Obesity-Related Kidney Disease: Current Understanding and Future Perspectives.

Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept of obesity-related kidney disease (OKD) has been introduced to describe the still incompletely understood interplay between obesity, CKD, and other cardiometabolic conditions, including risk factors for OKD and cardiovascular disease, such as diabetes and hypertension. Current therapeutics target obesity and CKD individually. Non-pharmacological interventions play a major part, but the efficacy and clinical applicability of lifestyle changes and metabolic surgery remain debatable, because the strategies do not benefit everyone, and it remains questionable whether lifestyle changes can be sustained in the long term. Pharmacological interventions, such as sodium-glucose co-transporter 2 inhibitors and the non-steroidal mineralocorticoid receptor antagonist finerenone, provide kidney protection but have limited or no impact on body weight. Medicines based on glucagon-like peptide-1 (GLP-1) induce clinically relevant weight loss and may also offer kidney benefits. An urgent medical need remains for investigations to better understand the intertwined pathophysiologies in OKD, paving the way for the best possible therapeutic strategies in this increasingly prevalent disease complex.

Acute kidney injury and risk of cardiovascular outcomes: A nationwide cohort study.

BACKGROUND: Acute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI. METHODS: In a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age <50 years, estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2, renal transplantation, index-admission due to cardiovascular disease or death during index-admission. The primary outcome was cardiovascular risk within one year from discharge, which was a composite of the secondary outcomes ischemic heart disease, heart failure or stroke. To estimate risks, we applied multiple logistic regression fitted by inverse probability of censoring weighting and stratified estimations by eGFR and age. We adjusted for proteinuria in the subcohort with measurements available. RESULTS: Among 565,056 hospital admissions, 39,569 (7.0%) cases of AKI were present. In total, 18,642 patients sustained a cardiovascular outcome. AKI was significantly associated with cardiovascular outcome with an adjusted OR [CI] of 1.33 [1.16-1.53], 1.43 [1.33-1.54], 1.23 [1.14-1.34], 1.38 [1.18-1.62] for eGFR ≥90, 60-89, 30-59 and 15-29ml/min/1.73m2, respectively. When omitting the outcome heart failure, these results were 1.24 [1.06-1.45], 1.22 [1.11-1.33], 1.05 [0.95-1.16], 1.25 [1.02-1.54]. Results did not change substantially in strata of age groups, in AKI stages and in the subcohort adjusted for proteinuria. CONCLUSION: Non-selected patients aged 50 years or above with AKI during admission had significantly higher one-year risk of cardiovascular event or death, especially, but not only due to heart failure, independent of age and eGFR.

Acute kidney injury and risk of cardiovascular outcomes: A nationwide cohort study / Lesión renal aguda y riesgo de resultados cardiovasculares: Un estudio de cohorte a nivel nacional

Background: Acute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI.MethodsIn a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age <50 years, estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2, renal transplantation, index-admission due to cardiovascular disease or death during index-admission. The primary outcome was cardiovascular risk within one year from discharge, which was a composite of the secondary outcomes ischemic heart disease, heart failure or stroke. To estimate risks, we applied multiple logistic regression fitted by inverse probability of censoring weighting and stratified estimations by eGFR and age. We adjusted for proteinuria in the subcohort with measurements available.ResultsAmong 565,056 hospital admissions, 39,569 (7.0%) cases of AKI were present. In total, 18,642 patients sustained a cardiovascular outcome. AKI was significantly associated with cardiovascular outcome with an adjusted OR [CI] of 1.33 [1.16–1.53], 1.43 [1.33–1.54], 1.23 [1.14–1.34], 1.38 [1.18–1.62] for eGFR ≥90, 60–89, 30–59 and 15–29ml/min/1.73m2, respectively. When omitting the outcome heart failure, these results were 1.24 [1.06–1.45], 1.22 [1.11–1.33], 1.05 [0.95–1.16], 1.25 [1.02–1.54]. Results did not change substantially in strata of age groups, in AKI stages and in the subcohort adjusted for proteinuria. ... (AU)

