Best practice for the selection, design and implementation of UK Kidney Association guidelines: a modified Delphi consensus approach.

BACKGROUND: Despite research into how to effectively implement evidence-based recommendations into clinical practice, a lack of standardisation in the commissioning and development of clinical practice guidelines can lead to inconsistencies and gaps in implementation. This research aimed to ascertain how topics in kidney care worthy of guideline development within the UK should be chosen, prioritised, designed and implemented. METHODS: Following a modified Delphi methodology, a multi-disciplinary panel of experts in kidney healthcare from across the UK developed 35 statements on the issues surrounding the selection, development and implementation of nephrology guidelines. Consensus with these statements was determined by agreement using an online survey; the consensus threshold was defined as 75% agreement. RESULTS: 419 responses were received. Of the 364 healthcare practitioners (HCPs), the majority had over 20 years of experience in their role (n=123) and most respondents were nephrologists (n=95). Of the 55 non-clinical respondents, the majority were people with kidney disease (n=41) and the rest were their carers or family. Participants were from across England, Northern Ireland, Scotland and Wales. Consensus between HCPs was achieved in 32/35 statements, with 28 statements reaching ≥90% agreement. Consensus between patients and patient representatives was achieved across all 20 statements, with 13/20 reaching ≥90% agreement. CONCLUSIONS: The current results have provided the basis for six recommendations to improve the selection, design and implementation of guidelines. Actioning these recommendations will help improve the accessibility of, and engagement with, clinical guidelines, contributing to the continuing development of best practice in UK kidney care.

Cost-effectiveness of empagliflozin as add-on to standard of care for chronic kidney disease management in the United Kingdom.

OBJECTIVE: The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK. METHODS: A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes. RESULTS: Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses. LIMITATIONS: This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression. CONCLUSIONS: Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.

Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full "lay" summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.

Association and progression of multi-morbidity with Chronic Kidney Disease stage 3a secondary to Type 2 Diabetes Mellitus, grouped by albuminuria status in the multi-ethnic population of Northwest London: A real-world study.

INTRODUCTION: The prevalence of Diabetic Kidney Disease (DKD) secondary to Type 2 Diabetes Mellitus (T2DM) is rising worldwide. However, real-world data linking glomerular function and albuminuria to the degree of multi-morbidity is lacking. We thus utilised the Discover dataset, to determine this association. METHOD: Patients with T2DM diagnosed prior to 1st January 2015 with no available biochemical evidence of CKD were included. Patients subsequently diagnosed and coded for CKD3a in 2015, were grouped by the degree of albuminuria. Baseline and 5-year co-morbidity was determined, as were prescribing practices with regards to prognostically beneficial medication. RESULTS: We identified 56,261 patients with T2DM, of which 1082 had CKD stage 3a diagnosed in 2015 (224-CKD3aA1,154-CKD3aA2,93-CKD3aA1; 611 patients with CKD3a but no uACR available in 2015 were excluded from follow up). No statistically significant difference was observed in the degree of co-morbidities at baseline. A significant difference in the degree of hypertension, retinopathy, ischaemic heart disease and vascular disease from baseline compared to study end point was observed for all 3 study groups. Comparing co-morbidities developed at study end point, highlighted a statistical difference between CKD3aA1 Vs CKD3aA3 for retinopathy alone and for hypertension and heart failure between CKD3aA2 Vs CKD3aA3. 40.8% of patients with CKD3aA2 or A3 were prescribed Renin Angiotensin Aldosterone inhibitors (RAASi) therapy between June-December 2021. Survival analysis showed 15% of patients with CKD3aA3 developed CKD stage 5 within 5 years of diagnosis. DISCUSSION: CKD3a secondary to DKD is associated with significant multimorbidity at baseline and 5 years post diagnosis, with CKD3aA3 most strongly associated with CKD progression to CKD 5, heart failure, hypertension and retinopathy compared to CKD3aA1 or CKD3aA2 at 5 years post diagnosis. The lack of uACR testing upon diagnosis and poor prescribing of RAASi, in those with CKD3aA2/A3, raises significant cause for concern. CONCLUSION: DKD is associated with significant multimorbidity. Significant work is needed to be done to ensure patients undergo testing for uACR, to allow for future risk stratification and ability to be started on prognostically beneficial medication.

