Slow Chronic Kidney Disease Progression Research Articles

Integrating the new pharmacological standard of care with traditional nutritional interventions in non-dialysis CKD.

Chronic kidney disease (CKD) is widely recognized as a leading and growing contributor to global morbidity and mortality worldwide. Nutritional therapy is the basic treatment for metabolic control, and may contribute to nephroprotection; however, the absence of solid evidence on slowing CKD progression together with poor adherence to dietary prescription limit de facto itsefficacy and prevent itsmore widespread use. Sodium-glucose transport protein 2 inhibitors (SGLT2is) are now considered the new standard of care in CKD; in addition, novel potassium binders, glucagon-like peptide-1 receptor antagonists (GLP1-RAs) and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) show either direct (SGLT2i, GLP1-RA, nsMRA) or indirect (potassium binders that enable the optimal use of renin-angiotensin-aldosterone system inhibitors) nephroprotective effects. These drugs could potentially lead to a more permissive diet, thereby allowing the patient to reap the benefits of this approach. In particular, SGLT2is, and to a lesser extent also GLP1-RAs and nsMRAsin patients with diabetic kidney disease, can counterbalance hyperfiltration as well as the higher protein intake often recorded in obese patients; on the other hand, potassium binders can facilitate following plant-based diets, which are considered healthy because of the high content of essential micronutrients such as antioxidant vitamins, minerals, alkalies, and fibers. In this review paper, we discuss the current pharmacological paradigm shift that places a new, broader standard of care in light of its interaction with nutritional therapy in order to optimize the global approach to patients with CKDnotondialysis.

SGLT2 Inhibition: A New Glimmer of Hope to Slow Chronic Kidney Disease Progression in Children?

SGLT2 Inhibition: A New Glimmer of Hope to Slow Chronic Kidney Disease Progression in Children?

Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Chronic Kidney Disease in France, Based on the EMPA-KIDNEY Clinical Trial.

The efficacy and safety of empagliflozin in the treatment of chronic kidney disease (CKD) were demonstrated in the EMPA-KIDNEY trial, which showed a 28% reduction in combined risks of kidney disease or death from cardiovascular causes (hazard ratio, 0.72; 95% confidence interval, 0.64-0.82; p < 0.001) compared with placebo. Based on these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of CKD in France. A Markov state microsimulation model was adapted to compare the health and economic outcomes in France, considering a healthcare system perspective, in patients treated with empagliflozin in addition to SoC versus patients treated with SoC alone. The model simulated the intention-to-treat population of the trial, transitioning between 18 mutually exclusive and collectively exhaustive health states defined based on the Kidney Disease: Improving Global Outcomes classification. For each arm, the model estimated (over a 25-year time horizon) the number of events and deaths, and the costs associated with these events, to calculate the incremental cost-effectiveness ratio. The resources used were derived using French authorities reports, literature, and French CKD guidelines. Both economic and health outcomes were discounted at a 2.5% annual rate according to French guidelines. The model predicted that using empagliflozin + SoC to treat patients with CKD would prevent CKD-related complications and deaths associated with a cardiovascular event or all-cause deaths while in kidney replacement therapy, resulting on average in a discounted gain of 1.29 years in overall survival (9.48 years vs. 8.19 with SoC alone). Empagliflozin costs (treatment, events, and disease management) were completely offset by the cost savings from avoided kidney failure events. Overall, empagliflozin + SoC would be more effective and less costly than SoC alone and would therefore be the dominant treatment strategy. The sensitivity analyses conducted support the results' robustness in showing the dominance of empagliflozin + SoC over SoC alone. The base-case results indicate that empagliflozin + SoC is a dominant strategy compared with the current SoC for the management of CKD in France. Empagliflozin + SoC would have a positive impact on patients with CKD by slowing CKD progression and leading to the prevention of kidney failure events on top of all-stages CKD complications.

Chronic Kidney Disease Progression-A Challenge.

