Adverse Renal Outcomes Research Articles

Importance of non-invasive liver fibrosis scores for mortality and complications development in individuals with type 2 diabetes.

To evaluate the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 score (FIB4) as predictors of complications development and mortality in a cohort of type 2 diabetes. 554 type 2 diabetic subjects had NFS and FIB4 calculated at baseline. Multivariate Cox and Poisson analyses evaluated the associations between fibrosis scores and the occurrence of microvascular and cardiovascular complications, and all-cause mortality. According to recommended cut-offs of NFS, 12.8% had advanced fibrosis and 45.9% had absence of advanced fibrosis and of FIB4, 3.8% and 86.1%, respectively. During a median follow-up of 11 years, 217subjects died, 172 had cardiovascular events (CVEs), 184 had renal events, and 139 had retinopathy and 185 neuropathy events. As continuous variables, both scores predicted all-cause mortality: NFS, HR: 1.30 (p = 0.032) and FIB4, HR: 1.24 (p = 0.021); an increased NFS implied in a significant 90% excess risk of mortality, whereas a higher FIB4 in a borderline 69% higher risk. The scores were mainly predictors of mortality in women and for non-cardiovascular deaths. The NFS was a predictor of renal events, mainly for renal function deterioration. The NFS and FIB4 predicted all-cause mortality, particularly in women and for non-cardiovascular causes. The NFS predicted adverse renal outcomes. These liver fibrosis scores may improve stratification risk in individuals with diabetes and NAFLD.

The Effects of SGLT2 Inhibitors on Lipid Metabolism.

Sodium glucose co-transporter 2 (SGLT2) inhibitors are effective antihyperglycemic agents by inhibiting glucose reabsorption in the proximal tubule of the kidney. Besides improving glycemic control in patients with type 2 diabetes, they also have additional favorable effects, such as lowering body weight and body fat. Several clinical studies have demonstrated their positive effect in reducing cardiovascular morbidity and mortality. Furthermore, the use of SGLT2 inhibitors were associated with fewer adverse renal outcomes comparing to other diabetic agents, substantiating their renoprotective effect in diabetic patients. SGLT2 inhibitors have also remarkable effect on lipid metabolism acting at different cellular levels. By decreasing the lipid accumulation, visceral and subcutaneous fat, they do not only decrease the body weight but also change body composition. They also regulate key molecules in lipid synthesis and transportation, and they affect the oxidation of fatty acids. Notably, they shift substrate utilization from carbohydrates to lipids and ketone bodies. In this review we intended to summarize the role of SGLT2 inhibitors in lipid metabolism especially on lipoprotein levels, lipid regulation, fat storage and substrate utilization.

Clinical Outcomes and Healthcare Resource Utilization in a Real-World Population Reflecting the DAPA-CKD Trial Participants.

IntroductionThe DAPA-CKD trial assessed dapagliflozin in patients with chronic kidney disease (CKD) with or without type 2 diabetes (T2D). To aid interpretation of results, renal and cardiovascular outcomes plus healthcare resource utilization (HCRU) and costs were assessed in a real-world population similar to that of DAPA-CKD.MethodsHenry Ford Health System (2006–2016) data were used to identify patients with CKD stages 2–4 [estimated glomerular filtration rate (eGFR) 25–75 ml/min/1.73 m2 at index and urine albumin-to-creatinine ratio (UACR) 0–5000 mg/g; n = 22,251]. Included patients had confirmatory eGFR ≥ 90 days post-index and no kidney transplant or progression to end-stage kidney disease during 12 months pre-index. The final population (n = 6557) was stratified by UACR (0–29, 30–199 and 200–5000 mg/g; the last comprising the DAPA-CKD-like cohort). Patients were followed for 5 years post-index.ResultsAdverse clinical outcomes incidence increased with UACR and was highest for the DAPA-CKD-like cohort (UACR 200–5000 mg/g) versus lower UACR categories (0–29 mg/g and 30–199 mg/g): renal composite outcome (progression to CKD stage 5, dialysis, transplant, ≥ 50% sustained eGFR decline): 26.0% versus 2.2% and 5.8%; heart failure (HF): 36.1% versus 13.9% and 24.6%; myocardial infarction: 11.3% versus 4.7% and 7.4%; stroke: 8.9% versus 4.0% and 5.7%; and mortality: 18.5% versus 6.0% and 11.7%, respectively. Within the DAPA-CKD-like cohort, patients with versus without T2D or HF had a higher frequency of adverse outcomes. The DAPA-CKD-like cohort also had significantly higher annualized per-patient healthcare costs ($39,222/year versus $19,547/year), hospital admission rate (0.55/year versus 0.20/year) and outpatient specialist visit rate (7.55/year versus 6.74/year) versus the lowest UACR category.ConclusionThe significant adverse renal and cardiovascular outcomes observed, particularly in the DAPA-CKD-like cohort, represent a substantial burden resulting in increased mortality, HCRU and costs, demonstrating the need for additional treatment options.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-020-01609-2.

