Untargeted metabolomics analysis of serum and urine unveils the protective effect of cilastatin on altered metabolic pathways during cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) is one of the most serious complications of cisplatin anticancer therapies. Cilastatin is a highly promising nephroprotective agent to eventually enter clinical use, but its biochemical mechanism is still not fully understood. We have employed an untargeted metabolomics approach based on capillary electrophoresis mass spectrometry (CE-MS) analysis of serum and urine from an in vivo rat model, to explore the metabolic pathways involved in cisplatin-induced AKI and cilastatin nephroprotection. A total of 155 and 76 identified metabolites were found to be significantly altered during cisplatin treatment in urine and serum, respectively. Most of these altered metabolites were either partially or totally recovered by cilastatin and cisplatin co-treatment. The main metabolic pathways disturbed by cisplatin during AKI involved diverse amino acids metabolism and biosynthesis, tricarboxylic acids (TCA) cycle, nicotinate and nicotinamide metabolism, among others. Cilastatin was proved to protect diverse cisplatin-altered pathways involving metabolites related to immunomodulation, inflammation, oxidative stress and amino acid metabolism in proximal tubules. However, cisplatin-altered mitochondrial metabolism (especially, the energy-producing TCA cycle) remained largely unprotected by cilastatin, suggesting an unresolved mitochondrial direct damage. Multivariate analysis allowed effective discrimination of cisplatin-induced AKI and cilastatin renoprotection based on metabolic features. A number of potential serum and urine biomarkers could also be foreseen for cisplatin-induced AKI detection and cilastatin nephroprotection.

Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?

Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked. The primary mechanism(s) by which SGLT2 inhibitors are cardio- and nephroprotective remain to be fully characterized. This paper reviews these suggested mechanisms in the context of the pathophysiology of progressive cardiovascular and kidney diseases in dogs and cats with the goal of predicting which categories of non-diabetic veterinary patients these drugs might be of most benefit.

[Non-pharmacological prevention of chronic kidney disease]. / Prévention non médicamenteuse de la maladie rénale chronique.

Preventing chronic kidney disease (CKD) is a major public health objective. CKD leads to significant cardiovascular morbidity and mortality, with a negative impact on quality of life and significant societal repercussions. Several drugs are effective in preventing and curbing CKD, including blockers of the renin/angiotensin/aldosterone system and inhibitors of the SGLT2 co-transporter. New molecules are currently in clinical trials focusing on the nephro-protection, such as non-steroidal mineralocorticoid receptor antagonists and GPL-1 receptor agonists. In addition to this drug arsenal, CKD prevention also relies on non-pharmacological optimization of hygienic-dietary measures, including smoking avoidance, physical activity and dietetics. The aim of this article is to detail this non-medicinal approach to the prevention and slow down of CKD.

La prévention de la maladie rénale chronique (MRC) est un objectif majeur de santé publique. La MRC engendre, en effet, une morbi-mortalité cardiovasculaire importante, avec un impact négatif sur la qualité de vie et des répercussions sociétales non négligeables. Plusieurs piliers médicamenteux sont efficaces dans la prévention et la freination de la MRC, tels que les bloqueurs du système rénine/angiotensine/aldostérone et les inhibiteurs du co-transporteur SGLT2. De nouvelles molécules sont en cours d'essais cliniques visant la néphro-protection, comme les antagonistes non stéroïdiens du récepteur aux minéralocorticoïdes et les agonistes du récepteur au GPL-1. Outre cet arsenal médicamenteux, la prévention de la MRC repose également sur une optimisation non pharmacologique des mesures hygiéno-diététiques, comprenant l'éviction tabagique, l'activité physique et la diététique. L'objectif de cet article est de détailler cette approche non médicamenteuse dans la prévention et la freination de la MRC.

SGLT2 Inhibitors in Kidney Diseases-A Narrative Review.

Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years, such a role has begun to be assigned to sodium-glucose cotransporter-2 (SGLT2) inhibitors. They increase the amount of glucose excreted in the urine. For this reason, they are currently used as a first-line drug in type 2 diabetes mellitus. Due to their demonstrated cardioprotective effect, they are also used in heart failure treatment. As for the renal effects of SGLT2 inhibitors, they reduce intraglomerular pressure and decrease albuminuria. This results in a slower decline in glomelular filtration rate (GFR) in patients with kidney disease. In addition, these drugs have anti-inflammatory and antifibrotic effects. In the following article, we review the evidence for the effectiveness of this group of drugs in kidney disease and their nephroprotective effect. Further research is still needed, but meta-analyses indicate SGLT2 inhibitors' efficacy in kidney disease, especially the one caused by diabetes. Development of new drugs and clinical trials on specific patient subgroups will further refine their nephroprotective effects.

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury.

The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.

Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110.

The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic properties. The aim of this study was to investigate the anti-inflammatory effect of synaptamide in ischemic AKI. For this purpose, we analyzed the expression of inflammatory mediators and the infiltration of different leukocyte populations into the kidney after injury, evaluated the expression of the putative synaptamide receptor G-protein-coupled receptor 110 (GPR110), and isolated a population of CD11b/c+ cells mainly representing neutrophils and macrophages using cell sorting. We also evaluated the severity of AKI during synaptamide therapy and the serum metabolic profile. We demonstrated that synaptamide reduced the level of pro-inflammatory interleukins and the expression of integrin CD11a in kidney tissue after injury. We found that the administration of synaptamide increased the expression of its receptor GPR110 in both total kidney tissue and renal CD11b/c+ cells that was associated with the reduced production of pro-inflammatory interleukins in these cells. Thus, we demonstrated that synaptamide therapy mitigates the inflammatory response in kidney tissue during ischemic AKI, which can be achieved through GPR110 signaling in neutrophils and a reduction in these cells' pro-inflammatory interleukin production.

The highlights in nephrology in 2023 / Les temps forts en néphrologie en 2023

This article aims to summarize the "Quoi de neuf en néphrologie?" session held at the 2023 SFNDT Congress in Liège and sessions focused on updates regarding IgA nephropathy (NIgA) and ANCA-associated vasculitis. The agenda for the nephrology "Quoi de neuf en néphrologie?" session this year was to review key publications from non-nephrology journals, discussing topics such as nephroprotection, treatment of glomerulopathies (IgA and APOL1), clinical trials on arterial hypertension, urinary lithiasis, and other areas of renal physiology, including glomerular filtration rate estimation.

Cet article a pour but de résumer d'une part la session « Quoi de neuf en néphrologie ? ¼ qui a eu lieu au congrès de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) 2023 à Liège en Belgique, mais également les sessions portant sur les actualités de la néphropathie à IgA (NIgA) et des vascularites associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA). Le cahier des charges du « Quoi de neuf en néphrologie ? ¼ cette année était de reprendre les principaux articles publiés dans des revues hors néphrologie et s'est articulé sur les publications autour de la néphroprotection, du traitement des glomérulopathies (IgA et APOL1), des essais cliniques sur l'hypertension artérielle ou dans la lithiase urinaire, ou dans d'autres champs de la physiologie rénale comme l'estimation du débit de filtration glomérulaire.

[Chronic kidney disease in geriatrics]. / La maladie rénale chronique en gériatrie.

Chronic kidney disease (CKD) affects almost 10% of the world's population, and over 30% of people aged over 70 [1,2]. The overall incidence of treated CKD is stable in France, but continues to rise sharply in people aged over 85 [3]. In its advanced stages, CKD is associated with numerous complications linked to disturbances in water, acid-base and phosphocalcium balance, as well as anemia and increased cardiovascular risk. A better understanding of risk factors, improved practices to promote nephroprotection, and progress in therapeutic education and preparation for suppletive techniques would help reduce this risk.

Natural Flavonoids: Fortifying Renal Defence Mechanism.