Narrative Review of Glycemic Management in People With Diabetes on Peritoneal Dialysis.

There is an increasing number of people with diabetes on peritoneal dialysis (PD) worldwide. However, there is a lack of guidelines and clinical recommendations for managing glucose control in people with diabetes on PD. The aim of this review is to provide a summary of the relevant literature and highlight key clinical considerations with practical aspects in the management of diabetes in people undergoing PD. A formal systematic review was not conducted because of the lack of sufficient and suitable clinical studies. A literature search was performed using PubMed, MEDLINE, Central, Google Scholar and ClinicalTrials.gov., from 1980 through February 2022. The search was limited to publications in English. This narrative review and related guidance have been developed jointly by diabetologists and nephrologists, who reviewed all available current global evidence regarding the management of diabetes in people on PD.We focus on the importance of individualized care for people with diabetes on PD, the burden of hypoglycemia, glycemic variability in the context of PD and treatment choices for optimizing glucose control. In this review, we have summarized the clinical considerations to guide and inform clinicians providing care for people with diabetes on PD.

The Accuracy of Continuous Glucose Sensors in People with Diabetes Undergoing Hemodialysis (ALPHA Study).

Objectives: Real-time and intermittently scanned continuous glucose monitoring are increasingly used for glucose monitoring in people with diabetes requiring renal replacement therapy, with limited data reporting their accuracy in this cohort. We evaluated the accuracy of Dexcom G6 and Abbott Freestyle Libre 1 glucose monitoring systems in people with diabetes undergoing hemodialysis. Methods: Participants on hemodialysis with diabetes (on insulin or sulfonylureas) were recruited. Paired sensor glucose from Dexcom G6 and Freestyle Libre 1 were recorded with plasma glucose analyzed using the Yellow Springs Instrument (YSI) method at frequent intervals during hemodialysis. Analysis of accuracy metrics included mean absolute relative difference (MARD), Clarke error grid (CEG) analysis and proportion of CGM values within 15% and 20% or 15 and 20 mg/dL of YSI reference values for blood glucose >100 or ≤100 mg/dL, respectively (% 15/15, % 20/20). Results: Forty adults (median age 64.7 [60.2-74.4] years) were recruited. Overall MARD for Dexcom G6 was 22.7% (2656 matched glucose pairs), and 11.3% for Libre 1 (n = 2785). The proportions of readings meeting %15/15 and %20/20 were 29.1% and 45.4% for Dexcom G6, respectively, and 73.5% and 85.6% for Libre 1. CEG analysis showed 98.9% of all values in zones A and B for Dexcom G6 and 99.8% for Libre 1. Conclusions: Our results indicate Freestyle Libre 1 is a reliable tool for glucose monitoring in adults on hemodialysis. Further studies are required to evaluate Dexcom G6 accuracy in people on hemodialysis.

Management of adults with diabetes on dialysis: Summary of recommendations of the Joint British Diabetes Societies guidelines 2022.

Diabetes is the commonest cause of end-stage kidney disease in many parts of the world, and many people on dialysis programmes live with diabetes. Such people are vulnerable to complications from their diabetes, and their care may be fragmented due to the many specialists involved. This updated guidance from the Joint British Diabetes Societies aims to review and update the 2016 guidance, with particular emphasis on glycaemic monitoring in the light of recent advances in this area. In addition, the guidance covers clinical issues related to the management of diabetes in people on peritoneal dialysis, along with acute complications such as hypoglycaemia and ketoacidosis, and chronic complications such as foot and eye disease.

Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease.

A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology.

