Diagnosis of diabetic nephropathy

Diagnosis and establishment of the stage of diabetic nephropathy are based on the history of the disease (duration and type of diabetes mellitus), the results of laboratory studies (detection of microalbuminuria, proteinuria, azotemia and uremia).

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

The markers of "preclinical" kidney damage in diabetic nephropathy are microalbuminuria, depletion of the functional renal reserve, or an increase in the filtration fraction of more than 22%, an excess of GFR values of more than 140-160 ml / min.

Microalbuminuria is considered the most reliable preclinical criterion for damage to the renal glomeruli. This term means the excretion of albumin with urine in low amounts (from 30 to 300 mg / day), which is not determined in a traditional urinalysis.

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

Microalbuminuria is a harbinger of not only the advanced stage of diabetic nephropathy, but also cardiovascular diseases. Therefore, the presence of microalbuminuria in patients serves as an indication for examination to identify 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%, the specificity is 93%. A positive test should be confirmed by a more accurate immunochemical method. Given daily fluctuations in albumin excretion, at least two positive results and sin for 3-6 months are necessary to confirm true microalbuminuria.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Classification of albuminuria

	Albumin excretion in urine		The concentration of albumin in the urine	Albumin / urine output 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 - in women.

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

The definition of functional renal reserve is one of the indirect methods of diagnosing intralubular hypertension, which is considered as the main mechanism of development of diabetic nephropathy. Functional renal reserve is understood as the ability of the kidneys to respond by increasing GFR to the stimulus effect (oral protein loading, the introduction of low doses of dopamine, the introduction of a certain set of amino acids). Excess of GFR after the introduction of the stimulus by 10% compared with 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 - the percentage of GFR to the renal plasma flux. Normally, the size of the filtration fraction is about 20%, its value above 22% indicates an increase in GFR due to increased pressure inside the renal glomerulus.

Absolute values of GFR, exceeding the values of 140-160 ml / min, also serve as an indirect sign of the development of intra-cerebral hypertension.

In the first and second stages of the development of diabetic nephropathy, the involvement of the kidneys in the pathological process is indirectly indicated by indicators reflecting the state of hypertension in the renal glomerulus: high GFR values exceeding 140-160 ml / min, absence or marked decrease in functional renal reserve and / faction. The detection of microalbuminuria makes it possible to diagnose diabetic nephropathy in the third stage of development.

[11], [12], [13], [14], [15]

Diagnosis of the clinical stage of diabetic nephropathy

The clinical stage of diabetic nephropathy begins with the IV stage of Mogensen. It develops, as a rule, in 10-15 years from the onset of diabetes and manifests itself:

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

As a prognostic unfavorable clinical sign of diabetic nephropathy, nephrotic syndrome is considered, which complicates the course of diabetic nephropathy in 10-15% of cases. It usually develops gradually; in some patients, the occurrence of resistance of edemas to diuretics is noted earlier. For a nephrotic syndrome against a background of diabetic nephropathy, a marked decrease in GFR, preservation of edematous 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.

[16], [17], [18], [19]

The diagnosis of diabetic nephropathy

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

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

Screening of diabetic nephropathy

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

In the absence of proteinuria, urine is examined for microalbuminuria. If urinary albumin excretion is 20 μg / min or a urine albumin / creatinine ratio of 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 given after a year. If the excretion of albumin with urine exceeds these values, then in order to avoid a possible error, repeat the test three times within 6-12 weeks. When two positive results are obtained, they diagnose "diabetic nephropathy, the stage of microalbuminuria" and prescribe the treatment.

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

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
	GFR	1 time per month (before switching to dialysis)
	Creatinine and serum 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 hemoglobin of blood	1 time per month
	Ocular fundus	On the recommendation of the ophthalmologist
Microalbuminuria	HbA1c	1 time in 3 months
	Albuminuria	1 time per year
	Blood pressure level	Once a month (at normal values)
	Creatinine and serum urea	1 time per year
	Serum lipids	Once a year (at normal values)
	ECG (stress tests if necessary)	1 time per year
	Ocular fundus	Ophthalmologist's recommendation
Proteinuria	HbA1c	1 time in 3 months
	Blood pressure level	Daily at high values
	Proteinuria	1 time in 6 months
	Total protein / albumin of serum	1 time in 6 months
	Creatinine and serum urea	1 time in 3-6 months
	GFR	1 every 6-12 months
	Serum lipids	1 time in 6 months
	ECG, echocardiography (stress tests if necessary)	1 time in 6 months
	Ocular fundus	1 time in 3-6 months (the ophthalmologist's recommendation)
	The study of autonomic and sensory neuropathy	Neuropathologist's recommendation

The recommended frequency of examination of patients with diabetes mellitus with diabetic nephropathy is to some extent conditional and depends on the patient's condition and the real need of each study. The necessary studies in all stages of kidney damage include the monitoring of glycemia, blood pressure, serum creatinine and urea, serum lipids and GFR (to predict the time of onset of terminal renal failure). In all stages of diabetic nephropathy, consultations of the oculist, neurologist, cardiologist are necessary to resolve the issue of therapeutic tactics of concomitant complications. In the stage of chronic renal failure, the tactics and type of renal replacement therapy should be determined.

The annual screening for diabetic nephropathy is necessary for the following categories of patients with diabetes mellitus:

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

Differential diagnosis of diabetic nephropathy

In patients with diabetes mellitus with newly detected microalbuminuria, diabetic nephropathy must be differentiated with other causes of microalbuminuria. The transient increase in albumin excretion is possible with 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, diabetic nephropathy should be differentiated from background kidney diseases (with a special emphasis on the history of renal disease, instrumental studies confirming the presence of urolithiasis, stenosis of the renal artery, etc.)

[20], [21], [22], [23], [24],