Chronic kidney disease (CKD) is a progressive condition characterized by a continuous decline in renal function, independent of the initial cause of damage or external factors such as infection, inflammation, or toxins. The accurate measurement of renal function, typically assessed using the glomerular filtration rate (GFR), is crucial for managing CKD. The most accepted hypothesis for CKD progression is glomerular damage caused by hyperfiltration. Various factors can accelerate CKD progression, and several biomarkers have been identified to monitor this progression. Numerous studies have explored the risk factors associated with CKD progression, and some of these factors can be modified. Additionally, several drugs are now available that can reduce CKD progression. This review summarizes recent publications and highlights potential future research directions in CKD progression. It discusses the evolution of GFR measurement methods, the mechanisms driving CKD progression, and the latest findings on biomarkers and risk factors. Furthermore, it explores therapeutic strategies, including dietary modifications and pharmacological interventions, to slow CKD progression. Understanding these mechanisms and interventions is crucial for developing effective therapeutic strategies to prevent or slow CKD progression.

Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients

Introduction: Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline. Methods: Changes in estimated glomerular filtration rate (eGFR) were analyzed post hoc in 126 adults with SHPT, stage 3–4 CKD, and low serum 25-hydroxyvitamin D (25D) treated for 1 year with ERC in pivotal trials. ERC was administered at 30 μg/day increasing, as needed, to 60 μg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor-23 (FGF23), bone turnover markers (BTMs), and urine albumin-to-creatinine ratio (uACR) were measured at baseline and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline. Results: For all participants, 25D increased 58.5 ± 2.3 (SE) ng/mL (p < 0.001) by the end of treatment (EOT), 1,25D increased 10.1 ± 1.8 pg/mL (p < 0.001), iPTH decreased from 143.8 ± 5.8 pg/mL to 108.8 ± 7.2 (p < 0.001), BTMs improved (p < 0.01), and eGFR declined 2.2 ± 0.5 mL/min/1.73 m2 (p < 0.001). The rate of eGFR decline was >5-fold higher (p = 0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2 ± 0.7; 12.7 ± 2.2%) than in those who did (0.6 ± 0.8; 2.9 ± 2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4 ± 0.9; 20.9 ± 3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression. Conclusion: Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3–4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.

Dietary sodium modulates mTORC1-dependent trained immunity in macrophages to accelerate CKD development

Chronic Kidney Disease (CKD) is a significant global health issue linked to dietary habits, especially high salt intake. However, the precise mechanisms driving this progression remain incompletely understood. This study reveals that a high-salt diet intensifies macrophage trained immunity, leading to a marked pro-inflammatory response upon repeated pathogenic exposures, as evidenced by increased renal damage and fibrosis. Under high-salt conditions, there was an induction of CD45+F4/80+ macrophage infiltration into the renal tissue, accompanied by heightened production of inflammatory cytokines. Distinct responses were observed between circulating and resident renal macrophages to a high-salt diet, with a notable upsurge in the migration of pro-inflammatory macrophages, driven by CCL2-CCR2 signaling and aberrant mTORC1 pathway activation. Treatment with rapamycin-liposome effectively reduced this inflammatory cascade by mitigating mTORC1 signaling. Transplantation of monocytes from CKD mice with a high-salt diet significantly exacerbates renal inflammatory damage in the host mice, showing increased migratory tendency and inflammatory activity. The cell co-culture experiment further confirmed that macrophages derived from CKD mice, particularly those under conditions of high salt exposure, significantly induced apoptosis and inflammatory responses in renal tubular cells. Taken together, recurrent exposure to LPS elicits the activation of trained immunity, consequently augmenting inflammatory response of monocytes/macrophages in the involved kidneys. The high-salt diet exacerbates this phenomenon, attributable at least in part to the overactivation of the mTORC1 pathway. This research emphasizes the importance of dietary modulation and targeted immunological interventions in slowing CKD progression, providing new insights into mTORC1-mediated pathophysiological mechanisms and potential management strategies for CKD.

Sodium glucose co-transporter 2 inhibitors in the treatment of glomerular diseases: a CKJ controversy.

Integrating sodium-glucose co-transporter 2 inhibitors (SGLT2i) into the treatment for chronic kidney disease (CKD) has marked a significant therapeutic advance in nephrology. Clinical trials such as DAPA-CKD and EMPA-KIDNEY have demonstrated the beneficial effects of SGLT2i in slowing CKD progression and reducing proteinuria. However, the applicability of these results to patients with glomerulonephritis is still unresolved due to various limitations. This manuscript combines the evidence supporting the use of SGLT2i in glomerular diseases, highlights the limitations and strikes a conclusive balance on their role in clinical practice.

