Background:Finerenone is associated with a lower, yet clinically relevant, risk of hyperkalemia compared with steroidal mineralocorticoid receptor antagonists in diabetic kidney disease (DKD) trials. However, real-world data on hyperkalemia and its associated factors are scarce. Methodology:FINE-TURK is a national, observational cohort of DKD patients who were initiated on finerenone. Eligible adults were included; demographic, clinical, and laboratory data were evaluated. The primary outcome was hyperkalemia risk signal (potassium ≥5.0 mEq/l), and the secondary outcome was clinically meaningful hyperkalemia (potassium ≥5.5 mEq/l) within 3 months. Multivariate logistic regression (LR) was used to define features associated with the both outcomes. Machine learning methods of LR, random forest (RF), extreme gradient boosting, and categorical boosting classifiers were used to define important features associated with the primary outcome. Results:Total 699 patients were included. Of them, 259 (37.1%) reached the primary outcome, and 51 (7.3%) reached the secondary outcome. Baseline serum potassium, estimated glomerular filtration rate (eGFR), and finerenone dose were associated with the both outcomes in multivariate LR. Machine learning analyses consistently identified baseline serum potassium and eGFR as the most influential factors associated with primary outcome, with thiazide use being associated with lower risk and 20 mg (compared to 10 mg) finerenone initiation being associated with higher risk. LR demonstrated the highest recall; RF achieved the highest precision in performance. Discussion:Real-world data suggest that the risk of clinically meaningful hyperkalemia is similar to that in the clinical trials. In parallel with the safety analysis of clinical trials, baseline potassium and eGFR were consistently the most important factors associated with hyperkalemia risk.

Introduction:Diabetic kidney disease (DKD) presents with distinct phenotypes, including albuminuric (ADKD) and non-albuminuric DKD (NADKD), which are not fully distinguished by conventional clinical markers. This study aimed to evaluate urinary biomarkers indicative of nephron injury - nephrin, epidermal growth factor (EGF), vascular cell adhesion molecule-1 (VCAM-1), interleukin-18 (IL-18), and Rac-1 (Ras-related C3 botulinum toxin substrate) across various DKD phenotypes. Methods:In this cross-sectional study, 211 patients with type 2 diabetes mellitus were categorized into four groups based on estimated glomerular filtration rate (eGFR ≥ or <60 mL/min/1.73 m2) and albuminuria (UACR ≥ or <30 mg/g). Urinary biomarker levels were quantified using ELISA. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to minimize confounding. Results:EGF levels were significantly higher in the NADKD compared to the ADKD group. VCAM-1 was elevated in individuals with albuminuria and those with mildly reduced eGFR (<90 mL/min/1.73 m2). IL-18 was increased in NADKD and correlated positively with Rac-1 (ρ = 0.19, p = 0.005) and nephrin (ρ = 0.19, p = 0.006). These associations remained robust after adjustment for PSM and IPTW. EGF demonstrated strong diagnostic performance in predicting reduced eGFR (AUC = 0.818, p < 0.001), and VCAM-1 moderately identified albuminuria (AUC = 0.722, p < 0.001). Conclusions:Higher EGF levels in the NADKD group suggest preserved tubular integrity, whereas elevated VCAM-1 in patients with albuminuria and mildly reduced eGFR indicate early vascular involvement. Positive correlations between IL-18, Rac-1, and nephrin imply a shared inflammatory and glomerular injury pathway. These results support the use of urinary biomarkers for early detection and phenotypic classification of DKD.

