Integrated Care Model by the Village Health Volunteers to Prevent and Slow down Progression of Chronic Kidney Disease in a Rural Community, Thailand.

INTRODUCTION: Chronic kidney disease (CKD) is a major health problem in Thailand and health behaviors are central to its risk and progression. Because of the shortage of healthcare personnel, village health volunteers (VHVs) have been collaborating in the primary health care system. However, the contribution of VHVs to CKD reduction has not been evaluated yet. This study aimed to evaluate the efficacy of the VHV-integrated model in preventing and slowing down CKD and its risk factors. METHODS: The population-based cohort study was conducted in a rural community of Thailand between 2017 and 2019. Baseline clinical and behavioral characteristics including CKD, diabetes, hypertension, and other high-risk factors of the participants were collected. The integrated care model was initiated by the multidisciplinary care team that facilitated, empowered, and trained VHVs targeting risk factors of CKD, health literacy, and health promotion. Then the participants were educated and trained for lifestyle modification and were monitored continuously for 18 months by VHVs. Changes in the CKD risk factors, and kidney functions before and after the application of integrated care model were compared. RESULTS: A total of 831 subjects participated in the study with an average age of 57.5 years, and 69.5% were female. Among them, 222 participants (26.7%) were diagnosed as having CKD, the vast majority (95%) of which were in the early stages (G1-G3 and A1-A2). CKD risk factors such as high salt intake, smoking, alcohol consumption, self-NSAID (non-steroidal anti-inflammatory drugs) use were significantly decreased after application of the care model. Also, hemoglobin A1c was significantly reduced in diabetic patients, and blood pressure was controlled better than before in the hypertensive patients. Most importantly, a decline of estimated glomerular filtration rate of the CKD group was improved and lower than the non-CKD group. CONCLUSION: The integrated care model through VHV significantly attenuated the risk factors associated with CKD in the general and high-risk population and effectively slowed down the progression of CKD.

Improving Chronic Kidney Disease Risk Factor Screening Among Older Adults: A Quality Improvement Project.

Evidence-based screening tools and guidelines for chronic kidney disease (CKD) are inconsistently utilized in primary care. A quality improvement (QI) project evaluated the impact of a CKD education workshop for interprofessional clinical staff and the implementation of the Screening for Occult Renal Disease (SCORED) risk assessment tool to improve identification of patients at risk for CKD in a primary care clinic. Results of the SCORED risk assessment indicated 92% of patient participants were at high risk for CKD. Overall, the SCORED risk assessment reinforced CKD risk factor knowledge among health care professionals.

Higher potassium intake is associated with a lower risk of chronic kidney disease: population-based prospective study.

BACKGROUND: High-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear. OBJECTIVE: The objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD. METHODS: This is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes. RESULTS: At baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2-4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome. CONCLUSIONS: Higher urinary potassium excretion and intake were associated with a lower risk of incident CKD.

Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis.

Chronic kidney disease (CKD) is characterized by a gradual loss of kidney function and affects ~13.4% of the global population. Progressive tubulointerstitial fibrosis, driven in part by proximal tubule (PT) damage, is a hallmark of late stages of CKD and contributes to the development of kidney failure, for which there are limited treatment options. Normal kidney development requires signaling by vitamin A (retinol), which is metabolized to retinoic acid (RA), an endogenous agonist for the RA receptors (RARα, ß, γ). RARα levels are decreased in a mouse model of diabetic nephropathy and restored with RA administration; additionally, RA treatment reduced fibrosis. We developed a mouse model in which a spatiotemporal (tamoxifen-inducible) deletion of RARα in kidney PT cells of adult mice causes mitochondrial dysfunction, massive PT injury, and apoptosis without the use of additional nephrotoxic substances. Long-term effects (3 to 4.5 mo) of RARα deletion include increased PT secretion of transforming growth factor ß1, inflammation, interstitial fibrosis, and decreased kidney function, all of which are major features of human CKD. Therefore, RARα's actions in PTs are crucial for PT homeostasis, and loss of RARα causes injury and a key CKD phenotype.

SGLT2 inhibitor dapagliflozin protects the kidney in a murine model of Balkan nephropathy.

