GLP-1RA vs DPP-4i Use and Rates of Hyperkalemia and RAS Blockade Discontinuation in Type 2 Diabetes.

Importance: Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. Objective: To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). Design, Setting, and Participants: This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. Exposures: GLP-1RAs or DPP-4is. Main Outcomes and Measures: The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). Results: A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. Conclusions: In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.

Protein Intake and Mortality in Older Adults With Chronic Kidney Disease.

Importance: Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. Objective: To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Design, Setting, and Participants: Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Exposures: Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. Main Outcomes and Measures: The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. Results: The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). Conclusions and Relevance: In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

A roadmap for implementing a successful clinical experience with intradialytic parenteral nutrition.

BACKGROUND AND AIMS: Intradialytic parenteral nutrition (IDPN) is a safe and effective patient-tailored nutritional strategy for providing nutrient supplementation to malnourished or at risk of malnutrition patients on hemodialysis (HD), who did not adequately respond to intensive dietary counselling and oral nutritional supplementation. Although IDPN is recommended by current ESPEN and KDOQI guidelines for nutrition in HD patients, none of these documents informs how to successfully implement this therapy, being the lack of knowledge on practical aspects of IDPN one of the main limitations to its use. The aim of this narrative review was to provide a practical roadmap for guiding the nephrologists, dietitians, and renal nurses in their everyday clinical practice about the use of IDPN. METHODS: A multidisciplinary group formed by specialists from the areas of Nephrology and Nutrition agreed to address different practical aspects related to IDPN in HD patients. Based on the available evidence in the literature and on the authors' clinical experience, different topics were selected to develop a detailed plan for implementing a successful experience with IDPN, proposing a practical IDPN roadmap. RESULTS: This IDPN roadmap provides practical information on when an IDPN should be started; what type of nutrients should be part of an IDPN; how the IDPN should be administered; how the effectiveness and safety of the IDPN should be monitored; how to determine the effectiveness of IDPN; and the conditions that advise discontinuing the IDPN. CONCLUSIONS: IDPN is a safe and effective nutritional therapy for HD patients, although the lack of staff training may limit its use. This review addresses different practical aspects of IDPN, helping interdisciplinary teams in their daily clinical practice to improve the nutritional care of HD patients, either malnourished or at risk of malnutrition.

Burden of CKD-Associated Pruritus and Adverse Clinical Outcomes in Patients Receiving Dialysis: The Stockholm CREAtinine Measurements (SCREAM) Project.

RATIONALE & OBJECTIVE: Pruritus is a common but not well-characterized complaint of patients receiving maintenance dialysis. This study sought to quantify the burden of pruritus and its associated adverse health outcomes in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: All patients receiving maintenance dialysis in Stockholm, Sweden, during 2005-2021. EXPOSURE: Clinically recognized pruritus, defined using ICD-10 codes or the prescription for anti-pruritus treatments (including UV-therapy). OUTCOMES: All-cause mortality, severe infection-related hospitalizations (composite of endocarditis, peritoneal dialysis-related peritonitis, hemodialysis/peritoneal dialysis-related catheter infection, sepsis due to Staphylococcus Spp., or skin infection) and incident diagnoses of anxiety/depression and sleep disorders. ANALYTICAL APPROACH: Multivariable logistic regression and cause-specific hazards models to analyze factors associated with prevalent and new-onset pruritus, respectively. Multivariable cause-specific hazards models with time-varying exposure to explore the association of prevalent and new-onset pruritus with adverse health outcomes. RESULTS: Among 3281 dialysis patients (median age 64 years, 66% men, 69% on hemodialysis,77% incident dialysis patients), 456 (14%) had pruritus at enrollment. During a median follow-up of 3.3 [IQR: 1.3-9.2] years, 539 (19%) additional patients developed pruritus. Older age, female sex, a lower serum albumin level, and higher C-reactive protein, serum calcium and phosphorus levels were independently associated with pruritus. Compared to patients without pruritus, patients with pruritus were at a higher risk of suffering sleep disorders (adjusted HR: 1.96 [95%CI 1.60-2.39]), developing anxiety/depression (aHR: 1.56 [1.23-1.98]), and being hospitalized for severe infections (aHR: 1.36 [1.18-1.57]), the latter attributed to higher risk of sepsis and peritoneal dialysis-related peritonitis. There was no detectable association between developing pruritus and all-cause mortality. LIMITATIONS: Potential misclassification bias if pruritus is not clinically recognized; lack of information on pruritus intensity/severity; use of diagnostic codes for exposure and outcome diagnoses. CONCLUSION: At least one-third of patients experience pruritus during their first years on dialysis, and pruritus was consistently associated with adverse health outcomes.

Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

INTRODUCTION: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). METHODS: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. RESULTS: Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). CONCLUSION: Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04034992.

The Assessment of the Association of Proton Pump Inhibitor Usage with Chronic Kidney Disease Progression through a Process Mining Approach.

Previous studies have suggested an association between Proton Pump Inhibitors (PPIs) and the progression of chronic kidney disease (CKD). This study aims to assess the association between PPI use and CKD progression by analysing estimated glomerular filtration rate (eGFR) trajectories using a process mining approach. We conducted a retrospective cohort study from 1 January 2006 to 31 December 2011, utilising data from the Stockholm Creatinine Measurements (SCREAM). New users of PPIs and H2 blockers (H2Bs) with CKD (eGFR < 60) were identified using a new-user and active-comparator design. Process mining discovery is a technique that discovers patterns and sequences in events over time, making it suitable for studying longitudinal eGFR trajectories. We used this technique to construct eGFR trajectory models for both PPI and H2B users. Our analysis indicated that PPI users exhibited more complex and rapidly declining eGFR trajectories compared to H2B users, with a 75% increased risk (adjusted hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.49 to 2.06) of transitioning from moderate eGFR stage (G3) to more severe stages (G4 or G5). These findings suggest that PPI use is associated with an increased risk of CKD progression, demonstrating the utility of process mining for longitudinal analysis in epidemiology, leading to an improved understanding of disease progression.

Adherence and persistence to novel glucose-lowering medications in persons with type 2 diabetes mellitus undergoing routine care.

AIMS: To assess adherence and persistence to sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) in routine care. METHODS: Using retrospective healthcare data from the Stockholm region, Sweden, we evaluated new-users of these agents during 2015-2020. We investigated adherence (≥80 % of days covered by an active supply), persistence (no treatment gap ≥ 60 days), and predictors for non-adherence and non-persistence. RESULTS: We identified 24,470 new-users of SGLT2i (10,743), GLP1-RA (10,315), and/or DPP4i (9,488). Over 2.8 years median follow-up, the proportion demonstrating adherence was higher for SGLT2i (57 %) than DPP4i (53 %, comparison p < 0.001), and for GLP1-RA than DPP4i (54 % vs 53 %, p < 0.001). Similarly, persistence was higher for both SGLT2i and GLP-RA than DPP4i (respectively, 50 % vs 44 %, p < 0.001; 49 % vs 44 %, p < 0.001). Overall adherence was better among users who were older, had a history of high blood pressure, used more non-diabetic medications, had lower Hba1c, had better kidney function, and had completed secondary schooling or university. Women had worse adherence to SGLT2i and GLP1-RA than DPP4i. CONCLUSIONS: We report adherence and persistence to SGLT2i, GLP1-RA and DPP4i in routine care, and identify prognostic factors that could inform implementation interventions to improve uptake of these important therapies.

Albuminuria predicts kidney events in IgA nephropathy.

BACKGROUND & HYPOTHESIS: KDIGO recommends proteinuria <1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain insufficiently studied. METHODS: We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between urine albumin-to-creatinine ratio (uACR, in categories < 0.3, ≥0.3-0.5, ≥0.5-1.0, ≥1.0-1.5, ≥1.5-2.0 and ≥ 2.0 g/g) and the occurrence of major adverse kidney events (MAKE, a composite of kidney replacement therapy [KRT] and > 30% decline in eGFR). We also explored the risk of kidney events associated with change in uACR within a year. RESULTS: We included 1269 IgAN patients (74% men, median 53 years, mean eGFR 33 mL/min/1.73m², median uACR 0.7 g/g). Over median follow-up of 5.5 [2.8;9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced > 30% eGFR decline. Compared with uACR < 0.3 g/g, any higher uACR category was strongly and incrementally associated with the risk of MAKE (adjusted HR ranging from 1.56 [95%CI 1.14-2.14] if uACR 0.3-0.5 g/g to 4.53 [3.36-6.11] if uACR ≥ 2.0 g/g), KRT (HR ranging from 1.39 to 4.65), and eGFR decline > 30% (HR ranging from 1.76 to 3.47). In 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR. CONCLUSIONS: There is substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low-risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.