A retrospective observational population-based study to assess the prevalence and burden of illness of type 2 diabetes with an estimated glomerular filtration rate < 90 mL/min/1.73 m2 in Ontario, Canada.

AimTo better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 in Ontario, Canada.Materials and MethodsWe used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m2 and adverse cardiovascular co‐morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes.ResultsWhile the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5‐year period (2011‐2012 to 2015‐2016), the prevalence of eGFR < 90 mL/min/1.73 m2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2‐year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes.ConclusionsThis real‐world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m2, and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes‐related complications.

Consensus acute kidney injury criteria integration identifies children at risk for long-term kidney dysfunction after multiple organ dysfunction syndrome.

The consensus definition of acute kidney injury (AKI) has evolved since developing the original multiple organ dysfunction syndrome (MODS) definitions. Whether or not risk for adverse short- and long-term outcomes can be identified using the refined AKI criteria in the setting of MODS has not been studied. We hypothesize that incorporation of Kidney Disease: Improving Global Outcome (KDIGO) AKI criteria into existing MODS definitions will have a higher association with major adverse kidney events at 30days (MAKE30) and will increase the number of patients with MODS. Post hoc analysis of 410 children admitted to a tertiary care pediatric intensive care unit (PICU) was conducted. MODS was defined using two existing criteria (Goldstein and Proulx) during the first 7days following ICU admission and then modified by replacement of the kidney injury criteria using the KDIGO AKI definitions (G' and P'). MAKE30 occurred in 65 of 410 (16%) children. After substituting KDIGO kidney injury criteria, identification of MAKE30 increased from 46 children (71%) to 53 (82%) and 29 children (45%) to 43 (66%) for the Goldstein and Proulx criteria, respectively. Additionally, identification of MODS increased from 194 (47%) by Goldstein to 224 (55%) by G' and 95 children (23%) by Proulx to 132 (32%) by P'. Substituting KDIGO AKI criteria into existing MODS criteria increases the sensitivity for major adverse kidney events as well as the identification of MODS, improving the detection of children at risk for long-term adverse renal outcomes.

Apolipoprotein L1 risk genotypes in Ghanaian patients with systemic lupus erythematosus: a prospective cohort study

ObjectiveTwo apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to conferred resistance to Trypanosoma brucei. These variants associate with adverse renal outcomes by multiple causes...

Renal outcomes and prognostic factors in patients with type-2 diabetes and chronic kidney disease confirmed by renal biopsy.

Aim:To evaluate the renal outcomes and prognostic factors among patients with type-2 diabetes (T2D) and biopsy-confirmed diabetic nephropathy (DN), non-diabetic renal disease (NDRD) and DN mixed with NDRD (MIX).Design and Methods:Patients with both T2D and chronic kidney disease (CKD) who underwent renal biopsy between January 2014 and December 2016 were recruited in this prospective observational study. Participants were divided into DN group, NDRD group, or MIX group according to the baseline pathological diagnosis. The primary endpoint was a composite renal event of end-stage renal disease (ESRD) or ⩾ 40% reduction in estimated glomerular filtration rate (eGFR).Results:Among the 292 participants included, 153 (52.4%) belonged to the DN group, 30 (10.3%) belonged to the NDRD group, and 109 (37.3%) belonged to the MIX group. During the median follow-up of 27 months, the adverse renal events occurred in 132 (44.2%) patients. Compared with NDRD group, the multiple adjusted hazard ratios (HRs) for renal events in patients with DN and MIX groups were 3.900 (95% confidence interval [CI]: 1.103–13.788) and 2.691 (95% CI: 0.662–10.936), respectively. Baseline lower eGFR (HR: 1.159, 95% CI: 1.060–1.266), severe proteinuria (HR: 2.047, 95% CI: 1.227–3.416), lower hemoglobin (HR: 1.170, 95% CI: 1.008–1.267), and a family history of diabetes (HR: 1.138, 95% CI: 1.008–2.285) were independent predictors for adverse renal outcomes in patients with DN.Conclusion:In patients with T2D and CKD, pure DN and MIX group displayed a worse renal prognosis than NDRD group. Worse renal function, severe proteinuria, lower hemoglobin, and a family history of diabetes may be associated with adverse renal outcomes in patients with DN.

