Kidney Disease:Improving Global Outcomes(KDIGO) CKD Work Group.KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease[J].Kidney Int Suppl,2013,3(1):1-150.
OJOA.Addressing the global burden of chronic kidney dis-ease through clinical and translational research[J].Trans Am Clin Climatol Assoc,2014,125(2):229-246.
Worldwide, an estimated 200 million people have chronic kidney disease (CKD). In the United States, African Americans (AAs) have a four-fold excess risk of CKD compared to non-Hispanic white people and globally, people in the low-to-middle income countries of Asia and Sub-Saharan Africa have the highest rates of CKD. Annually, more than 500,000 individuals develop end-stage renal disease (or CKD stage 5) in Sub-Saharan Africa alone and the vast majority of these patients suffer premature mortality. The health care costs and economic burden of CKD are huge and not sustainable even in advanced Western countries. A recent discovery on the role of Apolipoprotein 1 (APOL1) G1 and G2 renal risk variants in AAs has a huge potential to unravel the etiology of CKD in both AA and other black populations. Under the National Institutes of Health (NIH)-sponsored Human Heredity and Health in Africa (H3Africa) initiative, a large prospective genetic study of CKD is being conducted in 8000 participants in four African countries (Ethiopia, Ghana, Kenya, and Nigeria; for a total population of 320 million). This and other basic research studies in the United States could potentially shed great insight into the genetics and biologic mechanisms involved in the excess predilection of Africans and AAs to CKD.
DAVIESM,CHATTERJEES,KHUNTIK.The treatment of type 2 diabetes in the presence of renal impairment:what we should know about newer therapies[J].Clin Pharmacol,2016,8(1):61-81.
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2 5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS-R, will help determine the position of these new therapy classes and if they have renoprotective effects in patients with CKD.
IOANNIDISI.Diabetes treatment in patients with renal dis-ease:is the landscape clear enough?[J].World J Diabetes,2014,5(5):651-658.
Diabetes is the most important risk factors for chronic kidney disease(CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabolic disorders as well as for related comorbidities. They have to treat, often intensively, hypertension, dyslipidaemia, bone disease, anaemia, and frequently established cardiovascular disease. The treatment of hypoglycaemia in diabetic persons with CKD must tie their individual goals of glycaemia(usually less tight glycaemic control) and knowledge on the pharmacokinetics and pharmacodynamics of drugs available to a person with kidney disease. The problem is complicated from the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence. Metformin is globally accepted as the first choice in practically all therapeutic algorithms for diabetic subjects. The advantages of metformin are low risk of hypoglycaemia, modest weight loss, effectiveness and low cost. Data of UKPDS indicate that treatment based on metformin results in less total as well cardiovascular mortality. Metformin remains the drug of choice for patients with diabetes and CKD provided that their estimate Glomerular Filtration Rate(eGFR) remains above 30 mL/min per square meter. For diabetic patients with eGFR between 30-60 mL/min per square meter more frequent monitoring of renal function and dose reduction of metformin is needed. The use of sulfonylureas, glinides and insulin carry a higher risk of hypoglycemia in these patients and must be very careful. Lower doses and slower titration of the dose is needed. Is better to avoid sulfonylureas with active hepatic metabolites, which are renally excreted. Very useful drugs for this group of patients emerge dipeptidyl peptidase 4 inhibitors. These drugs do not cause hypoglycemia and most of them(linagliptin is an exception) require dose reduction in various stages of renal disease.
Canadian Diabetes Association Clinical Practice Guidelines Expert Commnittee,BOOTHG,CHENG AY.Canadian Diabetes Association.2013 clinical practice guidelines for the prevention and management of diabetes in Canada[J].Can J Diabetes,2013,37(Suppl1):S4-7.
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BSCPHM ML.Optimal medication dosing in patients with diabetes mellitus and chronic kidney disease[J].Can J Diabetes,2014,38(2):334-343.
Le diabète sucré est la cause principale de la néphropathie chronique (NC) au Canada. Les taux de diabète augmentent, tout comme la prévalence de la NC. Le diabète et la NC sont des maladies chroniques pour lesquelles le traitement exige de nombreux médicaments. Plusieurs des effets anticipés de ces médicaments sont altérés par les modifications physiologiques apparaissant au cours de la NC. Le fait de ne pas individualiser la posologie chez cette population peut mener à l’échec thérapeutique en raison d’une toxicité ou d’une diminution de la réponse thérapeutique. Parfois, cela pose tout un défi pour une multitude de raisons, notamment les limites des calculs disponibles pour estimer le fonctionnement rénal, les recommandations contradictoires de posologie et le manque de recommandations sur la posologie de certains médicaments. Les cliniciens soignant ces patients doivent envisager une approche de pharmacothérapie individualisée qui garantira des résultats optimaux. Plus la compréhension des cliniciens sur ces difficultés sera bonne, plus ils seront efficaces pour utiliser l’information disponible conjointement à leur jugement professionnel pour faire des changements appropriés de posologie. Cet article traite : 1) des modifications physiologiques apparaissant au cours de la NC et de leurs conséquences sur la posologie; 2) des avantages et des désavantages des divers calculs utilisés pour estimer le fonctionnement rénal; 3) des modifications pharmacocinétiques et pharmacodynamiques de certains des médicaments communément utilisés lors de diabète; 4) d’une approche d’individualisation de la posologie pour traiter cette population de patients.