Antecedentes: La lesión renal aguda (LRA) se ha asociado a la enfermedad cardiovascular, pero se ha estudiado poco en poblaciones no seleccionadas y se ha prestado escasa atención al efecto en la edad y la función renal. Utilizando datos administrativos a escala nacional, se investigó la hipótesis de un mayor riesgo de acontecimiento cardiovascular o muerte al cabo de un año asociado a la LRA.Métodos: En un estudio de cohortes se identificaron todos los ingresos que tuvieron lugar en Dinamarca entre 2008 y 2018. La LRA se definió como un aumento mayor o igual a 1,5 veces desde los valores iniciales hasta el pico de creatinina durante el ingreso o la diálisis. Se excluyeron a los pacientes con una edad inferior a 50 años, una tasa de filtración glomerular estimada (TFGe) inferior a 15ml/min/1,73m2, un trasplante renal, un ingreso inicial por enfermedad cardiovascular o la muerte durante el ingreso. El resultado primario fue riesgo cardiovascular en el plazo de un año desde el alta, entendido como una combinación de los criterios de valoración secundarios de cardiopatía isquémica, insuficiencia cardíaca o accidente cerebrovascular. Para estimar los riesgos, se aplicó una regresión logística múltiple ajustada por la ponderación de la probabilidad inversa de censura y las estimaciones estratificadas por la TFGe y la edad. Se ajustó por proteinuria en la subcohorte para la que se disponía de mediciones.ResultadosDe entre 565.056 ingresos hospitalarios, en 39.569 (7,0%) de los casos había LRA presente. En total, 18.642 pacientes mantuvieron un desenlace cardiovascular. La LRA estuvo asociada de forma significativa con los criterios de valoración cardiovasculares, con una tasa global (índice de confianza) de 1,33 (1,16-1,53); 1,43 (1,33-1,54); 1,23 (1,14-1,34); 1,38 (1,18-1,62) para una TFGe≥90, 60-89, 30-59 y 15-29ml/min/1,73m2, respectivamente. ...(AU)

Acute kidney injury and risk of cardiovascular outcomes: A nationwide cohort study.

BACKGROUND: Acute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI. METHODS: In a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age <50 years, estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2, renal transplantation, index-admission due to cardiovascular disease or death during index-admission. The primary outcome was cardiovascular risk within one year from discharge, which was a composite of the secondary outcomes ischemic heart disease, heart failure or stroke. To estimate risks, we applied multiple logistic regression fitted by inverse probability of censoring weighting and stratified estimations by eGFR and age. We adjusted for proteinuria in the subcohort with measurements available. RESULTS: Among 565,056 hospital admissions, 39,569 (7.0%) cases of AKI were present. In total, 18,642 patients sustained a cardiovascular outcome. AKI was significantly associated with cardiovascular outcome with an adjusted OR [CI] of 1.33 [1.16-1.53], 1.43 [1.33-1.54], 1.23 [1.14-1.34], 1.38 [1.18-1.62] for eGFR ≥90, 60-89, 30-59 and 15-29ml/min/1.73m2, respectively. When omitting the outcome heart failure, these results were 1.24 [1.06-1.45], 1.22 [1.11-1.33], 1.05 [0.95-1.16], 1.25 [1.02-1.54]. Results did not change substantially in strata of age groups, in AKI stages and in the subcohort adjusted for proteinuria. CONCLUSION: Non-selected patients aged 50 years or above with AKI during admission had significantly higher one-year risk of cardiovascular event or death, especially, but not only due to heart failure, independent of age and eGFR.

Is metformin associated with acute kidney injury? A case-control study of patients with type 2 diabetes admitted with acute infection.

INTRODUCTION: Despite the long-term renoprotective effects of Metformin, a recent study on data from the U.S. Food and Drug Administration reported a possible nephrotoxic effect, contributing to the development of acute kidney injury (AKI). We investigated the association between metformin and AKI in patients admitted with the AKI-prone condition of acute infection and compared results with corresponding results of other antidiabetics. METHODS: In a nationwide register-based case-control study, we identified Danish patients with type 2 diabetes hospitalized with acute infection between 2008 and 2018. Cases of AKI had an increase in plasma creatinine ≥ × 1.5 during admission, controls did not. Antidiabetics were identified up to 6 months before admission. Odds ratio (OR) of each antidiabetic was computed in separate multiple logistic regression models adjusted for relevant medication and comorbidities and results compared. RESULTS: We included 46,811 patients, hereof 9454 AKIs (20%) and 2186 (4.7%) severe AKIs. Overall, 56% were males, median age (IQR) was 73 (65-81). Sixty percent received metformin, 13% sulfonylurea, 31% insulin and 8% dipeptidyl peptidase-4 inhibitors (DPP-4i), with equal distribution between cases and controls. Metformin was associated with increased OR (CI) for AKI, 1.07 (1.02-1.12), equally to sulfonylurea, 1.10 (1.03-1.18) and DPP-4i, 1.11 (1.02-1.20), but not insulin, 0.99 (0.93-1.05). In severe AKI, results for metformin were 1.27 (1.25-1.40) but increased equivalently to other antidiabetics. CONCLUSIONS: In patients with type 2 diabetes hospitalized with acute infection, metformin was not independently associated with AKI, since other antidiabetics were also significantly associated, indicating confounding by indication.