The association of echocardiographic parameters on renal outcomes in chronic kidney disease

Background Patients with chronic kidney disease (CKD) often have structural abnormalities of the heart due to pressure and volume overload. The aim of this study was to evaluate associations between echocardiographic parameters and renal outcomes (estimated glomerular filtration rate [eGFR] slope and progression to dialysis) in patients with stage 3–5 CKD. Methods This longitudinal study enrolled 419 patients. Changes in renal function were assessed using the eGFR slope. Rapid renal progression was defined as an eGFR slope < −3 mL/min/1.73 m2/year, and the renal endpoint was defined as commencing dialysis. Results Increased left atrial diameter (LAD), ratio of left ventricular mass to body surface area (LVM/BSA), ratio of LVM to height2.7 (LVM/ht2.7), and ratio of observed to predicted LVM (o/p LVM) were associated with eGFR slope in an adjusted model, but left ventricular ejection fraction (LVEF) was not. Furthermore, LAD ≥ 4.7 cm, LVM/BSA > 115 g/m2 in males and > 95 g/m2 in females, and LVM/ht2.7 > 48 g/ht2.7 in males and > 44 g/ht2.7 in females were correlated with progression to dialysis, but o/p LVM and LVEF were not. The maximum change in χ2 change to predict renal outcomes was observed for LAD, followed by LVM/BSA and LVM/ht2.7. Conclusions A large LAD and increased LVM, regardless of how it was measured (LVM/BSA, LVM/ht2.7 and o/p LVM), were correlated with adverse renal outcomes in patients with CKD stage 3–5. LAD had superior prognostic value to LVM and LVEF.

Major Adverse Renal and Cardiovascular Events following Intra-Arterial Contrast Media Administration in Hospitalized Patients with Comorbid Conditions

Introduction: Several clinical studies and meta-analyses have demonstrated lower incidence of adverse renal and cardiovascular outcomes associated with the use of iso-osmolar contrast media (IOCM) than low-osmolar contrast media (LOCM) in patients with variable risk profiles undergoing intra-arterial interventional procedures. However, the association of contrast-type and major adverse renal and cardiovascular events (MARCE) has not been studied via comprehensive and robust real-world data analyses in patients with comorbid conditions considered at risk for post-procedural acute kidney injury (AKI). The objective of this study was therefore to retrospectively assess the MARCE rates comparing IOCM with LOCM in at-risk patients receiving iodinated intra-arterial contrast media using a real-world inpatient data source. Methods: Patients who underwent a diagnostic or treatment procedure with intra-arterial IOCM or LOCM administration were identified using the Premier Healthcare Database. Patient subgroups including those with diabetes, heart failure, chronic kidney disease (CKD) stages 1–4, CKD 3–4, or diagnosis of chronic total occlusion (CTO) were formed. Subgroups with combinations of diabetes and CKD 3–4 with and without CTO were also investigated. We compared the primary endpoint of MARCE (composite of AKI, AKI requiring dialysis, acute myocardial infarction, stroke/transient ischemic attack, stent occlusion/thrombosis, or death) after IOCM versus LOCM administration via adjusted multivariable regression analyses. Results: A total of 536,013 inpatient visits met the primary inclusion and exclusion criteria (IOCM = 133,192; LOCM = 402,821). After multivariable modeling, the use of IOCM was associated with a significantly lower incidence of MARCE than LOCM in patients with CKD 1–4, CKD 3–4, diabetes, or heart failure, with greatest absolute risk reduction (ARR) of 2.4% (p < 0.0001) in CKD 3–4 patients (relative risk reduction [RRR] = 13.8%, number needed to treat [NNT] = 43). Additionally, ARR associated with IOCM increased to 3.5% (p < 0.0001) in patients with combined comorbidities of diabetes and CKD 3–4 (RRR = 19.1%, NNT = 29). Statistically significant risk reduction was also found for the use of IOCM among patients who underwent revascularization for CTO (ARR = 1.6% [p < 0.0001], RRR = 22.3%, NNT = 62). Conclusion: Intra-arterial administration using IOCM in at-risk patients is associated with lower rates of MARCE than the use of LOCM. This difference is especially apparent in patients with a combination of CKD 3–4 and diabetes and in patients with CTO, providing real-world data validation with meaningful NNT in favor of IOCM.

Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction.

Rationale: Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup.Methods: Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand 68Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by ex vivo analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent 68Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome.Results: In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. Ex-vivo autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m2), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27).Conclusion: Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.

Developmental Origins of Kidney Disease: Why Oxidative Stress Matters?

The “developmental origins of health and disease” theory indicates that many adult-onset diseases can originate in the earliest stages of life. The developing kidney has emerged as being particularly vulnerable to adverse in utero conditions leading to morphological and functional changes, namely renal programming. Emerging evidence indicates oxidative stress, an imbalance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant systems, plays a pathogenetic role in the developmental programming of kidney disease. Conversely, perinatal use of antioxidants has been implemented to reverse programming processes and prevent adult-onset diseases. We have termed this reprogramming. The focus of this review is twofold: (1) To summarize the current knowledge on oxidative stress implicated in renal programming and kidney disease of developmental origins; and (2) to provide an overview of reprogramming effects of perinatal antioxidant therapy on renal programming and how this may prevent adult-onset kidney disease. Although early-life oxidative stress is implicated in mediating renal programming and adverse offspring renal outcomes, and animal models provide promising results to allow perinatal antioxidants applied as potential reprogramming interventions, it is still awaiting clinical translation. This presents exciting new challenges and areas for future research.

Outcomes of kidney donors with pre- and post-donation kidney stones.

Roughly 25% of US transplant centers exclude donor candidates with kidney stones fearing future obstructive consequences and the possible association between stones and CKD. We compared the development of hypertension, proteinuria, and reduced eGFR in 227 kidney donors with kidney stones to 908 propensity score-matched donor controls without kidney stones using data from The Renal and Lung Donor Evaluation (RELIVE) Study which studied intermediate and long-term outcomes of 8922 donors who donated between 1963 and 2007. 200 donors had kidney stones prior to donation, 21 had post-donation stones, and 6 had pre- and post-donation stones. Donors with stones were older, more likely to be Caucasian, less likely to be related to the recipient and had a higher fasting glucose. After 16.5±10.9years (range 0-44years) from donation to study close, no ESKD occurred in donors with stones. The multivariable risks of hypertension, proteinuria, and reduced GFR were similar in donors with and without kidney stones. We could not demonstrate an association between stones and adverse renal outcomes in kidney donors, and the occurrence of post-donation stones was distinctly rare. These data may provide a rationale for possibly a wider acceptance of donor candidates with low kidney stones burden.

The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes.