Trends in fluid overload-related hospitalisations among patients with diabetes mellitus The impact of chronic kidney disease.

Fluid overload is a known complication in patients with diabetes mellitus, particularly those with cardiovascular and/or chronic kidney disease (CKD). This study investigates the impact of fluid overload on healthcare utilisation and its association with diabetes-related complications. Electronic medical records from the SingHealth Diabetes Registry (2013-2022) were analysed. Hospitalisations due to fluid overload were identified using International Classification of Diseases, 10th Revision (ICD-10) discharge codes. Trends were examined using Joinpoint regression, and associations were assessed with generalised estimating equation models. Over a period of 10 years, 259,607 individuals treated at primary care clinics and tertiary hospitals were studied. The incidence of fluid overload-related hospitalisations decreased from 2.99% (n=2778) in 2013 to 2.18% (n=2617) in 2017. However, this incidence increased from 2.42% (n=3091) in 2018 to 3.71% (n=5103) in 2022. The strongest associations for fluid overload-related hospitalisation were found with CKD stages G5 (odds ratio [OR] 6.61, 95% confidence interval [CI] 6.26-6.99), G4 (OR 5.55, 95% CI 5.26-5.86) and G3b (OR 3.18, 95% CI 3.02-3.35), as well as with ischaemic heart disease (OR 3.97, 95% CI 3.84-4.11), acute myocardial infarction (OR 3.07, 95% CI 2.97-3.18) and hypertension (OR 3.90, 95% CI 3.45-4.41). Additionally, the prevalence of stage G5 CKD among patients with fluid overload increased between 2018 and 2022. Our study revealed a significant increase in fluid overload-related hospitalisations and extended lengths of stay, likely driven by severe CKD. This underscores an urgent need for initiatives aimed at slowing CKD progression and reducing fluid overload-related hospitalisations in diabetes patients.

Long-Term Follow-Up of Patients with Chronic Kidney Disease: Renal Function Decline and Associated Risk Factors

ABSTRACT Evaluating the chronic course of chronic kidney disease (CKD) and identifying associated risk factors is essential for effective management. This study aims to identify risk factors and monitor the decline in renal function through prolonged follow-up of CKD patients. This retrospective cohort study included 410 CKD patients diagnosed between 2015 and 2022. Data collected included demographics, comorbidities, and repeated measurements of glomerular filtration rate (GFR) and proteinuria. Statistical analyses examined the association between GFR decline and risk factors such as age, diabetes, hypertension, and proteinuria during the follow-up period. The cohort showed a progressive decline in GFR over time. Significant associations were found between GFR decline and age, diabetes, hypertension, and higher proteinuria levels (P &lt; 0.001). Age was associated with a 0.32 ml/min decline in GFR per 1.73 m², while the coefficients for hypertension and diabetes were -2.98 and -4.21, respectively. A strong correlation was found between proteinuria and GFR decline (β = -6.78, P &lt; 0.001). Early identification and management of risk factors are crucial for slowing CKD progression. These findings underscore the need for targeted interventions to preserve renal function and improve patient outcomes.

Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease.

Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease (CKD), but therapeutic options are limited. We discuss the epidemiology of pulmonary hypertension in patients with CKD and review therapies for pulmonary hypertension with a focus on emerging treatments for pulmonary arterial hypertension (PAH). The definition of pulmonary hypertension has been updated to a lower threshold of mean pulmonary artery pressures of more than 20 mmHg, potentially leading to more patients with CKD to qualify for the diagnosis of pulmonary hypertension. Endothelin receptor antagonists, a class of medications, which demonstrated efficacy in patients with PAH, have been shown to slow progression of CKD, but their efficacy in lowering pulmonary artery pressures and their effects on reducing cardiovascular mortality in this population remains unproven. Sotatercept, a novel activin signaling inhibitor, which was previously studied in dialysis patients has been shown to increase exercise capacity in patients with PAH. These studies may lead to new specific therapies for pulmonary hypertension in patients with CKD. Pulmonary hypertension is common in patients with CKD. Although our understanding of factors leading to pulmonary hypertension in this population have evolved, evidence supporting disease-specific therapy in CKD is limited arguing for larger, long-term studies.

