Management of Diabetes and Chronic Kidney Disease Stage 3b or higher-NDT Guideline

Published On 2016-07-02 16:48 GMT   |   Update On 2016-07-02 16:48 GMT

Chronic kidney disease (CKD) is associated with insulin resistance and, in advanced CKD, decreased insulin degradation. The latter can lead to a marked decrease in insulin requirement or even the cessation of insulin therapy in patients with type 2 diabetes. Both of these abnormalities are at least partially reversed with the institution of dialysis.Because of the uncertainty in predicting insulin requirements, careful individualised therapy is essential among patients who have advanced CKD or are initiating dialysis.The insulin requirement in any given patient depends upon the net balance between improving tissue sensitivity and restoring normal hepatic insulin metabolism. In addition, among patients on peritoneal dialysis, glucose contained in peritoneal dialysate tends to increase the need for diabetes therapy. Changes in dietary intake and exercise (ie, reduced intake due to anorexia prior to starting dialysis) can also affect the response to administered insulin. Furthermore, the uremic environment can affect methods used to assess glycemic control, and the metabolism of most oral diabetes agents is prolonged, making them more difficult to use.




In 2015, Nephrology Dialysis Transplantation published a clinical practice guideline on Management of Patients with Diabetes and Chronic Kidney Disease stage 3b or higher (eGFR <45 mL/min).


Following are its major recommendations:-


Issues Related to Renal Replacement Modality Selection in Patients with Diabetes and End-stage Renal Disease






Should patients with diabetes and chronic kidney disease (CKD) stage 5 start with peritoneal dialysis or haemodialysis (HD) as a first modality?




  • The Guideline Development Group (GDG) recommends giving priority to the patient's general status and preference in selecting renal replacement therapy as there is an absence of evidence of superiority of one modality over another in patients with diabetes and CKD stage 5 (1C).

  • The GDG recommends providing patients with unbiased information about the different available treatment options (1A).

  • In patients opting to start HD, the GDG suggests preferring high flux over low flux when this is available (2C).

  • The GDG suggests diabetes has no influence on the choice between HD or haemodiafiltration (HDF) (2B).


Should patients with diabetes and CKD stage 5 start dialysis earlier, i.e., before becoming symptomatic, than patients without diabetes?


The GDG recommends initiating dialysis in patients with diabetes on the same criteria as in patients without diabetes (1A).


In patients with diabetes and CKD stage 5, should a native fistula, graft or tunnelled catheter be preferred as initial access?




  • The GDG recommends that reasonable effort be made to avoid tunnelled catheters as primary access in patients with diabetes starting HD as renal replacement therapy (1C).

  • The GDG recommends that the advantages, disadvantages and risks of each type of access be discussed with the patient.


Is there a benefit to undergoing renal transplantation for patients with diabetes and CKD stage 5?


The GDG recommends providing education on the different options of transplantation and their expected outcomes for patients with diabetes and CKD stage 4 or 5 who are deemed suitable for transplantation (see Table 5 in the original guideline document) (1D).


Statements Only for Patients with Type 1 Diabetes and CKD Stage 5




  • The GDG suggests living donation kidney transplantation or simultaneous pancreas kidney transplantation to improve survival of suitable patients (2C).

  • The GDG suggests against islet transplantation after kidney transplantation with the aim to improve survival (2C).

  • The GDG suggests pancreas grafting to improve survival after kidney transplantation (2C).


Statements Only for Patients with Type 2 Diabetes and CKD Stage 5




  • The GDG recommends against pancreas or simultaneous kidney pancreas transplantation (1D).

  • The GDG recommends diabetes in itself should not be considered a contraindication to kidney transplantation in patients who otherwise comply with inclusion and exclusion criteria for transplantation (1C).


Issues Related to Glycaemic Control in Patients with Diabetes and CKD Stage 3b or Higher (Estimated Glomerular Filtration Rate [eGFR] <45 mL/min)


A. Should the aim be to lower glycated haemoglobin (HbA1C) by tighter glycaemic control in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min)?


B. Is an aggressive treatment strategy (in number of injections and controls and follow-up) superior to a more relaxed treatment strategy in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) and using insulin?




  • The GDG recommends against tighter glycaemic control if this results in severe hypoglycaemic episodes (1B).

  • The GDG recommends vigilant attempts to tighten glycaemic control with the intention to lower HbA1C when values are >8.5% (69 mmol/mol) (1C).

  • The GDG suggests vigilant attempts to tighten glycaemic control with the intention to lower HbA1C according to the flow chart in Figure 4 (in the original guideline document) in all other conditions (2D).

  • The GDG recommends intense self-monitoring only to avoid hypoglycaemia in patients at high risk for hypoglycaemia (2D).


Are there better alternatives than HbA1c to estimate glycaemic control in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2)?


The GDG recommends the use of HbA1C as a routine reference to assess longer term glycaemic control in patients with CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) (1C).


A. Is any oral drug superior to another in terms of mortality/complications/glycaemic control in patients with diabetes type 2 and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2)?


B. In patients with diabetes type 2 and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2), is maximal oral therapy better than starting/adding insulin at an earlier stage?




  • The GDG recommends metformin in a dose adapted to renal function as a first line agent when lifestyle measures alone are insufficient to get HbA1C in the desired range according to Figure 4 in the original guideline document (1B).

