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Introduction Chronic kidney disease (CKD) is a heterogeneous group of conditions affecting over 10% of the population, causing substantial morbidity and mortality (1-3). Genetic kidney disorders are well-recognized causes of [...], BACKGROUND. It is unknown whether the risk of kidney disease progression and failure differs between patients with and without genetic kidney disorders. METHODS. Three cohorts were evaluated: the prospective Cure Glomerulonephropathy Network (CureGN) and 2 retrospective cohorts from Columbia University, including 5,727 adults and children with kidney disease from any etiology who underwent whole-genome or exome sequencing. The effects of monogenic kidney disorders and APOL1 kidney-risk genotypes on the risk of kidney failure, estimated glomerular filtration rate (eGFR) decline, and disease remission rates were evaluated along with diagnostic yields and the impact of American College of Medical Genetics secondary findings (ACMG SFs). RESULTS. Monogenic kidney disorders were identified in 371 patients (6.5%), high-risk APOL1 genotypes in 318 (5.5%), and ACMG SFs in 100 (5.2%). Family history of kidney disease was the strongest predictor of monogenic disorders. After adjustment for traditional risk factors, monogenic kidney disorders were associated with an increased risk of kidney failure (hazard ratio [HR] = 1.72), higher rate of eGFR decline (-3.06 vs. 0.25 mL/min/1.73 [m.sup.2]/year), and lower risk of complete remission ([odds ratio.sub.Not achieving CR] = 5.25). High-risk APOL1 genotypes were associated with an increased risk of kidney failure (HR = 1.67) and faster eGFR decline (-2.28 vs. 0.25 mL/min/1.73 [m.sup.2]), replicating prior findings. ACMG SFs were not associated with personal or family history of associated diseases, but were predicted to impact care in 70% of cases. CONCLUSIONS. Monogenic kidney disorders were associated with an increased risk of kidney failure, faster eGFR decline, and lower rates of complete remission, suggesting opportunities for early identification and intervention based on molecular diagnosis. TRIAL REGISTRATION. NA. FUNDING. National Institute of Diabetes and Digestive and Kidney Diseases grants U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), U01DK100867 (formerly UM1DK100867), U24DK100845, DK081943, RC2DK116690, 2U01DK100876, 1R01DK136765, 5R01DK082753, and RC2-DK122397; NephCure Kidney International; Department of Defense Research Awards PR201425, W81XWH-16-1-0451, and W81XWH-22-1-0966; National Center for Advancing Translational Sciences grant UL1TR001873; National Library of Medicine grant R01LM013061; National Human Genome Research Institute grant 2U01HG008680.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Background and objectivesAnemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels.Design, setting, participants, & measurementsTrends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time.ResultsMean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period.ConclusionsIn contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation.

Predialysis volume overload is the sum of interdialytic weight gain (IDWG) and residual postdialysis volume overload. It results mostly from failure to achieve an adequate volume status at the end of the dialysis session. Recent developments in bioimpedance spectroscopy and possibly relative plasma volume monitoring permit noninvasive volume status assessment in hemodialysis patients. A large proportion of patients have previously been shown to be chronically volume overloaded predialysis (defined as >15% above 'normal' extracellular fluid volume, equivalent to >2.5 liters on average), and to exhibit a more than twofold increased mortality risk. By contrast, the magnitude of the mortality risk associated with IDWG is much smaller and only evident with very large weight gains. Here we review the available evidence on volume overload and IDWG, and question the use of IDWG as an indicator of 'nonadherence' by describing its association with postdialysis volume depletion. We also demonstrate the relationship between IDWG, volume overload and predialysis serum sodium concentration, and comment on salt intake. Discriminating between volume overload and IDWG will likely lead to a more appropriate management of fluid withdrawal during dialysis. Consensually, the present authors agree that this discrimination should be among the primary goals for dialysis caretakers today. In consequence, we recommend objective measures of volume status beyond mere evaluations of IDWG.

Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in‐center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per‐protocol approach to censor patients at treatment switch during follow‐up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient‐year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH‐independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking. We describe time to discontinuation and changes in serum potassium levels among German CKD stage 3–5 patients starting patiromer. Methods Duration of patiromer use was estimated by Kaplan–Meier curve, starting at patiromer initiation and censoring for death, dialysis, transplant or loss to follow-up. Serum potassium levels and renin–angiotensin–aldosterone system inhibitor (RAASi) use are described at baseline and during follow-up, restricted to patients remaining on patiromer. Results We identified 140 patiromer users within our analysis sample [81% CKD stage 4/5, 83% receiving RAASi, and median K+ 5.7 (5.4, 6.3) mmol/L]. Thirty percent of patiromer users had prior history of polystyrene sulfonate use. Overall, 95% of patiromer users stayed on treatment past 1 month, with 53% continuing for over a year. Mean serum potassium levels decreased after patiromer initiation and remained stable under treatment during follow-up (up to 180 days). Among these patients, 73%–82% used RAASis during the time periods before and after patiromer initiation, with no obvious trend indicating discontinuation. Conclusion Real-world evidence of patiromer use in Germany shows that, in line with what has been observed in clinical trials, patients on patiromer have a reduction in serum potassium when used long-term. Moreover, most patients on patiromer do not discontinue treatment prior to 1 year after initiation. [ABSTRACT FROM AUTHOR]

Background Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 <10.5, T2 10.5–15.1 and T3 ≥15.1 mmol/L). Cox proportional hazard models were used to estimate hazard ratios (HRs) for first atheromatous or non-atheromatous cardiovascular (CV) events and all-cause mortality before RRT. The models were adjusted for baseline comorbidities, laboratory data and medications. Findings Of the 2507 included patients {median [interquartile range (IQR)] age: 69 [61–77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events  = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events  = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR. [ABSTRACT FROM AUTHOR]

Background Conservative care is increasingly considered an alternative to kidney replacement therapy for kidney failure management, mostly among the elderly. We investigated its status and the barriers to its implementation from patients' and providers' perspectives. Methods We analysed data from 1204 patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2] enrolled at 40 nationally representative nephrology clinics (2013–16) who completed a self-administered questionnaire about the information they received and their preferred treatment option, including conservative care, if their kidneys failed. Nephrologists (n  = 137) also reported data about their clinics' resources and practices regarding conservative care. Results All participating facilities reported they were routinely able to offer conservative care, but only 37% had written protocols and only 5% had a person or team primarily responsible for it. Overall, 6% of patients were estimated to use conservative care. Among nephrologists, 82% reported they were fairly or extremely comfortable discussing conservative care, but only 28% usually or always offered this option for older (>75 years) patients approaching kidney failure. They used various terminology for this care, with conservative management and non-dialysis care mentioned most often. Among patients, 5% of those >75 years reported receiving information about this option and 2% preferring it. Conclusions Although reported by nephrologists to be widely available and easily discussed, conservative care is only occasionally offered to older patients, most of whom report they were not informed of this option. The lack of a person or team responsible for conservative care and unclear information appear to be key barriers to its implementation. [ABSTRACT FROM AUTHOR]