A meta-analysis of randomized controlled clinical trials for implications of acute treatment effects on glomerular filtration rate for long-term kidney protection

Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications. In 64 randomized controlled trials (RCTs), enrolling 154,045 participants, we estimated acute effects as the mean between-group difference in GFR slope from baseline to three months, effects on chronic GFR slope (starting at three months after randomization), and effects on three composite kidney endpoints defined by kidney failure (GFR 15 ml/min/1.73m2 or less, chronic dialysis, or kidney transplantation) or sustained GFR declines of 30%, 40% or 57% decline, respectively. We used Bayesian meta-regression to relate acute effects with treatment effects on chronic slope and the composite kidney endpoints. Overall, acute effects were not associated with treatment effects on chronic slope. Acute effects were associated with the treatment effects on composite kidney outcomes such that larger negative acute effects were associated with lesser beneficial effects on the composite kidney endpoints. Associations were stronger when the kidney composite endpoints were defined by smaller thresholds of GFR decline (30% or 40%). Results were similar in a subgroup of interventions with supposedly hemodynamic effects that acutely reduce GFR. For studies with GFR 60 mL/min/1.73m2 or under, negative acute effects were associated with larger beneficial effects on chronic GFR slope. Thus, our data from a large and diverse set of RCTs suggests that acute effects of interventions may influence the treatment effect on clinical kidney outcomes.

Kidney disease knowledge among patients visiting the nephrology clinic in the Kingdom of Saudi Arabia.

This study aimed to explore chronic kidney disease (CKD)-related knowledge and its predictors among non-dialysis patients with CKD in the Kingdom of Saudi Arabia (KSA). It was a cross-sectional survey conducted at 2 nephrology centers in KSA. Data were gathered using a survey questionnaire that included sociodemographic information and enquiries about CKD. The questionnaire used to explore CKD knowledge consisted of 24 questions with 3 multiple-choice answers for each question: "True," "False," and "I don't know." Data were obtained from 185 patients who visited a nephrology clinic. The major study population was drawn from the western region of the Kingdom of Saudi Arabia. The participants' mean (SD) total renal disease knowledge scores was 12.56 (3.55) out of a maximum of 24 points on the renal disease knowledge assessment. This suggests that the participants, on average, exhibited a moderate level of knowledge regarding renal disease. Most respondents correctly answered questions related to blood and urine tests (90.3% and 89.7%, respectively), living with a single kidney (88.1%), kidney function in blood cleansing (83.8%), risk factors like diabetes (82.7%), and hypertension (80%). Additionally, they recognized symptoms such as water retention (85.9%) and fatigue (61.6%) and the potential of certain medications to slow chronic kidney disease progression (72.4%). However, fewer respondents correctly identified nausea/vomiting (31.4%) and loss of appetite (31.4%) as signs of kidney disease, the role of kidneys in maintaining blood pressure (58.9%) and bone health (16.2%), and obesity as a risk factor (54.1%). Furthermore, there were notable differences in knowledge scores between genders, with men scoring significantly higher than women (2.05, P = .041). In general, the understanding of CKD within the CKD patient community in the KSA was at a moderate level. However, male respondents had a greater understanding of CKD than did female respondents. The findings of this study indicate an urgent need to conduct educational activities to improve CKD knowledge among patients with CKD in the KSA.

A practical approach to nutritional intervention for people with chronic kidney disease in Vietnam.

