Search

ObjectiveEvidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.MethodsWe conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists’ Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.ResultsThere were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was −11.1 (−11.3 to −10.8)/−5.6 (−5.7 to −5.4) mm Hg; between active treatment and placebo was −5.1 (−5.3 to −5.0)/−2.3 (−2.4 to −2.2) mm Hg; and between active and control arms for drug comparison trials was −1.4 (−1.5 to −1.3)/−0.6 (−0.7 to −0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use.ConclusionThese findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.

Ecosystem services encompass the tangible human benefits that ecosystems provide. Past efforts to maintain ecosystem services have focused on conserving and rehabilitating natural ecosystems, but there is growing consensus that the built environment must contribute these services as well. The field of regenerative design seeks to create infrastructure that contributes to and enhances local ecosystems, but a key challenge has been the development of baseline standards that reflect ecosystem health as opposed to business-as-usual design. To address this challenge, we draw on work by Biomimicry 3.8 and project partners to outline a framework for ecological performance standards (EPS) that can be applied to regenerative projects. While current sustainability frameworks quantify negative impacts of proposed designs and seek to reduce those impacts, EPS specifies positive-impact performance standards based on local ecosystems. The EPS process involves four steps: (1) identifying a local reference ecosystem, (2) quantifying ecosystem services at the reference ecosystem to develop EPS metrics, (3) designing to meet or exceed EPS metrics at the building site, and (4) implementing and assessing the proposed design. We outline these steps in detail and provide three case studies that highlight implementation successes and challenges at the city, development, and building scale.

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200–5000 mg/g and estimated glomerular filtration rate 25–75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury–related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury–related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.

Introduction:Anti-phospholipase A2 receptor (PLA2R) is detected in approximately 70% of biopsies of “primary” membranous nephropathy (MN). Crescents in MN in nonlupus patients suggest additional injury, such as antineutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM)-associated glomerulonephritis and are postulated to reflect injury by a mechanism that unmasks cryptic epitopes leading to the second autoantibody. Methods:We studied PLA2R staining in nonlupus patients with MN and crescents. Native renal biopsies in 16 nonlupus patients with MN and crescents were stained for PLA2R. Results:The patients included 5 women and 11 men, with mean age 61 years and elevated serum creatinine (mean 4.68 mg/dL). Hematuria and proteinuria (mean 4.97 g/day) were documented in 13 patients. Two patients had positive serum anti-GBM antibody. Nine of 11 patients tested for ANCA were positive, with p-ANCA (n= 4), c-ANCA (n= 2), or both (n= 1), with 2 not specified. On average, 27% of glomeruli had crescents. One patient had an initial biopsy with MN, 4 years later had MN with crescent, and 7 years later had rebiopsy with persistent MN with crescents. One patient had ANCA-associated vasculitis, and 5 years later had MN and crescent. The remaining 14 patients had concurrent diagnoses of MN and crescents. PLA2R was positive in 5 cases, 3 with ANCA positivity, 2 with unknown ANCA status, and none with anti-GBM disease. The patient with initial MN preceding crescent was PLA2R positive; the patient with initial ANCA-associated vasculitis preceding MN was PLA2R negative. Conclusions:Most patients (64%) presented with concomitant MN and crescents, with rare occurrence of an initial disease process followed later by the second injury. PLA2R was positive in 31% of patients, suggesting most are secondary MN. Further study to determine the cryptic epitopes may shed light on the triggering mechanisms for these rare but unlikely coincidental glomerular injuries.

The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.

IMPORTANCE: Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown. OBJECTIVE: To assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR). DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (<60 vs ≥60 mL/min/1.73 m2), urinary albumin to creatinine ratio (UACR; <30 vs ≥30 mg/g), and of chronic kidney disease (CKD) markers using these subgroups (0, 1, or 2). The study was conducted from May 2013 to September 2018. INTERVENTIONS: Dapagliflozin vs placebo. MAIN OUTCOMES AND MEASURES: The dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF. RESULTS: At baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, −0.5%; 1 marker, −1.0%; and 2 markers, −8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher. CONCLUSIONS AND RELEVANCE: The effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01730534

The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure.

