RU2333497C1 - Method predicting chronic renal insufficiency at patients with postcapillarotoxic glomerulonephritis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine area, namely, to nephrology, and can be used for predicting development of chronic renal insufficiency at patients with postcapillarotoxic glomerulonephritis. Tap clinical signs of an arterial hypertonia and a daily proteinuria more than 1 g. in the anamnesis is determined. A combination of a debut of a hemorrhagic vasculitis with the years the patient is defined, the creatinine maintenance in blood serum in the beginning of a glomerulonephritis, indicators of a plasma link of a hemostasis, and also the analysis of therapeutic treatment in a disease debut is carried out. If revealing debut of a hemorrhagic vasculitis at the age of 31-45 years, the content in blood serum of a creatinine above 130 micromole, a blood hypercoagulation in a plasma link of a hemostasis and absence of anticoagulant therapy in a disease debut, the forecast of development of chronic renal insufficiency is considered as adverse, in other cases the forecast is favourable.

EFFECT: allows providing more objective and early forecasting of development of chronic renal insufficiency at patients with postcapillarotoxic glomerulonephritis.

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Description

The present invention relates to medicine, namely to nephrology, and can be used to predict the development of chronic renal failure in patients with postcapillarotoxic glomerulonephritis.

A known method for predicting the development of chronic renal failure (CRF) in postcapillary toxic toxic glomerulonephritis, the essence of which is to identify clinical and morphological signs in the onset of the disease. Patients were divided into two groups depending on the presence or absence of half moon in histological preparations of the kidneys. It was found that children with revealed half moon after an average of 4.8 years had a worse prognosis of renal failure. Analysis of the values of proteinuria and concomitant arterial hypertension in the early stages of the onset of glomerulonephritis disease also indicates adverse signs of the possible development of chronic renal failure [1].

Closest to the proposed is a method for predicting chronic renal failure in patients with postcapillarotoxic glomerulonephritis, in which it was found that proteinuria is more than 1 g / l, as well as the formation of nephrotic syndrome, a combination of nephrotic syndrome with hypertension, pronounced persistent microhematuria, elderly patients have an unfavorable prognosis for the development of chronic renal failure (CRF). When the kidneys are involved in the pathological process a year or more after the skin debut of the disease, the outcome in chronic renal failure is more often observed [2].

However, the known methods have significant disadvantages, namely:

1. The prognosis of chronic renal failure using known technologies does not allow an objective forecast, since the conclusions are ambiguous and contradictory (some authors indicate that the prognosis when joining hypertension in the onset of the disease is considered unfavorable, others during the disease and only in combination with nephrotic syndrome; except Moreover, there is no indication of a specific age of the disease with a possible unfavorable prognosis).

2. There is no analysis of the early signs of postcapillarotoxic glomerulonephritis sufficient to predict the development of chronic renal failure in the initial stages of the disease: the specific age of the disease, the content of serum creatinine at the beginning of glomerulonephritis, blood coagulation in the plasma unit of hemostasis and the lack of adequate therapy at the onset of the disease.

3. Known methods do not take into account the prognostic effect of changes in the hemostatic system in case of kidney damage in hemorrhagic vasculitis, characterized by severe hypercoagulation and deposition of fibrin in the glomerular capillaries.

Based on the existing level of technology for predicting chronic renal failure in postcapillary toxic toxic glomerulonephritis, as well as eliminating the disadvantages of known technologies, the task was set: to provide a more objective and early prediction of the development of chronic renal failure in patients with postcapillary toxic toxic glomerulonephritis.

The problem is solved as follows.