A comprehensive nutritional management is necessary for favourable outcomes in patients with chronic kidney disease (CKD). We aimed to assess the changes in nutritional status and disease progression with nutritional management where renal replacement therapy (RRT) was not in place. A quasi-experiment intervention was conducted on 70 CKD patients at stages 3-5 from July to December 2022. Participants were excluded if they underwent RRT, including dialy-sis (hemodialysis or peritoneal dialysis), or kidney transplantation. The nutritional regimen covered nutrition-al counseling, samples of the dietary menu, and supplement products. We evaluated nutritional status using Subjective Global Assessment (SGA) scale and sub-clinical blood test at T0 (hospital admission) and T1 (two weeks after the admission or 24 hours before the discharge). After the intervention, the number of patients classified as malnutrition or at risk of malnourished reduced significantly (65.7% to 54.3% and 25.7% and 5.7%, respectively). The serum concentration of urea, creatinine and parathyroid hormone decreased remarkably, especially in patients receiving nutritional management. In the intervention group, the dietary pattern provided increased intakes of calcium and iron at T1, while phosphorus, sodium and potassium decreased after follow-up. Nausea/vomiting, loss of appetite, tiredness and sleep disorders were improved in the intervention compared to the control group. Nutritional therapy enhanced the nutritional sta-tus, and quality of dietary and renal function in CKD patients without RRT. Applying nutrition education and treatment at an early stage can slow CKD progression, which should be applicable elsewhere in Vietnam.

#2320 The impact of interventions for people with chronic kidney disease on health-related quality of life: a systematic review

Abstract Background and Aims Health-related quality of life (HRQoL) is poorer for those with chronic kidney disease (CKD) than the general population and worsens as CKD progresses. Evidence is mixed as to which interventions improve HRQoL for those with CKD, and HRQoL is often under-reported in randomised controlled trials where it is most commonly a secondary outcome. Reviews including HRQoL as an outcome have thus far focused on the impact per intervention, therefore we aimed to ascertain which interventions, of any type, have an impact on HRQoL outcomes for those with non-dialysis dependent CKD (NDD-CKD). Method The protocol was prospectively registered on PROSPERO (CRD42022364474) and PRISMA guidelines were followed. Inclusion criteria were randomised controlled trials in an NDD-CKD population (excluding transplant recipients), any intervention type, usual care/placebo comparators, using validated and reported HRQoL outcomes measures. Databases searched were Embase, Medline, PsychINFO, CINAHL plus, Web of Science, PubMed, and Google Scholar, with reference searching of included studies. Reports were independently screened by two researchers who also performed data extraction and quality assessment (using the Cochrane Risk of Bias 2.0 tool). Synthesis was undertaken using Synthesis without Meta-analysis (SWiM) methods. Conversion to one-sided p-values, synthesising outcomes in albatross plots and combining p-values via Fisher's method was performed using the metap package in R. HRQoL measures were broken down into physical, mental, kidney disease symptoms, adverse effects of kidney disease, burden of kidney disease, overall kidney disease, and overall HRQoL domains for analysis. Results Searches yielded 8983 records, and 39 studies met inclusion criteria, with a total of 11,940 participants. Nine groups were formed based on type of intervention, with data synthesis possible in the eight groups with more than one study (Fig. 1). 26 (66%) studies were rated as having high risk of bias, largely due to frequent lack of blinding and HRQoL being a patient reported outcome. 37 studies had sufficient data for presentation in albatross plots (Fig. 2). Using combined p-values for all HRQoL outcomes in each group of studies, benefit to HRQoL in at least one study was shown for education interventions (p &amp;lt; 0.001, seven studies, none with low risk of bias), exercise interventions (p &amp;lt; 0.001, eight studies, all with high risk of bias), medications to treat CKD-related anaemia (p &amp;lt; 0.001, eight studies, four with low risk of bias), nutritional interventions (p &amp;lt; 0.001, four studies, all with high risk of bias) and weight loss interventions (p &amp;lt; 0.001, two studies, one with low risk of bias). No benefit to HRQoL was shown for medications aimed at slowing CKD progression (p = 0.492, five studies), medications for depression (p = 0.266, two studies) and medications to treat acidosis (p = 0.99, two studies). Conclusion This review identified several interventions with evidence of benefit to HRQoL for people with NDD-CKD, including medications to treat anaemia and weight loss interventions. Studies of education, exercise and nutritional interventions showed potential benefit, but with high risk of bias. Further high-quality randomised controlled trials of interventions for people with NDD-CKD should include and report HRQoL outcomes, in addition to targeting potentially modifiable determinants of HRQoL in these groups.

