Chronic Kidney Disease In People Research Articles

Precision medicine implementation challenges for APOL1 testing in chronic kidney disease in admixed populations.

Chronic Kidney Disease (CKD) is a public health problem that presents genetic and environmental risk factors. Two alleles in the Apolipoprotein L1 (APOL1) gene were associated with chronic kidney disease; these alleles are common in individuals of African ancestry but rare in European descendants. Genomic studies on Afro-Americans have indicated a higher prevalence and severity of chronic kidney disease in people of African ancestry when compared to other ethnic groups. However, estimates in low- and middle-income countries are still limited. Precision medicine approaches could improve clinical outcomes in carriers of risk alleles in the Apolipoprotein L1 gene through early diagnosis and specific therapies. Nevertheless, to enhance the definition of studies on these variants, it would be necessary to include individuals with different ancestry profiles in the sample, such as Latinos, African Americans, and Indigenous peoples. There is evidence that measuring genetic ancestry improves clinical care for admixed people. For chronic kidney disease, this knowledge could help establish public health strategies for monitoring patients and understanding the impact of the Apolipoprotein L1 genetic variants in admixed populations. Therefore, researchers need to develop resources, methodologies, and incentives for vulnerable and disadvantaged communities, to develop and implement precision medicine strategies and contribute to consolidating diversity in science and precision medicine in clinical practice.

Shear wave elastography evaluation of cats with chronic kidney disease.

Chronic kidney disease (CKD) is a major health condition in cats that can lead to poor quality of life and financial implications for therapy. Currently staging and identification of CKD is limited by diagnostic testing such as creatinine and urine-specific gravity, which do not change until late in the disease course. Other methods to evaluate CKD would be valuable in the clinical setting. Shear wave elastography is one novel ultrasound method, which has shown promise in identifying increases in tissue stiffness and identifying CKD in people. As CKD is often histologically characterized by tubulointerstitial fibrosis, shear wave elastography has the potential to identify CKD and differentiate between stages of CKD in cats. This prospective observational case-control study with 78 cats found no difference in shear wave velocities between groups (P=0.33), a contradictory finding to one prior publication. There was no effect of weight (P=0.65), nor the presence of mineralization (P=0.31) or infarction (P=0.52) on cortical shear wave velocities. There was a significant effect of age on shear wave velocity (P=0.018) where velocities increased with age. The intraclass correlation coefficient was only moderate (0.62). Possible reasons for the difference in results between our work and that published prior, include differences in methodology and differences in instrumentation. Variability in measurements in our population may be due to the effects of respiratory motion or limitations in shear wave elastography software. As such, shear wave elastography is not currently recommended as a tool to evaluate CKD in cats and further work is necessary.

Development of minimal resource pre-screening tools for chronic kidney disease in people with type 2 diabetes

Regular chronic kidney disease (CKD) screening can facilitate earlier diagnosis of CKD and preventative action to reduce the risk of CKD progression. People with type 2 diabetes are at a higher risk of developing CKD; hence, it is recommended that they undergo annual screening. However, resources may be limited, particularly in lower-to-middle income countries, and those at the highest risk of having an abnormal CKD screening result should be prioritised for screening. We have developed models to determine which patients are at a high risk of renal impairment. We have shown that, for people with type 2 diabetes and no previous diagnosis of CKD stage 3-5, it is possible to use age, gender, body mass index, duration of type 2 diabetes and blood pressure information to detect those at a higher risk of a reduced glomerular filtration rate. When blood measurements are available, triglyceride and cholesterol measurements can be used to improve the estimate of the risk. Even though risk factors were associated with an increased urine albumin:creatinine ratio, we found no clinical benefit of using the model over a screen-all approach.