Background/Objectives: Finerenone improves cardiovascular and renal outcomes in diabetic kidney disease (DKD), but hyperkalemia remains a key safety concern. Patients with elevated baseline potassium levels (≥4.9 mEq/L) are largely excluded from clinical trials, and real-world data in this population are scarce. Methods: In this retrospective multicenter cohort study derived from the FINE-TURK cohort, adults with DKD who initiated finerenone with baseline potassium ≥ 4.9 mEq/L were included. The primary outcome was clinically significant hyperkalemia (K ≥ 5.5 mEq/L) within three months. Multivariable logistic regression analyses were used to identify associated factors, with multiple sensitivity analyses performed. Results: A total of 166 patients were included, of whom 47 (28.3%) had baseline potassium levels between 5.1 and 5.5 mEq/L. Of the 166 patients, 35 (21.1%) reached the primary outcome, and 10 (6%) patients had follow-up potassium ≥ 6.0 mEq/L. 126 (76.8%) patients required no intervention, 24 (14.6%) were initiated on potassium binders, and finerenone was discontinued in only 12 (7.3%) patients. Lower baseline estimated glomerular filtration rate, baseline urinary albumin, loop diuretic use and 20 mg finerenone dose were associated with the primary outcome. In contrast, baseline potassium was not associated with the primary outcome. Conclusions: In patients with DKD and elevated baseline potassium levels, finerenone initiation was associated with manageable rates of hyperkalemia. Our findings support the cautious use of finerenone in selected patients under close monitoring, as well as highlight the need for a multidimensional approach to hyperkalemia risk assessment.

Kidney diseases are among the fastest-growing global health burdens, with chronic kidney disease projected to become the third leading cause of death by 2050. Despite this, therapeutic innovation remains limited: no European Medicines Agency-approved treatment exists for acute kidney injury, and no drugs have demonstrated survival benefits in patients on dialysis. Randomized controlled clinical trials, although pivotal for advancing care, face persistent challenges in nephrology, including patient heterogeneity, multimorbidity, high dropout rates and small populations in rare diseases. In Europe, these intrinsic obstacles are compounded by fragmented implementation of the Clinical Trials Regulation (536/2014), excessive safety reporting demands and lack of nephrology-specific guidance, discouraging academic-led initiatives and limiting pragmatic research. The Coalition for Reducing Bureaucracy in Clinical Trials, a broad alliance of medical societies and patient advocates, has recently published the 'Clinical research in Europe: putting quality and patient safety first' recommendations calling for regulatory harmonization, simplified safety reporting and patient-centred consent. The European Renal Association, a member of the Coalition and contributor to the report, fully supports these recommendations. Implementing such measures is critical to fostering efficient, high-quality nephrology trials in Europe and delivering urgently needed, evidence-based, life-saving and safe therapies for patients with kidney disease.