  • The GDG recommends adding on a drug with a low risk for hypoglycaemia (see Figures 5, 6, and 7 in the original guideline document) as an additional agent when improvement of glycaemic control is deemed appropriate according to Figure 4 in the original guideline document (1B).

  • The GDG recommends instructing patients to temporarily withdraw metformin in conditions of pending dehydration, when undergoing contrast media investigations, or in situations with an increased risk for acute kidney injury (AKI) (1C).


Issues Related to Management of Cardiovascular Risk in Patients with Diabetes and CKD Stage 3b or Higher


In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) or on dialysis and with coronary artery disease (CAD), is percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or conservative treatment to be preferred?




  • The GDG recommends not omitting coronary angiography with the sole intention of avoiding potential contrast-related deterioration of kidney function in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) in whom a coronary angiography is indicated (1D).

  • The GDG recommends that optimal medical treatment should be considered as preferred treatment in patients with diabetes and CKD stage 3b to stage 5 who have stable CAD, unless there are large areas of ischaemia or significant left main or proximal left anterior descending (LAD) lesions (1C).

  • The GDG recommends that when a decision is taken to consider revascularization, CABG is preferred over PCI in patients with multi-vessel or complex (SYNTAX score >22) CAD (1C).

  • The GDG recommends that patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) who present with an acute coronary event should be treated no differently than patients with CKD stage 3b or higher (eGFR <45 mL/min) without diabetes or patients with diabetes without CKD stage 3b or higher (eGFR <45 mL/min) (1D).


In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) or on dialysis and with a cardiac indication (heart failure, ischaemic heart disease, hypertension) should inhibitors of the renin-angiotensin-aldosterone system (RAAS) as cardiovascular prevention be prescribed?




  • The GDG recommends that adults with CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2 or on dialysis) and diabetes who have a cardiovascular indication (heart failure, ischaemic heart disease) be treated with an angiotensin-converting enzyme inhibitor (ACE-I) at maximally tolerated dose (1B).

  • The GDG suggests there is insufficient evidence to justify the start of an angiotensin-receptor blocker (ARB) in adults with CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2 or on dialysis) and diabetes who have a cardiovascular indication (heart failure, ischaemic heart disease) but intolerance for ACE-I (2B).

  • The GDG recommends not combining different classes of renin angiotensin-blocking agents (ACE-I, ARBs or direct renin inhibitors) (1A).


In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) or on dialysis, should beta blockers be prescribed to prevent sudden cardiac death?




  • The GDG suggests starting a selective beta-blocking agent as primary prevention in patients with diabetes and CKD stage 3b or higher and then continuing it when tolerated (2C).

  • The GDG suggests prescribing lipophilic rather than hydrophilic beta-blocking agents in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) (2C).


In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2), should the aim be for lower blood pressure targets than in the general population?




  • The GDG suggests against applying lower blood pressure targets in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) than in the general population (2C).

  • The GDG suggests that in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) but without proteinuria, all blood pressure-lowering drugs can be used equally to lower blood pressure (2C).


In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2) or on dialysis, should lipid-lowering therapy in primary prevention be prescribed?




  • The GDG recommends starting a statin in patients with diabetes and CKD stage 3b and 4 (1B).

  • The GDG suggests a statin be considered in patients with diabetes and CKD stage 5 (2C).

  • The GDG recommends against starting a statin in patients with diabetes and CKD stage 5d (1A).

  • There was no consensus in the GDG on whether or not statins should be stopped in patients with diabetes with CKD stage 5d.

  • The GDG suggests fibrates can replace statins in patients with CKD stage 3b who do not tolerate statins (2B).


A. In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2), should interventions aimed at increasing energy expenditure and physical activity be recommended?


B. In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2), should interventions aimed at reducing energy intake be recommended?




  • The GDG suggests that patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) perform additional physical exercise at least three times 1/2 to 1 hour/week to reduce fat mass and improve quality of life (QoL) (2D).

  • The GDG suggests that there is no evidence of harm when promoting an individualized regimen of increased physical exercise (2C).

  • When promoting weight loss in patients with diabetes and with overweight, the GDG recommends supervision of this process by a dietician and to ensure that only fat mass is lost and malnutrition is avoided (1C).


In patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min/1.73 m2), should antiplatelet therapy be recommended, regardless of the cardiovascular risk?




  • The GDG recommends against adding glycoprotein IIb/IIIa inhibitors to standard care to reduce death, myocardial infarction, or need for coronary revascularization in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) and acute coronary syndromes (ACS) or high-risk coronary artery intervention (1B).

  • The GDG suggests not adding a thienopyridine or ticagrelor to standard care to reduce death, myocardial infarction, or need for coronary revascularization in patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) and ACSs or high-risk coronary artery intervention unless there is no additional risk factor for bleeding (2B).

  • The GDG recommends starting aspirin as secondary prevention, unless there is a contraindication, side effects or intolerance (1C).

  • The GDG suggests starting aspirin as primary prevention only in patients without additional risk factors for major bleeding (2C).


To read further click on the following link:


http://ndt.oxfordjournals.org/content/30/suppl_2/ii1.full.pdf






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