BACKGROUND: The kidneys, intricate organs responsible for maintaining fluid and electrolyte balance, are susceptible to damage from diverse nephrotoxic insults, including drugs, toxins, and metabolic disorders. In recent years, flavonoids, bioactive compounds abundant in fruits, vegetables, and herbal extracts, have emerged as promising candidates for renal protection due to their potent antioxidant and anti-inflammatory properties. METHODS: We have collected the data that supported this idea to conduct a comprehensive review by using scientific databases, such as Pub Med ®, ScienceDirect ®, Google Scholar ®, and MEDLINE ®. An attempt was made to refer to all English-language articles published between 2000 to 2020 using keywords like flavonoids potential in nephrotoxicity and nephrotoxicity treatment approaches with herbal remedies. CONCLUSION: This comprehensive review delves into the molecular mechanisms underlying the reno-protective effects of flavonoids. By scavenging reactive oxygen species, inhibiting inflammatory mediators, and modulating intracellular signalling pathways, flavonoids can mitigate oxidative stress and inflammation, thereby preserving renal function and integrity. Preclinical studies have demonstrated the potential of specific flavonoids in ameliorating drug-induced nephrotoxicity, renal ischemia-reperfusion injury, diabetic nephropathy, and other kidney diseases. Furthermore, epidemiological evidence highlights the inverse relationship between flavonoid intake and the risk of developing kidney diseases. Nevertheless, understanding the molecular mechanisms of flavonoids in nephroprotection offers exciting prospects for developing novel therapeutic strategies to combat kidney diseases and promote kidney health.

Secular Trend in GFR Decline in Non-Dialysis CKD Based on Observational Data From Standard of Care Arms of Trials.

RATIONALE & OBJECTIVE: The standard of care (SoC) group of randomized controlled trials (RCTs) is a useful setting to explore the secular trends in kidney disease progression because implementation of best clinical practices is pursued for all patients enrolled in trials. This meta-analysis evaluated the secular trend in the change of glomerular filtration rate (GFR) decline in the SoC arm of RCTs in chronic kidney disease (CKD) published in the last 30 years. STUDY DESIGN: Systematic review and meta-analysis of the SoC arms of RCTs analyzed as an observational study. SETTING & STUDY POPULATIONS: Adult patients with CKD enrolled in the SoC arm of RCTs. SELECTION CRITERIA FOR STUDIES: Phase 3 RCTs evaluating GFR decline as an outcome in SoC arms. DATA EXTRACTION: Two independent reviewers evaluated RCTs for eligibility and extracted relevant data. ANALYTICAL APPROACH: The mean of GFR declines extracted in the SoC arm of selected RCTs were pooled by using a random effects model. Meta-regression analyses were performed to identify factors that may explain heterogeneity. RESULTS: The SoC arms from 92 RCTs were included in the meta-analysis with a total of 32,202 patients. The overall mean GFR decline was-4.00 (95% CI, -4.55 to-3.44) mL/min/1.73m2 per year in the SoC arms with a high level of heterogeneity (I2, 98.4% [95% CI, 98.2-98.5], P<0.001). Meta-regression analysis showed an association between publication year (ß estimate, 0.09 [95% CI, 0.032-0.148], P=0.003) and reduction in GFR over time. When evaluating publication decade categorically, GFR decline was-5.44 (95% CI, -7.15 to-3.73), -3.92 (95% CI, -4.82 to-3.02), and -3.20 (95% CI, -3.75 to -2.64) mL/min/1.73m2 per year during 1991-2000, 2001-2010, and 2011-2023, respectively. Using meta-regression, the heterogeneity of GFR decline was mainly explained by age and proteinuria. LIMITATIONS: Different methods assessing GFR in selected trials and observational design of the study. CONCLUSIONS: In the last 3 decades, GFR decline has decreased over time in patients enrolled in RCTs who received the standard of care. TRIAL REGISTRATION: Registered at PROSPERO with record number CRD42022357704. PLAIN-LANGUAGE SUMMARY: This study evaluated the secular trend in the change in glomerular filtration rate (GFR) decline in the placebo arms of randomized controlled trials (RCTs) that were studying approaches to protect the kidneys in the setting of chronic kidney disease. The placebo groups of RCTs are useful for examining whether the rate of progression of kidney disease has changed over time. We found an improvement in the slope of change in GFR over time. These findings suggest that adherence to standards of kidney care as implemented in clinical trials may be associated with improved clinical outcomes, and these data may inform the design of future RCTs in nephrology.

