Now showing 1 - 10 of 16
  • Publication
    Validating the association between plasma tumour necrosis factor receptor 1 levels and the presence of renal injury and functional decline in patients with Type 2 diabetes
    AIMS: Elevated plasma soluble tumour necrosis factor receptor 1 (TNFR1) predicts long-term progression of chronic kidney disease. We investigated the association between elevated TNFR1 and the presence of renal disease in patients with Type 2 diabetes mellitus registering a haemoglobin A1c (HbA1c) >48mmol/mol despite medical therapy. METHODS: Using sensitivity, specificity and regression analyses we interrogated the association between plasma TNFR1 and presence of chronic kidney disease as assessed by the presence of microalbuminuria and/or an estimated glomerular filtration rate of less than 60ml/min/1.73m2 (stages 3-5 chronic kidney disease). The association of TNFR1 with C-reactive protein and leptin-adiponectin ratio as plasma markers of systemic inflammation and adipose stress respectively was also investigated. RESULTS: Upper quartile TNFR1 is independently associated with elevated urinary albumin-creatinine ratios, reductions in eGFR and strongly predicts the presence of stages 3-5 chronic kidney disease in regression modelling. Elevated TNFR1 levels are associated with increased plasma C-reactive protein and augmented leptin-adiponectin ratio. CONCLUSIONS: Our study confirms plasma TNFR1 as a surrogate of renal structural and functional impairment in patients with type 2 diabetes mellitus. Association of TNFR1 with markers of systemic inflammation and adipose stress indicates that TNFR1 may be a biomarker of these processes as components of the pathogenesis of diabetic kidney disease.
    Scopus© Citations 11  411
  • Publication
    Impact of bariatric surgery on cardiovascular and renal complications of diabetes: a focus on clinical outcomes and putative mechanisms
    Introduction: Cardiovascular and renal disease accounts for a substantial proportion of the morbidity and mortality associated with obesity and type 2 diabetes mellitus (T2DM). Bariatric surgery is associated with improved long-term cardiovascular and renal outcomes. Areas covered: All major case-control, cohort, and randomized controlled trial studies of bariatric surgery in adults with T2DM were screened and data on prespecified cardiovascular and renal outcomes collated. Bariatric surgery reduces all-cause mortality and risk of cardiovascular disease, albuminuria and progressive chronic kidney disease. Patients with poorer glycemic control and established microvascular disease preoperatively may stand to benefit the most from the surgical approach. Reduced sympathetic drive, remission of glomerular hypertension, enhanced natriuresis, gut microbiota shifts, reduced systemic and renal inflammation, improved lipoprotein profiles, and reductions in chronic cardiac remodeling may all be implicated. Expert commentary: Ongoing RCTs of bariatric surgery selectively recruiting patients with class 1 obesity and established microvascular complications of diabetes will help to better characterize which subgroups of patients benefit most from this effective therapy.
    Scopus© Citations 27  211
  • Publication
    Comment on: Impact of serum uric acid on renal function after bariatric surgery: a retrospective study
    Obesity is an independent risk factor for renal functional decline in people with chronic kidney disease and is highly prevalent among people with the leading cause of chronic kidney disease, diabetic kidney disease [1]. Intentional weight loss strategies hold promise as a means of arresting progressive renal functional decline in diabetic kidney disease [2]. Optimization of renal outcomes after metabolic surgery centers on blood pressure and glycemic control, as well as addressing proteinuria. The role of uric acid–lowering in this setting is controversial. Purines (adenine, guanine) from nucleic acids (RNA, DNA) are metabolized to xanthine and hypoxanthine, and subsequently converted to uric acid by xanthine oxidase [3]. Uric acid is a nitrogenous waste product, which is excreted via the urine. Epidemiologic studies highlight a relationship between hyperuricemia and renal functional decline, proteinuria, and cardiovascular disease [4]. Whether serum uric acid plays a causal role in chronic kidney disease progression or is simply a biomarker of kidney function remains a controversial question, which is currently being addressed by placebo-controlled, randomized controlled studies, such as the PERL study in which people with diabetic kidney disease and hyperuricemia are randomized to uric acid–lowering therapy or placebo [5]. The present study by Hung et al. [6] adds to the observational evidence implicating uric acid as a marker of adverse renal outcomes and, importantly, is the first study to examine this phenomenon in patients with and without baseline chronic kidney disease after metabolic surgery.
    Scopus© Citations 1  162
  • Publication
    Metabolic Surgery to Treat Obesity in Diabetic Kidney Disease, Chronic Kidney Disease, and End-Stage Kidney Disease; What Are the Unanswered Questions?