Proximal tubular uptake of aristolochic acid (AA) forms aristolactam (AL)-DNA adducts, which cause a p53/p21-mediated DNA damage response and acute tubular injury. Recurrent AA exposure causes kidney function loss and fibrosis in humans (Balkan endemic nephropathy) and mice and is a model of (acute kidney injury) AKI to chronic kidney disease (CKD) transition. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. C57BL/6J mice (15-wk-old) were administered vehicle or AA every 3 days for 3 wk (10 and 3 mg/kg ip in females and males, respectively). Dapagliflozin (dapa, 0.01 g/kg diet) or vehicle was initiated 7 days prior to AA injections. All dapa effects were sex independent, including a robust glycosuria. Dapa lowered urinary kidney-injury molecule 1 (KIM-1) and albumin (both normalized to creatinine) after the last AA injection and kidney mRNA expression of early DNA damage response markers (p53 and p21) 3 wk later at the study end. Dapa also attenuated AA-induced increases in plasma creatinine as well as AA-induced up-regulation of renal pro-senescence, pro-inflammatory and pro-fibrotic genes, and kidney collagen staining. When assessed 1 day after a single AA injection, dapa pretreatment attenuated AL-DNA adduct formation by 10 and 20% in kidney and liver, respectively, associated with reduced p21 expression. Initiating dapa application after the last AA injection also improved kidney outcome but in a less robust manner. In conclusion, the first evidence is presented that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.NEW & NOTEWORTHY Recurrent exposure to aristolochic acid (AA) causes kidney function loss and fibrosis in mice and in humans, e.g., in the form of the endemic Balkan nephropathy. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. Here we provide the first evidence in a murine model that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.

Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.

AIMS: Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. METHODS: A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of ＜60 ml/min/1.73 m2. Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. RESULTS: During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. CONCLUSIONS: A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.

Coffee consumption and risk of kidney function decline in a Dutch population-based cohort.

BACKGROUND AND AIMS: Whether coffee consumption is associated with changes in estimated glomerular filtration rate (eGFR) is unknown. We investigated the relationship between coffee consumption and annual eGFR change in a large Dutch population-based study. METHODS AND RESULTS: This study was performed in 78,346 participants without chronic kidney disease (CKD) in the population-based Lifelines Cohort Study. Coffee consumption was assessed at baseline using food frequency questionnaires. Outcomes were annual eGFR change and a composite kidney outcome (defined as eGFR <60 mL/min per 1.73 m2 or >20 % eGFR decline). Multivariable linear and logistic regression analyses were used to evaluate the associations of coffee consumption (categories and cups/day) with kidney outcomes. Overall, 90 % of the participants drank coffee daily and 36 % drank >2-4 cups/day. Unadjusted mean ± SD annual eGFR change ranged from -2.86 ± 2.96 (for non-coffee drinkers) to -2.35 ± 2.62 (for participants consuming >6 cups/day) mL/min per 1.73 m2. During 3.6 ± 0.9 years follow-up, 11.1 % of participants reached the composite kidney outcome. As compared to non-coffee drinkers, higher coffee consumption was associated with less annual eGFR decline in multivariable models (ß [95 % CIs] ranged from 0.15 [0.07, 0.22] for >0-2 cups/day to 0.29 [0.20, 0.38] for >6 cups/day, P-trend <0.001). Consumption of one more cup of coffee per day was associated with a 3 % lower risk of the composite kidney outcome (OR [95%CI], 0.97 [0.96, 0.99]). The inverse association was more pronounced in a subgroup of individuals with diabetes. CONCLUSION: Coffee consumption was inversely associated with annual eGFR change and CKD risk in a large Dutch population-based cohort.

