Management of Atherosclerotic Cardiovascular Disease and Chronic Kidney Disease Risk in People With Type 2 Diabetes: Collaborative Care Plans for Primary Care Physicians Using Effective Communication Styles

To investigate the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes mellitus. We conducted a retrospective cohort study and followed up a population with Type 2 diabetes who were chronic kidney disease-free (n = 48,715) using national health insurance claims data in Taiwan. Exposure status to non-steroidal anti-inflammatory drugs in 2007 was measured. A total of 6406 subjects with incident chronic kidney disease were identified from the period 2008 to 2011. Multivariable proportional hazards models were applied to determine the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease. We observed a significant temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes. Compared with people not taking any non-steroidal anti-inflammatory drug in 2007, those who were taking such drugs for at least 90 days in 2007 had a higher risk of chronic kidney disease development (adjusted hazard ratio 1.37, 95% CI 1.26-1.49). In subgroup analyses, those people (irrespective of age, sex, various comorbidities and use of anti-hypertensive drugs, aspirin or acetaminophen) who were taking non-steroidal anti-inflammatory drugs for at least 90 days were more likely to develop chronic kidney disease than people who were not taking any non-steroidal anti-inflammatory drug. The results suggest that there is a positive temporal relationship between non-steroidal anti-inflammatory drug use and increased risk of chronic kidney disease in people with Type 2 diabetes. The use of non-steroidal anti-inflammatory drugs should be based on clinical evaluations of benefits and risks, and should be prescribed with caution for people with Type 2 diabetes.

Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trials

Chronic kidney disease (CKD) is one of the most frequent complications faced by people with diabetes mellitus. The ability to accurately predict the onset of this disease at an early stage and adjust the individual therapy and lifestyle appropriately has the potential to prevent or at least slow down the progression of the disease significantly. We have previously published a 3-year CKD risk engine based on longitudinal U.S. EHRs data (Indiana Network for Patient Care and IBM Explorys) from more than 600,000 PwDs and have demonstrated a superior performance compared to previously published risk algorithms developed solely on clinical trial data (AUC = 0.794 vs. AUC = 0.718 for the best benchmark algorithm). Nevertheless, our previous analysis was limited to healthcare data from the U.S. and the risk prediction was only tested for patients at the time point of the initial diabetes diagnosis. To prove that our algorithm has a broader applicability, we have independently validated our risk engine on a dataset of general practitioners from the UK (Clinical Practice Research Datalink) including longitudinal data from more than 140,000 PwDs, thereby showing the transferability of our algorithm into a European context (AUC = 0.763 +/- 0.005 vs. AUC = 0.594 +/- 0.006 for the best benchmark). Moreover, we used this analysis to apply our risk engine at variable time points after the initial diabetes diagnosis within the U.S. and European data and could thereby demonstrate that our algorithm is not limited to the initial time of diagnosis (average AUC = 0.79 irrespective of the time after diagnosis). This validation analysis further corroborates the external validity of our approach to use Real-World-Data from EHRs in the development of CKD risk prediction algorithms and thereby supports a broader use of those algorithms in standard clinical practice. Disclosure T. Huschto: Employee; Self; Roche Diabetes Care. H. König: Employee; Self; Roche Diabetes Care. C.E. Marriott: Employee; Self; Roche Diabetes Care. D. Militz: Employee; Self; Roche Diabetes Care. C. Ringemann: Employee; Self; Roche Diabetes Care.