The Turkish Hypertension Consensus Report (THCR) was first published in 2015 and subsequently updated in 2019 to provide practical guidance for clinicians involved in the diagnosis and management of hypertension in outpatient clinical settings. The report was prepared as a joint initiative of the Turkish Society of Cardiology, the Turkish Society of Internal Medicine, the Turkish Society of Endocrinology and Metabolism, the Turkish Society of Nephrology, and the Turkish Society of Hypertension and Renal Diseases. In recent years, substantial changes have occurred in the definition and staging of hypertension, and various professional organizations have proposed different blood pressure thresholds and cardiovascular risk scoring systems in their guidelines. These developments necessitated a further update of the consensus report. In addition to the original five societies, the Turkish Academic Geriatrics Society and the Turkish Association of Family Physicians contributed to the preparation of the 2025 update of the THCR. In the updated 2025 report, 'normal blood pressure' was defined as systolic blood pressure (SBP) <120 mmHg and diastolic blood pressure (DBP) <80 mmHg, based on measurements obtained in outpatient clinical settings. SBP values of 120-139 mmHg or DBP values of 80-89 mmHg were classified as 'elevated blood pressure,' whereas SBP ≥140 mmHg or DBP ≥90 mmHg was defined as 'hypertension.' Hypertension was categorized as Stage 1 (SBP 140-159 mmHg or DBP 90-99 mmHg) and Stage 2 (SBP ≥160 mmHg or DBP ≥100 mmHg). In addition to office blood pressure measurements, the use of home and ambulatory blood pressure monitoring in the diagnosis of hypertension was emphasized. Laboratory investigations were updated and categorized into baseline tests and additional tests aimed at detecting target organ damage in hypertensive patients, and the diagnostic criteria for secondary hypertension were revised. Age- and frailty-based treatment thresholds and blood pressure targets were defined independently of comorbidities for three subgroups: patients aged 18-79 years (treatment threshold ≥140/90 mmHg; target 120-130/70-80 mmHg), patients aged ≥80 years (threshold ≥140 mmHg; target 130-140 mmHg), and frail patients (threshold ≥160 mmHg; target 140-150 mmHg). Immediate initiation of combination antihypertensive therapy was recommended for all patients with SBP/DBP ≥140/90 mmHg (Stage 1 and Stage 2 hypertension). In the elevated blood pressure treatment subgroup (SBP 130-139 mmHg, DBP 80-89 mmHg), antihypertensive therapy was recommended if blood pressure remained uncontrolled despite three months of lifestyle modification in the presence of diabetes mellitus (age >40 years, diabetes duration >10 years, diabetes-related complications, or additional risk factors such as obesity or active smoking), chronic kidney disease (albuminuria >30 mg/day or spot urine albumin-to-creatinine ratio >30 mg/g), established cardiovascular disease (coronary artery disease, peripheral artery disease, heart failure), stroke, or increased cardiovascular risk as assessed by SCORE2 (>15%) or SCORE2-OP (>20%). A stepwise combination treatment algorithm was provided based on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), thiazide or thiazide-like diuretics, and mineralocorticoid receptor antagonists (MRAs). The algorithm includes initiation with low- or full-dose dual therapy ('ACEI or ARB + CCB' or 'ACEI or ARB + diuretic') as the first step; escalation to full-dose dual therapy (for those started on low doses) or to low- or full-dose triple therapy (ACEI or ARB + CCB + diuretic) as the second step; escalation to full-dose triple therapy as the third step; and use of quadruple therapy (ACEI or ARB + CCB + diuretic + MRA) as the fourth step. Monotherapy was recommended primarily in selected clinical situations, including patients aged >80 years, frail patients, those with elevated blood pressure, and patients with orthostatic hypotension. Overall, seven new sections were added to the 2025 report: frailty assessment in hypertension, resistant hypertension, isolated systolic hypertension, isolated diastolic hypertension, orthostatic hypotension, hypertensive emergencies, and recommendations addition, four supplementary files were provided, addressing key considerations for patients and physicians during manual aneroid and ambulatory blood pressure measurements, medications and substances that may increase blood pressure, definitions of frailty and fitness and their implications for antihypertensive therapy, and non-cardiovascular drugs that may lower blood pressure below target levels during antihypertensive treatment. Although the evidence-based recommendations presented in this report are applicable to most hypertensive outpatients, clinical decision-making by the treating physician remains essential for the delivery of individualized, patient-centered care.