Letramento funcional em saúde em renais crônicos: um desafio na abordagem preventiva / Alfabetización funcional en salud en pacientes renales crónicos: un desafío en el enfoque preventivo / Functional health literacy in chronic kidney disease patients: a challenge in the preventive approach

Resumo Objetivo Identificar a prevalência de letramento funcional em saúde e analisar a associação entre os níveis de letramento funcional em saúde e as variáveis clínicas e sociodemográficas em pacientes renais crônicos não dialíticos. Métodos Estudo transversal realizado com 167 renais crônicos em acompanhamento no ambulatório de nefrologia de um município de grande porte do estado de Minas Gerais, Brasil. Para as entrevistas foram utilizados questionário sociodemográfico e clínico e a versão brasileira do Short Assessment of Health Literacy for Portuguese Speaking Adults - SAHLPA-18, para mensurar o letramento funcional em saúde. Realizado estatística descritiva para variáveis sociodemográficas e clínicas; testes de correlação e modelos de regressão lineares para associação com letramento funcional em saúde. Resultados A maior parte dos participantes era idosa com mediana de idade de 68 anos, 33,3% (56 pacientes) se encontravam no estágio 3B da doença renal crônica e 53,9% (90 pacientes) apresentaram letramento funcional em saúde inadequado. Não houve associação entre os níveis de letramento funcional em saúde e as variáveis clínicas. A maioria referiu não usar internet e o estágio mais avançado da doença renal crônica apresentou menores escores de letramento. Piores escores de letramento funcional em saúde também foi identificado naqueles com menor renda. Conclusão A maioria dos participantes apresentou letramento funcional em saúde inadequado. As variaveis clínicas não foram preditoras dos ecores de letramento. No entanto, escores mais baixos de letramento em saúde foram identificados naqueles em estágio mais avancado da doença renal, menor renda e menor uso da internet.

Resumen Objetivo Identificar la prevalencia de la alfabetización funcional en salud y analizar la asociación entre los niveles de alfabetización funcional en salud y las variables clínicas y sociodemográficas en pacientes renales crónicos no dializados. Métodos Estudio transversal realizado con 167 pacientes renales crónicos con seguimiento en consultorios externos de nefrología de un municipio de gran porte del estado de Minas Gerais, Brasil. Para las entrevistas se utilizó un cuestionario sociodemográfico y clínico y la versión brasileña del Short Assessment of Health Literacy for Portuguese Speaking Adults - SAHLPA-18, para medir la alfabetización funcional en salud. Se realizó estadística descriptiva para variables sociodemográficas y clínicas, pruebas de correlación y modelos de regresión lineales para asociación con alfabetización funcional en salud. Resultados La mayoría de los participantes eran personas mayores de 68 años de mediana de edad, el 33,3 % (56 pacientes) se encontraba en la etapa 3B de la enfermedad renal crónica y el 53,9 % (90 pacientes) presentó alfabetización funcional en salud inadecuada. No hubo asociación entre los niveles de alfabetización funcional en salud y las variables clínicas. La mayoría relató que no usaba internet y la etapa más avanzada de la enfermedad renal crónica presentó menor puntaje de alfabetización. Se identificaron peores puntajes de alfabetización funcional en salud en aquellos con menores ingresos. Conclusión La mayoría de los participantes presentó alfabetización funcional en salud inadecuada. Las variables clínicas no fueron predictoras de los puntajes de alfabetización. Sin embargo, se identificaron puntajes más bajos de alfabetización en salud en aquellos en etapa más avanzada de la enfermedad renal, con menores ingresos y menor uso de internet.

Abstract Objective To identify the prevalence of functional health literacy and analyze the association between functional health literacy levels and clinical and sociodemographic variables in non-dialysis chronic kidney disease patients. Methods This is a cross-sectional study carried out with 167 chronic kidney disease patients being monitored at the nephrology outpatient clinic of a large city in the state of Minas Gerais, Brazil. For the interviews, a sociodemographic and clinical questionnaire and the Brazilian version of the Short Assessment of Health Literacy for Portuguese Speaking Adults (SAHLPA-18) were used to measure functional health literacy. Descriptive statistics were performed for sociodemographic and clinical variables, and correlation tests and linear regression models for association with functional health literacy. Results Most participants were older adults with a median age of 68 years, 33.3% (56 patients) were in stage 3B of chronic kidney disease and 53.9% (90 patients) had inadequate functional health literacy. There was no association between functional health literacy levels and clinical variables. The majority reported not using the internet and the more advanced stage of chronic kidney disease had lower literacy scores. Worse functional health literacy scores were also identified in those with lower income. Conclusion Most participants had inadequate functional health literacy. Clinical variables were not predictors of literacy scores. However, lower health literacy scores were identified in those with more advanced stage kidney disease, lower income and less internet use.

Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease.

Antrodia cinnamomea (AC), a medicinal mushroom, has multiple beneficial actions, such as acting as a prebiotic. The incidence of chronic kidney disease (CKD) in children has steadily increased year by year, and CKD is related to gut microbiota dysbiosis. Herein, we investigated the renoprotection of solid-state cultivated AC in adenine-induced CKD juvenile rats. CKD was induced in 3-week-old male rats by feeding with adenine (0.5%) for three weeks. Treated groups received oral administration of AC extracts at either a low (10 mg/kg/day) or high dose (100 mg/kg/day) for six weeks. At nine weeks of age, the rats were sacrificed. Renal outcomes, blood pressure, and gut microbiome composition were examined. Our results revealed that AC treatment, either low- or high-dose, improved kidney function, proteinuria, and hypertension in CKD rats. Low-dose AC treatment increased plasma concentrations of short-chain fatty acids (SCFAs). Additionally, we observed that AC acts like a prebiotic by enriching beneficial bacteria in the gut, such as Akkermansia and Turicibacter. Moreover, the beneficial action of AC against CKD-related hypertension might also be linked to the inhibition of the renin-angiotensin system. This study brings new insights into the potential application of AC as a prebiotic dietary supplement in the prevention and treatment of pediatric CKD.

Shifts in KDIGO CKD risk groups with empagliflozin: Kidney-protection from SGLT2 inhibition across the spectrum of risk.

T2D is a well-established risk factor for development and progression of CKD. KDIGO recommends categorization of risk by likelihood of progression to ESKD. Compared to placebo, empagliflozin decreases likelihood of worsening (OR 0.70, 95 % CI 0.62-0.78) and increases likelihood of improvement (OR 1.56, 95 % CI 1.30-1.86) in KDIGO risk category.

Adherence to healthy lifestyle was associated with an attenuation of the risk of chronic kidney disease from metabolic dysfunction-associated fatty liver disease: Results from two prospective cohorts.

AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) are important risk factors of chronic kidney disease (CKD). Whether adherence to a healthy lifestyle can modify these effects remain unknown. This study aimed to evaluate the modification effects of healthy lifestyle on the associations among NAFLD, MAFLD, and the risk of CKD, with taking into the effect of genetic risk. METHODS: The Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH), the UK Biobank Study (UKB). The outcome was incident CKD. The exposures including NAFLD, MAFLD, healthy lifestyle, and a genetic risk score (GRS) for CKD. RESULTS: After 1,135,334 person-year follow-up, we documented 2975 incident CKD cases in the two cohorts. MAFLD and NAFLD were associated with a higher risk of CKD, particularly in patients with MAFLD. In the TCLSIH and UKB, the hazard ratios (95% confidence intervals) of incident CKD for MAFLD were 1.47 (1.30, 1.66) and 1.73 (1.57, 1.91), respectively. Adherence to a healthier lifestyle decreased the risk of CKD from MAFLD with significant interaction effects (TCLSIH: Pinteraction = 0.02; UKB: Pinteraction = 0.04). Participants with a lower CKD-GRS experienced a higher risk of CKD from MAFLD, but achieved two healthy lifestyles can significantly decreased the risk of CKD in patients with MAFLD. CONCLUSIONS: MAFLD and NAFLD are associated with a higher CKD risk, particularly MAFLD. Adherence to a healthier lifestyle was associated with a lower risk of CKD from MAFLD. These results highlight the important role of following a healthy lifestyle to prevent CKD.

[Renoprotection. About World Kidney Day]. / Renoprotección. A propósito del Día Mundial del Riñón.