Protective effect of chicory and/or artichoke leaves extracts on carbon tetrachloride and gamma-irradiation-induced chronic nephrotoxicity in rats.

The prevalence of chronic kidney disease (CKD) is in progress that causes kidney failure, leading to global problems. This manuscript investigated the nephroprotective effects of chicory (CLE) and/or artichoke (ALE) leaves extracts on carbon tetrachloride (CCl4 ) and gamma-irradiation (Rad)-induced chronic nephrotoxicity in rats. Rats were divided into 10 groups (10 animals/group): group 1: control, groups 2-7 rats were treated with CLE, ALE, CLE/ALE, CCl4 , Rad, and CCl4 /Rad, respectively. Groups 8 to 10, rats were intoxicated with CCl4 /Rad, and treated with CLE, ALE, and CLE/ALE extracts, respectively, for 4 weeks. The data demonstrated that CCl4 administration or Rad exposure induced high levels of urea and creatinine, with low levels of total protein and albumin in the serum. However, high levels of malondialdehyde (MDA), nitric oxide (NO), hydrogen peroxide (H2 O2 ), some pro-inflammatory markers such as interleukins (IL-1ß, IL-2, IL-6), TNF-α, NF-κB, the fibrotic marker; TGF-ß1, calcium, and copper, low contents of reduced glutathione (GSH), iron, and zinc, and suppression of the antioxidant enzymes' activity, superoxide dismutase (SOD), and catalase (CAT) were observed. In addition, the Wnt and ß-catenin protein expression ratios were up-regulated in the kidney tissues of the CCl4 , and Rad intoxicated animals. However, the combined treatment CCl4 /Rad augmented these measurements. On the other hand, CLE, ALE, and CLE/ALE treatments demonstrated nephroprotection in the kidney tissues of CCl4 /Rad intoxicated animals, in the order of CLE/ALE>ALE>CLE by ameliorating the investigated parameters. Kidney tissues' histopathological examinations confirmed these results. In conclusion, CLE and/or ALE demonstrated nephroprotection against CCl4 /Rad co-toxicity mediated by down-regulation of renal Wnt/ß-catenin protein expressions.

[Finerenone (Kerendia®), a new weapon against the chronic kidney disease of a patient with type 2 diabetes]. / Le médicament du mois. La finérénone (Kerendia®), une nouvelle arme contre la maladie rénale chronique du patient avec diabète de type 2.

Finerenone, a new nonsteroidal mineralocorticoid receptor antagonist, showed a significant reduction in a primary composite renal outcome in FIDELIO-DKD and a significant reduction in a primary composite cardiovascular outcome in FIGARO-DKD in patients with type 2 diabetes (T2D) and a chronic kidney disease (CKD). In a subsequent analysis that combined these two clinical trials (FIDELITY), the reduction becomes statistically significant when compared to placebo for both outcomes, with a hazard ratio of 0.86 (95 % confidence interval 0.78-0.95; P = 0.0018) for the cardiovascular outcome and 0.77 (0.67-0.88; P = 0.0002) for the renal outcome. Furthermore, all renal events occurred less frequently with finerenone than with placebo, including the progression to end-stage CKD independently of the baseline levels of glomerular filtration rate and albuminuria and regardless of associated medications (including gliflozins). The safety profile was excellent. However, a significant increase in serum potassium level was observed. Even if it is less pronounced than the increase usually seen with spironolactone, the risk of hyperkalemia requires some caution regarding both patient selection and monitoring. Finerenone (Kerendia®) is indicated in the treatment of CKD with albuminuria in adult patients with T2D. In Belgium, it is reimbursed with conditions in combination with a renin-angiotensin blocker.