Prediction of chronic renal failure in patients with postcapillarotoxic glomerulonephritis includes a history of clinical signs of arterial hypertension, daily proteinuria of more than 1 g. A new solution to the problem is to determine the combination of hemorrhagic vasculitis debut with the patient’s age, and serum creatinine in serum neuron at the beginning , indicators of the plasma link of hemostasis, as well as an analysis of therapeutic treatment in the debut of the disease. When revealing the onset of hemorrhagic vasculitis at the age of 31-45 years, the content of creatinine in the blood serum is higher than 130 μmol / L, blood hypercoagulation in the plasma unit of hemostasis and the absence of anticoagulant therapy in the onset of the disease, the prognosis of chronic renal failure is considered unfavorable, in other cases, the prognosis is favorable.

We explain the significant distinguishing features of the proposed method for predicting chronic renal failure:

Revealing the debut of hemorrhagic vasculitis at the age of 31-45 years allows predicting the development of chronic renal failure, which is confirmed statistically. Using the case-control method, a high relative risk of developing chronic renal failure was determined in patients with the onset of hemorrhagic vasculitis (HB) aged 31-45 years (rr = 2.66). When using the Kaplan-Meier moment method (the development of renal failure was taken as the “endpoint”), a significant decrease in survival was found in patients at the age of manifestation of hepatitis B 31-45 years old compared with patients in whom hepatitis B debuted before 15 years (p <0.001) ( see figure 1). Using the Cox proportional risk model, it was established that the age of onset of hepatitis B is 31-45 years old is an independent predictor of chronic renal failure (-2 Loglikelihood - 8.798). Therefore, the glomerulonephritis associated with HB has a more favorable course in patients with childhood illness. This is consistent with many authors who point to the full recovery of children in 50% of cases, a very rare but possible similar outcome of nephritis in adults under 30 years of age [2, 3]. Age is an unmodifiable risk factor. Therefore, regular monitoring of the functional state of the kidneys is necessary, especially in patients with a disease aged 31-45 years, because renal damage may not manifest itself with any clinical signs, and the calm, latent course of glomerulonephritis is sometimes underestimated until there are signs of impaired renal excretory function.

An increase in serum creatinine above 130 μmol / L in the debut of glomerulonephritis causes a high relative risk of developing chronic renal failure (rr = 15.73) and significantly reduces the survival of patients (p <0.001) (see figure 2), in addition, it is an independent factor in the development of chronic renal failure with postcapillarotoxic glomerulonephritis (-2 Loglikelihood - 17.578). The presence of hyperazotemia at the onset of the disease indicates a high degree of activity of glomerular inflammation as a trigger mechanism for nephrosclerosis.

In the prognosis of any chronic glomerulonephritis, an important role is given to the concentration of creatinine and its clearance [4, 5]. A good evidence base has been created with respect to an increase in serum creatinine> 130 μmol / L and / or a decrease in glomerular filtration rate (GFR) below 80 ml / min in the onset and during the disease as independent risk factors for the progression of IgA nephropathy [6]. We can assume their effect in relation to postcapillarotoxic glomerulonephritis, because between glomerulonephritis in hepatitis B and IgA nephropathy there is a similarity of clinical and morphological signs [2].

Hypercoagulation of blood in the plasma unit of hemostasis in patients with postcapillary toxic toxic glomerulonephritis contributes to the development of chronic renal failure, being an unfavorable prognostic sign with a high relative risk (rr = 7.6) of complications of chronic renal failure and significantly reduced survival (p <0.05) (see Fig. 3). Fibrin formed during local intravascular coagulation stimulates the proliferation of endothelial and mesangial cells, impairs microcirculation in the glomeruli, and ultimately leads to glomerulosclerosis [7]. The initial factor of hypercoagulation in the early stages is immune inflammation with the subsequent inclusion of hemodynamic mechanisms with the damaging effect of the shock wave of blood on the endothelium [8]. It is likely that in our study, the high blood coagulation potential in patients with post-capillarotoxic glomerulonephritis also reflects the presence of high activity of the inflammatory renal process, which largely determines the rate of progression of glomerulonephritis.