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.

IMPORTANCE: There are concerns with translating results from the Systolic Blood Pressure Intervention Trial (SPRINT) into clinical practice because the standardized protocol used to measure blood pressure (BP) may not be consistently applied in routine clinical practice. OBJECTIVES: To evaluate the concordance between BPs obtained in routine clinical practice and those obtained using the SPRINT protocol and whether concordance varied by target trial BP. DESIGN, SETTING, AND PARTICIPANTS: This observational prognostic study linking outpatient vital sign information from electronic health records (EHRs) with data from 49 of the 102 SPRINT sites was conducted from November 8, 2010, to August 20, 2015, among 3074 adults 50 years or older with hypertension without diabetes or a history of stroke. Statistical analysis was performed from May 21, 2019, to March 20, 2020. MAIN OUTCOMES AND MEASURES: Blood pressures measured in routine clinical practice and SPRINT. RESULTS: Participant-level EHR data was obtained for 3074 participants (2482 men [80.7%]; mean [SD] age, 68.5 [9.1] years) with 3 or more outpatient and trial BP measurements. In the period from the 6-month study visit to the end of the study intervention, the mean systolic BP (SBP) in the intensive treatment group from outpatient BP recorded in the EHR was 7.3 mm Hg higher (95% CI, 7.0-7.6 mm Hg) than BP measured at trial visits; the mean difference between BP recorded in the outpatient EHR and trial SBP was smaller for participants in the standard treatment group (4.6 mm Hg [95% CI, 4.4-4.9 mm Hg]). Bland-Altman analyses demonstrated low agreement between outpatient BP recorded in the EHR and trial BP, with wide agreement intervals ranging from approximately −30 mm Hg to 45 mm Hg in both treatment groups. In addition, the difference between BP recorded in the EHR and trial BP varied widely by site. CONCLUSIONS AND RELEVANCE: Outpatient BPs measured in routine clinical practice were generally higher than BP measurements taken in SPRINT, with greater mean SBP differences apparent in the intensive treatment group. There was a consistent high degree of heterogeneity between the BPs recorded in the EHR and trial BPs, with significant variability over time, between and within the participants, and across clinic sites. These results highlight the importance of proper BP measurement technique and an inability to apply 1 common correction factor (ie, approximately 10 mm Hg) to approximate research-quality BP estimates when BP is not measured appropriately in routine clinical practice. TRIAL REGISTRATION: SPRINT ClinicalTrials.gov Identifier: NCT01206062

We report 3 cases of patients with HIV/AIDS in whom Fanconi syndrome and nephrogenic diabetes insipidus developed secondary to use of an antiretroviral regimen containing tenofovir disoproxil fumarate and didanosine. These patients presented with a history of polydipsia, polyuria, weight loss, anorexia, and wasting. Interestingly, 1 patient was not taking protease inhibitors. This response is a well-documented yet uncommon complication of tenofovir use in the HIV population. We recommend continued monitoring for renal toxicity when using the NRTI combination of tenofovir and didanosine. Key words: HIV/AIDS * Fanconi syndrome * Kidney disease * Diabetes * Antiretroviral therapy * NRTIs * Tenofovir * Didanosine, The availability of highly active antiretroviral therapy has improved the survival and quality of life of patients infected with HIV. Clinicians are now focusing on the management of metabolic complications [...]

Sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown beneficial effects on renal outcomes mainly in patients with established atherosclerotic cardiovascular disease. Here we report analyses of renal outcomes with the SGLT2 inhibitor dapagliflozin in the DECLARE–TIMI 58 cardiovascular outcomes trial, which included patients with type 2 diabetes both with and without established atherosclerotic cardiovascular disease and mostly with preserved renal function.

In September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis.