Glycaemic variability and progression of chronic kidney disease in people with diabetes and comorbid kidney disease: Retrospective cohort study

AimTo investigate the association between glycaemic variability and the development of End-Stage-Kidney-Disease (ESKD) among individuals with diabetes and chronic kidney disease. MethodsA cohort study using UK electronic primary care health records from the Clinical Practice Research Datalink. Glycaemic variability was assessed using a variability score and intra-individual coefficient of variation (CV) of HbA1c. We calculated sub-distribution hazard ratios (sHR) for developing ESKD using competing risk regression analysis. ResultsThere were 37,222 eligible participants (45.5 % male), with a mean age of 76.4 years (SD ± 9.2), and a mean baseline eGFR 40.7 (±10.7) ml/min/1.73 m2. There were 5,086 incidents of ESKD in the follow-up period. The adjusted sHR (95 %CI) for each variability score group, were as follows: 21–40, 1.38 (1.27–1.50); 41–60, 1.54 (1.41–1.68); 61–80, 1.61 (1.45–1.79); and 81–100, 1.42 (1.19–1.68), compared with the group (score 0–20) with least variability. The adjusted sHR for CV were as follows: 6.7–9.9, 1.29 (1.15–1.45); 10.0–13.9, 1.55 (1.39–1.74); 14.0–20.1, 1.79 (1.60–2.01) and ≥20.2, 2.10 (1.88–2.34) compared to reference group 0–6.6. ConclusionsGlycaemic variability was strongly associated with the development of ESKD in people with diabetes and CKD.

Impact of SGLT2 inhibitors treatment on the chronic kidney disease in people with type 2 diabetes

Diabetes is the most common cause of CKD (chronic kidney disease). CKD is also one of the most important diabetic complication. SGLT2 (sodium glucose co‐transporter‐2) inhibitors are new class of medication used to lower high blood glucose level in people with type 2 diabetes. In new researches SGLT2 inhibitors demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. This review focuses on the therapeutic effectiveness of using SGLT2 inhibitors for the treatment of CKD in type 2 diabetes.

Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration

In the past decade, advances in the validation of surrogate end points for chronic kidney disease (CKD) progression have heightened interest in evaluating therapies in early CKD. In December 2020, the National Kidney Foundation sponsored a scientific workshop in collaboration with the US Food and Drug Administration (FDA) to explore patient, provider, and payor perceptions of the value of treating early CKD. The workshop reviewed challenges for trials in early CKD, including trial designs, identification of high-risk populations, and cost-benefit and safety considerations. Over 90 people representing a range of stakeholders including experts in clinical trials, nephrology, cardiology and endocrinology, patient advocacy organizations, patients, payors, health economists, regulators and policy makers attended a virtual meeting. There was consensus among the attendees that there is value to preventing the development and treating the progression of early CKD in people who are at high risk for progression, and that surrogate end points should be used to establish efficacy. Attendees also concluded that cost analyses should be holistic and include aspects beyond direct savings for treatment of kidney failure; and that safety data should be collected outside/beyond the duration of a clinical trial. Successful drug development and implementation of effective therapies will require collaboration across sponsors, patients, patient advocacy organizations, medical community, regulators, and payors.

Clinical Characteristics and Outcomes of Chronic Kidney Disease in People Living with HIV in a Resource-Limited Center of Central China.

Clinical management and optimal treatment are essential to improving outcomes for people living with HIV (PLWH). We assessed trends and outcomes of chronic kidney disease (CKD) in PLWH in a resource-limited center of central China. All PLWH who were followed up in a tertiary referral center in Wuhan, China, from July 2016 to June 2021 were evaluated. CKD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m2 during two consecutive measurements 3 months apart. Baseline characteristics of the participants were extracted from the hospital medical records. The prevalence rate and associated risk factors of CKD were analyzed. A total of 863 PLWH with normal kidney function at baseline were analyzed. The median age was 33 (interquartile ranges: 26-49) years, and 778 (90.2%) were male and 85 (9.8%) were female. Among them, 50 (5.8%) had their GFR falling below 60 mL/min/1.73 m2 after a median of 54 months. Adjusted multivariate logistic regression revealed older age [adjusted odds ratio (aOR) = 1.04, 95% confidence interval (95% CI): 1.01-1.07], female sex (aOR = 3.17, 95% CI: 1.14-8.84), lower body weight (aOR = 0.95, 95% CI: 0.91-1.00), lower hemoglobin (aOR = 3.54, 95% CI: 1.51-8.30), longer duration of antiretroviral therapy exposure (aOR = 1.02, 95% CI: 1.00-1.04), and a baseline GFR between 60 and 90 mL/min/1.73 m2 (aOR = 3.89, 95% CI: 1.21-12.46) were associated with the development of CKD. Our findings showed that CKD is not infrequent in PLWH with a combination of traditional and HIV-specific risk factors for kidney disease, highlighting the suboptimal monitoring and treatment options of CKD in PLWH in resource-limited settings. Scalable monitoring strategy to improve care for this population is warranted.

Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria.

Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review discusses albuminuria as a marker of kidney damage and cardiorenal risk, highlights the importance of early screening and routine testing for albuminuria in people with T2D, and provides new insights on the optimum management of CKD in T2D using albuminuria as a target in a proposed algorithm. Elevated urine albumin can be used to detect CKD in people with T2D and monitor its progression; however, obstacles preventing early detection exist, including lack of awareness of CKD in the general population, poor adherence to clinical guidelines, and country-level variations in screening and treatment incentives. With albuminuria being used as an entry criterion and a surrogate endpoint for kidney failure in clinical trials, and with novel treatment interventions available to prevent CKD progression, there is an urgent need for early screening and diagnosis of kidney function decline in people with T2D or pre-diabetes.

The Negative Association Between NAFLD Severity and CKD in a Non-Diabetic Gouty Population.

Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and risk factors. We aim to evaluate the association between NAFLD and CKD in a non-diabetic gouty population. The retrospective cross sectional study was performed on 1049 non-diabetic gouty participants, who were hospitalized between 2014 and 2020, across 4 districts in Shandong, China. Demographic and clinical characteristics of the study population were collected. The odds ratios (OR) and corresponding 95% confidence intervals (CI) about the NAFLD severity determined by ultrasonography were obtained by multiple logistic regression analysis. An unexpectedly inverse relationship was found between NAFLD severity and the risk of CKD in people with gout. Multivariate logistic regression analysis demonstrated that a higher degree of NAFLD severity is independently associated with a lower risk of CKD in people with gout, after adjusted for age, sex, smoking, gout duration, and metabolic risk factors including obesity, hypertension, hyperglycemia, hyperuricemia, and dyslipidemia, with OR 0.392 (95% CI 0.248-0.619, p<0.001), 0.379 (95% CI 0.233-0.616, p<0.001) and 0.148 (95% CI 0.043-0.512, p=0.003) in participants with mild, moderate, and severe NAFLD, respectively, compared to those without NAFLD. We also observed a weakened association of serum uric acid (SUA) with metabolic risk factors and NAFLD under circumstances of CKD in people with gout (r=-0.054, p=0.466). In conclusion, the presence and severity of NAFLD were negatively associated with the risk of CKD in the non-diabetic gouty population.

Protecting the Kidneys: Update on Therapies to Treat Diabetic Nephropathy.

This article provides an update on pharmacotherapy for diabetic nephropathy. ACE inhibitor or angiotensin 2 receptor blocker therapy is a standard of care for hypertension management in people with diabetes and albuminuria. Additionally, recent trials have elucidated the roles of additional therapeutic agents, including the sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and the recently approved mineralocorticoid receptor antagonist finerenone, in the treatment of chronic kidney disease in people with type 2 diabetes. This article provides an evidence-based review of therapies that may delay the progression of kidney disease in this population, including discussion of recent outcomes trials.

Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021

People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice

Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes.

Are skin conditions associated with kidney disease?