Objective: To evaluate the association between hypertension duration and risk for chronic kidney disease in residents in China. Methods: Participants aged 18-74 years from the sixth round of China Chronic Disease and Risk Factor Surveillance in 2018 were included. The age/date at hypertension diagnosis was reported by them, and hypertension duration was calculated based on the age at diagnosis and the age at survey. The hypertension duration was calculated as 0 year (i.e., normotensive participants), 0.1- year, 5.0- years, 10.0- years, and ≥15.0 years. Serum creatinine, urinary albumin, and urinary creatinine levels were measured, and chronic kidney disease was diagnosed when glomerular filtration rate was <60 ml·min-1·(1.73 m2)-1 and/or urine albumin-to-creatinine ratio was ≥30 mg/g. Multivariable logistic regression analysis, which took intra-group correlation into account, was used to evaluate the association of hypertension duration with chronic kidney disease. Results: A total of 140 662 residents were finally included in the analysis. After adjusting the confounders, including blood pressure, the odds ratio of chronic kidney disease was 1.16 (95%CI: 1.09-1.23), 1.33 (95%CI: 1.20-1.48), 1.33 (95%CI: 1.18-1.49), and 1.43 (95%CI: 1.29-1.60) in study subjects with hypertension durations of 0.1-4.9 years, 5.0-9.9 years, 10.0-14.9 years, and ≥15.0 years, respectively, in comparison with normotensive people. This result was further supported by the positive association between hypertension duration and chronic kidney disease in people with previously diagnosed hypertension. The results of restricted cubic spline suggested that the risk for chronic kidney disease showed a steep increase within 0.1- 4.9 years after hypertension diagnosis, then showed neither increase nor decrease. The above association seemed to be stronger in those with hypertension diagnosed age <45 years. Compared with those with hypertension duration of 0.1-4.9 years, the odds ratio was 1.38 (95%CI: 1.04-1.84), 1.22 (95%CI: 0.91-1.65), and 1.47 (95%CI: 1.04-2.07) in those with hypertension durations of 5.0-9.9 years, 10.0-14.9 years, and ≥15.0 year, respectively. In those with hypertension diagnosis at ≥45 years, the corresponding odds ratio was 1.08 (95%CI: 0.98-1.19), 1.08 (95%CI: 0.97-1.21), and 1.16 (95%CI: 1.02-1.32), respectively. Conclusions: Hypertension duration is positively associated with the risk for chronic kidney disease in residents in China, and this association is independent of blood pressure level. Early diagnosis of hypertension and long-term control of blood pressure are effective strategies for secondary prevention of hypertension-related chronic kidney disease.

ObjectivesTo assess the risk of chronic kidney disease (CKD) associated with tenofovir disoproxil fumarate (TDF) use by baseline D:A:D CKD risk score.MethodsAdult antiretroviral therapy (ART)‐naïve people living with HIV (PLWH) initiating treatment, with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, were identified in the OPERA cohort. CKD was defined as two or more consecutive eGFR < 60 mL/min/1.73 m2, > 90 days apart. Associations between TDF use, baseline D:A:D CKD risk and incident CKD were assessed with incidence rates (IRs; Poisson regression) and adjusted pooled logistic regression. The impact of pharmacoenhancers on the observed association between TDF and CKD was also evaluated.ResultsOf 9802 PLWH included, 6222 initiated TDF and 3580 did not (76% and 79% low D:A:D CKD risk, respectively). Overall, 125 CKD events occurred over 24 382 person‐years of follow‐up. Within strata of D:A:D CKD risk score, IRs were similar across TDF exposure, with high baseline CKD risk associated with highest incidence. Compared with the low‐risk group without TDF, there was no statistical difference in odds of incident CKD in the low‐risk group with TDF (adjusted odds ratio = 0.55, 95% confidence interval: 0.19–1.54). Odds of incident CKD did not differ statistically significantly by pharmacoenhancer exposure, with or without TDF.ConclusionsIn this large cohort of ART‐naïve PLWH, incident CKD following ART initiation was infrequent and strongly associated with baseline CKD risk. TDF‐containing regimens did not increase the odds of CKD in those with a low baseline D:A:D CKD risk, the largest group of ART‐naïve PLWH, and may remain a viable treatment option in appropriate settings.