Hypertension is a global health problem and without adequate diagnosis and treatment is a risk factor for morbidity and mortality. Proper assessment of blood pressure is key to diagnosis and management of hypertension. Different methods of measurement are available for use and varying techniques are applied to patient care. Understanding the proper methods of blood pressure measurement both in and out of the physician's office is crucial for providing appropriate care to an individual patient. In addition, understanding the techniques used in research, on which current guidelines are based, is critical for proper application to daily practice. In this article, we review the types of blood pressure measurement techniques, discuss the benefits and limitations to each, explore future technological advances in measurement devices, and provide insight into research techniques, which ultimately guide our practice.

Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30–59 ml/min/1.73 m2, to those without impaired renal function eGFR ≥60 ml/min/1.73 m2. A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24–104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hocefficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment.

Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events.

Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels.

Hyperphosphatemia is highly prevalent among patients with end-stage kidney disease and is a major risk factor for cardiovascular disease and mortality. The contemporary management of hyperphosphatemia consists of oral phosphate binders for maintenance of normal serum phosphorus levels. Although several phosphate binders are currently available, limitations related to tolerability, safety, effectiveness, cost and pill burden have prompted the development of newer agents. Ferric-based compounds have been recognized to reduce phosphate absorption since the 1930s. In this manuscript, we review the recently available data on the use of ferric citrate with a focus on human studies that have led to its approval as a phosphate binder by the US FDA.

AbstractBackground/Aims:Pyridoxamine dihydrochloride (Pyridorin™) blocks pathogenic oxidative pathways in the progression of diabetic nephropathy. The pyridoxamine pilot study was designed to test entry criteria and outcomes. Subjects had SCr 1.3-3.5 mg/dl, protein-to-creatinine ≥1,200 mg/g and used a surrogate outcome of ΔSCr over 52 weeks. Subjects had to be on a maximally tolerated dose of ACE/ARB for 3 months; stable other antihypertensive doses for 2 months; stable diuretic dose for 2 weeks, and BP ≤160/90 mm Hg; or enter a Pharmaco-Stabilization Phase (PSP). This pilot failed to detect an effect on ΔSCr in intent-to-treat analysis. Methods:We queried the locked clinical trial database for subgroups in which there was a treatment effect. Results:Subjects not requiring PSP and those with entry SCr <2.0 mg/dl had a treatment effect. Subjects entering PSP required more changes in antihypertensive medications and experienced larger ΔSCr over 52 weeks. PSP subjects with BP >140/90 mm Hg had no treatment effect, but those ≤140/90 mm Hg did. Conclusion:Time required for acute effects of ACE/ARB to stabilize is unknown, but these data suggest >3 months. Thus, subjects in the pivotal trial must be on ACE/ARB for 6 months. Frequent antihypertensive adjustment could engender SCr changes unrelated to CKD progression. Thus, we will require subjects to have BP ≤150/90 mm Hg and on stable antihypertensives for 26 weeks, or ≤140/90 mm Hg and on stable antihypertensives for 13 weeks. Since ΔSCr over 52 weeks is limited as a surrogate outcome, the pivotal trial uses a time-to-event analysis of baseline SCr to at least a 50 increase in SCr or ESRD as the primary outcome. This substantial ΔSCr is protected from noise and is clinically relevant. The pyridoxamine pilot provided critical information to inform the design of PIONEER-CSG-17, which we conducted under the SPA agreement with FDA.© 2014 S. Karger AG, Basel

Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy.

Hypertension is a common problem among patients with glomerular disease and CKD. Optimal blood pressure targets for these patients have been the source of much debate. Careful review of the available data supports a blood pressure target of less than 140/90 mmHg. Consideration for a lower goal of less than 130/80 mmHg should be given for patients with heavy proteinuria. Renin-angiotensin system inhibitors should be used as the cornerstone of therapy for all patients with glomerular disease and CKD.

A doubling of serum creatinine value, corresponding to a 57% decline in estimated glomerular filtration rate (eGFR), is used frequently as a component of a composite kidney end point in clinical trials in type 2 diabetes. The aim of this study was to determine whether alternative end points defined by smaller declines in eGFR would improve the statistical power of these clinical trials.