Background:Hypertension (HTN) is a leading risk factor for cardiovascular (CV) and renal morbidity and mortality, yet blood pressure (BP) control remains suboptimal worldwide. Understanding management patterns, especially among patients with coexisting Type 2 diabetes mellitus (T2DM), chronic kidney diseases (CKDs), or heart failure (HF), and assessing uncontrolled HTN burden across diverse health systems are critical to inform guideline-concordant strategies to improve care. Methods:Cross-sectional analysis includes participants with HTN, with or without comorbid T2DM, CKD, or HF enrolled in iCaReMe Global Registry across 29 countries. Demographic and clinical characteristics, antihypertensive treatment patterns, prevalence of uncontrolled HTN (defined as SBP ≥ 130 mmHg or DBP ≥ 80 mmHg), and its associated factors were assessed. Results:Among 23,063 participants, comorbidities included T2DM (71.4%), CKD (38.2%), and HF (14.6%). Key CV risk factors were family history of CV disease (34.3%), obesity (40.5%), and dyslipidemia (51.0%). Echocardiography (available in 28.6%) revealed left ventricular hypertrophy (LVH) in 30.6% and diastolic dysfunction in 42.4%. Overall, 88.7% were prescribed antihypertensive drugs: renin-angiotensin system (RAS) blockers (76.6%), calcium channel blockers (CCBs, 42.0%), beta-blockers (41.4%), diuretics (23.7%), with a majority (62.3%) on combination regimens. Uncontrolled HTN was prevalent in 75.4%, who were younger (59.8 vs 61.8 years) and exhibited higher burden of obesity (42.5% vs 34.6%), CKD (39.3% vs 33.1%), LVH (32.9% vs 24.8%), and treated less intensively with antihypertensives (60.2% vs 88.7%) and combinations (46.2% vs 61.8%) when compared to the controlled HTN group. Multivariate analysis confirmed independent association of non-use of RAS blockers/CCB/diuretics combinations (dual/triple therapy), obesity, and comorbid CKD, with uncontrolled HTN (OR [95% CI], 2.8 [2.44-3.18]/2.3 [1.66-3.16], 1.5 [1.38-1.65], and 1.4 [1.27-1.53], respectively, p < 0.0001). Conclusion:This study uncovers alarming rates of uncontrolled HTN in real-world settings, exacerbated by comorbid T2DM/CKD/HF, underscoring the need to identify HTN management gaps and tailor innovative strategies to mitigate CV risk. Trial Registration: ClinicalTrials.gov identifier: NCT03549754.

In 2025, the World Health Assembly of the World Health Organization (WHO) adopted a resolution on reducing the burden of noncommunicable diseases (NCDs) by promoting kidney health and strengthening the prevention and control of kidney disease. Following the WHO resolution, the United Nations (UN) included kidney health in its 2025 Political Declaration on NCDs. These measures are a clear response to the growing burden of kidney diseases. This achievement for kidney health was facilitated by years of effort by multiple stakeholders and decision-makers, including nephrology associations, particularly the International Society of Nephrology, the European Renal Association (ERA) and the American Society of Nephrology, gathering evidence on the growing burden of chronic kidney disease (CKD), raising awareness of this burden, advancing research and innovation, and adopting scientific and policy recommendations for the early detection, prevention and treatment of CKD. The WHO and UN measures add kidney disease to a list of major NCDs (e.g. cancer, cardiovascular diseases, diabetes, respiratory diseases) that should be prioritized by healthcare systems. The kidney health resolution is fully aligned with the ERA's activities and recommendations, as well as with the 2025 KDIGO document on the prevention of CKD and maintenance of kidney health. This novel preventive approach has been tried and tested for other conditions, such as cardiovascular disease, the age-adjusted mortality of which is falling dramatically, compared with the equally dramatic increase in CKD mortality. The next step would be to define an actionable condition of very high risk of CKD, that may be termed pre-CKD. This should be complemented by programs for the early diagnosis and treatment of CKD, such as the one promoted by ERA's 'Protect Your Kidneys, Protect Your Future' campaign which emphasizes the need to know and treat the ABCDE numbers (Albuminuria, Blood pressure, Cholesterol, Diabetes, Estimated glomerular filtration rate) to improve cardiovascular-kidney-metabolic health.

PURPOSE:Hypertension remains the leading modifiable risk factor for cardiovascular morbidity and premature mortality worldwide. While its prevalence has declined across much of Europe in recent decades, this trend has not been observed in the Balkan region, where rates remain persistently high. This narrative review aims to synthesise current evidence on the epidemiology of hypertension in the Balkans and to explore potential determinants underlying this sustained burden. MATERIALS AND METHODS:We conducted a narrative review of available literature, including population-based surveys, reports from the World Health Organization, and national epidemiological data from Balkan countries. Relevant studies were identified to evaluate prevalence patterns and associated determinants of hypertension across the region. RESULTS:Data consistently indicate that hypertension prevalence in most Balkan countries approaches or exceeds 50% of the adult population. However, notable intra-regional variation exists, with Türkiye and Greece demonstrating prevalence levels closer to global averages. The excess burden of hypertension in the Balkans appears to be multifactorial, associated with persistently high dietary salt intake, socioeconomic disparities, structural limitations in healthcare systems, and region-specific environmental influences. These factors act synergistically rather than independently. CONCLUSION:The Balkan region represents a distinct epidemiological hotspot for hypertension within Europe. The sustained high prevalence is likely driven by the convergence of multiple interacting determinants, in contrast to Western Europe where long-term investments in primary care-based prevention have led to declining rates. Effective management of hypertension in the Balkans will require integrated, context-specific strategies that extend beyond individual-level interventions.