British Journal of DermatologyVolume 185, Issue 4 p. e163-e163 Plain Language Summary Are skin conditions associated with kidney disease? First published: 04 October 2021 https://doi.org/10.1111/bjd.20673AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Schonmann et al. Br J Dermatol 2021; 185:772–780. Chronic kidney disease (CKD) affects up to 13% of the population and may progress to kidney failure and death. Some risk factors for CKD are well known such as high blood pressure and diabetes. There is some evidence that inflammatory skin diseases such as eczema and psoriasis may also increase the risk of CKD. This group of researchers from Israel and the UK used a large database to see whether people with CKD stages 3 (moderate loss of kidney function) to 5 (renal failure) are more likely to have skin disease than people without CKD. They compared over 56,000 adults with CKD and over 268,000 people without kidney disease, taking into account known risk factors for CKD (age, sex, medical deprivation score, diabetes, smoking, harmful alcohol use and obesity). They found that people with CKD were slightly more likely to have a history of atopic eczema, psoriasis or hidradenitis suppurativa than those without, and less likely to have rosacea. Severity of eczema and psoriasis was associated with more severe CKD. These findings support the assumption that inflammatory skin diseases are indeed linked with an increased risk for CKD. While such factors have been accounted for in the analysis, the results also might simply reflect the fact that people with skin disease may have been treated with drugs that damage the kidney. The authors also looked at over 335,000 patients with diabetes, who have regular kidney function tests. Among these patients with diabetes, who already have a high risk of CKD, there was no evidence of CKD incidence being associated with atopic eczema or psoriasis. The inconclusive results of the study require further investigation, for example, to explore whether targeted screening for CKD in people with inflammatory skin diseases is justified. Volume185, Issue4October 2021Pages e163-e163 RelatedInformation

A Cross-Sectional Study for Prevalence and Association of Risk Factors of Chronic Kidney Disease Among People With Type 2 Diabetes in the Indian Setting.

Introduction: Current evidence demonstrates that people with type 2 diabetes (T2D) are at a higher risk of developing chronic kidney disease (CKD) with greater morbidity and mortality. We, therefore, aimed to document and categorize demographic, anthropometric, and physiological risk factors of CKD in people with T2D in India. Additionally, we also attempted to evaluate the magnitude of each risk factor, namely age, duration of diabetes, HbA1c, and body mass index (BMI) in its etiology.Methods: This observational, single-center, and cross-sectional study was performed at a diabetes care center in Lucknow, India. Out of a total of 504 eligible patients, we could get the required data from 435 patients. The following data were collected: demographic data, estimated glomerular filtration rate (eGFR), serum creatinine, urinary albumin creatinine ratio (UACR), and HbA1c levels. Appropriate statistical tests were applied.Result: The 435 eligible people with diabetes had a mean age (SD) of 51 (±10.52) years; female 48.02%, duration of diabetes 7 (±5.4) years; HbA1c 8.6 (±2.3)% and eGFR values 80.2 (±26.6) mL/min/1.73m2 at the time of presentation. The eGFR values correlated negatively with age and duration of diabetes, and positively with increasing BMI. The Spearman correlation coefficient showed that clinical parameters such as age, duration of diabetes, and BMI have a weak, but statistically significant correlation with eGFR while eGFR did not correlate with HbA1c level in the study. Further, we did not find a correlation between eGFR and UACR.Conclusion: In people with T2D, age and duration of diabetes are important risk factors for the development of CKD based on the eGFR. Hence, even in the absence of high UACR values, a low eGFR should prompt periodic monitoring to reduce the risk of progression of CKD, especially, in older people with long-standing T2D. Our study did not find HbA1c as a suitable tool to assess the CKD progression risk, but historical glycaemic control over longer periods revealed by sequential values of HbA1c over the duration of disease may correlate with the progression of CKD.

Estimation of the Prevalence of Chronic Kidney Disease in People with Diabetes by Combining Information from Multiple Routine Data Collections

Abstract Health care claims databases maintained by social insurance institutions provide rich and sometimes easily accessible data sources for epidemiological research. Interpreting the registered claims, for example, drug prescriptions, as proxies for the condition of interest, for example, diabetes, they allow for nationwide prevalence estimation. We illustrate a more subtle use of health care claims data in estimating the stage-specific prevalence of chronic kidney disease in the Austrian population with diabetes. The main difficulty was that information on the type of disease (chronic or acute) and information on the stage of disease were only available for small, almost disjoint subsets of the health care claims data. Using high-dimensional regression models, we could combine the information and provide nationwide estimates of the stage-specific prevalence of diabetic chronic kidney disease. Validating our estimates by comparing to other studies, we found the level of agreement satisfying.