Measurement of glomerular filtration rate in patients undergoing obesity surgery.

BACKGROUND: Most studies on obesity surgery have measured renal function using the estimated GFR. However, due to the reduction of muscle mass, and therefore creatinine that accompanies weight loss, such measures can falsely suggest an improvement in renal function. To balance the risks of surgery versus any potential benefits on renal function, we need to be able to determine renal function using valid and reliable methodologies. In this pilot study we aimed to measure renal function in patients with CKD undergoing obesity surgery using the gold standard 51Cr-EDTA GFR clearance methodology which is independent of measures of muscle mass. METHODS: Nine consecutive obese patients with CKD underwent obesity surgery. Their renal function was assessed using 51Cr-EDTA GFR, cystatin C and serum creatinine as well as using eGFR equations including MDRD CKD Epi, Cockcroft Gault and CKD Epi cystatin before and 12 months after surgery. RESULTS: Renal function using the 51Cr-EDTA measured GFR did not change significantly after surgery. Similar results were obtained when Cystatin C, CKD Epi cystatin, CKD Epi cystatin creatinine and adjusted Cockcroft Gault Creatinine clearance methods were used. In contrast there were either trends or significant improvements in renal function measured using the MDRD and CKD Epi equations. CONCLUSIONS: In this pilot study using the gold standard 51Cr-EDTA method we found stabilisation in renal function after obesity surgery. Until further definitive data emerge it is critical to balance the risk and benefits of surgery, especially if renal function may not improve as often as previously suggested. TRIAL REGISTRATION: ClinicalTrials.gov NCT01507350 . Registered June 2011.

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort.

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.

CCL18 synergises with high concentrations of glucose in stimulating fibronectin production in human renal tubuloepithelial cells.

BACKGROUND: Diabetic nephropathy is the leading cause of end stage kidney disease worldwide. The pathogenesis of this disease remains elusive and multiple factors have been implicated. These include the effects of hyperglycaemia, haemodynamic and metabolic factors, and an inflammatory process that stimulates cellular signalling pathways leading to disease progression and severe fibrosis. Fibronectin (Fn) is an important protein of the extracellular matrix that is essential in fibrosis and its presence in increased amounts has been identified in the kidney in diabetic nephropathy. METHODS: Proximal tubuloepithelial (HK-2) cells were stimulated with high glucose (30 mM D-glucose) or glycated albumin (500 µg/mmol) + 4 mM D-glucose or their controls, Mannitol (26 mM + 4 mM D-glucose) and 4 mM D-glucose, respectively. Following 48 h of stimulation the supernatant was collected and MTT [3-(4,5-dimethylthiazole-2,5-diphenyltetrazolium bromide] assay performed to assess cell viability. HK-2 cells were also stimulated in the above environments with recombinant CCL18 (rCCL18) or MCP-1 (rMCP-1) for 48 h with quantification of Fn levels using ELISA. RESULTS: Co-stimulation of HK-2 cells with high concentrations of glucose and rCCL18 significantly increased Fn (p < 0.001), in comparison to high concentrations of glucose alone. HK-2 cells stimulated with glycated albumin consistently produced Fn and this did not alter following co-stimulation with rCCL18 or rMCP-1. CONCLUSION: This study demonstrates how stimulation with a specific chemokine CCL18 in high glucose upregulates the production of Fn from proximal tubuloepithelial cells. This may be relevant to the development of renal fibrosis in diabetic nephropathy.

Early detection of subclinical left ventricular myocardial dysfunction in patients with chronic kidney disease.

