The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Abstract Background The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D.

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FEATURES OF CHRONIC KIDNEY DISEASE IN ELDERLY PATIENTS

Успехи геронтологии ◽

10.34922/ae.2020.33.1.015 ◽

2020 ◽

pp. 113-120

Author(s):

О. Н. Курочкина

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Elderly Patients ◽

Clinical Situation ◽

Chronic Glomerulonephritis ◽

Hypertensive Nephropathy ◽

Number Of Patients ◽

Rate Of Decline ◽

People Group ◽

Group 1

Изучены особенности течения хронической болезни почек (ХБП) у пожилых пациентов на основании анализа регистра ХБП за 2015-2018 гг. В регистре 484 пациента, из них 231 (47,7%) мужчина, 253 (52,3%) женщины, средний возраст - 58,8±15,8 года. Пациенты были разделены на три группы: 1-я - 218 человек до 59 лет; 2-я - 207 человек 60-74 лет; 3-я - 59 человек 75 лет и старше. В 1-й группе ведущей причиной ХБП явился хронический гломерулонефрит -27,1%, во 2-й - хронический тубулоинтерстициальный нефрит (ТИН) - 21,7%, диабетическая нефропатия (ДН) - 20,8% и гипертоническая нефропатия - 15,9%; в 3-й - ТИН (27,1%), хронический пиелонефрит (ПН) - 15,9% и ДН (13,6%). С возрастом увеличивалась частота встречаемости ТИН ( р <0,1), ПН ( р <0,05), ишемической болезни почек ( р <0,05), подагрической нефропатии ( р <0,1). Среднее снижение СКФ - 3,99 мл/мин на 1,73 мза год наблюдения. Темп снижения СКФ в 1-й группе - 3,36±1,8 мл/мин на 1,73 мза год, во 2-й - 2,43±1,2 ( р <0,001 между 1-йи 2-й группой), в 3-й - 1,82±1,1 мл/мин на 1,73 мза год. Наблюдали отрицательную корреляцию с возрастом ( р <0,05). Формирование регистра больных с ХБП позволяет знать количество больных и причины ХБП у пациентов пожилого и старческого возраста, оценивать клиническую ситуацию, темпы снижения СКФ и выбирать лечебную тактику у этих пациентов. The purpose of the work is to study the characteristics of the course of chronic kidney disease in elderly patients based on the analysis of the register of chronic kidney disease (CKD) for 2015-2018. in the Department of Nephrology, the Komi Republican Clinical Hospital. There are 484 patients in the register, of whom 231 are men (47,7%), 253 women (52,3%). The average age is 58,8±15,8 years old. The patients were divided into 3 groups: persons under the age of 59 years old - 218 people (group 1); from 60 to 74 years old - 207 people (group 2); and over 75 years old - 59 people (group 3). Most patients are between the ages of 60 and 69 years old. In the 1 group, the chronic glomerulonephritis is the leading cause of CKD - 27,1%; in the 2 group - the chronic tubulo-interstitial nephritis (TIN) - 21,7%, the diabetic nephropathy (DN) - 20,8% and the hypertensive nephropathy - 15,9%; in the 3 group - TIN (27,1%), the chronic pyelonephritis (PN) (15,9%) and DN (13,6%). With increasing age, the incidence of TIN ( p <0,1), MO ( p <0,05), coronary kidney disease (IBP) ( p <0,05), gouty nephropathy ( p <0,1) were raised. The average reduction in GFR is 3,99 ml/min/1,73 m per year of observation. The rate of decline in GFR in the 1st group is 3,36±1,8 ml/min/1,73 m per year, in the 2 - 2,43±1,2 ( p <0,001 between group 1 and 2), in the 3 group - 1,82±1,1; with aging the negative correlation was observed ( p <0,05). 39 patients received hemodialysis, including: in the 1 group - 20 people (9%), in the 2 group - 18 (8,7%), in the 3 group - 1 patient (1,7%). Making the register of the patients with CKD allows us to know the number of patients and the causes of CKD among the patients of elderly and senile ages, to assess the clinical situation, the rate of decline in GFR and treatment tactics in these patients.