#1637 Diverging trends in kidney replacement therapy (KRT) incidence in Madrid and Catalonia in the past decade

Abstract Background and Aims Chronic kidney disease (CKD) is one of the fastest growing global causes of death and the number of persons on KRT is increasing. A critical assessment of current clinical practice across regions may identify best clinical practice, providing a benchmark to improve outcomes. Given the long life expectancy in Spain and its high proportion of the population over 65 y/o, analysis of Spanish data may provide insight for the future for other European countries. Catalonia (Cat) and Madrid (Mad) are two of the most populated Spanish Autonomous Communities, have similar life expectancy (above 83 years) and GDP per capita, and together account for 30% of Spanish population and 38% of GDP. The aim was to set the basis for benchmarking in CKD care and KRT initiation by comparing the evolving KRT incidence of two representative Spanish Autonomous Communities. Method We compared the KRT incidence in Cat and Mad from 2012 to 2021, using data from European Renal Association (ERA) Registry annual reports and the Spanish Instituto Nacional de Estadistica's (INE) census. Results From 2012 to 2021, the incidence of KRT (day 1) adjusted for age and sex increased by 69.7 pmp (59% increase) in Cat (from 118.7 to 188.4 pmp) and by 14.2 pmp (12% increase) in Mad (from 115.5 to 129.7 pmp). The differential incidence of KRT between Cat and Mad increased from 3.2 to 58.7 pmp, i.e., 1734% increase (Fig. 1A). As a result, the incidence of KRT was 45% higher in Cat than in Mad in 2021 (up from 3% higher in 2012). During the same period, the median age to start KRT increased from 67.0 to 69.6 years (2.6 years, 3.9%) in Cat and from 66.1 to 66.9 years (0.8 years, 1.2%) in Mad. Median age at KRT initiation in 2021 was 3 years older in Cat in both men (Cat 70.0 (58.4-77.8), Mad 67.3 (56.9-76.2)) and women (Cat 69.0 (58.4-77.2), Mad 66.1 (51.7-75.8)). In subgroup analysis by age and sex, the largest difference in KRT incidence in 2021 was observed for women and for those aged 75+ years: Cat/Mad KRT incidence (pmarp) ratio was 1.79 in women 75+, 1.62 in men 75+, 1.49 in women &amp;lt;75 y/o, 1.34 in men &amp;lt;75 y/o (Fig. 1B). The gap between Cat and Mad increased progressively with age in both men and women and the slope was steeper for women. The contribution of diabetes to the overall incidence of KRT ranged from 16.8% to 23.2% in Cat and from 24.3% to 29.0% in Mad between 2012 and 2021, remaining grossly stable or decreasing slightly over time. For most causes, the incidence adjusted for age and sex in Cat and Mad was similar, with largest differences observed for unknown cause (the most common cause in Cat: Cat 45.9 pmp, Mad 7.9 pmp) and missing (the 3rd most common cause in Cat after unknown and diabetes: Cat 25.4 pmp, Mad 0) (Fig. 1C). Together, unknown and missing causes of CKD accounted for 38.1% of incident KRT cases in Cat in 2021. Pre-emptive transplantation was 3-fold more common in Cat in 2021 (7.6% vs 2.7%), while incidence of haemodialysis and peritoneal dialysis were similar (Fig. 1D). Conclusion In conclusion, trends for KRT incidence differed for two Autonomous Communities from the same country, broadly comparable in terms of population, life expectancy and GDP. The incidence of KRT was higher in Catalonia, and the gap increasing over time, especially among the elderly and older women, with unknown cause of CKD being the leading cause of incident KRT. An in-depth analysis of the drivers of these differences may bring interesting insight into best practice for CKD prevention, treatment to slow CKD progression and prescription and initiation of KRT.