15-LB: Prediction of Chronic Kidney Disease (CKD) in People with Diabetes

Background: People with diabetes in general have a higher risk of developing Chronic Kidney Disease (CKD). The early detection of CKD in people with diabetes helps their health care providers to adjust their therapy to slow down the disease progression to higher stages, prevent complications, and reduce cardiovascular-related conditions. It also takes a great financial burden off the insurance companies in the long run by way of future treatment costs. We have developed a model that uses the historical data from the past 2 years of people with diabetes (PwD) and predicts the chance of them having CKD in the next 3 years. Methods: Our model employed the XGBoost (eXtreme Gradient Boosting) algorithm. It used more than 860,000 PwD data from the IBM EHR (Electronic Health Records) database for training and optimizing the model parameters. It was then independently verified using more than 500,000 PwD data from the CPRD (Clinical Praxis Research Datalink) database from the UK, and close to 140,000 PwD data from the INPC (Indiana Network for Patient Care) database from the US. We considered an incident of CKD based on the appearance of a relevant ICD code. The major benefit of the XGBoost algorithm in the context of risk prediction based on EHR data is that there is no need for imputation of the missing values. Results: We evaluated the performance of the Roche XGBoost model for CKD in terms of the area under the receiver operating characteristic curve (AUC). While we obtain comparable results for the US-based data sets (prediction model: AUCExplorys=0.83, AUCINPC=0.84), we observe a performance decrease for the validation on CPRD data (AUCCPRD=0.74). However, on all data sources our XGBoost model shows a superior performance when compared to appropriate benchmark algorithms from literature. Conclusions: The XGBoost model for CKD disease prediction has a superior performance over benchmark models from literature. Disclosure N. Afshar: Employee; Self; Roche Diabetes Care. I. Singh: Employee; Self; Roche Diabetes Care. T. Huschto: Employee; Self; Roche Diabetes Care. M. Andorrà: Advisory Panel; Self; Attune Neurosciences Inc., Employee; Self; Roche Diabetes Care, Stock/Shareholder; Self; Bionure, S. L., Goodgut, S. L. S. Chittajallu: Employee; Self; Roche Diabetes Care. C. Ringemann: Employee; Self; Roche Diabetes Care. J. T. Odegard: Employee; Self; Roche Diabetes Care. H. Mikulski: None. V. N. Babinsky: Employee; Self; Roche Diabetes Care. H. König: Employee; Self; Roche Diabetes Care.

1046-P: Automated Early Flagging of Undiagnosed CKD Using Real-World Data

Aims: Early diagnosis and treatment of chronic kidney disease (CKD) may delay disease progression since 45% of patients are not diagnosed until stage 3. We examine the Kidney Disease Improving Global Outcomes (KDIGO) clinical guidelines that define rules based on the longitudinal progression of urine albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) for flagging CKD in people with type 2 diabetes (T2-PwD). Methods: EHR data from over 400,000 T2-PwDs in the Indiana Network for Patient Care (INPC) database were used for this analysis. The KDIGO clinical practice guidelines defines CKD as persistently elevated urine albumin excretion (&amp;gt;=30 mg/g), or persistently reduced eGFR (&amp;lt; 60 ml/min per 1.73m2), or both, for more than 3 months. Our automated system scanned each patient’s longitudinal record and identified those patients with abnormal UACR and eGFR values in the cases where sufficient values were available. A flag associated with either UACR or eGFR or both and the date of flagging is indicated by the system if abnormal marker values persist for more than 3 months. CKD is indicated if one or both flags are triggered. Results: Out of 422,089 patients 35,573 (8%) were identified as diagnosed with CKD. Only 3% of these patients had at least 2 UACR readings and, therefore, the automated system considered primarily eGFR as the marker for flagging CKD. Out of 35,573 patients with CKD diagnosis, 16,342 (46%) had an eGFR warning flag that predated the CKD diagnosis date. The system flagged a potential identification as much as 599 days (median value) in advance of the diagnosis of CKD in the dataset. Conclusion: Our results show that earlier identification of CKD onset can be automated to flag patients wherein a positive diagnosis of CKD is likely. This flag can then prompt a confirmatory diagnosis of CKD, allowing better treatment interventions and management of CKD, reducing the burden of disease, and potentially decreasing costs associated with treatments in later CKD stages. Disclosure D. Malagarriga: None. S. Chittajallu: Employee; Self; Roche Diabetes Care. P. J. Galley: Employee; Self; Roche Diabetes Care. I. Singh: Employee; Self; Roche Diabetes Care. J. T. Odegard: Employee; Self; Roche Diabetes Care.