An increase in albuminuria is associated with a higher incidence of malignancies.

Background: A single albuminuria measurement is reported to be an independent predictor of cancer risk. Whether change in albuminuria is also independently associated with cancer is not known. Methods: We included 64 303 subjects of the Stockholm CREAtinine Measurements (SCREAM) project without a history of cancer and with at least two urine albumin-creatinine ratio (ACR) tests up to 2 years apart. Albuminuria changes were quantified by the fold-change in ACR over 2 years, and stratified into the absence of clinically elevated albuminuria (i.e. never), albuminuria that remained constant, and albuminuria that increased or decreased. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidences. Results: During a median follow-up of 3.7 (interquartile range 3.6-3.7) years, 5126 subjects developed de novo cancer. After multivariable adjustment including baseline estimated glomerular filtration rate and baseline ACR, subjects with increasing ACR over 2 years had a 19% (hazard ratio 1.19; 95% confidence interval 1.08-1.31) higher risk of overall cancer compared with those who never had clinically elevated ACR. No association with cancer risk was seen in the groups with decreasing or constant ACR. Regarding site-specific cancer risks, subjects with increasing ACR or constant ACR had a higher risk of developing urinary tract and lung cancer. No other associations between 2-year ACR changes and site-specific cancers were found. Conclusions: Increases in albuminuria over a 2-year period are associated with a higher risk of developing overall, urinary tract and lung cancer, independent of baseline kidney function and albuminuria. These data add important weight to the link that exists between albuminuria and cancer incidence.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Clinical impact of the Kidney Failure Risk Equation for vascular access planning.

BACKGROUND: Risk-based thresholds for arteriovenous (AV) access creation has been proposed to aid vascular access planning. We aimed to assess the clinical impact of implementing the kidney failure risk equation (KFRE) for vascular access referral. METHODS: 16,102 nephrology-referred chronic kidney disease (CKD) patients from the Swedish Renal Registry 2008-2018 were included. The KFRE was calculated repeatedly, and the timing was identified for when the KFRE risk exceeded several pre-defined thresholds and/or the estimated glomerular filtration rate <15 ml/min/1.73m2 (eGFR15). To assess the utility of the KFRE/eGFR thresholds, cumulative incidence curves of kidney replacement therapy (KRT) or death, and decision-curve analyses were computed at 6, 12 months, and 2 years. The potential impact of using the different thresholds was illustrated by an example from the Swedish access registry. RESULTS: The 12-month specificity for KRT initiation was highest for KFRE>50% 94.5 (95% Confidence interval [CI] 94.3-94.7), followed by KFRE>40% 90.0 (95% CI 89.7-90.3), while sensitivity was highest for KFRE>30% 79.3 (95% CI 78.2-80.3) and eGFR<15 ml/min/1.73m2 81.2 (95% CI 80.2-82.2). The 2-year positive predictive value was 71.5 (95% CI 70.2-72.8), 61.7 (95% CI 60.4-63.0) and 47.2 (95% CI 46.1-48.3) for KFRE>50%, KFRE>40%, and eGFR<15 respectively. Decision curve analyses suggested the largest net benefit for KFRE>40% over two years and KFRE>50% over 12 months when it is important to avoid the harm of possibly unnecessary surgery. In Sweden, 54% of nephrology-referred patients started hemodialysis in a central venous catheter (CVC) of which only 5% had AV access surgery >6 months before initiation. 60% of the CVC patients exceeded KFRE>40% a median of 0.8 years (interquartile range 0.4-1.5) before KRT initiation. CONCLUSIONS: The utility of using KFRE>40% and KFRE>50% is higher compared to the more traditionally used eGFR threshold <15 ml/min/1.73m2 for vascular access planning.

Association of Low Glomerular Filtration Rate With Adverse Outcomes at Older Age in a Large Population With Routinely Measured Cystatin C.