La finérénone, un nouvel antagoniste non stéroïdien du récepteur des minéralocorticoïdes, a montré, dans deux grandes études réalisées chez des patients avec un diabète de type 2 (DT2) et une maladie rénale chronique (MRC), une réduction significative du critère composite rénal dans FIDELIO-DKD et du critère composite cardiovasculaire dans FIGARO-DKD. Dans une analyse combinant les deux études (FIDELITY), la réduction est statistiquement significative dans le groupe finérénone par rapport au groupe placebo pour les deux critères, avec un hasard ratio de 0,86 (intervalle de confiance à 95 % 0,78-0,95; P = 0,0018) pour le critère cardiovasculaire et de 0,77 (0,67-0,88; P = 0,0002) pour le critère rénal. De plus, tous les événements rénaux surviennent moins fréquemment sous finérénone que sous placebo, y compris la progression vers l'insuffisance rénale terminale et ce, indépendamment du niveau du débit de filtration glomérulaire et de l'albuminurie à l'inclusion dans les essais ou des traitements associés (y compris les gliflozines). Le profil de sécurité est excellent, avec cependant une élévation de la kaliémie. Si elle est moindre que celle observée avec la spironolactone, elle nécessite néanmoins des précautions d'usage en termes de sélection des patients et de leur surveillance. La finérénone (Kerendia®) est indiquée dans le traitement de la MRC avec albuminurie chez le patient adulte avec DT2 et est remboursée en Belgique, sous conditions, en association avec un bloqueur du système rénine-angiotensine.

[State-of-the-art trends in the treatment of immune-mediated inflammatory kidney diseases: Translation of the fundamental science into clinical practice. A review].

Immune-mediated kidney diseases like glomerulonephritis and tubulointerstitial nephritis are not the most common cause of chronic kidney disease in the population, however the difficulties in their management, as well as a more rapid deterioration of kidney function, compared to diabetes mellitus and hypertension, justify the importance of this problem for internal medicine. Due to the fundamental discoveries in pathology and to the introduction of various methods of laboratory and instrumental investigation in the second half of the XX century substantial progress was made in the diagnostic approaches and treatment of these conditions. State-of-the-art diagnostic approach requires complex evaluation of the clinical, laboratory and morphological data to identify the nosological form of the disease. The accumulation of knowledge in the field of diseases' pathogenesis led to the revision of the current classification of glomerulonephritis that should be based on the immunopathogenesis of these conditions. The following phenotypes were suggested: autoimmunity-related, autoinflammation-related, alloimmunity-related, infections-related, and monoclonal gammopathy-related. The assessment of disease activity and chronicity in the kidney tissue should be mandatory. Personalized selection of the optimal treatment modality on the basis of the diagnosis, severity, and individual features of the patient is currently possible. The leading trends include rational prescription of glucocorticoids (steroid-sparing regimens) and cytotoxic agents, e.g. cyclophosphamide, as well as the introduction of multitarget regimens that include biologic agents or small molecules selectively suppressing B-cells or various complement pathways. Another mandatory component of treatment on par with immune suppression is nephroprotective therapy, which currently comprises not only traditional renin-angiotensin-aldosterone antagonists, but also endothelin receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Current guidelines emphasize the importance of the non-pharmacological interventions for the implementation of the nephroprotective strategy. Rational combination of the aforementioned approaches allows for the optimization of the management of patients with immune-mediated kidney diseases, although it requires high competencies and strict adherence to the principles of the evidence-based medicine from the healthcare providers.

The Nephroprotective Potential of Brassica nigra Sprout Hydroalcoholic Extract against Carbon Tetrachloride-Induced Renal Toxicity in Rats.