DEACON CF.Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes:a comparative review[J].Diabetes Obes Metab,2011,13(1):7-18.
The dipeptidyl peptidase (DPP)-4 inhibitors are a new class of antihyperglycaemic agents which were developed for the treatment of type 2 diabetes by rational drug design, based on an understanding of the underlying mechanism of action and knowledge of the structure of the target enzyme. Although they differ in terms of their chemistry, they are all small molecules which are orally available. There are some differences between them in terms of their absorption, distribution, metabolism and elimination, as well as in their potency and duration of action, but their efficacy, both in terms of inhibiting plasma DPP-4 activity and as antidiabetic agents, appears to be similar. They improve glycaemic control, reducing both fasting and postprandial glucose levels to lower HbA1c levels, without weight gain and with an apparently benign adverse event profile. At present, there seems to be little to distinguish between the different inhibitors in terms of their efficacy as antidiabetic agents and their safety. Long-term accumulated clinical experience will reveal whether compound-related characteristics lead to any clinically relevant differences.
GROOP PH,COOPER ME,PERKOCICV,et al.Linagli-ptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction[J].Diabetes Care,2013,36(11):3460-3468.
OBJECTIVEPreclinical data suggest that linagliptin, a dipeptidyl peptidase-4 inhibitor, may lower urinary albumin excretion. The ability of linagliptin to lower albuminuria on top of renin-angiotensin-aldosterone system (RAAS) inhibition in humans was analyzed by pooling data from four similarly designed, 24-week, randomized, double-blind, placebo-controlled, phase III trials.RESEARCH DESIGN AND METHODSA pooled analysis of four completed studies identified 217 subjects with type 2 diabetes and prevalent albuminuria (defined as a urinary albumin-to-creatinine ratio [UACR] of 30-3,000 mg/g creatinine) while receiving stable doses of RAAS inhibitors. Participants were randomized to either linagliptin 5 mg/day (n = 162) or placebo (n= 55). The primary end point was the percentage change in geometric mean UACR from baseline to week 24.RESULTSUACR at week 24 was reduced by 32% (95% CI -42 to -21; P < 0.05) with linagliptin compared with 6% (95% CI -27 to +23) with placebo, with a between-group difference of 28% (95% CI -47 to -2; P = 0.0357). The between-group difference in the change in HbA(1c) from baseline to week 24 was -0.61% (-6.7 mmol/mol) in favor of linagliptin (95% CI -0.88 to -0.34% [-9.6 to -3.7 mmol/mol]; P < 0.0001). The albuminuria-lowering effect of linagliptin, however, was not influenced by race or HbA(1c) and systolic blood pressure (SBP) values at baseline or after treatment.CONCLUSIONSLinagliptin administered in addition to stable RAAS inhibitors led to a significant reduction in albuminuria in patients with type 2 diabetes and renal dysfunction. This observation was independent of changes in glucose level or SBP. Further research to prospectively investigate the renal effects of linagliptin is underway.
KIM YG,HAHNS,OH TJ,et al.Differences in the glu-cose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asian and non-Asians:a systematic review and meta-analysis[J].Diabetologia,2013,56(4):696-708.
The aim of this work was to compare the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors between Asian and non-Asian patients with type 2 diabetes.We searched MEDLINE, EMBASE, LILACS, CENTRAL, ClinicalTrials.gov and conference proceedings. Studies were eligible if they were randomised controlled trials with a treatment duration of at least 12weeks, compared a DPP-4 inhibitor with a placebo as either monotherapy or oral combination therapy, had information on ethnicity and HbA1c values and were published or described in English. A systematic review and meta-analysis with a meta-regression analysis was conducted.Among 809 potentially relevant studies, 55 trials were included. A meta-analysis revealed that DPP-4 inhibitors lowered HbA1c to a greater extent in studies with ≥50% Asian participants (weighted mean difference [WMD] -0.92%; 95% CI -1.03, -0.82) than in studies with <50% Asian participants (WMD -0.65%; 95% CI -0.69, -0.60). The between-group difference was -0.26% (95% CI -0.36, -0.17, p65<650.001). The baseline BMI significantly correlated with the HbA1c-lowering efficacy of DPP-4 inhibitors. The RR of achieving the goal of HbA1c <7.0% (53.0mmol/mol) was higher in studies with ≥50% Asian participants (3.4 [95% CI 2.6, 4.7] vs 1.9 [95% CI 1.8, 2.0]). The fasting plasma glucose-lowering efficacy was higher with monotherapy in the Asian-dominant studies, but the postprandial glucose-lowering efficacy and changes in body weight were comparable between the two groups.DPP-4 inhibitors exhibit a better glucose-lowering efficacy in Asians than in other ethnic groups; this requires further investigation to understand the underlying mechanism, particularly in relation to BMI.
, 王义俊