#1611 Diverging epidemiology of kidney replacement therapy (KRT) prevalence in Madrid and Catalonia between 2012 and 2021

Abstract Background and Aims Chronic kidney disease (CKD) is one of the fastest growing global causes of death and the number of persons on kidney replacement therapy (KRT) is increasing. A critical assessment of current clinical practice in different regions may identify best clinical practice and provide a benchmark to improve outcomes. Given the current long-life expectancy in Spain and its high proportion of elderly population, analysis of Spanish data may provide insight of interest for the future for other European countries. Catalonia (Cat) and Madrid (Mad) are among the three most populated Spanish Autonomous Communities and have similar life expectancy, gross domestic product (GDP) and GDP per capita, accounting for 30% of Spain's population and 38% of GDP. The aim was to set the basis for benchmarking in CKD care and KRT initiation and care by comparing the evolving prevalence of KRT in Cat and Mad. Method We compared KRT prevalence in Cat and Mad over the past years using data from European Renal Association (ERA) Registry annual reports and Spanish Instituto Nacional de Estadística's (INE) census. Results From 2012 to 2021, the adjusted prevalence of KRT per million population (pmp) increased by 275.8 (1221 to 1479, 22.6% increase) in Cat and by 134.8 (1046 to 1118, 12.9% increase) in Mad. The difference between Cat and Mad increased from 175 to 316 pmp (60% increase), resulting in a 26.8% higher KRT prevalence in Cat than in Mad in 2021 (up from 16.7% higher in 2012) (Fig. 1A). During the same period, the median age of prevalent KRT patients increased from 63.2 to 65.4 years (yrs) (2.2 yrs, 3.5%) in Cat and from 62.2 to 63.8 years (1.6 yrs, 2.6%) in Mad. In 2021, median age for prevalent patients on KRT was 1.6 yrs older in Cat (65.4 (53.9, 75.3)) than in Mad (63.8 (52.6, 74.1)), this difference being of 2.5 yrs in women (Cat 65.5 (53.6, 75.7), Mad (63 (51, 73.8), difference) and 1.1 yrs in men (Cat 65.3 (53.9, 75); Mad 64.2 (53.4, 74.3)). In subgroup analysis by age and sex, prevalence of KRT per million age-related population (pmarp) in 2021 was always higher in Cat than in Mad, except for women aged 20-44 yrs (363.7 in Cat, 370.5 in Mad, Cat/Mad ratio 0.98), and the largest gap was observed for women &amp;lt;19 yrs (Cat 77.4, Mad 41.5, Cat/Mad ratio 1.86). The Cat-Mad ratio increased with age in women &amp;gt;45 yrs, but not in men (Fig. 1B) The contribution of diabetes to KRT prevalence remained stable or increased slightly in both Cat (13.9-15.5%) and Mad (17.4-17.7%) between 2012 and 2021. In 2021 for most causes of KRT the prevalence adjusted for age and sex was higher in Cat, except for hypertension and miscellaneous. The largest differences were observed for unknown cause (most common cause in Cat: Cat 330.8, Mad 85.5, difference 245.3 pmp), miscellaneous (most common cause in Mad: Cat 165.9, Mad 271.5, difference −105.6 pmp), and missing (Cat 53.8, Mad 0, difference 53.8 pmp) (Fig. 1C). Prevalence of kidney transplantation in 2021 was higher in Cat than Mad (60.0% vs 54.9%), while prevalence of hemodialysis and peritoneal dialysis was higher in Mad (39.6% and 5.5%, respectively) than in Cat (36.2% and 3.9%) (Fig. 1D). Conclusion In conclusion, a stark difference in prevalence trends and in current KRT was observed for two Autonomous Communities within the same country which are broadly comparable in terms of population, life expectancy and GDP. An in-depth analysis of the drivers of these differences may bring insight into best practices for CKD prevention, treatment to slow CKD progression, timing and criteria for initiation of KRT and standard of care for KRT.

Cost-effectiveness of empagliflozin as add-on to standard of care for chronic kidney disease management in the United Kingdom

Objective The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK. Methods A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes. Results Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses. Limitations This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression. Conclusions Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

Copeptin as a potential biomarker of chronic kidney disease to predict the disease progression in children with chronic kidney disease.