The World Kidney Day was founded in 2003 by doctor Joel D. Kopple, American nephrologist, who in the session in the Congress of the International Federation of Kidney Foundations explained the need to implement the celebration on a day that alludes to this organ, in order to direct preventive actions for kidney disease and raise awareness in the medical community and the general population on the importance of caring for the kidneys. 3 years later, the proposal was accepted and as of 2006 World Kidney Day is celebrated. The diffusion is found throughout the world and in each place there are talks, courses, workshops, cultural activities and even marathons related to the prevention, diagnosis and treatment of kidney disease. Chronic kidney disease (CKD) is a disorder with a chronic, degenerative, and lethal evolution. Managing CKD requires a large amount of human, financial, and infrastructure resources. It impairs the quality of life and negatively affects survival. On the other hand, it leads to dialysis and kidney transplant treatments, which are expensive enough to put any health institution at financial risk, especially those most vulnerable. The main idea of these non-profit international organizations is to promote the well-being and improve the quality of life of people with CKD with and without dialysis, and to promote kidney transplantation as the first treatment option.

El Día Mundial del Riñón se fundó en el año 2003 por el doctor Joel D. Kopple, nefrólogo norteamericano, quien en el pleno del Congreso de la Federación Internacional de Fundaciones Renales expuso la necesidad de implementar la celebración en un día que aludiera a este órgano, con el fin de dirigir acciones de prevención para la enfermedad renal y concientizar a la comunidad médica y a la población en general de la importancia de cuidar los riñones. Tres años después, la propuesta fue aceptada y a partir del 2006 se celebra el Día Mundial del Riñón. La difusión se encuentra en todo el mundo y en cada lugar se desarrollan pláticas, cursos, talleres, actividades culturales y hasta maratones relacionados con la prevención, el diagnóstico y el tratamiento de la enfermedad renal. La enfermedad renal crónica (ERC) es un trastorno de evolución crónica, degenerativa y letal. Su atención demanda gran cantidad de recursos humanos, financieros y de infraestructura. Es una enfermedad que deteriora la calidad de vida y afecta negativamente la supervivencia. Por otra parte, conduce a realizar tratamientos costosos de diálisis y trasplante renal que ponen en riesgo financiero a cualquier institución de salud, sobre todo a aquellas más vulnerables. La idea principal de estos organismos internacionales sin fines de lucro es promover el bienestar y mejorar la calidad de vida de las personas con ERC con y sin diálisis, y promover el trasplante renal como primer opción de tratamiento.

Implications of Renal Disease in Patients Undergoing Structural Interventions.

Percutaneous structural interventions have a major impact on the morbidity, mortality, and quality of life of patients by providing a lower-risk alternative to cardiac surgery. However, renal disease has a significant impact on outcomes of these interventions. This review explores the incidence, outcomes, pathophysiology, and preventative measures of acute kidney injury and chronic kidney disease on transcatheter aortic valve replacement, transcatheter mitral valve repair, and percutaneous balloon mitral valvuloplasty. Given the expanding indications for percutaneous structural interventions, further research is needed to identify ideal patients with chronic kidney disease or end-stage renal disease who would benefit from intervention.

Abnormal kidney ultrasound and function in a five-year-old boy born prematurely with a birth weight of 370 grams.

It is known that prematurity and low birth weight are associated with chronic kidney disease and hypertension. A positive correlation between kidney volume and birth weight was also described. In our ongoing observational study in 5-year-old children, we perceived highly abnormal kidney ultrasound and functions of a male patient born weighing 370 grams. It was his first nephrology examination since discharge from the hospital. We believe that thorough follow up and timely diagnosis of developing renal insufficiency may help us to initiate proper treatment in high-risk children (Tab. 1, Fig. 1, Ref. 7). Text in PDF www.elis.sk Keywords: prematurity; extremely low birth weight; chronic kidney disease; renal ultrasound; renal function.

Physical activity and nutrition in chronic kidney disease.