The absence of anticoagulant therapy in the onset of the disease is an unfavorable factor in terms of the development of chronic renal failure (rr = 7.4), significantly reducing renal survival (p <0.05), compared with patients who underwent heparin therapy (see figure 4). This fact once again confirms the prognostic significance of hypercoagulation that we have identified, and the appointment of anticoagulants in the early stages of the disease will inhibit the progression of glomerulonephritis.

A statistically significant analysis of the prototype features was carried out: the presence of arterial hypertension and daily proteinuria of more than 1 g.

A significantly high risk of complications of renal failure was found in patients with arterial hypertension in the debut of glomerulonephritis (rr = 10.96). An unfavorable prognostic value is confirmed by a significant decrease in renal survival (p <0.001) in patients with this initial sign (see Fig. 5), in addition, arterial hypertension at the onset of the disease is an independent predictor of the progression of postcapillary toxic glomerulonephritis (-2 Loglikelihood - 30.761). Hypertension in the onset of the disease is a reflection of the activity of immune renal inflammation, which becomes the trigger for the development of nephrosclerosis. Subsequently, the leading role of arterial hypertension (AH) is assigned as the non-immune hemodynamic mechanism of glomerulonephritis progression.

The action of systemic hypertension corresponds to modern ideas about the mechanisms of nephrosclerosis. Activation of the systemic and especially local renal renin-angiotensin-aldosterone system leads to the production of angiotensin II, which contributes to spasm of the efferent arteriole and the development of intracranial hypertension due to an increase in the gradient of renal transcapillary pressure. Intrastellar hypertension and hyperfiltration lead to a violation of the porosity of the basement membrane of the glomerular capillaries; as a result, macromolecules are deposited in the mesangium, stimulating the proliferation of mesangial cells and overproduction of the extracellular matrix, which results in nephrosclerosis [9]. In addition, angiotensin II is a powerful growth factor, affecting the mesangial cells and renal tubule epithelial cells, as well as stimulating the production of other growth factors.

It was found that daily proteinuria of more than 1 g is a significant unfavorable risk factor for the progression of postcapillarotoxic glomerulonephritis, leading to the development of chronic renal failure (rr = 22.8). Significant daily proteinuria significantly reduces renal survival (p <0.001) compared with a minimum proteinuria of less than 1 g / day (see Fig.6) and is an independent predictor of the development of chronic renal failure (-2 Loglikelihood - 26.367).

Pronounced daily urinary protein excretion is a marker of maintaining high activity of chronic glomerulonephritis, and immune inflammation leads to a further progressive loss of renal function due to the development of sclerosis. Proteinuria also indicates the attachment of glomerular hyperfiltration and is a non-immune mechanism of progression of renal pathology, leading to aggravation of nephrosclerosis. It is known that the penetration of large protein molecules through the basement membrane of glomerular capillaries, mesangia, and epithelial cells has a damaging effect on these structures, and also leads to dysfunction of proximal tubule cells due to overloading of the tubules with proteins [10]. Ultimately, damage to the mesangium and inflammation of the interstitium lead to nephrosclerosis. Controlled studies (REIN, 1997; MDRD study, etc.) have shown that the amount of proteinuria acts as an independent progression factor: the higher the degree of proteinuria, the higher the risk of developing terminal CRF. In principle, this applies to all glomerulopathies accompanied by proteinuria, and we have confirmed with respect to postcapillary toxic glomerulonephritis.

The prognosis of postcapillarotoxic glomerulonephritis is considered unfavorable in the presence of the following factors: the onset age of hemorrhagic vasculitis is 31-45 years, hyperazotemia and arterial hypertension in the debut of glomerulonephritis, daily proteinuria of more than 1 g, having the properties of independent predictors. Blood coagulation and the absence of anticoagulant therapy in the onset of the disease also contribute to an unfavorable prognosis.

It should be noted that in many respects the prognosis of postcapillarotoxic glomerulonephritis is determined by the onset of the disease. In this regard, factors associated with high activity of renal damage and reflecting immune inflammation are of paramount importance. Therefore, the appointment of immunosuppressive therapy in the debut of glomerulonephritis in patients with arterial hypertension and an increase in serum creatinine above 130 μmol / l can be considered legitimate. All patients at the beginning of glomerulonephritis need to carry out anticoagulant treatment. Adequate and timely therapeutic measures will stop the activity of inflammation and slow down the onset of chronic renal failure.