BackgroundContemporaneous data are required for women with chronic kidney disease (CKD) Stages 3–5 to inform pre-pregnancy counselling and institute appropriate antenatal surveillance.MethodsA retrospective cohort study in women with CKD Stages 3–5 after 20 weeks’ gestation was undertaken in six UK tertiary renal centres in the UK between 2003 and 2017. Factors predicting adverse outcomes and the impact of pregnancy in accelerating the need for renal replacement therapy (RRT) were assessed.ResultsThere were 178 pregnancies in 159 women, including 43 women with renal transplants. The live birth rate was 98%, but 56% of babies were born preterm (before 37 weeks’ gestation). Chronic hypertension was the strongest predictor of delivery before 34 weeks’ gestation. Of 121 women with known pre-pregnancy hypertension status, the incidence of delivery before 34 weeks was 32% (31/96) in women with confirmed chronic hypertension compared with 0% (0/25) in normotensive women. The risk of delivery before 34 weeks doubled in women with chronic hypertension from 20% [95% confidence interval (CI) 9–36%] to 40% (95% CI 26–56%) if the gestational fall in serum creatinine was <10% of pre-pregnancy concentrations. Women with a urinary protein:creatinine ratio >100 mg/mmol prior to pregnancy or before 20 weeks’ gestation had an increased risk for birthweight below the 10th centile (odds ratio 2.57, 95% CI 1.20–5.53). There was a measurable drop in estimated glomerular filtration rate (eGFR) between pre-pregnancy and post-partum values (4.5 mL/min/1.73 m2), which was greater than the annual decline in eGFR prior to pregnancy (1.8 mL/min/1.73 m2/year). The effect of pregnancy was, therefore, equivalent to 1.7, 2.1 and 4.9 years of pre-pregnancy renal disease in CKD Stages 3a, 3b and 4–5, respectively. The pregnancy-associated decline in renal function was greater in women with chronic hypertension and in those with a gestational fall in serum creatinine of <10% of pre-pregnancy concentrations. At 1 year post-partum, 46% (58/126) of women had lost ≥25% of their pre-pregnancy eGFR or required RRT. Most women with renal transplants had CKD Stage 3 and more stable renal function prior to pregnancy. Renal transplantation was not independently associated with adverse obstetric or renal outcomes.ConclusionsContemporary pregnancies in women with CKD Stages 3–5 are complicated by preterm delivery, low birthweight and loss of maternal renal function. Chronic hypertension, pre- or early pregnancy proteinuria and a gestational fall in serum creatinine of <10% of pre-pregnancy values are more important predictors of adverse obstetric and renal outcome than CKD Stages 3–5. Pregnancy in women with CKD Stages 3–5 advances the need for dialysis or transplantation by 2.5 years.

Design of a prospective patient-level pooled analysis of two parallel trials of empagliflozin in patients with established heart failure.

AimThe EMPEROR‐Reduced trial demonstrated that empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with a reduced ejection fraction, and the EMPEROR‐Preserved trial is currently evaluating the effect of the drug on the same endpoint in patients with an ejection fraction >40%. However, neither the trial was designed to have adequate statistical power to evaluate the effects of empagliflozin and dapagliflozin on major adverse renal outcomes or on mortality. Herein we describe the design of a prospective individual patient‐level pooled analysis of two large‐scale trials with empagliflozin (EMPEROR‐Reduced and EMPEROR‐Preserved) in patients with heart failure across the spectrum of ejection fraction.MethodsThe trials were carried out in parallel using the same administrative structure and committees, randomization procedure, schedule of study visits and adjudication criteria and similar groups of investigators and case report forms. The two component trials specified the same primary and key secondary endpoints and used an identical hierarchical testing procedure, which included a pooled analysis of the two trials as a key component of the hierarchy. Consequently, the pooled analysis has been prospectively assigned a false positive error rate, which is conditional on one or both trials first achieving success on their primary and one or both key secondary endpoints. The pooled analysis has its own statistical plan with its own endpoints, and this plan was finalized before either trial had begun recruitment of patients into either study. The primary endpoint of the pooled analysis is a composite of serious adverse renal outcomes, defined by chronic dialysis, renal transplantation and a profound or sustained decrease in glomerular filtration rate. All‐cause and cardiovascular mortality are specified as secondary endpoints.ConclusionThe planned pooled analysis has an unusually high degree of statistical rigour that will allow it to address important questions that cannot be fully addressed by the individual trials.

Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD)

Background Patients with chronic kidney disease (CKD) are at high risk of adverse renal and cardiovascular (CV) outcomes, particularly heart failure. We investigated the effects of dapagliflozin inpatients with CKD, with and without type 2 diabetes (T2D). DAPA-CKD is the first trial to test the effects of a SGLT2 inhibitor on renal and CV outcomes in CKD patients without T2D and included patients with a lower eGFR than in prior trials. Methods We enrolled CKD patients with and withoutT2D with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and UACR200-5000 mg/g, randomized (1:1) to dapagliflozin (10 mg once daily) or placebo. Patients were maintained on a stable dose of ACE inhibitor or ARB for ≥4 weeks before screening, if not contraindicated. The primary composite endpoint was worsening of kidney function (≥50% decline in eGFR, occurrence of end-stage kidney disease [ESKD]), or renal or CV death. Secondary endpoints were (in hierarchical order): (1) renal composite (primary endpoint without CV death); (2) composite of CV death or hospitalization for heart failure (hHF); and (3) death from any cause. The trial was stopped early following routine review by the data monitoring committee, because of overwhelming evidence of efficacy. Results Overall, 4304 patients were randomized at386 centers in 21 countries; 2152 to dapagliflozin, 2152 to placebo. The mean age was 62 years and 67% were male. Mean eGFR was 43.1 mL/min/1.73m2 and mean UACR was 949 mg/g. At baseline, 2906 (67.5%) patients had T2D, 96% had a history of hypertension, 37% other CV disease, and 11% heart failure. 4174(97%) were receiving an ACEi/ARB or another renin-angiotensin system blocker. Baseline characteristics were balanced between treatment groups. The sponsor has announced that in DAPA-CKD the primary and each of the secondary endpoints was reduced significantly by dapagliflozin compared with placebo. Conclusions Dapagliflozin significantly reduced the risk of CKD progression, the incidence of CV death/hHF, and prolonged survival in patients with CKD, with and without T2D. This presentation will report the prespecified primary and secondary outcomes in detail, along with additional information on heart failure outcomes. (Funded by AstraZeneca; NCT03036150)