Biomarkers to predict the onset and progression of chronic kidney disease (CKD) in children are lacking, and no such definite biomarkers have been implicated in the diagnosis of CKD. We conducted this study to evaluate copeptin as a CKD marker and predict the disease progression by estimating the copeptin levels at baseline and 12 months follow-up in children with CKD stage 2 and above. This prospective single-centre cohort study was conducted in children under 14 years with CKD stages 2-4. Blood and urine samples were collected at enrolment and 1-year follow-up for routine investigations and serum copeptin, cystatin C and urinary neutrophil gelatinase-associated lipocalcin (uNGAL) estimation. A total of 110 children (60 cases and 50 controls) were enrolled in the study. The mean estimated glomerular filtration rate (eGFR) of cases was 58.3 ± 18.7 ml/min/1.73 m2. Among the cases, there was a significant rise in the serum copeptin levels from baseline 483.08 ± 319.2 pg/ml to follow-up at 1 year, that is, 1046.82 ± 823.53 pg/ml (P < 0.0001). A significant difference was noted in the baseline values of serum cystatin C, that is, 1512.98 ± 643.77 ng/ml and 719.68 ± 106.96 ng/ml (P < 0.0001), and uNGAL, that is, 13.53 ± 11.72 and 1.76 ± 2.37 ng/ml (P < 0.0001) between the cases and controls. There was no significant correlation (correlation coefficient = 0.10) between change in eGFR and copeptin levels during 12 months of follow-up. No significant correlation was found between the change in eGFR and copeptin levels during 12 months of follow-up. This can be due to the slow deterioration of renal functions, as most of the cases had underlying congenital anomalies of the kidney and urinary tract (CAKUT), which is known to have a slow progression of CKD and a small sample size.

Correlation between Urinary Angiotensinogen (AGT) and Albuminuria in Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is a global health concern associated with significant morbidity and mortality. Albuminuria, a hallmark of kidney damage, is a strong predictor of CKD progression and adverse outcomes. Recent research has focused on understanding the correlation between urinary angiotensinogen (AGT) levels, a component of the renin-angiotensin system (RAS), and albuminuria in CKD patients. This review article synthesizes evidence from various studies exploring this correlation and elucidates its mechanistic insights and clinical implications. Clinical studies consistently demonstrate a positive correlation between urinary AGT levels and albuminuria in CKD patients. Elevated urinary AGT levels are associated with increased albuminuria, independent of traditional risk factors, suggesting a potential role for AGT in the pathogenesis of kidney damage and proteinuria in CKD. Mechanistic insights suggest that increased intrarenal RAS activity may lead to enhanced AGT production and secretion, contributing to glomerular hypertension, inflammation, and fibrosis, ultimately promoting albuminuria and CKD progression. The clinical implications of this correlation are profound. Elevated urinary AGT levels may serve as a non-invasive biomarker for assessing intrarenal RAS activity and predicting CKD progression and adverse outcomes. Furthermore, interventions targeting the RAS pathway, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may help reduce urinary AGT levels and mitigate albuminuria, offering promising therapeutic opportunities for improving patient outcomes in CKD. In conclusion, the correlation between urinary AGT and albuminuria in CKD represents a complex interplay between renal physiology, RAS activation, and kidney damage. By elucidating this correlation, we gain valuable insights into the pathogenesis of CKD and identify urinary AGT as a potential biomarker and therapeutic target for personalized CKD management. Further research is warranted to validate these findings, explore the clinical utility of urinary AGT measurement, and develop targeted interventions aimed at mitigating albuminuria and slowing CKD progression. Through continued investigation, we can strive to improve outcomes and quality of life for patients living with CKD.

Sodium-Glucose Cotransporter 2 Inhibitors for Chronic Kidney Disease: A Comprehensive Review

Chronic Kidney Disease (CKD) is a major global health burden. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated potential in slowing CKD progression. We evaluated the expanding role of SGLT2 inhibitors, emphasizing their renoprotective benefits in diabetic and non-diabetic CKD patients. We also investigated the underlying mechanisms, including the reduction of glomerular hypertension via modulation of tubuloglomerular feedback. Our study critically analyzed current indications for SGLT2 inhibitor therapy based on recent clinical trial data. To optimize patient outcomes, we present a comprehensive analysis of practical considerations for the prescription of SGLT2 inhibitors, including the potential initial decline in the estimated glomerular filtration rate and a review of adverse events.