Background: Patients with chronic kidney disease (CKD), including autosomal dominant polycystic kidney disease (ADPKD), have been reported to be at higher risk for adverse outcomes during the COVID-19 pandemic. We aimed to obtain the characteristics and outcome data obtained in the follow-up of patients with ADPKD who survived COVID-19 and to compare these data with a control group with ADPKD who were COVID-19 naive. Methods: In this national, multicenter observational study, adult ADPKD patients who survived COVID-19 were included, and ADPKD patients without a history of COVID-19 from the same outpatient clinics were selected as a control group. Baseline characteristics and post-COVID-19 first- and third-month data were recorded. Results: In this study, a total of 72 ADPKD patients from 16 centers were included in the study (COVID-19 group, n: 40, non-COVID-19 control group, n: 32). Fourteen (33.3%) patients in the COVID-19 group were hospitalized during active COVID-19. During the first and third months after COVID-19, none of the patients died in either group. Urinary tract infection was significantly higher in the non-COVID-19 group than in the COVID group in the third month (0% vs. 12.5%, p = 0.021). All other follow-up outcomes, including respiratory symptoms and initiation of kidney replacement therapy (KRT), were not different between the groups in the first and third months. The laboratory data of the groups in the first and third months were not significantly different. Hematuria and leukocyturia ratios were also not statistically significantly different between the groups. Conclusions: ADPKD patients who survive COVID-19 have no worse short-term outcomes than non-COVID-19 ADPKD patients, including respiratory symptoms, initiation of KRT, and death.

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improves cardiorenal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease. However, real-world data on its use in patients with concomitant heart failure remain limited. This study aimed to evaluate the baseline characteristics and short-term renal safety and efficacy of finerenone in patients with type 2 diabetes, kidney disease, and heart failure from the FINE-TURK Registry. This was a retrospective, multicenter, observational registry analysis conducted across 56 centers in Türkiye. Among 1,168 patients initially enrolled, 918 patients with available heart failure status and ejection fraction data were included. Patients were categorized according to the presence of heart failure, and heart failure patients were further classified as HFrEF or HFmrEF/HFpEF. Three-month changes in serum potassium, estimated glomerular filtration rate, and albuminuria were assessed. Safety endpoints included serum potassium ≥ 5.5 mEq/L and eGFR ≤ 25 mL/min/1.73 m² at three months. The primary renal efficacy endpoint was a > 30