AIMS: To identify subclinical left ventricular (LV) myocardial dysfunction using speckle tracking echocardiography (STE) in patients with chronic kidney disease (CKD), preserved LV ejection fraction (LVEF), and no cardiovascular history or symptoms. METHODS AND RESULTS: Cross-sectional comparisons of conventional and STE parameters were performed between controls and patients with different stages of CKD. CKD patients were followed up for major adverse cardiovascular events (MACEs). We recruited 106 CKD patients and 38 controls. Mean age was 54.4 ± 15.1 and 36.9 ± 11.5 years, respectively (P < 0.001), with 49.1 vs. 52.6% being female (P = 0.705). There were 29 (27.4%) patients with CKD stages 1/2, 38 (35.8%) with stage 3, and 39 (36.8%) with stages 4/5. Global longitudinal strain (GLS) was more impaired when moving from controls to CKD stages 4/5 (-20.67 ± 3.06, -20.39 ± 2.29, -18.33 ± 3.81, -18.01 ± 2.64, controls vs. CKD stages 1/2, vs. CKD stage 3, vs. CKD stages 4/5, respectively, Padjusted = 0.016), whereas LV twist (16.2 ± 4.8, 18.51 ± 4.36, 19.91 ± 5.35, 24.6 ± 5.35, Padjusted < 0.001) and LV twist rate (101.7 ± 30.3, 110.4 ± 30.1, 121 ± 31.4, 154.8 ± 36.7, Padjusted < 0.001) increased. Risk factor-adjusted GLS (standardized beta ß = -0.245, P = 0.025), strain rate (SR) [global longitudinal strain rates (GLSRs); ß = -0.236, P = 0.019], and early diastolic longitudinal strain rate (GLSRe; ß = 0.247, P = 0.019) were significantly associated with estimated glomerular filtration rate (eGFR), whereas LV twist (ß = -0.432, P < 0.001), LV twist rate (ß = -0.433, P < 0.001), and number of segments with diastolic dysfunction (ß = -340, P < 0.001) were inversely and independently associated with eGFR. Impaired GLS (more than -16%) was observed in almost a quarter of CKD patients and associated with a reduced estimated MACE-free survival at 12-month follow-up (88.5 vs 93.7%, Plogrank = 0.038). CONCLUSION: In CKD patients with no cardiovascular symptoms or history and preserved LVEF, STE can identify subclinical abnormalities of both systolic (decreased GLS and GLSR, increased LV twist, and twist rate) and diastolic (decreased GLSRe and increased number of segments with diastolic dysfunction) LV function.

Problems associated with hemodialysis and travel.

BACKGROUND: While there is a recognized risk of hepatitis C acquisition associated with dialysis away from the "home" center, there is little documented data on the effect that dialysis while traveling has on the dialysis patient's health. This study was designed to examine the incidence of travel within a hemodialysis population and to ascertain whether travel was associated with morbidity for patients on hemodialysis. METHODS: Travel data were collected prospectively over a 6-month period, from April 2009, for all patients receiving maintenance hemodialysis across our dialysis centers. Biochemical, microbiological, and hematological parameters as well as hepatitis serology and antibiotic starts were recorded for 12 weeks prior to and following dialysis away from center. RESULTS: A total of 172 individuals traveled on 200 occasions. The blood stream infection rate for travelers with a central venous catheter was 0.25 versus 0.83/1,000 access days (p = 0.038) in the 12 weeks pre-travel versus post-travel. Parenteral and oral antibiotic starts were both significantly elevated post-travel and were mainly instituted for either chest or urinary sepsis. There was evidence of raised inflammatory markers and anemia on return to center but no evidence of hepatitis B or hepatitis C seroconversion. CONCLUSIONS: Travel and dialysis away from a patient's usual hemodialysis unit is a common occurrence but is associated with an increased risk of bacterial infection, anemia, and inflammatory response. This study provides evidence for the concern that hemodialysis away from center is associated with increased morbidity.

The effect of bariatric surgery on renal function and disease: a focus on outcomes and inflammation.