The nephroprotective potential of the Brassica nigra sprout (BNS) hydroalcoholic extract against carbon tetrachloride (CCl4)-induced renal toxicity in rats was the object of this study. B. nigra sprouts were prepared in the lab to monitor the bio-changes in bioactive compounds during the sprouting for up to 7 days at 17 ± 1 °C and 90% relative humidity. Subsequently, 6-day sprouts of B. nigra were selected according to their phenolics and antioxidant activity, extracted, and examined for their nephroprotective and antioxidative stress potential at 250 and 500 mg sprout extracts kg-1 bw, in vivo. Weight gain, organ weight, lipid profile, atherogenic index, kidney functions, and oxidative stress biomarkers were assessed. The results indicated that the most proficient treatment for weight gain improvement was BNS extract at 500 mg kg-1. BNS at 250 mg kg-1 was remarked as the lowest weight gain enhancer compared to the NR group. A significant increase in TG, TC, LDL-c, and VLDL-c levels in the rats with CCl4-induced renal toxicity, and a significant decrease in HDL level, was noted. The administration of the BNS extract at 250 and 500 mg kg-1 considerably attenuated TG, TC, LDL-c, and VLDL-c levels, compared to the NR group. The most efficient treatment for improving the lipid profile was the BNS extract at 500 mg kg-1, even better than 250 mg kg-1. Administrating the BNS extract substantially attenuated the alterations in the creatinine, urea, and BUN caused by the CCl4 injection. The most efficient improvement was markedly recorded with the BNS extract at 500 mg kg-1, compared to the NR group. The rats treated with the BNS extract showed significant enhancement in GSH, CAT, and SOD activities and a considerable reduction in MDA levels. Administering the BNS extract at 250 and 500 mg kg-1 can efficiently reverse CCl4 inhibition of antioxidant enzyme activities, significantly increase GSH, CAT, and SOD, and decrease the MDA levels dose-dependently. The BNS extract at 250 and 500 mg kg-1 exhibits nephroprotection and antioxidative stress in a dose-dependent matter. The total nephroprotection % was recorded at 65.18% and 99.21% for rats treated with 250 and 500 mg kg-1, respectively. These findings could prove and potentiate the nephroprotective activities of the BNS extract in the range of the given doses. Further clinical studies are highly recommended for confirming the nephroprotection efficiency of the B. nigra sprout.

[Nephroprotection: General principles and application to the patients with cancers - when nephroprotection is essential for oncological care plan]. / Néphroprotection : principes généraux et application au patient de cancérologie ­ quand la protection du rein est indispensable à la bonne conduite du plan de soin oncologique.

Nephroprotection is a set of recommendations that aim to prevent the risks of acute and/or chronic renal failure and to limit the progression of renal failure towards an end stage. Nephroprotection is not limited to nephrology and applies to all patients at risk of renal failure. Cancer patients are particularly at risk of developing intrinsic and extrinsic renal failure, as well as the toxicity of specific treatments. However, they are poorly included in nephroprotection studies. Thus, current guidelines have not been adapted to these pathologies and oncology-specific comorbidities, such as malnutrition or prognosis, are often not taken into account. In this article, we review the established recommendations by transposing them to the cancer patient as a whole. In addition to the reminder of hygiene and dietary rules to control blood pressure and diabetes, we discuss the importance of therapeutic education, iatrogeny and treatment options to control renal failure in this context. The lack of clearly established data in cancer confirms the needs to strengthen links between oncologists, hematologists and nephrologists and reinforces the emergence of onco-nephrology as a new discipline.

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist.

Diabetic kidney disease, a common complication in patients with type 2 diabetes mellitus, is associated with a markedly increased morbidity and mortality, especially of cardiovascular origin, and faster progression to end-stage renal disease. To date, reducing cardiovascular and renal risk in this population was based on strict control of cardiovascular risk factors and the renin-angiotensin system blockade. More recently, sodium-glucose cotransporter type 2 inhibitors have demonstrated to offer cardiovascular and renal protection, but the residual risk remains high and their antihyperglycemic efficacy is limited in moderate-severe CKD. Therefore, drugs with a potent antihyperglycemic effect, independent of the glomerular filtration rate, with a low risk of hypoglycemia, that reduce weight in overweight/obese patients and that provide cardiovascular and renal protection, such as GLP-1 receptor agonists, are needed. However, these drugs require subcutaneous administration, which may limit their early use. The recent availability of oral semaglutide may facilitate the early introduction of this family with proven cardiovascular and renal benefits and excellent safety profile. In this review the family is analyzed as well as their cardiovascular and renal effects.

Phytocompounds from Amazonian Plant Species against Acute Kidney Injury: Potential Nephroprotective Effects.