KEY POINTS:Semaglutide reduced kidney outcome risk across broad CKD severity strata (eGFR; albuminuria). Reduced risk for all-cause death also carried through strata of CKD severity. In a population with type 2 diabetes, semaglutide improved kidney and survival outcomes irrespective of CKD severity, including advanced CKD. BACKGROUND:Semaglutide improved kidney and overall survival in participants with type 2 diabetes (T2D) and CKD in the Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial. The aim of the present analyses was to quantify these benefits across broad strata of CKD severity. METHODS:FLOW was a double-blind, randomized, placebo-controlled trial (median follow-up 3.4 [interquartile range, 2.9-4.0] years). Participants with T2D and eGFR 50-75 ml/min per 1.73 m 2 and urine albumin-to-creatinine ratio (UACR) >300 to <5000 mg/g, or eGFR 25 to <50 ml/min per 1.73 m 2 and UACR >100 to <5000 mg/g, were randomized to subcutaneous semaglutide 1 mg once-weekly or placebo. Subgroups were categorized by baseline eGFR (<30 to ≥60 ml/min per 1.73 m 2 ) or UACR (<100 to ≥2000 mg/g) to assess the primary outcome and individual components (≥50% eGFR decline, eGFR <15 ml/min per 1.73 m 2 , dialysis, kidney transplant, and death due to kidney or cardiovascular causes), all-cause death, eGFR, and UACR. RESULTS:At baseline, the mean±SD eGFR was 47±15 ml/min per 1.73 m 2 , and the median (5th-95th percentile) UACR was 568 (51-3225) mg/g. The primary outcome occurred in 19% (331 of 1767) versus 23% (410 of 1766) with semaglutide treatment versus placebo (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66 to 0.88). Death occurred in 13% (227 of 1767) versus 16% (279 of 1766), respectively (HR, 0.80; 95% CI, 0.67 to 0.95). Across eGFR and UACR subgroups, HRs for the primary outcome remained consistent ( P for interaction 0.83 and 0.42, respectively). For death, HRs were consistent among eGFR subgroups ( P for interaction 0.54), but the HR was lowest (0.47; 95% CI, 0.31 to 0.70) for those with UACR ≥2000 mg/g ( P for interaction 0.02). Estimated treatment effects on eGFR and UACR were generally consistent among subgroups. CONCLUSIONS:Semaglutide reduced risks of major kidney disease events and all-cause death across wide-ranging categories of baseline eGFR and UACR, supporting semaglutide treatment in T2D throughout the spectrum of CKD severity represented in FLOW, including advanced CKD.Clinical Trial registry name and registration number: NCT03819153 .

Real-world evidence describing the early laboratory course after finerenone initiation in contemporary nephrology practice remains limited, particularly in cohorts with high background use of sodium-glucose co transporter 2 inhibitors (SGLT2i). We evaluated early kidney-function, potassium, and albuminuria trajectories and short-term treatment tolerability. FINE-TURK was a multicenter retrospective cohort study without a comparator group. Adults with diabetes and chronic kidney disease who initiated finerenone in routine care were evaluated at baseline and using the first available values recorded in the 1–3-month follow-up fields. Primary outcomes were within-patient changes in estimated glomerular filtration rate (eGFR), serum potassium, and urinary albumin-to-creatinine ratio (UACR). Complete and incomplete follow-up groups were compared, UACR responder analyses were performed, and exploratory multivariable and subgroup models were fitted. The analytic cohort contained 1,091 patients (mean age 60.6 ± 11.5 years; 55.0

Background/Objectives: Finerenone improves cardiovascular and renal outcomes in diabetic kidney disease (DKD), but hyperkalemia remains a key safety concern. Patients with elevated baseline potassium levels (≥ 4.9 mEq/L) are largely excluded from clinical trials, and real-world data in this population are scarce. Methods: In this retrospective multicenter cohort study derived from the FINE-TURK cohort, adults with DKD who initiated finerenone with baseline serum potassium ≥ 4.9 mEq/L were included. The primary outcome was clinically significant hyperkalemia (CSH) (≥ 5.5 mEq/L) within three months. Multivariable logistic regression analyses were used to identify associated factors, with multiple sensitivity analyses performed. Results: 166 patients were included, of whom 47 (28.3%) had baseline potassium levels between 5.1 to 5.5 mEq/L. Of the 166 patients, 35 (21.1%) developed CSH, and 10 (6%) patients had follow-up potassium ≥ 6.0 mEq/L. 126 (76.8%) patients required no intervention, 24 (14.6%) were initiated on potassium binders, and finerenone was discontinued only in 12 (7.3%) patients. Baseline eGFR, baseline urinary albumin, loop diuretic use and 20mg finerenone dose were associated with CSH. In contrast, baseline serum potassium was not associated with CSH. Conclusions: In patients with DKD and elevated baseline potassium levels, finerenone initiation was associated with manageable rates of hyperkalemia. Our findings support the cautious use of finerenone in selected patients under close monitoring, as well as highlight the need for a multidimensional approach to hyperkalemia risk assessment.

