General practice management of type 2 diabetes


Nephropathy
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☰ Table of contents


Recommendations

Reference

Grade*

Assessment

Kidney status in people with type 2 diabetes should be assessed by:

  • annual screening for albuminuria (note that dipstick urine test is not adequate to identify albuminuria)

166 NHMRC, 2009

B

  • annual estimated glomerular filtration rate (eGFR; in mL/ min/1.73 2))

166 NHMRC, 2009

B

Management

Reducing the risk or slowing the progression of nephropathy can be achieved by:

  • blood glucose control should be optimised aiming for a general glycated haemoglobin (HbA1c) target ≤7%

166 NHMRC, 2009

A

  • optimising blood pressure control

166 NHMRC, 2009

A

In people with type 2 diabetes and microalbuminuria or macroalbuminuria, angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEI) antihypertensive should be used to protect against progression of kidney disease

166 NHMRC, 2009

A

People with type 2 diabetes should be informed that smoking increases the risk of chronic kidney disease

166 NHMRC, 2009

B

People with diabetes and microalbuminuria are considered at high cardiovascular disease risk, and should be treated with multifactorial interventions (refer to Chapter 9. Managing cardiovascular risk)

149
NVDPA, 2012

D

*Refer to Summary, explanation and source of recommendations for an explanation of the level of evidence and grade of evidence

 

Clinical context


Diabetic nephropathy occurs in one in four women and one in five men with type 2 diabetes,167 and is the single leading cause of end-stage renal disease.

Diabetic nephropathy is more common in Aboriginal and Torres Strait Islander peoples.Some non-European groups (eg South-East Asian, African American, Afro-Caribbean, Maori peoples) have high rates of end-stage diabetic nephropathy, possibly, but not entirely, due to later diagnosis and poorer care.30

There is strong evidence that treatment in the early stages of CKD reduces progression of kidney damage, morbidity and mortality. Therefore, people with type 2 diabetes should be screened and retested regularly to detect early indications of kidney damage and to monitor the effects of treatment.

SBP appears to be the best indicator of the risk of CKD in type 2 diabetes. However, the optimum and safest lower limit of SBP has not been clearly defined. Refer to general goals for diabetes (refer to Chapter 9. Managing cardiovascular risk) for appropriate individual targets for BP.


In practice


Assessment

Screening for microalbuminuria can be performed by measurement of the urine albumin-to-creatinine ratio (UACR) in a random spot collection (preferred method). Any positive UACR needs to be confirmed with a repeated collection and also a mid-stream urine to exclude urinary tract infection as a contributor to proteinuria.

The automatic calculation of eGFR on measurement of serum creatinine is now implemented within Australia.

Review of possible nephrotoxic medication, investigations to exclude treatable causes of kidney disease, and the assessment of a patient’s CVD risk form a baseline approach to patients with confirmed kidney disease. Figure 5 provides an algorithm for the initial detection of CKD.168
 

Figure 5. Algorithm for initial detection of chronic kidney disease

Figure 5. Algorithm for initial detection of chronic kidney disease
 

Note: This algorithm does not allow for checks for people with glomerulonephritis, systemic lupus erythematosus or people on nephrotoxic drugs.
 

Management

Due to potential reno-protective effects, the use of ACEIs or an ARB should be considered for the small subgroup of people with normal BP who have type 2 diabetes and microalbuminuria.169 It is not recommended that ACEIs and ARB medication be used together.

ACEIs reduce the incidence of end-stage renal disease by 40%, and ARBs reduce this progression by 22%. However, the absolute benefit was small (1.5% versus 0.8% over approximately one year; number needed to treat = 160). Both drug classes reduced the risk of disease-oriented renal outcomes such as doubling of creatinine concentration and progression of micro-albuminuria to macro-albuminuria. Both classes of medication also increased rates of regression from micro albuminuria- to normoalbuminuria. There are no direct comparative trials of ACEIs and ARBs to determine which is more effective. However, there is clear evidence of both classes having benefits in comparison with placebo.170,171

A meta-analysis of RCTs demonstrated that ACEIs and ARBs differentially affect the risk of all-cause mortality, cardiovascular deaths and cardiovascular events in patients with diabetes.172 ACEIs reduce the risk of mortality, MI and heart failure, while ARBs do not affect the risk of mortality and major cardiovascular events. No effect on stroke was seen with either treatment.

Medication considerations:

  • Metformin – should be used with caution (as risks of lactic acidosis increases), and dose should be reduced when eGFR is 30–60 mL/min/1.73 2). It is not recommended and should be ceased when eGFR is <30 mL/min/1.73 2).
  • DPP-4i173 – reduction of dose of alogliptin, saxagliptin, sitagliptin and vildagliptin are required with eGFR <60 mL/min/1.73 2) due to pharmacologic accumulation without toxicity. All except saxagliptin can be used in end-stage renal failure. Linagliptin has no dose adjustment requirement in renal impairment due to hepatic metabolism.
  • Sulphonylureas173 – as renal function declines, the half-life of sulphonylureas increases, raising the risk of hypoglycaemia.
  • SGLT2i – require renal function for glycaemic effect, dapagliflozin may be used if the eGFR is >60 mL/min/1.732) and empagliflozin may be used if the eGFR is >45 mL/min/1.73 m2.
  • Acarbose173 – avoid if eGFR < 25mL/min/1.73 2).
  • Glitazones – dose adjustment in patients with renal dysfunction is not recommended. No information is available for patients on dialysis, therefore pioglitazone should not be used in such patients.
  • GLP-1 RA173 – exenatide and liraglutide use is not recommended below eGFR  <30 mL/min/1.73 2).
  • Insulin – dose review with increasing renal impairment as risks of hypoglycaemia increase
  • any potentially nephrotoxic medications (eg non-steroidal anti-inflammatory drugs [NSAIDs]) should be avoided.

Box 8 shows the criteria for referral to a renal specialist.

 

Box 8. Referral criteria for specialist renal care168

Referral criteria for specialist renal care may include:

  • estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 2)(Stage 4 or 5 chronic kidney disease [CKD] of any cause)
  • persistent significant albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/mmol)
  • a sustained decrease in eGFR of ≥25% OR a sustained decrease in eGFR of 15 mL/min/1.73 2)within 12 months
  • CKD with hypertension that is hard to get to target despite at least three antihypertensive agents

Diabetes Australian and RACGP logo's
 
  1. Australian Institute of Health and Welfare. The health and welfare of Australia’s Aboriginal and Torres Strait Islander peoples 2015. Canberra: AIHW, 2015.
  2. Thomas MC, Weekes AJ, Broadley OJ, Cooper ME, Mathew TH. The burden of chronic kidney disease in Australian patients with type 2 diabetes (the NEFRON study). Med J Aust 2006;185(3):140–44.
  3. Kidney Health Australia. Chronic kidney disease (CKD) management in general practice, 3rd edn. Melbourne: Kidney Health Australia, 2015.
  4. Strippoli GF, Bonifati C, Craig M, Navaneethan SD, Craig JC. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev 2006(4):CD006257.
  5. Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressurelowering agents in adults with diabetes and kidney disease: A network meta-analysis. Lancet 2015;385(9982):2047–56.
  6. Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: A meta-analysis. JAMA Intern Med 2014;174(5):773–85.
  7. Arnouts P, Bolignano D, Nistor I, et al. Glucose-lowering drugs in patients with chronic kidney disease: A narrative review on pharmacokinetic properties. Nephrol Dial Transplant 2014;29(7):1284–300.