The essence of the proposed "Method for predicting chronic renal failure in patients with postcapillary toxic glomerulonephritis" is as follows.

For patients with a diagnosis of postcapillarotoxic glomerulonephritis for an earlier prevention of development in subsequent chronic renal failure, a thorough study of the clinical and biochemical parameters of blood, urine, and an analysis of the medical history are carried out.

Prediction of chronic renal failure in patients with postcapillarotoxic glomerulonephritis includes a history of clinical signs of arterial hypertension, daily proteinuria, a combination of hemorrhagic vasculitis debut with the patient’s age, serum creatinine content at the beginning of glomerulonephritis, and plasma treatment in the debut of the disease. When revealing the onset of hemorrhagic vasculitis at the age of 31-45 years, the serum creatinine content is higher than 130 μmol / L, blood hypercoagulation in the plasma unit of hemostasis and the absence of anticoagulant therapy in the onset of the disease, the prognosis of chronic renal failure is considered unfavorable. In other cases, the prognosis is favorable.

In the study of plasma-coagulation hemostasis in favor of hypercoagulation, the shortened activated partial thromboplastin time (APTT, average value of 30-40 sec, the value may vary depending on the reagents used), activated recalcification time (ABP, average value of 80-120 sec, may indicate vary depending on the reagents used), prothrombin time (PTV, according to Quick - 11-15 seconds), thrombin time (TV, normal value - 15-18 seconds), an increase in prothrombin index ksa (PTI, normal value - 80-105%).

The essence of the proposed method is illustrated by clinical examples.

Example 1

Patient A., 45 years old. Diagnosis: Hemorrhagic vasculitis, initial period, cutaneous abdominal-renal variant, acute course.

During the examination, he complained of abdominal pain of a diffuse nature, aggravated after eating, rashes on the lower extremities, pain in the lumbar region on both sides of the aching character, a change in the color of urine (dark color). Ill 5 days ago after hypothermia.

Objective status: General state of moderate severity. Consciousness is clear. The skin is of normal humidity, on the lower extremities a hemorrhagic small-pointed palpable symmetrical rash that does not disappear with pressure. The tongue is wet, clean. Peripheral lymph nodes are not enlarged, painless. Edema is absent. The thyroid gland is not enlarged.

Respiratory: Dyspnea absent. With auscultation: vesicular breathing, is carried out in all departments, rales are absent.

Cardiovascular system: During auscultation: heart sounds are clear, the rhythm is correct, heart rate is 70 beats. in min, BP 160/100 mm Hg

Digestive organs: The abdomen is soft, painful on palpation in all departments. The liver is not enlarged, painless. The spleen is not palpable.

Urinary organs: The kidneys are not palpable, there is no soreness. The symptom of striking is negative on both sides. Urination is free, painless.