People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

Target blood pressure and kidney protection

To highlight advances in understanding of host factors, in particular host genetics, in the development of chronic kidney disease (CKD) in people with HIV. In Black populations, the G1 and G2 variants of the apolipoprotein L1 (APOL1) gene predispose to HIV-associated nephropathy (HIVAN). The risk of HIVAN is mostly confined to individuals with two APOL1 variants (kidney-risk genotypes). APOL1 kidney-risk genotypes are present in approximately 80% of patients with HIVAN and account for nearly half the burden of end-stage CKD in people of African ancestry with HIV. Progress has been made in elucidating the mechanisms of kidney injury in APOL1 nephropathy, and several targeted molecular therapies are being investigated in clinical trials. Genome- and epigenome-wide association studies are identifying additional genes and pathways that may be involved in the pathogenesis of CKD in people with HIV. Genetic variants of APOL1 are strongly associated with severe CKD and contribute to the high rates of CKD in Black populations with HIV. Most individuals with APOL1 kidney-risk genotypes, however, do not develop kidney disease and further studies are required to understand the role of additional genetic and environmental factors that may affect CKD risk in this population.

Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. The Highly Active Antiretroviral Therapy Oversight Committee.

Nutrition and Kidney Health: Processing Emerging Evidence About Foods

Comparison of benzbromarone and allopurinol on the risk of chronic kidney disease in people with asymptomatic hyperuricemia

To investigate the association between long-term fine particulate matter(PM_(2.5)) exposure and the risk of chronic kidney disease(CKD) in people with abnormal metabolism syndrome(MS) components. Based on health checkup data from a hospital in Beijing, a retrospective cohort study was used to collect annual checkup data from 2013-2019. A questionnaire was used to obtain information on demographic characteristics and lifestyle habits. We measured blood pressure, height, weight, waist circumference, concentrations of triglycerides(TG), fasting glucose, and high-density lipoprotein cholesterol(HDL-C). Longitude and latitude were also extracted from the addresses of the study subjects for pollutant exposure data estimation. Logistic regression models were used to explore the estimated effect of long-term PM_(2.5) exposure on the risk of CKD prevalence in people with abnormal MS components. Two-pollutant and multi-pollutant models were developed to test the stability of these result. Subgroup analysis was conducted based on age, the presence of MS, individual MS component abnormalities, and dual-component MS abnormalities. The study included 1540 study subjects with abnormal MS components at baseline, 206 with CKD during the study period. The association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions was statistically significant, with a 2.26-fold increase in risk of CKD for every 10 μg/m~3 increase in PM_(2.5) exposure(OR=3.26, 95% CI 2.72-3.90). The result in the dual-pollutant models and multi-pollutant models suggested that the association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions remained stable after controlling for contemporaneous confounding by other air pollutants. The result of subgroup analysis revealed that individuals aged 45 or older, without MS, with TG&lt;1.7 mmol/L, HDL-C≥1.04 mmol/L, without hypertension, and with central obesity and high blood sugar had a stronger association between PM_(2.5) exposure and CKD-related health effects. Long-term exposure to PM_(2.5) may increase the risk of CKD in people with abnormal MS components. More attention should be paid to middle-aged and elderly people aged ≥45 years, people with central obesity and hyperglycemia.

Kidney Disease in People With Diabetes: The Expanding Epidemic

To investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal. The Hoorn Diabetes Care System cohort is a large prospective cohort consisting of individuals with type 2 diabetes from the northwest part of the Netherlands. In this cohort we assessed the association of baseline plasma levels of 172 metabolites with incident (Ntotal = 462/Ncase = 81) and prevalent (Ntotal = 1247/Ncase = 120) CKD using logistic regression. Additionally, replication in the UK Biobank, body mass index (BMI) mediation and causality of the association with Mendelian randomization was performed. Elevated levels of total and individual branched-chain amino acids (BCAAs)-valine, leucine and isoleucine-were associated with an increased risk of incident CKD, but with reduced odds of prevalent CKD, where BMI was identified as an effect modifier. The observed inverse effects were replicated in the UK Biobank. Mendelian randomization analysis did not provide evidence for a causal relationship between BCAAs and prevalent CKD. Our study shows the intricate relationship between plasma BCAA levels and CKD in individuals with type 2 diabetes. While an association exists, its manifestation varies based on disease status and BMI, with no definitive evidence supporting a causal link between BCAAs and prevalent CKD.

Does Inflammation Fuel the Fire in CKD?