    Obesity is a major factor in contemporary clinical practice in nephrology. Obesity accelerates the progression of both diabetic and non-diabetic chronic kidney disease and, in renal transplantation, both recipient and donor obesity increase the risk of allograft complications. Obesity is thus a major driver of renal disease progression and a barrier to deceased and living donor kidney transplantation. Large observational studies have highlighted that metabolic surgery reduces the incidence of albuminuria, slows chronic kidney disease progression, and reduces the incidence of end-stage kidney disease over extended follow-up in people with and without type 2 diabetes. The surgical treatment of obesity and its metabolic sequelae has therefore the potential to improve management of diabetic and non-diabetic chronic kidney disease and aid in the slowing of renal decline toward end-stage kidney disease. In the context of patients with end-stage kidney disease, although complications of metabolic surgery are higher, absolute event rates are low and it remains a safe intervention in this population. Pre-transplant metabolic surgery increases access to kidney transplantation in people with obesity and end-stage kidney disease. Metabolic surgery also improves management of metabolic complications post-kidney transplantation, including new-onset diabetes. Procedure selection may be critical to mitigate the risks of oxalate nephropathy and disruption to immunosuppressant pharmacokinetics. Metabolic surgery may also have a role in the treatment of donor obesity, which could increase the living kidney donor pool with potential downstream impact on kidney paired exchange programmes. The present paper provides a comprehensive coverage of the literature concerning renal outcomes in clinical studies of metabolic surgery and integrates findings from relevant mechanistic pre-clinical studies. In so doing the key unanswered questions for the field are brought to the fore for discussion.
      180Scopus© Citations 28
  • Publication
    Characterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney disease
    Introduction Roux-en-Y gastric bypass surgery (RYGB) reduces albuminuria and the long-term incidence of end-stage renal disease in patients with obesity and diabetes. Preclinical modeling in experimental diabetic kidney disease demonstrates that improvements in glomerular structure likely underpin these findings. Research design and methods In adult male Zucker diabetic fatty (ZDF) rats, we profiled the effect of RYGB on weight and metabolic control as well biochemical, structural and ultrastructural indices of diabetic renal injury. Furthermore, we sequenced the renal cortical transcriptome in these rats and used bioinformatic pathway analyses to characterize the transcriptional alterations governing the renal reparative response to RYGB. Results In parallel with improvements in weight and metabolic control, RYGB reduced albuminuria, glomerulomegaly, podocyte stress and podocyte foot process effacement. Pathway analysis of RYGB-induced transcriptomic changes in the renal cortex highlighted correction of disease-associated alterations in fibrosis, inflammation and biological oxidation pathways. RYGB reversed disease-associated changes in the expression of transforming growth factor (TGF)-β superfamily genes that strongly correlated with improvements in structural measures of glomerulopathy. Conclusions Improved glomerular structure in ZDF rats following RYGB is underpinned by pathway level changes, including interruption of the TGF-β-driven early profibrotic programme. Our data provide an important layer of experimental support for clinical evidence demonstrating that RYGB arrests renal damage in patients with obesity and type 2 diabetes.
    Scopus© Citations 9  133
  • Publication
    The Impact of CKD on Perioperative Risk and Mortality after Bariatric Surgery
    Background Twenty percent of patients with CKD in the United States have a body mass index (BMI) ≥35 kg/m2. Bariatric surgery reduces progression of CKD to ESKD, but the risk of perioperative complications remains a concern. Methods The 24-month data spanning 2017–2018 were obtained from the Metabolic and Bariatric Surgery Quality Improvement Program (MBSAQIP) database and analyzed. Surgical complications were assessed on the basis of the length of hospital stay, mortality, reoperation, readmission, surgical site infection (SSI), and worsening of kidney function during the first 30 days after surgery. Results The 277,948 patients who had primary bariatric procedures were 44±11.9 (mean ± SD) years old, 79.6% were women, and 71.2% were White. Mean BMI was 45.7±7.6 kg/m2. Compared with patients with an eGFR≥90 ml/min per BSA, those with stage 5 CKD/ESKD were 1.91 times more likely to be readmitted within 30 days of a bariatric procedure (95% CI, 1.37 to 2.67; P<0.001). Similarly, length of hospital stay beyond 2 days was 2.05-fold (95% CI, 1.64 to 2.56; P<0.001) higher and risk of deep incisional SSI was 6.92-fold (95% CI, 1.62 to 29.52; P=0.009) higher for those with stage 5 CKD/ESKD. Risk of early postoperative mortality increased with declining preoperative eGFR, such that patients with stage 3b CKD were 3.27 (95% CI, 1.82 to 5.89; P<0.001) times more likely to die compared with those with normal kidney function. However, absolute mortality rates remained relatively low at 0.53% in those with stage 3b CKD. Furthermore, absolute mortality rates were <0.5% in those with stages 4 and 5 CKD, and these advanced CKD stages were not independently associated with an increased risk of early postoperative mortality. Conclusions Increased severity of kidney disease was associated with increased complications after bariatric surgery. However, even for the population with advanced CKD, the absolute rates of postoperative complications were low. The mounting evidence for bariatric surgery as a renoprotective intervention in people with and without established kidney disease suggests that bariatric surgery should be considered a safe and effective option for patients with CKD.
