DIABETES is the most common cause of kidney failure ( 37 % non-Indigenous Australians ; 69 % Indigenous Australians ) and around 50 % of people with type 2 diabetes ( T2DM ) will develop diabetic nephropathy . 1 , 2 The natural history is initial hyperfiltration before the onset of albuminuria which progresses to overt proteinuria after which the eGFR declines . In the setting of type 1 diabetes ( T1DM ) this develops over the course of 20-plus years . However , the subclinical nature of T2DM means that complications such as nephropathy may be present at the time of diagnosis . Is it diabetic nephropathy ?
Other pathologies may account for chronic kidney
disease ( CKD ). Box 1 outlines features that are unusual in the setting of diabetic nephropathy and should prompt consideration of alternative diagnoses . 3
Dietary advice
T2DM is a state of carbohydrate intolerance and
reducing dietary carbohydrates improves glycaemic control . 4 Small , targeted changes can be very impactful and often more manageable to enact . Reducing carbohydrates at breakfast can be useful and will reduce insulin requirements . 5 This might entail substituting cereal ( 20.1g carbohydrate , 3.7g protein / serve ), or other bakery products ( eg , crumpets — 16.7g carbohydrate , 2.9g protein / serve ) for an omelette ( three eggs — 3.6g
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Box 1 . Features that suggest an alternative cause of chronic kidney disease in diabetes
• Short duration of diabetes
• Absence of diabetic retinopathy
• Nephrotic syndrome with proteinuria > 3.5g / d ; hypoalbuminaemia and peripheral oedema
• Haematuria
• Absence of typical chronology , eg , acute onset of proteinuria , progressive decline in renal function
• Presence of systemic disease
carbohydrate , 18g protein / serve ). Doses of oral hypoglycaemics may need pre-emptive adjustment , for example , those prescribed gliclazide may need to stop this to avoid hypoglycaemia . Additionally , patients who usually require insulin will need dose reduction in the setting of carbohydrate reduction . 6 , 7 Glicazide and all sulfonylureas contribute to weight gain as does exogenous insulin . Lowering dietary carbohydrates can allow cessation of these medications and aid weight loss . Lower weight , glycaemic and blood pressure control are advantageous in the management of CKD . Indeed , for participants in the Dietary Intervention Randomized Controlled Trial , a low carbohydrate diet improved kidney function and reduced albuminuria over two years , effects likely mediated by weight loss-induced improvements
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in insulin sensitivity and systolic blood pressure . 8
Choice of hypoglycaemic agent in chronic kidney disease
Kidney function needs to be considered when
prescribing oral and injectable hypoglycaemics and insulin , and doses may require adjustment . The treatment algorithm for T2DM and CKD has changed with the advent of SGLT2i agents , which are now recommended as first-line agents alongside metformin ( see figure 1 ).
Metformin This has long been the backbone of treatment for T2DM . As kidney function decreases , a dose reduction and eventually discontinuation is recommended to decrease the risk of lactic acidosis ( see table 1 ). 10
SGLT2i These agents are recommended in combination with metformin for the management of T2DM . There are different eGFR cut-offs for the initiation of SGLT2i depending on the indication ( T2DM , heart failure or proteinuric kidney disease ) and reference to the specific agent product information is advised .
GLP-1 receptor agonists GLP-1 receptor agonists reduce proteinuria and possibly slow decline in eGFR . 11 Once again , eGFR can impact prescribing which is generally
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There are various resources available for those living with chronic kidney disease .
contraindicated with an eGFR < 30mL / min / 1.73m 2 .
Dipeptidyl peptidase-4 inhibitors ( DPP4i ) Sitagliptin , saxagliptin and linagliptin are the three drugs currently available in this class . Sitagliptin and saxagliptin need dose adjustment because they are renally excreted . Linagliptin is metabolised in the liver , so no dose adjustment is needed in the setting of impaired kidney function .
Sulfonylureas Care is required with use of sulfonylureas in advanced CKD due to reduced metabolism resulting in prolonged hypoglycaemia .
Thiazolidinediones ( TZDs ) While these drugs reduce albuminuria and do not require dose adjustment in the setting of CKD , there is no evidence that they improve kidney outcomes in patients with diabetic nephropathy . Moreover , TZDs cause fluid retention and increase the risk of heart failure . As a result TZDs are not a preferred class of drugs for T2DM treatment in CKD .
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Lifestyle therapy |
Physical activity Nutrition Weight loss |
First-line therapy |
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+ |
SGLT2i eGFR < 30
Do not initiate
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Dialysis
Discontinue
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Figure 1 . Treatment algorithm for selecting antihyperglycaemic drugs for patients with type 2 diabetes and chronic kidney disease . 9 |
Additional drug therapy as needed for glycaemic control |
GLP-1 receptor agonist ( preferred )
DPP-4i
Sulfonylurea
Insulin
TZD
Alpha-glucosidase inhibitor
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• Guided by patient preferences , comorbidities , eGFR and cost
• Includes patients with eGFR < 30mL / min / 1.73m 2 or treated with dialysis
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