of renal function is also important for potential kidney donors. In recent years, with the introduction of new chemotherapeutic drugs and targeted therapy, oncologic patients treated with nephrotoxic drugs have become more commonly referred for measuring GFR. The monitoring of renal function is important during treatment in order to detect the transformation from reversible acute kidney injury to irreversible chronic kidney disease as well as in the cases of renal insufficiency reduce the dosage and prevent accumulation of the drug and avoid dosage related toxic effects. Assessment of kidney function using measured mGFR will be an important milestone in the creation of more accurate and expanding personalized medicine principle in current onconephrology practice.

Predictive Admission Risk Factors, Clinical Features and Kidney Outcomes in Covid-19 Hospitalised Patients with Acute Kidney Injury.

Introduction: In COVID-19 patients, acute kidney injury (AKI) is recognized as a cause of high mortality. The aim of our study was to assess the rate and the predictors of AKI as well as survival among COVID-19 patients. Methods: We analyzed clinical and laboratory admission data, predictors of AKI and outcomes including the need for renal replacement therapy (RRT) and mortality at 30 days. Results: Out of 115 patients, 62 (53.9%) presented with AKI: 21 (33.9%) at stage 1, 7(11.3%) at stage 2, and 34 (54.8%) at stage 3. RRT was required in 22.6% of patients and was resolved in 76%. Pre-existing CKD was associated with a 13-fold risk of AKI (p= 0.0001). Low albumin (p = 0.017), thrombocytopenia (p = 0.022) and increase of creatine kinase over 350UI (p = 0.024) were independently associated with a higher risk for AKI. Mortality rates were significantly higher among patients who developed AKI compared to those without (59.6% vs 30.2%, p= 0.003). Low oxygen blood saturation at admission and albumin were found as powerful independent predictors of mortality (OR 0.937; 95%CI: 0.917 - 0.958, p = 0.000; OR 0.987; 95%CI: 0.885-0.991, p= 0.024, respectively). Longer survival was observed in patients without AKI compared to patients with AKI (22.01± 1.703 vs 16.69 ± 1.54, log rank p= 0.009). Conclusion: Renal impairment is significant in hospitalized COVID-19 patients. The severity of the disease itself is emphasized as main contributing mechanism in the occurrence of AKI, and lower blood saturation at admission is the strongest mortality predictor, surpassing the significance of the AKI itself.