BACKGROUND:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly prescribed because of their renal and cardiovascular benefits. However, polypharmacy is common among patients with chronic kidney disease (CKD), raising concerns about cumulative nephrotoxic medication exposure. This study aimed to evaluate drug-related problems (DRPs), nephrotoxic medication burden, kidney failure risk, and patient-reported outcomes in patients receiving SGLT2i in a nephrology outpatient clinic. METHODS:This observational study was conducted in a nephrology outpatient clinic of a university hospital between September 2022-February 2023. Patients ≥18 years who were newly prescribed an SGLT2 inhibitor were included. A clinical pharmacist performed comprehensive medication reviews, identified and categorized DRPs using the Pharmaceutical Care Network Europe (PCNE) classification system, and assessed nephrotoxic exposure by a structured nephrotoxicity score based on drug-specific risk categories. Kidney failure risk was estimated using the Kidney Failure Risk Equation, and quality of life was assessed using the KDQOL-36 questionnaire. RESULTS:Seventy-two patients were included, and 69 DRPs were identified through clinical pharmacist-led medication review. The most common DRPs were inappropriate duration of therapy (20.3%), medication without indication (15.9%), and untreated symptoms (13.0%). Pharmacist's recommendations were highly accepted (85.5%). The median number of nephrotoxic drugs per patient was 2 (IQR:1-3), while the median nephrotoxicity score was 1.5 (IQR: 1-2). No clinically overt nephrotoxic events were observed during follow-up, and nephrotoxicity burden was not significantly associated with estimated kidney failure risk. CONCLUSION:This study provides real-world descriptive data on nephrotoxic medication exposure, drug-related problems, and clinical pharmacist-led medication review among CKD patients receiving SGLT2i in a nephrology outpatient setting. Further prospective controlled studies are needed to clarify the clinical impact of pharmacist-led medication review on patient.

Chronic kidney disease (CKD) significantly impacts healthcare systems and economies. The kidney failure risk equation (KFRE), developed in 2011, predicts the risk of progression to kidney failure more accurately. KFRE may guide better management of healthcare resources and is increasingly used in practice. The primary objectives of this study were to estimate the risk of progression to end-stage kidney disease (ESKD) in patients diagnosed with stage G3-G4 CKD using KFRE and to examine the impact on healthcare resource utilization. This single-center, retrospective observational study was conducted in the Department of Nephrology at Hacettepe University Hospitals. Patients aged 18 years and older, with an estimated glomerular filtration rate between 15-60 mL/min/1.73 m² and who were regularly followed up from 2014 to 2019 were included in the study. Patients with missing data at the time of admission, pregnancy status, malignancy, and history of renal replacement therapy were excluded, and a total of 822 patients were included in the study. 4- and 8-variable KFRE were calculated. Stage G3 and G4 CKD patients were analyzed in all risk categories as low, intermediate, and high risk according to KFRE. The term “end stage kidney disease-free survival” (ESKD-fs) was used to report the survival rates of patients who did not undergo dialysis and/or kidney transplantation. Hospital resource use and costs were evaluated separately in all risk categories. In stage G3 patients, according to the 4- and 8-variable KFRE, the 5-year ESKD-fs rate was significantly higher in low-risk patients compared to those in the intermediate- and high-risk groups (P < 0.001 and P < 0.001, respectively) (Figs 1 and 2). In stage G4 patients, according to the 4- and 8-variable KFRE, the 2-year ESKD-fs rate was significantly higher in low-risk patients compared to those in the other risk groups (P < 0.001 and P < 0.001, respectively) (Figs 3 and 4). In addition, according to the 4-variable KFRE classification, the median annual outpatient treatment cost in stage G3 patients was found to be $121 in the high-risk group, $98 in the intermediate-risk group, and $94 in the low- risk group (P = 0.017). According to the 4-variable KFRE classification for patients with stage G3, the median annual hospitalization costs were $622 in the high-risk group, $447 in the intermediate-risk group, and $433 in the low-risk group (P = 0.025). According to the 8- variable KFRE classification, the median annual hospitalization costs in patients with stage G3 were $628 in the high-risk group, whereas they were $478 and $423 in the intermediate- and low-risk groups, respectively (P = 0.045). Furthermore, according to the 4- variable KFRE for patients with stages G3 and G4, the median annual hospitalization numbers were significantly higher in the high-risk group (P < 0.001 and P = 0.006, respectively). This study demonstrated that KFRE models accurately predict the 2- and 5-year risk of progression to ESKD in patients with stage 3–5 CKD. We demonstrated that patients with stage G3 CKD, who are at higher risk of progression to renal failure according to KFRE, have higher hospital outpatient and hospitalization costs compared to patients in the low-risk category. Effective application of KFRE emerges as a powerful tool for early diagnosis and cost-effective management of at-risk patients.