Renal dysfunction and disease, including hyperfiltration, proteinuria and hypofiltration, are commonly associated with obesity. Diabetic kidney disease is also common in obese cohorts. Weight loss interventions, including bariatric surgery, can effectively reduce weight and improve renal outcomes. Some of this effect may be due to the remission of Type 2 diabetes and hypertension. However, other mechanisms, including the resolution of inflammatory processes, may also contribute. The effect of bariatric surgery on renal function has only recently become a focus of particular investigation. In this study, we will review the effects of bariatric surgery on obesity-associated kidney disease. We will discuss the pitfalls in assessing renal function in obese cohorts and will examine the effect of bariatric surgery on renal function and urinary protein excretion using different mechanisms. We will give particular attention to the evidence for bariatric surgery in cohorts with established renal disease and suggest future directions. In particular, we will outline the evidence for inflammation as an important therapeutic target, and the emerging medical therapies being considered to exploit this target in obesity- and diabetes-related kidney disease.

Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study.

BACKGROUND: Bariatric surgery improves arterial hypertension and renal function; however, the underlying mechanisms and effect of different surgical procedures are unknown. In the present prospective study, we compared the 12-month follow-up results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function, and inflammatory status. METHODS: A total of 34 morbidly obese patients were investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10), laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve gastrectomy (n = 11) for hypertension, kidney function, urinary and serum cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic protein-1, and chemokine ligand-18. RESULTS: At 12 months after surgery, the patients in all 3 treatment arms showed a significant decrease in the mean body mass index, mean arterial pressure, and urinary and serum inflammatory markers (all P < .001). The reduction in urinary and serum cytokine levels correlated directly with body weight loss (P < .05). Patients with impaired renal function at baseline (corresponding to serum cystatin C >.8 mg/L) had a marked improvement in renal function 12 months after surgery (P < .05). CONCLUSION: Surgically induced weight loss is associated with a marked decrease in renal and systemic inflammation and arterial hypertension and improvement in renal function in patients with pre-existing renal impairment. These effects appear to be independent of surgical procedure. The improvement in renal inflammation could be 1 of the mechanisms contributing to the beneficial effects of bariatric surgery on arterial blood pressure, proteinuria, and renal function.

Oral cholecalciferol decreases albuminuria and urinary TGF-ß1 in patients with type 2 diabetic nephropathy on established renin-angiotensin-aldosterone system inhibition.

The anti-inflammatory, antifibrotic, and antiproteinuric properties of vitamin D have been defined in studies using active vitamin D analogs. In this prospective observational study we determined whether nutritional vitamin D repletion can have additional beneficial effects in patients with type 2 diabetic nephropathy already established on renin-angiotensin-aldosterone system inhibition. During a 7-month period, 63 patients were enrolled and those with low levels of 25(OH)D were treated with oral cholecalciferol for 4 months. Baseline serum 25(OH)D and 1,25(OH)(2)D showed no significant correlation with baseline urinary MCP-1, TGF-ß1, or albuminuria measured as the urinary albumin-to-creatinine ratio. Of the 63 patients, 54 had insufficient or deficient levels of serum 25(OH)D and 49 complied with cholecalciferol therapy and follow-up. Both 25(OH)D and 1,25(OH)(2)D were significantly increased at 2 and 4 months of treatment. Albuminuria and urinary TGF-ß1 decreased significantly at both time points compared to their baseline values, while urinary MCP-1 did not change. Thus, in the short term, dietary vitamin D repletion with cholecalciferol had a beneficial effect in delaying the progression of diabetic nephropathy above that due to established renin-angiotensin-aldosterone system inhibition.

Urine proteomics and biomarkers in renal disease.

The application of urine proteomics is a useful approach to the study of the proteins involved in healthy and diseased kidneys and may provide a noninvasive approach to assess disease activity and to monitor clinical response in patients with renal diseases. This technique may provide an additional tool in clinical trials and for the assessment of prognosis for patients. Both soluble proteins and membrane-bound (exosomal) proteins may be studied, and multiple approaches are available. Discovery proteomics is an unbiased approach to detect novel proteins in urine samples. Mass spectrometry (MS) is often needed to identify specific protein fragments. Targeted proteomics often involves specific immunoassays or modified MS, which enables a hypothesis-based design. These approaches may be integrated. For example, specific proteins may be identified by the discovery approach or laboratory study of disease mechanisms. These proteins will then be studied further by targeted proteomics. In order to translate to clinical practice, the specific assays need vigorous validation by means of sufficiently statistically powered clinical trials.