Laboratory examination: OAK: er - 3.3 · 10 ¹² / l, Hb - 119 g / l, L - 10.3 · 10 ⁹ / l, ESR - 40 mm / h. Biochemical blood test: creatinine - 169 μmol / l, glomerular filtration rate - 81 ml / min, urea - 17 mmol / l, cholesterol - 8.4 mmol / l. OAM: brown, specific gravity 1010, protein 1.68 g / l, erythrocytes more than 200, single white blood cells, cylinders 1-0 in the field of view. Daily proteinuria 1.9 g. Coagulogram: APTT - 29 sec (37 sec), ABP - 70 sec (78 sec), PTV - 11 sec (15 sec), IPT - 108% (80-100%). The prognosis for the development of chronic renal failure in this patient is poor. The disease began at the age of 45 years. At the beginning of the disease, there is arterial hypertension - 160/100 mm Hg, impaired nitrogen excretory function of the kidneys with an increase in blood creatinine level - 169 μmol / L, pronounced daily proteinuria - 1.9 g, hypercoagulation in plasma-coagulation hemostasis (listed indicators evidence in favor of a high activity of immune renal inflammation, which is also confirmed by nephrobiopsy: mesangioproliferative glomerulonephritis of a high degree of activity). In order to slow down the progression of glomerulonephritis and the development of chronic renal failure, immunosuppressive therapy (prednisone 1 mg / kg body weight per day for 4 weeks with a gradual decrease in dose by 1/4 tablet in 10 days to 5-10 mg / day), anticoagulants ( heparin 5.0 thousand units 4 times a day s / c - 2 weeks), antiplatelet agents (plavica 75 mg / day for 1-1.5 months), antihypertensive therapy (amlodipine 10 mg / day, indapamide 2.5 mg / day), lipid-lowering drugs.

As a result of the treatment, the patient's condition improved. Discharged in satisfactory condition with recommendations:

OAM, OAK control once a month and against intercurrent diseases, blood creatinine control at least 1 time in 2 months, dynamic observation by a nephrologist.

When examining the patient for several years, there were no signs of chronic renal failure.

Example 2

Patient V., 21 years old. Diagnosis: Secondary chronic (postcapillarotoxic) glomerulonephritis, isolated urinary syndrome, chronic renal failure 0.

Anamnesis. The disease began 12 years ago after suffering hemorrhagic vasculitis, a cutaneous-renal variant with relapses once a year. Glomerulonephritis made its debut with isolated urinary syndrome, treatment was performed: ascorutin, chimes. Coagulograms at the onset of the disease were within normal limits.

During the examination: blood pressure 120/80 mm Hg, complete blood count - normal, creatinine - 105 μmol / L. In urine: specific gravity 1020, protein 0.055 g / l, red blood cells 5-10, white blood cells 1-3; daily proteinuria 0.134 g

The prognosis of chronic renal failure in postcapillary toxic glomerulonephritis in this patient is favorable, because the disease debuted at the age of 9 years with isolated urinary syndrome, coagulation was within normal limits, and minimal proteinuria (less than 1 g / day) was determined during the examination. 12 years after the manifestation of glomerulonephritis, there are no signs of renal failure. The patient was given recommendations:

1. Avoid hypothermia, insolation, unreasonable medication, exclude nephrotoxic drugs. Timely rehabilitation of foci of infection.

2. Diet with restriction of salted, canned foods. Liquid intake up to 1.5-2.0 liters per day.

3. Disaggregants: Curantil 75 mg per day - up to 2 months.

4. ACE inhibitors with nephroprotective purpose for a long time: Enap 5 mg 2 times a day.

5. Dynamic observation by a nephrologist. OAM control, OAK once a month, blood creatinine control at least 1 time in 2 months.

During dynamic observation of the patient for several years, CRF was not detected.

Example 3

Patient K., 41 years old. Diagnosis: Secondary chronic (postcapillarotoxic) glomerulonephritis, hypertonic variant, chronic renal failure. Regular hemodialysis.

Anamnesis: The disease began 4 years ago after the transfer of hemorrhagic vasculitis, a cutaneous-articular-renal variant. In the future, relapses of extrarenal manifestations of hemorrhagic vasculitis were observed up to 2 times a year. Since the onset of the disease, there was an increase in blood pressure to 170/100 mmHg, an increase in creatinine to 170 μmol / L, daily proteinuria - 1.08 g, hypercoagulation prevailed in coagulation hemostasis (ABP - 67 sec (69 sec), APTT - 21 sec (29 sec), TV-11 sec (14 sec), IPT - 107% (80 - 100%)). The treatment was carried out: chimes 25 mg 3 r / day, antihypertensive therapy (enap 10 mg 2 r / day). Symptoms of chronic renal failure appeared 3 years after the onset of glomerulonephritis and have been observed for the past 12 months.