Short-Course Systemic and Topical Non-Steroidal Anti-Inflammatory Drugs: Impact on Adverse Renal Events in Older Adults with Co-Morbid Disease.

Prolonged systemic non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with adverse renal outcomes among older adults. However, there is scant data regarding the renal safety of topical and short-course systemic NSAIDs. We aimed to evaluate the risk of acute adverse renal outcomes among older adults prescribed topical and short-term systemic NSAIDs. We conducted a retrospective cohort study of all older adults, age 60 years and above, who received prescriptions between July 2015 and December 2017 from the largest tertiary hospital and a major public primary care institution in Singapore. Data from 6 months before until 30 days after the first prescription were retrieved from electronic medical records. The primary outcome was the incidence of acute kidney injury (serum creatinine increased >26.5 µmol/L or >50% from baseline) and/or hyperkalemia within 30 days. A multi-variate analysis taking into account age, sex, co-morbidities, baseline-estimated glomerular filtration rate and serum potassium, NSAID route of administration, and concurrent renin-angiotensin-aldosterone system blocker and diuretic prescription was performed to evaluate factors associated with the primary outcome. We identified 12,773 older adults with incident prescriptions: 3982 (31.2%) received short-course systemic NSAIDs, 3784 (29.6%) received topical NSAIDs, and 5007 (39.2%) did not receive any NSAID. Both short-course systemic NSAIDs (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.41-1.80, p < 0.001) and topical NSAIDs (adjusted OR 1.48, 95% CI 1.31-1.67, p < 0.001), compared with the no-NSAID group, were independently associated with the primary outcome. Among older adults with co-morbid conditions and prescribed NSAIDs, topical NSAIDs had a reduced odds of 30-day incident acute kidney injury and/or hyperkalemia in diabetes mellitus (adjusted OR 0.78, 95% CI 0.65-1.06, p = 0.007), chronic kidney disease (adjusted OR 0.74, 95% CI 0.60-0.90, p = 0.003), and cardiovascular disease (adjusted OR 0.54, 95% CI 0.37-0.79, p < 0.001), compared with short-course systemic NSAIDs. NSAIDs increased the risk of acute adverse renal events. Topical NSAIDs, compared with short-course systemic NSAIDs, were associated with a reduced incidence of acute kidney injury and/or hyperkalemia among older adults with additional risk factors.

Hypertension

Hypertension is a common chronic disorder with an increasing prevalence in the context of an aging population. Patients with hypertension are at risk for adverse cardiovascular, renal, and neurologic outcomes. Treatment of hypertension reduces this associated risk; therefore, early diagnosis and systematic management are critical in reducing morbidity and mortality. Although hypertension is multifactorial, a large component is related to lifestyle, including excess sodium intake, lack of physical activity, and obesity. Lifestyle intervention and education, therefore, are critical to both prevention and treatment of hypertension. Patients diagnosed with hypertension should be evaluated for their overall risk, with specific therapies and treatment targets guided by their characteristics and comorbidities. Several professional and guideline societies have published recommendations with regard to the diagnosis and treatment of hypertension, which have many similarities but also several areas of discussion and ongoing debate. Recent evolutions in the field include the expanded indications for home-based and ambulatory blood pressure monitoring and outcomes trials, which add important data regarding optimal treatment targets. These evolutions are likely to be addressed in ongoing guideline updates. This review contains 10 figures, 15 tables, and 67 references. Key words: ambulatory blood pressure monitoring, antihypertensive therapy, blood pressure, blood pressure targets, cardiovascular risk, high blood pressure, home blood pressure monitoring, hypertension, screening, secondary hypertension

