Renal damage

Microalbuminuria provides early warning of renal damage – check for its presence at each annual review. Microalbuminuria is also an indicator of high cardiovascular risk.

Up to a third of people with diabetes develop kidney failure without microalbuminuria. Annual assessment of GFR is also indicated – most easily by an automatically reported eGFR from a serum creatinine measurement.

Check other risk factors for macrovascular disease. Control of blood glucose and blood pressure minimises the risk of renal damage.

Watch for asymptomatic urinary tract infections. 

1. Proteinuria is the principal hallmark of diabetic nephropathy. Initially this manifests as microalbuminuria.

2. Normal urinary protein excretion is <150mg/day. Normal albumin excretion is lower <20mg/day.

3. The timing of onset of proteinuria and rate of increase is variable in diabetic kidney disease.

4. Initially microalbuminuria develops (20-200 μg/min) and is intermittent. Microalbuminuria of 20-200μg/min equates to albuminuria of 30-300mg/day.

5. Persistent microalbuminuria is indicative of likely diabetic nephropathy. At this stage good control of blood pressure and glycaemia may stabilise renal function and reduce progression of nephropathy. The use of ACEi or ARB medications can stabilize the amount of microalbuminuria or allow it to regress to the normal range.

6. Maintaining good blood glucose control also appears to be effective in preventing the progression form normal to microalbuminuria.

7. Once clinical proteinuria occurs (dipstick positive, >500 mg/L) progressive renal damage is likely. (The magnitude of proteinuria – ie, all proteins in the urine - is more than albuminuria, the albumin component. As a guide, 500 mg/L of proteinuria is roughly equivalent to 300mg/L of albuminuria.)

8. The rate of decline in renal function is accelerated by hypertension.

9. The effect of glycaemic control on established renal damage is not as clear, however, ideal glycaemic control in patients without renal damage and in those with microalbuminuria has been shown to reduce the risk of progression of renal damage. In addition, tight glycaemic control to help prevent diabetes complications in other organs in such patients is often appropriate.

10. The albumin to creatinine ratio is an accepted screening test for microalbuminuria and obviates the need for timed specimens. The normal range is 0-3.5mg/mmol in women, 0-2.5mg/mmol in men. To demonstrate that a person has established microalbuminuria, two abnormal range results on separate occasions are required, where other potential causes of microalbuminuria other than diabetes, such as urinary tract infection and fever, have been excluded.

Significance of Proteinuria

Patient ten-year survival is poor once persistent significant proteinuria is present (ie: 2+ or more). Retinopathy will usually be present in type 1 diabetes and is usually but not always present in type 2 diabetes with proteinuria. The patient should be reviewed for retinal problems and have treatment initiated (eg: photocoagulation) if necessary. Hypertension should be treated actively and the BP maintained at lower levels (<130/80mmHg; <125/75 if proteinuria > 1g/d exists), in order to help slow the progression of nephropathy.

Metformin should be used with caution in patients with diabetic nephropathy if the serum creatinine is significantly increased because of the risk of medication accumulation and lactic acidosis. The renal threshold level for its contraindication is controversial, although metformin use is absolutely contraindicated if the eGFR(glomerular filtration rate)* is less than 30 mL/min/1.73m2.

ACEi can slow progression of microalbuminuria and ARBs have been shown to slow progression of micro and macro albuminuria to clinical events.

If microalbuminuria or proteinuria is established then the use of an ARB or ACE inhibitor should be considered even in the absence of hypertension. Radiographic contrast media and other nephrotoxic agents may precipitate a sudden deterioration in renal function. Tetracyclines may also precipitate sudden deterioration. 

Goals for management

As a general guide, encourage people with diabetes to reach the following goals for optimum management of their diabetes:

Renal function is best assessed by an estimation of the GFR (eGFR). This is now automatically reported with each serum creatinine measurement and has been validated in diabetics to be more precise than the previously used Cockcroft-Gault formula.  This is particularly in the important range of GFR <60mL/min/1.73m2  when complications from chronic kidney disease can be expected and need to be managed.

Assessment

*              imaging or biopsy abnormalities, or proteinuria/haematuria
**           hypertension, diabetes, smoker, age > 50 yrs, obesity, family history of kidney disease, Aboriginal and Torres Strait Islander people

In the early stages of renal impairment, hyper-filtration through the kidney is frequently found and may confuse interpretation by showing a greater than normal GFR. Therefore GFR needs to be checked more frequently in these patients (e.g. 6 monthly).

Anaemia develops earlier in patients with diabetic kidney disease compared with other forms of renal disease, and even moderate reduction in GFR in diabetes may require the commencement of recombinant erythropoietin by a nephrologist.

Conclusion

The introduction of automatic reporting of eGFR each time a test for serum creatinine is requested has increased the awareness of significant kidney dysfunction in clinical practice. It appears the eGFR is here to stay- it is already the basis of CKD staging and clinical management and of changes to the International classification of disease (ICD-10-AM) coding of CKD that are currently under review.

Further studies assessing the outcomes and impact of automatic reporting of eGFR are highly desirable.

One outcome of the recent focus on serum creatinine concentrations and its use for eGFR determination has been the commitment to improve the accuracy of laboratory measurement and the reduction in the variability previously seen in Australasia and overseas. Undoubtedly, refinements in the measurement of serum creatinine concentration and the eGFR formula will continue to occur, leading to increased accuracy and thus improved application of this important new tool.

References

Diabetes Management in General Practice 2007/8 pages 52, 53 and 54.
Kidney Health Australia. www.kidney.org.au
Chronic Kidney disease and automatic reporting of estimated glomerular filtration rate: revised recommendations.
Timothy H Mathew, David W Johnson, Graham RD Jones on behalf of the Australian Creatinine Consensus Working Group.