Current evidence and practical guidance for the use of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes.

The burden of type 2 diabetes (T2D) and its associated complications continues togrow in Australia. In recent years, sodium-glucose co-transporter-2 (SGLT2) inhibitors have become a key component of diabetes care with rapid uptake into routine clinical practice. There is growing evidence of their clinical efficacy, but also potential adverse effects. The aim of this article is to review the use of SGLT2 inhibitors in T2D by exploring data surrounding clinical efficacy and safety as well as providing practical advice for prescribing clinicians. SGLT2 inhibitors have multiple metabolic benefits including reducing glycated haemoglobin, weight and blood pressure. Additionally, there are strong cardiovascular benefits and renoprotective effects in selected populations. Current evidence suggests that SGLT2 inhibitors should be considered for the secondary prevention of cardiovascular disease and to delay progression of early chronic kidney disease in people with T2D. Clinicians should also be aware of common side effects and potential rare severe complications.

Outcome trends in people with heart failure, type 2 diabetes mellitus and chronic kidney disease in the UK over twenty years.

BackgroundHeart failure (HF) together with type 2 diabetes (T2D) and chronic kidney disease (CKD) are major pandemics of the twenty first century. It is not known in people with new onset HF, what the distinct and combined associations are between T2D and CKD comorbidities and cause-specific hospital admissions and death, over the past 20 years.MethodsAn observational study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics in England (1998–2017). Participants were people aged ≥30 years with new onset HF. Exposure groups were HF with: (i) no T2D and no CKD (reference group); (ii) CKD-only (estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2); (iii) T2D-only; (iv) T2D and CKD. CKD severity groups were: CKD-3a (eGFR 45–59); CKD-3b (30–44); CKD-4 (15–29); CKD-5 (<15). Outcomes were cardiovascular and non-cardiovascular hospitalisations and all-cause death.FindingsIn 87,709 HF patients (mean age, 78 years; 49% female), 40% had CKD-only, 12% T2D-only, and 16% both. Age-standardised first-year CVD hospitalisation rates were significantly higher in HF patients with CKD-only (46.4; 95% CI 44.9,47.9 per 100 person years) and T2D-only (49.2; 46.7,58.8) than in the reference group (35.1; 34.0,36.1); the highest rate was in patients with T2D-CKD-5: 89.1 (65.8,112.4). Similar patterns were observed for non-CVD hospitalisations and deaths. Group differences remained significant after adjustment for potential confounders. Median survival was highest in the reference (4.4 years) and HF-T2D-only (4.1 years) groups, compared to HF-CKD-only (2.2 years). HF-T2D-CKD group survival ranged from 2.8 (CKD-3a) to 0.7 years (CKD-5). Over time, CVD hospitalisation rates significantly increased for HF-CKD-only (+26%) and reduced (-24%) for HF-T2D-only groups; no reductions were observed in any of the HF-T2D-CKD groups. Trends were similar for non-CVD hospitalisations and death: whilst death rates significantly reduced for HF-T2D-only (-37%), improvement was not observed in any of the T2D-CKD groups.InterpretationIn a cohort of people with new onset HF, hospitalisations and deaths are high in patients with T2D or CKD, and worst in those with both comorbidities. Whilst outcomes have improved over time for patients with HF and comorbid T2D, similar trends were not seen in those with comorbid CKD. Strategies to prevent and manage CKD in people with HF are urgently needed.Funding10.13039/100006662NIHR fellowship [reference: NIHR 30011]

Renal morphology and glomerular capillarisation in young adult sheep born moderately preterm.

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman's spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman's space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.