Diagnosis of diabetic nephropathy

Diagnosis and staging of diabetic nephropathy are based on anamnesis data (duration and type of diabetes mellitus), laboratory test results (detection of microalbuminuria, proteinuria, azotemia and uremia).

The earliest method for diagnosing diabetic nephropathy is the detection of microalbuminuria. The criterion for microalbuminuria is highly selective excretion of albumin in urine in an amount of 30 to 300 mg/day or 20 to 200 μg/min in the night portion of urine. Microalbuminuria is also diagnosed by the albumin/creatinine ratio in morning urine, which eliminates errors in daily urine collection.

Markers of “preclinical” kidney damage in diabetic nephropathy include microalbuminuria, depletion of the functional renal reserve or an increase in the filtration fraction of more than 22%, and an excess of SCF values of more than 140-160 ml/min.

Microalbuminuria is considered the most reliable preclinical criterion for damage to the renal glomeruli. This term refers to the excretion of albumin in urine in low quantities (from 30 to 300 mg/day), which is not determined by traditional urine testing.

The stage of mycoralbuminuria is the last reversible stage of diabetic nephropathy with timely prescribed therapy. Otherwise, 80% of patients with type 1 diabetes mellitus and 40% of patients with type 2 diabetes mellitus with microalbuminuria develop a pronounced stage of diabetic nephropathy.

Microalbuminuria is a precursor not only to the advanced stage of diabetic nephropathy, but also to cardiovascular diseases. Therefore, the presence of microalbuminuria in patients serves as an indication for examination to detect cardiovascular pathology, as well as for active therapy aimed at risk factors for cardiovascular diseases.

For qualitative determination of microalbuminuria, test strips are used, the sensitivity of which reaches 95%, specificity - 93%. A positive test should be confirmed by a more accurate immunochemical method. Considering the daily fluctuations in albumin excretion, to confirm true microalbuminuria it is necessary to have at least two positive results and three within 3-6 months.

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Classification of albuminuria

	Albumin excretion in urine		Urine albumin concentration	Urine albumin/creatin ratio
	In the morning portion	Per day
Normoalbuminuria	<20 mg/min	<30 mg	<20 mg/l	<2.5 mg/mmol' <3.5 mg/mmol 2
Microalbuminuria	20-200 mg/min	30-300 mg	20-200 mg/l	2.5-25 mg/mmol' 3.5-25 mg/mmol 2
Macroalbuminuria	>200 mg/min	>300 mg	>200 mg/l	>25 mg/mmol

1 - for men. 2 - for women.

According to the recommendations of the American Diabetes Association (1997) and the European Group for the Study of Diabetes (1999), the study of microalbuminuria is included in the list of mandatory methods of examination of patients with diabetes mellitus types 1 and 2.

Determination of the functional renal reserve is one of the indirect methods for diagnosing intraglomerular hypertension, which is considered to be the main mechanism for the development of diabetic nephropathy. The functional renal reserve is understood as the ability of the kidneys to respond to a stimulus (oral protein load, administration of low doses of dopamine, administration of a certain set of amino acids) by increasing the SCF. An increase in the SCF after the stimulus by 10% compared to the basal level indicates a preserved functional renal reserve and the absence of hypertension in the renal glomeruli.

Similar information is provided by the filtration fraction indicator - the percentage ratio of the SCF value to the renal plasma flow. Normally, the filtration fraction value is about 20%, its value over 22% indicates an increase in SCF due to increased pressure inside the renal glomerulus.

Absolute values of SCF exceeding 140-160 ml/min also serve as an indirect sign of the development of intraglomerular hypertension.

In stages I and II of diabetic nephropathy development, kidney involvement in the pathological process is indirectly indicated by indicators reflecting the state of hypertension in the renal glomerulus - high values of SCF exceeding 140-160 ml/min, absence or significant decrease in functional renal reserve and/or high values of filtration fraction. Detection of microalbuminuria makes it possible to diagnose diabetic nephropathy in stage III of development.

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Diagnosis of the clinical stage of diabetic nephropathy

The clinical stage of diabetic nephropathy begins with stage IV according to Mogensen. It develops, as a rule, 10-15 years after the onset of diabetes mellitus and is manifested by:

• proteinuria (in 1/3 of cases with the development of nephrotic syndrome);
• arterial hypertension;
• development of retinopathy;
• a decrease in SCF during the natural course of the disease at an average rate of 1 ml/month.

Nephrotic syndrome, which complicates the course of diabetic nephropathy in 10-15% of cases, is considered as a prognostic unfavorable clinical sign of diabetic nephropathy. It usually develops gradually; some patients experience early development of edema resistance to diuretics. Nephrotic syndrome against the background of diabetic nephropathy is characterized by a marked decrease in SCF, persistence of edema syndrome and high proteinuria, despite the development of chronic renal failure.

The fifth stage of diabetic nephropathy corresponds to the stage of chronic renal failure.