Sodium and water handling after gastric bypass surgery in a rat model.

BACKGROUND: It was the aim to investigate the influence of gastric bypass on renal sodium and water handling. The relationship between sodium and water absorption along the gastrointestinal tract and their renal excretion is poorly understood. Beneficial effects on blood pressure have been seen after bariatric surgery before significant weight loss has occurred. METHODS: Male Wistar rats (348 ± 19 g) underwent either gastric bypass (n = 14) or sham operation (n = 7) and were given a low-sodium diet with deionized water ad libitum. Before and after surgery, the rats received an oral sodium load (1.5 mmol/kg) as hyperosmolar saline (616 mM), and were then placed in individual metabolic cages so the urine volume, sodium content, and water intake for 8 hours could be recorded. The urine sodium concentration was also measured. RESULTS: The rats that had undergone gastric bypass had a significantly lower body weight than the sham-operated controls throughout the follow-up period (346 ± 21 g versus 501.3 ± 8.0 g at day 60; P = .0004). An oral sodium load after gastric bypass led to an increase in water intake (.07 ± .01 mL/g versus .03 ± .01 mL/g; P = .023), urine output (.03 ± .01 mL/g versus .02 ± .002 mL/g; P = .027), and sodium excretion (65.99 ± 10.7 mol versus 31.71 ± 8.7 mol; P = .020). No change was seen in water intake, urine output, or sodium excretion after sham surgery. CONCLUSION: Urine output, water intake, and sodium excretion are all increased after gastric bypass surgery in rats given an oral sodium load compared with sham-operated controls. More rapid excretion, and less retention, of a dietary sodium load could be a part of the mechanism underlying the beneficial effect of bariatric surgery on blood pressure.

Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.

Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease.

Assessing glycemic control in maintenance hemodialysis patients with type 2 diabetes.

OBJECTIVE: Optimizing glycemic control in diabetic patients undergoing maintenance hemodialysis requires accurate assessment. We hypothesize that 1) 48-h continuous glucose monitoring (CGM) provides additional, clinically relevant, information to that provided by the A1C measurement and 2) glycemic profiles differ significantly between day on and day off dialysis. RESEARCH DESIGN AND METHODS: With the use of GlucoDay S, 48-h CGM was performed in 19 type 2 diabetic subjects undergoing hemodialysis to capture consecutive 24-h periods on and off dialysis. Energy intake was calculated using food diaries. A1C was assayed by a high-performance liquid chromatography method. RESULTS: CGM data were available for 17 subjects (13 male) with a mean (range) age of 61.5 years (42-79 years) and diabetes duration of 18.8 years (4-30 years). The 24-h CGM area under the glucose curve and 24-h mean glucose values were significantly higher during the day off dialysis than on dialysis (5,932.1 +/- 2,673.6 vs. 4,694 +/- 1,988.0 mmol x 3 min(-1) x l(-1), P = 0.022, and 12.6 +/- 5.6 vs. 9.8 +/- 3.8 mmol/l, P = 0.013, respectively), independent of energy intake. Asymptomatic hypoglycemia occurred in 4 subjects, 3 within 24 h of dialysis, and the glucose nadir in 14 subjects occurred within 24 h of dialysis. CONCLUSIONS: Glucose values are significantly lower on dialysis days than on nondialysis days despite similar energy intake. The risk of asymptomatic hypoglycemia was highest within 24 h of dialysis. Physicians caring for patients undergoing hemodialysis need to be aware of this phenomenon and consider enhanced glycemic monitoring after a hemodialysis session. CGM provides glycemic information in addition to A1C, which is potentially relevant to clinical management.