PURPOSE OF REVIEW: Lifestyle intervention is considered a cornerstone in chronic kidney disease management and has been recommended in different international or regional clinical practice guidelines in chronic kidney disease. However, evidence was largely based on the general population. Here we summarized the latest evidence supporting lifestyle intervention in chronic kidney disease. RECENT FINDINGS: Both observational cohort studies as well as randomized controlled trials have demonstrated health benefits with more physical activity in chronic kidney disease. There are compelling observational data supporting different health and kidney benefits with a healthy dietary pattern rich in fruits and vegetables, whole grains, plant-based foods and low in salt, low in sugar, saturated fat, red meat and ultraprocessed foods, a plant-based diet or Mediterranean diet in chronic kidney disease population. Clinical and epidemiologic studies also showed that higher 24 h urine potassium excretion (as proxy of higher dietary potassium intake) may be associated with lower blood pressure, better kidney outcomes and lower mortality in chronic kidney disease population. Randomized controlled trials also suggested that salt substitutes improved blood pressure control, reduced all-cause death and cardiovascular event risk in the general population compared with regular salt. SUMMARY: Accumulating evidence supports the current recommendation of encouraging physical activity and promoting a healthy dietary pattern in chronic kidney disease patients. Whether potassium needs restriction in chronic kidney disease diet requires further review. The safety versus benefits of salt substitutes in patients with moderate and advanced chronic kidney disease warrants further investigation.

Renoprotective effects of genetically proxied fibroblast growth factor 21: Mendelian randomization, proteome-wide and metabolome-wide association study.

BACKGROUND: Fibroblast growth factor 21 (FGF21) has demonstrated efficacy for reducing liver fat and reversing non-alcoholic steatohepatitis in phase 2 clinical trials. It is also postulated to have anti-fibrotic effects and therefore may be amenable to repurposing for the prevention and treatment of chronic kidney disease (CKD). METHODS: We leverage a missense genetic variant, rs739320 in the FGF21 gene, that associates with magnetic resonance imaging-derived liver fat as a clinically validated and biologically plausible instrumental variable for studying the effects of FGF21 analogs. Performing Mendelian randomization, we ascertain associations between instrumented FGF21 and kidney phenotypes, cardiometabolic disease risk factors, as well as the circulating proteome (Somalogic, 4907 aptamers) and metabolome (Nightingale platform, 249 metabolites). RESULTS: We report consistent renoprotective associations of genetically proxied FGF21 effect, including higher glomerular filtration rates (p = 1.9 × 10-4), higher urinary sodium excretion (p = 5.1 × 10-11), and lower urine albumin-creatinine ratio (p = 3.6 × 10-5). These favorable effects translated to lower CKD risk (odds ratio per rs739320 C-allele, 0.96; 95%CI, 0.94-0.98; p = 3.2 × 10-4). Genetically proxied FGF21 effect was also associated with lower fasting insulin, waist-to-hip ratio, blood pressure (systolic and diastolic BP, p < 1.0 × 10-07) and blood lipid (low-density lipoprotein cholesterol, triglycerides and apolipoprotein B, p < 6.5 × 10-24) profiles. The latter associations are replicated in our metabolome-wide association study. Proteomic perturbations associated with genetically predicted FGF21 effect were consistent with fibrosis reduction. CONCLUSION: This study highlights the pleiotropic effects of genetically proxied FGF21 and supports a re-purposing opportunity for the treatment and prevention of kidney disease specifically. Further work is required to triangulate these findings, towards possible clinical development of FGF21 towards the treatment and prevention of kidney disease.

Mineralocorticoid Receptor Antagonists for Preventing Chronic Kidney Disease Progression: Current Evidence and Future Challenges.

Regulation and action of the mineralocorticoid receptor (MR) have been the focus of intensive research over the past 80 years. Genetic and physiological/biochemical analysis revealed how MR and the steroid hormone aldosterone integrate the responses of distinct tubular cells in the face of environmental perturbations and how their dysregulation compromises fluid homeostasis. In addition to these roles, the accumulation of data also provided unequivocal evidence that MR is involved in the pathophysiology of kidney diseases. Experimental studies delineated the diverse pathological consequences of MR overactivity and uncovered the multiple mechanisms that result in enhanced MR signaling. In parallel, clinical studies consistently demonstrated that MR blockade reduces albuminuria in patients with chronic kidney disease. Moreover, recent large-scale clinical studies using finerenone have provided evidence that the non-steroidal MR antagonist can retard the kidney disease progression in diabetic patients. In this article, we review experimental data demonstrating the critical importance of MR in mediating renal injury as well as clinical studies providing evidence on the renoprotective effects of MR blockade. We also discuss areas of future investigation, which include the benefit of non-steroidal MR antagonists in non-diabetic kidney disease patients, the identification of surrogate markers for MR signaling in the kidney, and the search for key downstream mediators whereby MR blockade confers renoprotection. Insights into these questions would help maximize the benefit of MR blockade in subjects with kidney diseases.