An examination currently defines arterial hypertension (blood pressure 180/110 mm Hg). In the blood: hemoglobin - 83 g / l, creatinine level - 1048 mmol / l, urea - 40.4 mmol / l, cholesterol - 6.4 mmol / l, creatinine clearance - 10 ml / min. In urine: specific gravity 1003, protein 1.06 g / l, erythrocytes 21-39, leukocytes 2-3 in the field of view, daily proteinuria - 1.82 g.

The prognosis of the development of chronic renal failure in postcapillary toxic glomerulonephritis in this patient was unfavorable, because the disease began at the age of 37, in the debut of glomerulonephritis there was arterial hypertension, an increase in blood creatinine above 130 μmol / L, pronounced daily proteinuria, an increase in blood coagulation potential and there was no prescription of anticoagulants. In addition, there was no appointment of immunosuppressive therapy, and the patient’s criteria at the beginning of the disease testified to the activity of immune renal inflammation, which “triggered” the process of glomerulosclerosis. After 3 years from the onset of the disease, the patient developed symptoms of chronic renal failure, due to the development of the terminal stage of chronic renal failure, regular hemodialysis is currently prescribed.

Thus, the proposed "Method for predicting chronic renal failure in patients with postcapillarotoxic glomerulonephritis" allows, in comparison with known technologies, to provide a more objective and early prediction of the development of chronic renal failure in patients with postcapillarotoxic glomerulonephritis. Adequate timely therapeutic measures will reduce the risk of progression of postcapillarotoxic glomerulonephritis, delay the onset of chronic renal failure and, therefore, the appointment of renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplantation) to patients of working age (25-45 years).

Information sources

1. Kirschstein M., Ehrich J.H. Schoenlein-Henoch-Nephritis // Monatsschr Kinderheilkd. - 2004 .-- Vol. 146. - P.1208-1217.

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3. Yoshikawa N., Ito H., Yoshiya K. et al. Henoch-Schonlein nephritis and IgA nephropathy in children: a comparision of clinical course // Clin. Nephrol. - 1987. - Vol. 27. - P.233-237.

4. Tov N.L., Valentik M.F., Vlazneva V.A. Comparative evaluation of the clinical course and dynamics of morphological changes in chronic glomerulonephritis // Ter. arch. - 1986. - T. 58, No. 7. - S.10-13.

5. Kobayashi Y., Hiki Y., Fujii K. et al. Moderately proteinuric IgA nephropathy: prognostic prediction of individual clinical courses and steroid therapy in progressive cases // Nephron. - 1989. - Vol. 53, No. 3. - P.250-256.

6. Johnston P.A., Brown J.S., Braumholtz D.A., Davison A.M. Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulinephritis Registre // Q.J. Med. - 1992. - Vol. 84, No. 304. - P.619-627.

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9. Kang M.J., Ingram A., Hao Ly et al. Effects of diabetes and hypertension on glomerular transforming growth factor - P receptor expression // Kidney Int. - 2000. Vol. 58. - P.1677-1685.

10. Plotkin V.Ya. One of the possible mechanisms for the development and progression of chronic glomerulonephritis // Ter. arch. - 1988. - T.60, No. 6. - S.19-24.

Claims (1)

A method for predicting chronic renal failure in patients with postcapillarotoxic glomerulonephritis, including the identification of a history of clinical signs of arterial hypertension and daily proteinuria of more than 1 g, characterized in that the combination of hemorrhagic vasculitis debut with the patient’s age, serum creatinine content at the beginning of glomerulone, hemostasis, as well as an analysis of therapeutic treatment in the debut of the disease, and when revealing a hemorrhagic debut of vasculitis aged 31-45 years, serum creatinine greater than 130 mmol / l, blood hypercoagulation in the plasma link of hemostasis and lack of anticoagulant therapy at the onset of the disease, prognosis of chronic renal failure is considered unfavorable, in other cases, the prognosis is favorable.

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