Diabetic Nephropathy
Diabetic Nephropathy
Diabetic nephropathy refers to the presence of elevated urinary protein excretion in a person with diabetes in the absence of other renal disease. The histologic changes accompanying this rise in protein excretion are referred to as diabetic glomerulosclerosis.
The primary constituent of urinary protein in diabetic nephropathy is albumin. Consequently, quantification
of urinary albumin excretion is central to any description of diabetic renal disease. Albumin excretion can be determined from timed urine collections, and 24- hour, overnight, or even shorter collection periods are used. Measurement of the urinary albumin-to-creatinine ratio in untimed urine specimens is a convenient alternative way to assess albumin excretion. Because of the relative constancy of urinary creatinine excretion, the albumin-to-creatinine ratio is highly correlated with the timed excretion rate. Several terms are used to describe the level of urinary albumin excretion measured by these methods.
Microalbuminuria or incipient diabetic nephropathy generally refers to levels of urinary albumin excretion below those detected by standard dipstick methods, and macroalbuminuria refers to higher levels of urinary albumin excretion. Proteinuria refers to a positive dipstick test for protein or to a daily output of protein above a certain cutpoint, typically ³500 mg protein/day. Thus, macroalbuminuria and proteinuria may be relatively equivalent measures of urinary protein excretion. Differences in methods of measurement and lack of standardized terminology often make comparisons between studies difficult.
Clinical diabetic nephropathy is said to be present when a patient who has had diabetes for more than five years and has evidence of diabetic retinopathy develops clinically apparent albuminuria (>300 mg per 24 hours) and has no evidence of any other cause of kidney disease. When these criteria are fulfilled, a clinical diagnosis of diabetic nephropathy can generally be made without performing a renal biopsy.
Screening for Albuminuria
Routine screening for microalbumin should be performed yearly in adults with type 2 diabetes. If the screening is positive for microalbumin, a quantitative measure is helpful in developing a treatment plan.
After the initial screening and in the absence of previously demonstrated microalbuminuria, a test for the presence of microalbuminuria should be performed annually.
Three methods to screen for microalbuminuria are shown below:
- measurement of the albumin to creatinine ratio in a random spot urine collection
- 24-hour urine collection with creatinine, allowing the simultaneous measurement of creatinine clearance
- timed (4-hour or overnight) urine collection
The first method is often preferred in an office-based setting and generally provides accurate information. There is marked day-to-day variability in albumin excretion, so at least 2 of 3 samples done in a 3- to 6-month period should show elevated levels before designating a patient as having microalbuminuria. If normal, repeat yearly.
Screening for microalbumin with dipsticks or reagent tablets may also be done if assays are not readily available. Reagents and tablets show a 95% sensitivity when performed by trained personnel. All positive tests by reagent strips or tablets should be confirmed using one of the quantitative urine assays listed below.
|
Category
|
Spot Collection
(μg/mg creatinine)
|
24-Hour Collection
(mg/24hours)
|
Timed Collection
(μg/min)
|
| Normal |
< 30 |
< 30 |
< 20 |
| Microalbuminuria |
30 - 300 |
30 - 300 |
20 - 200 |
Clinical
Albuminuria |
> 300 |
> 300 |
> 200 |
Several factors may influence the albumin excretion rate. Screening should be postponed in the following situations: short term hyperglycemia, exercise, marked hypertension, urinary tract infection, acute febrile illness, or heart failure. ACE inhibitors or NSAIDs may also influence results.
Hypertension and Nephropathy
Both systolic and diastolic hypertension markedly accelerate the progression of diabetic nephropathy. Control of hypertension—regardless of agent used—has been demonstrated conclusively to reduce the rate and progression of nephropathy and to reduce the complications of cerebrovascular disease and cardiovascular disease. Refer also to the Cardiovascular and Hypertension sections.
In patients with underlying nephropathy, treatment with ACE inhibitors should also be part of initial therapy. ACE inhibitors are recommended for all type 1 patients with microalbuminuria, even if normotensive. The use of ACE inhibitors in normotensive type 2 diabetic patients is less well substantiated. For type 2 patients with hypertension or progressive albuminuria, ACE inhibitors are recommended. When ACE inhibitors are contraindicated, other antihypertensive agents should be used. Angiotensin II receptor blockers are being studied in humans with regard to renal protective effects.
Clinical diabetic nephropathy is said to be present when a patient who has had diabetes for more than five years and has evidence of diabetic retinopathy develops clinically apparent albuminuria (>300 mg per 24 hours) and has no evidence of any other cause of kidney disease. When these criteria are fulfilled, a clinical diagnosis of diabetic nephropathy can generally be made without performing a renal biopsy.