    Scopus© Citations 6  144
  • Publication
    Can Metabolic Surgery Be Used to Improve Access to and Outcomes of Kidney Transplantation?
    Obesity is common in people with chronic kidney disease (CKD) (1) and associated with a higher risk of kidney allograft complications (2); thus, BMIs 35 kg/m2 and 40 kg/m2 are generally considered relative and absolute contraindications to kidney transplantation (2). Metabolic surgery improves renal outcomes in patients with type 2 diabetes (3) and diabetes is an important risk factor for renal functional decline after kidney transplantation, raising the possibility that metabolic surgery may improve graft survival and mortality in this setting (2). An understanding of the efficacy and safety of metabolic surgery in people with end-stage kidney disease (ESKD) and in kidney transplant recipients is required.
  • Publication
    Comment on: Metabolic surgery improves renal injury independent of weight loss: a meta-analysis
    (Elsevier, 2019-06-01) ;
    Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and significantly elevates cardiovascular disease risk [1]. Persons with DKD accounted for 45.4% and 38.2% of incident and prevalent cases of end-stage renal disease in the United States in 2015, respectively [2]. Current management of DKD focuses on control of hyperglycemia and hypertension along with renin-angiotensin-aldosterone system blockade to minimize proteinuria. The most notable recent advances in DKD care include sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 agonists, which reduce glycosylated hemoglobin (A1C), blood pressure, weight, cardiovascular mortality, and nephropathy progression [ 3]. Despite this, existing therapies for DKD slow the rate of renal functional decline rather than reversing it.
    Scopus© Citations 7  84
  • Publication
    How Ethical Is Our Current Delivery of Care to Patients with Severe and Complicated Obesity?
    Despite overwhelming evidence that bariatric interventions reduce morbidity and mortality and are cost-effective, access for affected patients is limited. We sought to describe the extent to which health policy makers and publically funded health services have an ethical obligation to provide bariatric care. We conducted a narrative review of the literature pertaining to the efficacy, safety, and cost-effectiveness of bariatric surgical interventions, in the context of the core principles of medical ethics. We found that in relation to autonomy (i.e., the right to self-determination), beneficence, non-maleficence, and justice (i.e., the obligation to provide fair and equitable treatment to all patients), the current provision of bariatric surgical care fell short of meeting internationally recognized medical ethical standards. These findings have important implications for government policy and healthcare resource allocation. Respecting the individual’s right of self-determination, to do good, prevent harm, and provide equity in access to services is paramount, even when that individual is obese.
    Scopus© Citations 14  287
  • Publication
    Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross-sectional study in a tertiary nephrology centre
    Obesity is a treatable risk factor for chronic kidney disease progression. We audited the reporting of body-mass index in nephrology outpatient clinics to establish the characteristics of individuals with obesity in nephrology practice. Body-mass index, clinical information and biochemical measures were recorded for patients attending clinics between 3rd August, 2018 and 18th January, 2019. Inferential statistics and Pearson correlations were used to investigate relationships between body-mass index, type 2 diabetes, hypertension and proteinuria. Mean ± SD BMI was 28.6 ± 5.8 kg/m2 (n = 374). Overweight and obesity class 1 were more common in males (P = .02). Amongst n = 123 individuals with obesity and chronic kidney disease, mean ± SD age, n (%) female and median[IQR] eGFR were 64.1 ± 14.2 years, 52 (42.3%) and 29.0[20.5] mL/min/BSA, respectively. A positive correlation between increasing body-mass index and proteinuria was observed in such patients (r = 0.21, P = .03), which was stronger in males and those with CKD stages 4 and 5. Mean body-mass index was 2.3 kg/m2 higher in those treated with 4-5 versus 0-1 antihypertensives (P = .03). Amongst n = 59 patients with obesity, chronic kidney disease and type 2 diabetes, 2 (3.5%) and 0 (0%) were prescribed a GLP-1 receptor analogue and SGLT2-inhibitor, respectively. Our data provides a strong rationale not only for measuring body-mass index but also for acting on the information in nephrology practice, although prospective studies are required to guide treatment decisions in people with obesity and chronic kidney disease.
      332Scopus© Citations 16