BACKGROUND: The commonly accepted threshold of glomerular filtration rate (GFR) to define chronic kidney disease (CKD) is less than 60 mL/min/1.73 m2. This threshold is based partly on associations between estimated GFR (eGFR) and the frequency of adverse outcomes. The association is weaker in older adults, which has created disagreement about the appropriateness of the threshold for these persons. In addition, the studies measuring these associations included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFRcr), which may be less accurate in older adults. OBJECTIVE: To evaluate associations in older adults between eGFRcr versus eGFR based on creatinine and cystatin C levels (eGFRcr-cys) and 8 outcomes. DESIGN: Population-based cohort study. SETTING: Stockholm, Sweden, 2010 to 2019. PARTICIPANTS: 82 154 participants aged 65 years or older with outpatient creatinine and cystatin C testing. MEASUREMENTS: Hazard ratios for all-cause mortality, cardiovascular mortality, and kidney failure with replacement therapy (KFRT); incidence rate ratios for recurrent hospitalizations, infection, myocardial infarction or stroke, heart failure, and acute kidney injury. RESULTS: The associations between eGFRcr-cys and outcomes were monotonic, but most associations for eGFRcr were U-shaped. In addition, eGFRcr-cys was more strongly associated with outcomes than eGFRcr. For example, the adjusted hazard ratios for 60 versus 80 mL/min/1.73 m2 for all-cause mortality were 1.2 (95% CI, 1.1 to 1.3) for eGFRcr-cys and 1.0 (CI, 0.9 to 1.0) for eGFRcr, and for KFRT they were 2.6 (CI, 1.2 to 5.8) and 1.4 (CI, 0.7 to 2.8), respectively. Similar findings were observed in subgroups, including those with a urinary albumin-creatinine ratio below 30 mg/g. LIMITATION: No GFR measurements. CONCLUSION: Compared with low eGFRcr in older patients, low eGFRcr-cys was more strongly associated with adverse outcomes and the associations were more uniform. PRIMARY FUNDING SOURCE: Swedish Research Council, National Institutes of Health, and Dutch Kidney Foundation.

Evaluation of the introduction of novel potassium binders in routine care; the Stockholm CREAtinine measurements (SCREAM) project.

BACKGROUND: The pharmacological management of hyperkalemia traditionally considered calcium or sodium polystyrene sulfonate and, since recently, the novel binders patiromer and sodium zirconium cyclosilicate. We evaluated their patterns of use, duration of treatment and relative effectiveness/safety in Swedish routine care. METHODS: Observational study of adults initiating therapy with sodium polystyrene sulfonate or a novel binder (sodium zirconium cyclosilicate or patiromer) in Stockholm 2019-2021. We quantified treatment duration by repeated dispensations, compared mean achieved potassium concentration within 60 days, and potential adverse events between treatments. RESULTS: A total of 1879 adults started treatment with sodium polystyrene sulfonate, and 147 with novel binders (n = 41 patiromer and n = 106 sodium zirconium cyclosilicate). Potassium at baseline for all treatments was 5.7 mmol/L. Sodium polystyrene sulfonate patients stayed on treatment a mean of 61 days (14% filled ≥3 consecutive prescriptions) compared to 109 days on treatment (49% filled ≥3 prescriptions) for novel binders. After 15 days of treatment, potassium similarly decreased to 4.6 (SD 0.6) and 4.8 (SD 0.6) mmol/L in the sodium polystyrene sulfonate and novel binder groups, respectively, and was maintained over the 60 days post-treatment. In multivariable regression, the odds ratio for novel binders (vs sodium polystyrene sulfonate) in reaching potassium ≤ 5.0 mmol/L after 15 days was 0.65 (95% CI 0.38-1.10) and after 60 days 0.89 (95% CI 0.45-1.76). Hypocalcemia, hypokalemia, and initiation of anti-diarrheal/constipation medications were the most-commonly detected adverse events. In multivariable analyses, the OR for these events did not differ between groups. CONCLUSION: We observed similar short-term effectiveness and safety for all potassium binders. However, treatment duration was longer for novel binders than for sodium polystyrene sulfonate.

Oral anticoagulant treatment and risk of kidney disease-a nationwide, population-based cohort study.