Most dialysis patients require phosphate binders to control hyperphosphatemia. Ferric citrate has been tested in phase 2 trials as a phosphate binder. This trial was designed as a dose-response and efficacy trial.

AbstractBackground:A phase II open-label study was conducted in hemodialysis patients evaluating the short-term safety, tolerability, and iron absorption with ferric citrate when used as a phosphate binder. Methods:Enrollment occurred in two periods. Period 1 recruited patients taking 6–15 pills/day of binder with phosphorus of ≥2.5 mg/dl. Period 2 recruited patients taking ≥12 pills/day of binder with phosphorus of ≥3.5 mg/dl. Participants with ferritin ≥1,000 μg/l or transferrin iron saturation (TSAT) ≥50 at screening were excluded. Subjects discontinued their previous binders and started 4.5 g/day of ferric citrate (period 1) or 6 g/day (period 2) and were titrated for 4 weeks to maintain a phosphorus of 3.5–5.5 mg/dl. Chemistries and complete blood count were obtained weekly and a gastrointestinal questionnaire was administered at drug initiation and final visit. Iron therapy was permitted if the ferritin was <500 μg/l and TSAT <30. Results:Fifty-five subjects were enrolled. Four serious adverse events were reported; none were related to the study drug. Findings from the gastrointestinal questionnaire included stool discoloration (69), constipation (15), and bloating (7). Mean iron parameters at the beginning of the study were ferritin 554 ± 296 μg/l, iron 68 ± 21 μg/dl, and iron saturation 30 ± 7.8. At the end of study, mean ferritin was 609 ± 340 μg/l (p = 0.02), iron 75 ± 27 μg/dl (p = 0.04), and TSAT was 35 ± 13 (p = 0.001). Mean phosphorus and calcium levels were unchanged from baseline at the end of study. Conclusion:Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure.Copyright © 2012 S. Karger AG, Basel

Previous studies have shown that patients with chronic kidney disease, including those with diabetic nephropathy, are more likely to die of cardiovascular disease than reach end-stage renal disease (ESRD). This analysis was conducted to determine whether ESRD is a more common outcome than cardiovascular death in patients with type 2 diabetic nephropathy, significant proteinuria, and decreased kidney function who were selected for participation in a clinical trial.

AbstractType 2 diabetic nephropathy (type 2 DN) patients traditionally develop significant proteinuria prior to the development of renal impairment. However, this clinical paradigm, based on observations prior to the widespread usage of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), has recently been questioned. 2,303 patients enrolled in the Sulodexide Overt Nephropathy Study (OVERT) were analyzed. Prior therapy with ACEi and/or ARB at the time of screening was recorded in 951 patients. 22 of patients had significant renal impairment with a PCR at screening of <500 mg/g. Therapy with ACEi and/or ARB at the time of screening was recorded in 94, where prior medication data was available. In patients with type 2 DN and advanced renal impairment, levels of proteinuria below that which traditionally defines overt diabetic nephropathy, are found in more than one fifth of patients. We suggest that the high prevalence of ACEi and ARB usage in patients with type 2 DN may be effecting the traditional clinical paradigm of type 2 DN.Copyright © 2011 S. Karger AG, Basel

Current phosphate management strategies in end-stage renal disease (dietary phosphate restriction, dialysis, and phosphate binders) are inadequate to maintain target phosphate levels in most patients. Dietary phosphate restriction is challenging due to “hidden phosphates” in processed foods, and dialysis and phosphate binders are insufficient to match average dietary phosphate intake. As phosphate binders must be taken with each meal, patients need to ingest many, large pills several times a day, negatively impacting quality of life. Recent advances in our understanding of phosphate absorption pathways have led to the development of new non-binder therapies that block phosphate absorption. This review describes the limitations of current phosphate management strategies and discusses new therapies in development that inhibit phosphate absorption pathways. These new therapies present an opportunity to rethink phosphate management, potentially by prescribing phosphate absorption inhibitors as a primary therapy and adding phosphate binders if needed.