BACKGROUND:Patients undergoing maintenance dialysis for kidney failure are at substantial risk of cardiovascular morbidity and mortality. We aimed to establish if spironolactone reduces heart failure and cardiovascular deaths in these patients. METHODS:ACHIEVE was an international, parallel-group, randomised controlled trial done in 143 dialysis programmes in 12 countries. Patients were aged 45 years or older, or aged 18 years or older with a history of diabetes, and were receiving maintenance dialysis for kidney failure for at least 3 months at the time of recruitment. Patients who were able to tolerate and adhere to spironolactone 25 mg daily orally during an open-label run-in were randomly assigned (1:1) to continue spironolactone or matching placebo, using a central computerised block randomisation system (block sizes of 4) stratified by centre. Participants, health-care providers, and those assessing outcomes were masked to group assignment. The primary outcome was a composite of cardiovascular mortality or hospitalisation for heart failure analysed as time-to-event in all randomly assigned participants. The trial was registered at ClinicalTrials.gov, NCT03020303. FINDINGS:After a planned interim analysis of 75% of the expected primary outcome events, the external safety and efficacy monitoring committee recommended the trial be stopped early for futility. From Sept 19, 2017, to Oct 31, 2024, 3689 patients were screened for inclusion, 3565 of whom were enrolled in the open-label run-in phase, and 2538 were randomly assigned to spironolactone (n=1260) or placebo (n=1278). 931 (36·7%) participants were female and 1607 (63·3%) were male. Median follow-up was 1·8 years (IQR 0·85-3·35). The composite primary outcome occurred in 258 participants (10·46 events per 100 patient-years) in the spironolactone group and in 276 participants (11·33 per 100 patient-years) in the placebo group (hazard ratio [HR] 0·92 [95% CI 0·78-1·09]; p=0·35). Death from any cause was similar between groups (HR 0·95 [0·83-1·09]) as was hospitalisation for any cause (HR 0·96 [0·87-1·06]). INTERPRETATION:Among patients receiving maintenance dialysis, spironolactone 25 mg daily orally did not reduce the composite outcome of cardiovascular mortality and hospitalisation due to heart failure compared with placebo. This trial did not identify a benefit of initiating spironolactone in patients receiving maintenance dialysis. Future research should consider alternatives to steroidal mineralocorticoid receptor antagonism to reduce cardiovascular morbidity and mortality in patients receiving maintenance haemodialysis. FUNDING:The Canadian Institutes of Health Research, The Medical Research Future Fund, The Health Research Council, The British Heart Foundation, Population Health Research Institute/Hamilton Health Sciences Research Institute, St Joseph's Healthcare Hamilton Division of Nephrology, Accelerating Clinical Trials Consortium, Can-SOLVE CKD Network, and the Dalhousie Department of Medicine.