Background: Direct oral anticoagulants (DOACs) are recommended as first-line treatment of atrial fibrillation. Whether DOAC use is associated with lower risks of kidney complications compared with vitamin K antagonists (VKAs) remains unclear. We examined this association in a nationwide, population-based cohort study. Methods: We conducted a cohort study including patients initiating oral anticoagulant treatment within 3 months after an atrial fibrillation diagnosis in Denmark during 2012-18. Using routinely collected creatinine measurements from laboratory databases, we followed patients in an intention-to-treat approach for acute kidney injury (AKI) and chronic kidney disease (CKD) progression. We used propensity-score weighting to balance baseline confounders, computed weighted risks and weighted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing DOACs with VKAs. We performed several subgroup analyses and a per-protocol analysis. Results: We included 32 781 persons with atrial fibrillation initiating oral anticoagulation (77% initiating DOACs). The median age was 75 years, 25% had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2, and median follow-up was 2.3 (interquartile range 1.1-3.9) years. The weighted 1-year risks of AKI were 13.6% in DOAC users and 15.0% in VKA users (HR 0.86, 95% CI 0.82; 0.91). The weighted 5-year risks of CKD progression were 13.9% in DOAC users and 15.4% in VKA users (HR 0.85, 95% CI 0.79; 0.92). Results were similar across subgroups and in the per-protocol analysis. Conclusions: Initiation of DOACs was associated with a decreased risk of AKI and CKD progression compared with VKAs. Despite the potential limitations of observational studies, our findings support the need for increased clinical awareness to prevent kidney complications among patients who initiate oral anticoagulants.

Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care.

BACKGROUND: New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. METHODS: We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). RESULTS: Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. CONCLUSIONS: In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions.

Differences in the epidemiology, management and outcomes of kidney disease in men and women.

Improved understanding of differences in kidney disease epidemiology, management and outcomes in men and women could help nephrologists to better meet the needs of their patients from a sex- and gender-specific perspective. Evidence of sex differences in the risk and outcomes of acute kidney injury is mixed and dependent on aetiology. Women have a higher prevalence of chronic kidney disease (CKD) stages 3-5 than men, whereas men have a higher prevalence of albuminuria and hence CKD stages 1-2. Men show a faster decline in kidney function, progress more frequently to kidney failure and have higher mortality and risk of cardiovascular disease than women. However, the protective effect of female sex is reduced with CKD progression. Women are less likely than men to be aware of, screened for and diagnosed with CKD, started on antiproteinuric medication and referred to nephrologist care. They also consistently report a poorer health-related quality of life and a higher symptom burden than men. Women experience greater barriers than men to access the waiting list for kidney transplantation, particularly with respect to older age and obesity. However, women also have longer survival than men after transplantation, which may partly explain the comparable prevalence of transplantation between the sexes.

Glucose-lowering treatment pathways of individuals with chronic kidney disease and type 2 diabetes according to the Kidney Disease: Improving Global Outcomes 2012 risk classification.

AIMS: To describe treatment pathways for key glucose-lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992). METHODS: Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008-2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012-2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15-<75 mL/min/1.73 m2 ; 90-730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose-lowering therapies prescribed on or after CKD index to end of follow-up were computed. Median time and proportion of overall follow-up time on treatment were described for each therapy by database and by eGFR and urinary albumin-to-creatinine ratio (UACR) categories. RESULTS: Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m2 ; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow-up was 917 (390-1671) and 454 (192-850) days (accounting for ~75% of follow-up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category. CONCLUSIONS: Individuals with CKD and T2D had many combinations of therapies and substantial follow-up time on therapy. These results highlight opportunities for improved CKD management.

N-terminal pro-B-type natriuretic peptide concentrations, testing and associations with worsening heart failure events.

AIMS: In patients with heart failure (HF), we aimed to assess (i) the time trends in N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing; (ii) patient characteristics associated with NT-proBNP testing; (iii) distribution of NT-proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT-proBNP levels over time. METHODS AND RESULTS: NT-proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT-proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and ≥3000 ng/L at the second measurement = increased; (iii) ≥3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) ≥3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT-proBNP testing and (ii) changes in NT-proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT-proBNP testing increased over time, up to 55% in 2018, and was almost two-fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT-proBNP was 3070 ng/L (Q1-Q3: 1220-7395), approximately three-fold higher in WHFE vs. NWHFE. Compared with stable low NT-proBNP levels, increased (OR 4.27, 95% CI 2.47-7.37) and stable high levels (OR 2.48, 95% CI 1.58-3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population. CONCLUSIONS: NT-proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT-proBNP testing in clinical practice.