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Formulation of the diagnosis of diabetic nephropathy

The following formulations of the diagnosis of diabetic nephropathy have been approved:

• diabetic nephropathy, microalbuminuria stage;
• diabetic nephropathy, proteinuria stage, with preserved nitrogen-excreting function of the kidneys;
• diabetic nephropathy, stage of chronic renal failure.

Screening for diabetic nephropathy

For early diagnosis of diabetic nephropathy and prevention of late vascular complications of diabetes, a program of screening for diabetic nephropathy in patients with diabetes was developed and proposed within the framework of the Saint Vincent Declaration. According to this program, detection of diabetic nephropathy begins with a general clinical urine analysis. If proteinuria is detected, confirmed by multiple studies, then a diagnosis of "diabetic nephropathy, proteinuria stage" is made and appropriate treatment is prescribed.

In the absence of proteinuria, urine is tested for microalbuminuria. If the urinary albumin excretion is 20 mcg/min or the urine albumin/creatinine ratio is less than 2.5 mg/mmol in men and less than 3.5 mg/mmol in women, the result is considered negative and a repeat urine test for microalbuminuria is prescribed in a year. If the urinary albumin excretion exceeds the specified values, the test should be repeated three times over 6-12 weeks to avoid possible error. If two positive results are obtained, a diagnosis of "diabetic nephropathy, microalbuminuria stage" is made and treatment is prescribed.

The development of diabetic nephropathy is always associated with the worsening of other vascular complications of diabetes and acts as a risk factor for the development of coronary heart disease. Therefore, in addition to regular albuminuria testing, patients with diabetes of both type 1 and type 2 need regular monitoring by an ophthalmologist, cardiologist, and neurologist.

Necessary studies in patients with diabetes mellitus depending on the stage of diabetic nephropathy

Stage of nephropathy	Study	Frequency of studies
Chronic renal failure	Glycemia	Daily
	Blood pressure level	Daily
	Proteinuria	1 time per month
	SKF	1 time per month (before switching to dialysis)
	Serum creatinine and urea	1 time per month
	Serum potassium	1 time per month
	Serum lipids	1 time in 3 months
	ECG	On the recommendation of a cardiologist
	Total blood hemoglobin	1 time per month
	Fundus of the eye	On the recommendation of an ophthalmologist
Microalbuminuria	HbA1c	1 time in 3 months
	Albuminuria	Once a year
	Blood pressure level	1 time per month (with normal values)
	Serum creatinine and urea	Once a year
	Serum lipids	1 time per year (under normal values)
	ECG (stress tests if necessary)	Once a year
	Fundus of the eye	Ophthalmologist's recommendation
Proteinuria	HbA1c	1 time in 3 months
	Blood pressure level	Daily at high values
	Proteinuria	1 time in 6 months
	Total serum protein/albumin	1 time in 6 months
	Serum creatinine and urea	1 time in 3-6 months
	SKF	1 time in 6-12 months
	Serum lipids	1 time in 6 months
	ECG, EchoCG (stress tests if necessary)	1 time in 6 months
	Fundus of the eye	1 time every 3-6 months (optometrist's recommendation)
	Research into autonomic and sensory neuropathy	Neurologist's recommendation

The recommended frequency of examination of patients with diabetes mellitus and diabetic nephropathy is somewhat arbitrary and depends on the patient's condition and the actual need for each examination. Necessary examinations at all stages of kidney damage include monitoring of glycemia, blood pressure, serum creatinine and urea, serum lipids and SCF (to predict the time of onset of terminal renal failure). At all stages of diabetic nephropathy, consultations with an ophthalmologist, neurologist, and cardiologist are necessary to decide on the treatment tactics for concomitant complications. At the stage of chronic renal failure, the tactics and type of renal replacement therapy should be determined.

Annual screening for diabetic nephropathy is necessary for the following categories of patients with diabetes:

• patients with type 1 diabetes mellitus with the onset of the disease in post-pubertal age - 5 years from the onset of the disease;
• patients with type 1 diabetes mellitus with the onset of the disease in early childhood - from the age of 10-12 years;
• patients with type 1 diabetes mellitus with the onset of the disease in puberty - from the moment of diagnosis of diabetes mellitus;
• patients with type 2 diabetes mellitus - from the moment of diagnosis of diabetes mellitus.

Differential diagnosis of diabetic nephropathy

In patients with diabetes mellitus with newly diagnosed microalbuminuria, it is necessary to differentiate diabetic nephropathy from other causes of microalbuminuria. A transient increase in albumin excretion is possible in the following diseases and conditions:

• decompensation of carbohydrate metabolism;
• high protein diet;
• heavy physical exertion;
• urinary tract infections;
• heart failure;
• fever;
• severe arterial hypertension.

In patients with type 2 diabetes mellitus, diabetic nephropathy should be differentiated from background kidney diseases (in this case, the history of renal pathology, instrumental studies confirming the presence of urolithiasis, renal artery stenosis, etc. are of particular importance).

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