Seus rins estão saudáveis? Saiba o que é a doença renal crônica e como preveni-la

Os rins são os órgãos responsáveis por eliminar toxinas, controlar a pressão sanguínea, regular a formação do sangue e dos ossos e equilibrar o balanço químico e de líquidos do organismo.

Beyond Blood Glucose and Blood Pressure Control in Type 2 Diabetes: Alternative Management Strategies to Prevent the Development and Progression of CKD.

Chronic kidney disease associated with Type 2 diabetes is linked to significant increase in morbidity, reduced quality of life, and early death. Current guidelines recommend targets for the management of hyperglycemia, hypertension, and dyslipidemia but there remains a residual risk of chronic kidney disease progression and adverse cardiovascular outcomes in patients with Type 2 diabetes. The 2022 consensus report from the American Diabetes Association and Kidney Disease: Improving Global Outcomes support the use of sodium-glucose co-transporter 2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists to improve kidney and cardiovascular outcomes. Coordination between those working in the primary care setting and those in endocrinology and nephrology clinics may optimize the prevention of chronic kidney disease progression in patients with Type 2 diabetes. Nurse practitioners, physician assistants, and primary care physicians play an important role in making timely patient referrals to kidney specialists. This article explores the use of novel therapies capable of reducing the risk of cardiovascular disease and chronic kidney disease progression beyond what can be achieved with control of blood glucose, blood pressure, and lipid levels. It also discusses the importance of monitoring at-risk patients to facilitate early diagnosis and initiation of effective kidney-protective therapy.[Media: see text][Figure: see text].

The health and budget impact of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in The Netherlands.

OBJECTIVES: Type-2 Diabetes mellitus (T2DM) increases both the patient risk of cardiovascular disease (CVD) and renal outcomes, such as chronic kidney disease (CKD). Recent clinical trials of the glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown benefits in preventing CVD events and progression of CKD, leading to an update of the Dutch T2DM treatment guideline for patients at risk. The aim of this study is to assess the health and economic impact of the guideline-recommended utilization of SGLT2is in the Netherlands. METHODS: The patient population at risk was determined by multiplying Dutch T2DM prevalence rates with the total numbers of inhabitants of the Netherlands in 2020. Subsequently, two analyses, comparing a treatment setting before and after implementation of the new guideline for SGLT2is, were conducted. Clinical and adverse event rates in both settings as well as direct healthcare costs were sourced from the literature. Total costs were calculated by multiplying disease prevalence, event rates and costs associated to outcomes. One-time disutilities per event were included to estimate the health impact. The potential health and economic impact of implementing the updated guideline was calculated. RESULTS: Using a 5-year time horizon, the guideline-suggested utilization of SGLT2is resulted in a health impact equal to 4835 quality adjusted life years gained (0.0031 per patient per year) and €461 million cost-savings. The costs of treatment with SGLT2is were €813 million. Hence the net budget impact was €352 million for the total Dutch T2DM population, which translated to €0,57 per patient per day. CONCLUSION: SGLT2is offer an option to reduce the number of CVD and CKD related events and associated healthcare costs and health losses in the Netherlands. Further research is needed to include the benefits of improved T2DM management options from a broader societal perspective.HighlightsThe glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) has shown benefits in preventing cardiovascular events and progression of kidney disease in patients with type-2 diabetes leading to a revision of the respective Dutch treatment guideline.The 5-year budget impact of the adoption of SGLT2is in the new treatment guideline was equal to €352 million or €0.57 per patient per day, with a total of 4385 quality adjusted life years gained.The introduction of SGLT2is for Dutch type-2 diabetes patients has the potential to substantially reduce the number of cardiovascular as well as renal disease events and related healthcare costs while also delivering a health benefit.