Hypertension

Hypertension is a common chronic disorder with an increasing prevalence in the context of an aging population. Patients with hypertension are at risk for adverse cardiovascular, renal, and neurologic outcomes. Treatment of hypertension reduces this associated risk; therefore, early diagnosis and systematic management are critical in reducing morbidity and mortality. Although hypertension is multifactorial, a large component is related to lifestyle, including excess sodium intake, lack of physical activity, and obesity. Lifestyle intervention and education, therefore, are critical to both prevention and treatment of hypertension. Patients diagnosed with hypertension should be evaluated for their overall risk, with specific therapies and treatment targets guided by their characteristics and comorbidities. Several professional and guideline societies have published recommendations with regard to the diagnosis and treatment of hypertension, which have many similarities but also several areas of discussion and ongoing debate. Recent evolutions in the field include the expanded indications for home-based and ambulatory blood pressure monitoring and outcomes trials, which add important data regarding optimal treatment targets. These evolutions are likely to be addressed in ongoing guideline updates. This review contains 10 figures, 15 tables, and 67 references. Key words: ambulatory blood pressure monitoring, antihypertensive therapy, blood pressure, blood pressure targets, cardiovascular risk, high blood pressure, home blood pressure monitoring, hypertension, screening, secondary hypertension

Sodium-Glucose Co-Transporter2 (SGLT2) Inhibitors: Are They All the Same? A Narrative Review of Cardiovascular Outcome Trials.

Clinically important improvements in cardiovascular risk factors and adverse cardiovascular, heart failure and renal outcomes have been observed in numerous cardiovascular outcome trials (CVOTs) investigating the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors over the last 5 years. However, differences in study outcomes between the various SGLT2 inhibitor CVOTs are often challenging to interpret because of differences in the study design, participant characteristics and primary outcomes of the various trials. In clinical practice, this frequently challenges the clinician when choosing between the different SGLT2 inhibitors for a patient with type 2 diabetes and various cardiovascular or renal comorbidities. Discussion around the choice of SGLT2 inhibitor has been again revived by the recent publication of results from the VERTIS-CV, EMPEROR-reduced and DAPA-CKD trials investigating cardiovascular, heart failure and renal outcomes associated with various SGLT2 inhibitors.This narrative review gives an overview of the mechanism of action and differences in the underlying pharmacology of the various SGLT2 inhibitors and discusses the key cardiovascular, heart failure and renal outcomes from completed CVOTs for SGLT2 inhibitors. Discussion highlights important differences in the study design and participant characteristics which limit the comparison of trials and medications within this drug class.

Intra-individual variability of eGFR trajectories in early diabetic kidney disease and lack of performance of prognostic biomarkers

Studies reporting on biomarkers aiming to predict adverse renal outcomes in patients with type 2 diabetes and kidney disease (DKD) conventionally define a surrogate endpoint either as a percentage of decrease of eGFR (e.g. ≥ 30%) or an absolute decline (e.g. ≥ 5 ml/min/year). The application of those study results in clinical practise however relies on the assumption of a linear and intra-individually stable progression of DKD. We studied 860 patients of the PROVALID study and 178 of an independent population with a relatively preserved eGFR at baseline and at least 5 years of follow up. Individuals with a detrimental prognosis were identified using various thresholds of a percentage or absolute decline of eGFR after each year of follow up. Next, we determined how many of the patients met the same criteria at other points in time. Interindividual eGFR decline was highly variable but in addition intra-individual eGFR trajectories also were frequently non-linear. For example, of all subjects reaching an endpoint defined as a decrease of eGFR by ≥ 30% between baseline and 3 years of follow up, only 60.3 and 45.2% lost at least the same amount between baseline and year 4 or 5. The results were similar when only patients on stable medication or subpopulations based on baseline eGFR or albuminuria status were analyzed or an eGFR decline of ≥ 5 ml/min/1.73m2/year was used. Identification of reliable biomarkers predicting adverse prognosis is a strong clinical need given the large interindividual variability of DKD progression. However, it is conceptually challenging in early DKD because of non-linear intra-individual eGFR trajectories. As a result, the performance of a prognostic biomarker may be accurate after a specific time of follow-up in a single population only.