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Cardiorenal Fat: A Cardiovascular Risk Factor With Implications in Chronic Kidney Disease

Frontiers in Medicine ◽

10.3389/fmed.2021.640814 ◽

2021 ◽

Vol 8 ◽

Author(s):

Luis D'Marco ◽

María Jesús Puchades ◽

Nayara Panizo ◽

María Romero-Parra ◽

Lorena Gandía ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Risk Factor ◽

Kidney Disease ◽

Kidney Diseases ◽

Clinical Importance ◽

Adverse Outcomes ◽

Epicardial Fat ◽

Metabolic Disturbances ◽

Fat Deposits ◽

Perirenal Fat

There is a growing interest in the potential role of adipose tissues in cardiac and renal pathophysiology, and determining the mechanisms by which fat compartments around the heart and kidneys influence cardiovascular disease is of clinical importance in both general and high-risk populations. Epicardial fat and perirenal fat have been associated with adverse outcomes in chronic kidney disease (CKD) patients. Epicardial fat is a rich source of free fatty acids and is capable of secreting inflammatory and pro-atherogenic cytokines that promote atherosclerosis through a local paracrine effect. Recent evidence has demonstrated that perirenal fat has a closer correlation with kidney diseases than other visceral fat deposits in obesity or metabolic disturbances. Moreover, perirenal fat has been reported as an independent risk factor for CKD progression and even associated with cardiorenal dysfunction. Accordingly, these forms of organ-specific fat deposits may act as a connecter between vascular and cardiorenal disease. This review explores the possible links between epicardial and perirenal fat and its significant role as a modulator of cardiorenal dysfunction in CKD patients.

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Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz290 ◽

2020 ◽

Vol 35 (2) ◽

pp. 274-282 ◽

Cited By ~ 48

Author(s):

Hiddo J L Heerspink ◽

Bergur V Stefansson ◽

Glenn M Chertow ◽

Ricardo Correa-Rotter ◽

Tom Greene ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Cardiovascular Events ◽

Controlled Trial ◽

Sglt2 Inhibitor ◽

Maximum Tolerated Dose ◽

Adverse Outcomes ◽

Double Blind

Abstract Background Recent cardiovascular outcome trials have shown that sodium–glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. Methods DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2–4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin–angiotensin system inhibitor at enrolment. Results After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). Conclusion DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes.

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P0795OUTCOME COMPARISON STUDY ACCORDING TO THE CAUSE OF CHRONIC KIDNEY DISEASE: RESULTS FROM KNOW-CKD STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0795 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Hyunjin Ryu ◽

Yeji Hong ◽

Jayoun Kim ◽

Curie Ahn ◽

Yun Kyu Oh ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Mixed Model ◽

Linear Mixed Model ◽

Adverse Outcomes ◽

Hypertensive Nephropathy ◽

Linear Pattern ◽

Hazard Ratios ◽

Egfr Slope

Abstract Background and Aims The cause of chronic kidney disease (CKD) is one of important factors for predicting the outcome. However, relative risks for the adverse outcomes according to the specific causes of CKD is unknown. Method Using the longitudinal data of prospective cohort of Korean predialysis CKD, KNOW-CKD cohort, the relative risk of end-stage renal disease (ESRD), composite of ESRD development or creatinine doubling, and composite of cardiovascular disease (CVD) and all-cause mortality according to the cause of CKD were compared. The patients were subgrouped in to four categories at the study entry according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), and polycystic kidney disease (PKD). Since the baseline characteristics differed according to the causes of CKD, the inverse probability of treatment weighting (IPTW) methods was used to exclude the effects of other variables on the outcomes. The estimated glomerular filtration rate (eGFR) slope during follow-up was calculated for each cause of CKD using linear mixed model Results During the median follow-up of 4.1 years (interquartile range 1.12-7.12 years) total 441 (21.5%) of ESRD, 556 (27.1%) of composite of ESRD or creatinine doubling and 190 (9.3%) composite of CVD and all cause death occurred. In the IPTW adjusted cohorts, DN and PKD showed significantly increased hazard ratios of 1.85 and 5.57 for ESRD development and 1.74 and 4.57 for composite of ESRD developement or creatinine doubling, respectively, compared to GN in the fully adjusted model. Regarding compsite of CVD and all-cause death, also DN and PKD showed significantly increased hazard ratios of 1.93 and 2.16 compared to GN. The adjusted eGFR slope for DN, HTN and PKD was -2.32, -0.90, and -2.41 mL/min/1.73m2 per year, respectively, and all differ statistically significantly compared to GN (eGFR slope of -1.49 mL/min/1.73m2 per year). During the follow-up, GN and DN showed linear declining pattern however, HTN and PKD showed convex linear pattern. Conclusion The DN and PKD showed relatively higher risks for renal progression and composite of CVD and death compared to GN.

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Carnosine and Kidney Diseases: What We Currently Know?