There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury-caused by several factors, including ischemia, toxins, and inflammation-has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. This article is a brief review of phytocompounds with potential nephroprotective effects against acute kidney injury (AKI). The classes of Amazonian plant compounds with significant biological activity most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids, and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although with insufficiently explored potential, mainly in the face of AKI, a clinical condition with high morbidity and mortality.

Agonistas del receptor de péptido similar al glucagón tipo 1 (GLP-1) en el manejo del paciente con diabetes mellitus tipo 2. Una aproximación para el nefrólogo / Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: An approach for the nephrologist

La enfermedad renal diabética, frecuente en pacientes con diabetes mellitus tipo 2, se asocia con un marcado incremento de la morbimortalidad, especialmente cardiovascular, y de progresión a enfermedad renal crónica terminal. Hasta la fecha la reducción del riesgo cardiovascular y renal en esta población se ha basado en el control estricto de los factores de riesgo cardiovascular y en el uso de inhibidores del sistema renina-angiotensina. Mas recientemente los inhibidores del cotransportador sodio-glucosa tipo 2 han demostrado ofrecer protección cardiovascular y renal, pero el riesgo residual sigue siendo alto y su eficacia antihiperglucemiante es limitada en ERC moderada-severa. Por ello se precisan fármacos con un potente efecto antihiperglucemiante, independiente del filtrado glomerular, con bajo riesgo de hipoglicemia, que reduzcan el peso en pacientes con sobrepeso/obesidad y que proporcionen una protección cardiovascular y renal, como los agonistas del receptor de GLP-1. Sin embargo, estos fármacos precisan de su administración subcutánea, lo que puede limitar su uso temprano. La reciente disponibilidad de semaglutida oral puede ayudar a la introducción precoz de esta familia con beneficios cardiovasculares y renales probados y excelente perfil de seguridad. En esta revisión se describe la familia y sus efectos cardiovasculares y renales. (AU)

Diabetic kidney disease, a common complication in patients with type 2 diabetes mellitus, is associated with a markedly increased morbidity and mortality, especially of cardiovascular origin, and faster progression to end-stage renal disease. To date, reducing cardiovascular and renal risk in this population was based on strict control of cardiovascular risk factors and the renin–angiotensin system blockade. More recently, sodium-glucose cotransporter type 2 inhibitors have demonstrated to offer cardiovascular and renal protection, but the residual risk remains high and their antihyperglycemic efficacy is limited in moderate-severe CKD. Therefore, drugs with a potent antihyperglycemic effect, independent of the glomerular filtration rate, with a low risk of hypoglycemia, that reduce weight in overweight/obese patients and that provide cardiovascular and renal protection, such as GLP-1 receptor agonists, are needed. However, these drugs require subcutaneous administration, which may limit their early use. The recent availability of oral semaglutide may facilitate the early introduction of this family with proven cardiovascular and renal benefits and excellent safety profile. In this review the family is analyzed as well as their cardiovascular and renal effects. (AU)

Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations.

Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys. Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers. Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis. Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA's antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes. Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA's potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques.

Nephroprotective Properties of Antidiabetic Drugs.

Chronic kidney disease (CKD) is associated with increased morbidity and mortality, especially from cardiovascular (CV) causes, and especially in people with diabetes mellitus (DM). Already the presence of DM increases CV risk and potentiates the risk of CKD. Therefore, besides glycemic control, prevention and treatment of CKD to slow its progression are of clinical importance. A significant nephroprotective effect of novel antidiabetic drugs, namely sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide 1 receptor agonists (GLP1-RA), has been shown on top of their glucose-lowering effects and was confirmed in cardiovascular outcome trials. GLP1-RA mainly reduced the risk of macroalbuminuria, whereas SGLT2-I were also associated with a lower risk of declining glomerular filtration rate (GFR) over time. The nephroprotective effects of SGLT2-I are also evident in people without DM. According to current guidelines, SGLT2-I and/or GLP1-RA are recommended for people with DM who have chronic kidney disease and/or increased cardiovascular risk. However, other antidiabetic drugs offer nephroprotective properties, which will also be discussed in this review.