Final Stage of Chronic Kidney Disease with Conservative Kidney Management or Renal Replacement Therapy: A Primary-Care Population Study.

Bundó D ，Cunillera O ，Arbiol-Roca A ，Cobo-Guerrero S ，Romano J ，Gil-Terron N ，Fulladosa X ，Comas J ，Rama I ，Cruzado JM ，Salvador-Gonzalez B ... -  《Journal of Clinical Medicine》

CKD Progression and Mortality Among Men and Women: A Nationwide Study in Sweden.

Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis. Observational cohort study. Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD). Sex. Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR). CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models. 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease. Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting. Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR.

Swartling O ，Rydell H ，Stendahl M ，Segelmark M ，Trolle Lagerros Y ，Evans M ... -  《-》

Long-term efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease, on dialysis or after kidney transplantation: a national prospective observational cohort study.

COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT. In this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection. The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events. This study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT. The study protocol has been registered in clinicaltrials.gov ( NCT04841785 ). Current knowledge about this subject COVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation. Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups. Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints. Contribution of this study Assessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5. Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group. Monitoring of (serious) adverse events and development of anti-HLA antibodies. Impact on practice or policy Publication of the study design contributes to harmonization of SARS-CoV-2 vaccine study methodology in kidney patients at high-risk for severe COVID-19. Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy.

Bouwmans P ，Messchendorp AL ，Sanders JS ，Hilbrands L ，Reinders MEJ ，Vart P ，Bemelman FJ ，Abrahams AC ，van den Dorpel MA ，Ten Dam MA ，de Vries APJ ，Rispens T ，Steenhuis M ，Gansevoort RT ，Hemmelder MH ，RECOVAC Collaborators ... -  《BMC Nephrology》

Independent External Validation and Comparison of Death and Kidney Replacement Therapy Prediction Models in Advanced CKD.

The Kidney Failure Risk Equation (KFRE) is widely used to predict the risk of kidney replacement therapy (KRT) initiation in chronic kidney disease (CKD) stages G3-G5. The new Grams calculator developed for advanced CKD (stage G4+) predicts KRT initiation, cardiovascular events, and death by uniquely incorporating the competing risk of death. We aimed to validate this tool in a stage G4+ cohort for death and KRT. Retrospective cohort study. 442 patients with CKD stage G4+ (mean ± SD age, 73 ± 12 years; mean ± SD estimated glomerular filtration rate, 20 ± 6.2 mL/min/1.73 m2) who visited the multidisciplinary CKD clinic at Kingston Health Sciences Center in Ontario, Canada. Discrimination and calibration were examined for the outcome of death using the 2- and 4-year Grams scores. The 2- and 5-year KFRE and 2- and 4-year Grams scores were compared in terms of discrimination and calibration for KRT. There were 91, 161, and 206 death events and 90, 145, and 159 KRT events in our cohort at 2, 4, and 5 years, respectively. The Grams model demonstrated modest discrimination for death at 4 years (area under the curve [AUC] 0.70; 95% CI, 0.65-0.75) and performed worse at 2 years (AUC, 0.63; 95% CI, 0.57-0.70). It only overpredicted death by approximately 10% across most of the predicted range. Both models had similar discrimination for KRT at 2 years (KFRE AUC, 0.83; 95% CI, 0.78-0.88 and Grams AUC, 0.8; 95% CI, 0.76-0.87), 4 years (Grams AUC, 0.82; 95% CI, 0.77-0.86), and 5 years (KFRE AUC, 0.81; 95% CI, 0.76-0.85). There was excellent calibration for KRT using the 2-year KFRE and Grams values for predicted risk thresholds of ≤15% and using the 5-year KFRE and 4-year Grams values for predicted risk thresholds of ≤20%. At higher risk ranges, KFRE overpredicts and Grams underpredicts the KRT risk. This is a single-center study with a primarily White cohort limited by smaller sample sizes at the higher ranges of the predicted risks, particularly for the Grams calculator. The Grams model provides moderately accurate death predictions, and consideration should be given to its incorporation into patient education and advanced care planning. Both the Grams and KFRE models remain clinically useful for determining KRT risks in advanced CKD.

Thanabalasingam SJ ，Iliescu EA ，Norman PA ，Day AG ，Akbari A ，Hundemer GL ，White CA ... -  《-》

Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study.

It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. Observational study in the Swedish Renal Registry, 2007 to 2017. 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. RAS inhibitor versus CCB therapy initiation. Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. Potential confounding by indication. Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.

Fu EL ，Clase CM ，Evans M ，Lindholm B ，Rotmans JI ，Dekker FW ，van Diepen M ，Carrero JJ ... -  《-》