Current Medicinal Chemistry ◽

10.2174/0929867326666190730130024 ◽

2020 ◽

Vol 27 (11) ◽

pp. 1764-1781 ◽

Cited By ~ 4

Author(s):

Katarzyna Kilis-Pstrusinska

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Enzyme Inhibitor ◽

Kidney Diseases ◽

Ischemia Reperfusion ◽

Public Health Issue ◽

Global Public Health ◽

Drug Induced ◽

Treatment And Prevention

: Carnosine (beta-alanyl-L-histidine) is an endogenously synthesised dipeptide which is present in different human tissues e.g. in the kidney. Carnosine is degraded by enzyme serum carnosinase, encoding by CNDP1 gene. Carnosine is engaged in different metabolic pathways in the kidney. It reduces the level of proinflammatory and profibrotic cytokines, inhibits advanced glycation end products’ formation, moreover, it also decreases the mesangial cell proliferation. Carnosine may also serve as a scavenger of peroxyl and hydroxyl radicals and a natural angiotensin-converting enzyme inhibitor. : This review summarizes the results of experimental and human studies concerning the role of carnosine in kidney diseases, particularly in chronic kidney disease, ischemia/reperfusion-induced acute renal failure, diabetic nephropathy and also drug-induced nephrotoxicity. The interplay between serum carnosine concentration and serum carnosinase activity and polymorphism in the CNDP1 gene is discussed. : Carnosine has renoprotective properties. It has a promising potential for the treatment and prevention of different kidney diseases, particularly chronic kidney disease which is a global public health issue. Further studies of the role of carnosine in the kidney may offer innovative and effective strategies for the management of kidney diseases.

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Comparison of Outcomes of Chronic Kidney Disease Based on Etiology: A Prospective Cohort Study

10.21203/rs.3.rs-889188/v1 ◽

2021 ◽

Author(s):

Hyunjin Ryu ◽

Yeji Hong ◽

Eunjeong Kang ◽

Minjung Kang ◽

Jayoun Kim ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Kidney Failure ◽

Adverse Outcomes ◽

Hypertensive Nephropathy ◽

Relative Risks ◽

Hazard Ratios ◽

Renal Progression ◽

Egfr Decline

Abstract Background and objectivesThe cause of chronic kidney disease (CKD) affects outcomes. However, relative risks for adverse outcomes according to specific causes of CKD are not well studied.Design, setting, participants and measurementsProspective cohort study from KNOW-CKD cohort were analyzed using overlap propensity score weighting methods. Patients were grouped into four categories according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), or polycystic kidney disease (PKD). From a total of 2,070 patients, the relative risk of kidney failure, composite of cardiovascular disease (CVD) and mortality, and the slope of the estimated glomerular filtration rate (eGFR) decline according to the cause of CKD were compared between causative groups pairwisely.ResultsThere were 565 cases of kidney failure and 259 cases of composite CVD and death over 6.0 years of follow-up. Hazard ratios of the PKD group for kidney failure were significantly increased at 1.82, 2.23, and 1.73 compared to GN, HTN, and DN, respectively. Hazard ratios of the DN group for the composite of CVD and death were also significantly increased at 2.07, and 1.73 compared to GN, and HTN, respectively. The adjusted eGFR decline slope for DN and PKD groups was -3.07, and -3.37 mL/min/1.73m2 per year, respectively, and all of these values were significantly different than those of the GN and HTN groups (-2.16, and -1.42 mL/min/1.73m2 per year, respectively).ConclusionsRisks for renal progression were relatively higher in patients with PKD compared to other causes of CKD. However, the composite of CVD and death were relatively higher in patients with DN-related CKD than those with GN- and HTN-related CKD.

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Stroke in chronic renal failure

Orvosi Hetilap ◽

10.1556/oh.2008.28292 ◽

2008 ◽

Vol 149 (15) ◽

pp. 691-696

Author(s):

Dániel Bereczki

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

Chronic Renal Disease ◽

Kidney Diseases ◽

Cerebrovascular Diseases ◽

Lipid Lowering ◽

Increased Risk ◽

Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

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Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

Nature Reviews Nephrology ◽

10.1038/s41581-021-00418-2 ◽

2021 ◽

Author(s):

John R. Prowle ◽

Lui G. Forni ◽

Max Bell ◽

Michelle S. Chew ◽

Mark Edwards ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Kidney Disease ◽

Kidney Injury ◽

Adverse Outcomes ◽

Baseline Risk ◽

Major Surgery ◽

Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

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