Creatinine increase following initiation of antihypertensives is associated with cardiovascular risk: a nationwide cohort study.

OBJECTIVE: Abrupt decline in renal function following initiation of renin-angiotensin system inhibitor is associated with increased risk of cardiovascular disease, but studies of other antihypertensive drugs are sparse. We investigated the risk of cardiovascular event associated with increased plasma creatinine after initiating first-line antihypertensive treatment. METHODS: In a nationwide cohort study, we identified adult Danish primary care patients initiating either renin-angiotensin system inhibitor, calcium channel blocker or thiazide, between 2008 and mid-2018. Patients with prior end-stage renal disease, renal transplantation, or cardiovascular disease were excluded. Percentual plasma creatinine increase was calculated between the nearest creatinine measurement up to 1 year before redeeming the prescription (baseline), and the nearest measurement 90 days or less after (index). Multiple logistic regression and restricted cubic splines were applied to estimate the 6-month absolute risk of cardiovascular event (ischemic heart disease, heart failure or stroke) associated with this creatinine increase. RESULTS: We included 20 789 patients. Within the first 6 months of follow-up, 283 (1.4%) cardiovascular events and 93 (0.4%) all-cause deaths were registered. With a creatinine increase of 0 and 30%, 6-month absolute risk [CI] of cardiovascular event was 1.4% [1.1-1.9] and 3.5% [2.4-5.2], respectively (in men aged 50-79 years with estimated glomerular filtration rate at least 60 ml/min per 1.73 m and no diabetes). Higher age and reduced renal function, but not the type of antihypertensive treatment, were associated with higher cardiovascular risk. CONCLUSION: In primary care, patients initiating first-line antihypertensive treatment, an increase in plasma creatinine above 30% was associated with increased absolute 6-month risk of cardiovascular event.

Impact of extracorporeal blood flow rate on blood pressure, pulse rate and cardiac output during haemodialysis.

BACKGROUND: If blood pressure (BP) falls during haemodialysis (HD) [intradialytic hypotension (IDH)] a common clinical practice is to reduce the extracorporeal blood flow rate (EBFR). Consequently the efficacy of the HD (Kt/V) is reduced. However, only very limited knowledge on the effect of reducing EBFR on BP exists and data are conflicting. The aim of this study was to evaluate the effect and the potential mechanism(s) involved by investigating the impact of changes in EBFR on BP, pulse rate (PR) and cardiac output (CO) in HD patients with arteriovenous-fistulas (AV-fistulas). METHODS: We performed a randomized, crossover trial in 22 haemodynamically stable HD patients with AV-fistula. After a conventional HD session each patient was examined during EBFR of 200, 300 and 400 mL/min in random order. After 15 min when steady state was achieved CO, BP and PR were measured at each EFBR, respectively. RESULTS: Mean (SD) age was 71 (11) years. Systolic BP was significantly higher at an EBFR of 200 mL/min as compared with 300 mL/min [133 (23) versus 128 (24) mmHg; P < 0.05], but not as compared with 400 mL/min [133 (23) versus 130 (19) mmHg; P = 0.20]. At EBFR of 200, 300 and 400 mL/min diastolic BP, mean arterial pressure, PR and CO remained unchanged. CONCLUSION: Our study does not show any consistent trend in BP changes by a reduction in EBFR. Reduction in EBFR if BP falls during IDH is thus not supported. However, none of the patients experienced IDH. Further studies are required to evaluate the impact of changes in EBFR on BP during IDH.