Kliniczno-laboratoryjna analiza infekcji wirusem HIV u osób z przewlekłą chorobą nerek

Vasyl D. Moskaliuk, Margarita O. Andrushchak, Yurii M. Andreychyn, Irina V. Balanyk, Ivanna V. Rudan,
Andriy V. Andrushchak, Myroslava S. Berezova

HSEI BUKOVINIAN STATE MEDICAL UNIVERSITY, CHERNIVTSI, UKRAINE

ABSTRACT

Introduction: One of the most important problems of our time is the HIV epidemic. Over a 30-year history of this disease, more than 75 million people were infected with HIV, nearly of which 30 million adults and children died [1, 2]. In the coming decades, they will continue to play a significant role in world premature mortality rates.

The aim of the work is to determine the incidence of CKD, concomitant hepatitis B and C, and other most common opportunists in HIV infection, as well as to assess the diagnostic value of clinical and laboratory symptoms of renal impairment in immunocompromised patients.

Materials and methods: 292 HIV-infected patients were screened on an outpatient screening at the Chernivtsi Regional AIDS Center. To be based on the main markers of kidney damage, the persistent proteinuria (PU) and velocity of glomerular filtration (GFR) <60 ml / min / 1.73 m2 – in 16.4% of cases, chronic kidney disease (CKD) was diagnosed, which was accompanied by a high frequency with a violation functions of these organs.

Results: A high frequency of opportunistic diseases of viral etiology was detected in persons with PU, which may be due to the involvement of the kidneys in the pathological process of cytomegalovirus infection and, accordingly, the more frequent use of potentially nephrotoxic antiviral drugs.

Significantly more arterial hypertension (AG) is detected in the case of PU than in the absence of protein in the urine (p <0.001). In addition, hemoglobin and GFR levels in patients with persistent PU were lower in comparison with patients without this symptom, indicating a relationship between proteinuria and anemia and renal dysfunction.

Conclusions: There was a tendency to decrease the level of proteinuria with age (p> 0.05), which may be due to the lesser development of glomerular kidney damage in the older age group.

GFR in women is significantly lower than in men (p> 0.05), which indicates a more significant renal dysfunction in women.

 

Wiad Lek 2018, 71, 6, -1185

 

INTRODUCTION

The defeat of the kidneys, which is often characterized by severe clinical manifestations, can significantly affect the prognosis of life of HIV-infected [3, 4]. Including the growing number of HIV-infected people in the world and an increase in the life expectancy of such patients, an increase of number of HIV-infected people of expensive substitution renal therapy as well as kidney transplantation should be expected.

In the world scientific literature, factors associated with renal impairment for HIV infection are identified: history of kidney disease, uncontrolled HIV infection, time spent on HAART, older age, female sex, African origin (APOL1 genetic variant), CD4 + lymphocytes <200 cells / ml, as well as the use of nephrotoxic drugs [5].

However, despite the large number of foreign publications devoted to this topic, the issue of kidney damage in HIV infection in Ukraine remains insufficiently highlighted.

THE AIM

The aim of the work is to determine the incidence of CKD, concomitant hepatitis B and C, and other most common opportunists of HIV infection, as well as to assess the diagnostic value of clinical and laboratory symptoms of renal impairment of immunocompromised patients.

MATERIALS AND METHODS

292 HIV-infected patients were examined, who were on an outpatient screening at the Chernivtsi Regional AIDS Center (head physician Mochulsky VM).

When diagnosis was made, clinical and epidemiological data and results of laboratory research methods: serological and immunological (including determination of CD4 + -lymphocyte contents) were considered. Initial screening of HIV-infected people was carried out when they were taken to a dispensary account in accordance with the CP №580 of 12.12.2003.

The average age of all patients was (29.3 ± 8.2) years (range from 19 to 55 years). There were 188 (64.4%) men and 104 (35.6%) women among all patients. There were included mostly patients younger (25-44 years old) in the research.

Among the patients who were included in the research – I clinical stage of HIV infection was detected in 26 (8.9%) patients, II – in 40 (13.7%), III – in 108 (37.0%) and IV clinical stage – in 118 (40,4%) patients.

The ELISA method determined HBsAg, HBeAg, HBcAg and total anti-HCV, as well as species-specific IgG, IgM antibodies to Toxoplasma gondii, cytomegalovirus, Epstein-Barr virus. Immuno-enzyme test systems were used for diagnostic systems “Diagnostic Systems” (Nizhny Novgorod, Russia) in accordance with the recommendations. The PCR method tested blood on the basis of detection of the genetic material of HBV and / or HCV in persons with positive serological markers of viral hepatitis.

The urinary strips (Aution Sticks-2EA) were used in the research, screening of kidney damage markers – albuminuria /
proteinuria test systems. The results obtained using the test strips were considered to be indicative. In the presence of a screening test of proteinuria ≥1 + corresponding to a gradation of 30 mg / l, repeated urinalysis was performed on a quantitative protein determination on a MIKROLAB-600 spectrophotometer using UNI-TEST-BM reagents separated in the time period from 3 days to one week.

Functional status of the kidneys was estimated by the integral index, which characterizes the degree of preservation / loss of mass of active nephrons. The criterion of renal dysfunction was a decrease in GFR <60 ml / min on 1.73 m2 [6, 7].

Chronic kidney disease was diagnosed when proteinuria or proteinuria in combination with a decrease in GFR was detected from 3 months or more.

A screening study is conducted according the recommendations of the Kidney Disease Outcome Quality Initiative, K / DOQI, 2002, and the American Association for Infectious Diseases Society of America (IDSA, 2005) to identify kidney damage markers (permanent proteinuria, reduction in GFR that is detected for 3 or more months) in HIV-infected patients [4, 7].

The control group comprised 40 patients with HIV without signs of kidney damage, comparable in age, sex and anthropometric indices with the study population of persons with kidney pathology.

RESULTS AND DISCUSSION

PU was detected in 105 (36.0%), of which 73 (25.0%) cases were transitory, and 32 (11.0%) were persistent during the primary examination of 292 patients with HIV. In this case, 11 patients with transient PU and 6 patients with persistent PU had a chronic kidney disease in the history of HIV infection.

HIV-associated nephropathy was detected in 48 out of 292 (16.4%) patients (31 patients, 17 women), in which the markers of kidney damage were identified and confirmed in the course of the examination – persistent proteinuria or proteinuria in combination with decreased GFR.

Thus, albuminuria / proteinuria is detected in HIV-infected patients with high frequency (36.0%), which testifies to transient kidney damage, systemic inflammation syndrome, endothelial dysfunction, and the presence of CKD. CKD was diagnosed, based on the main markers of kidney damage – persistent PU and GFR <60 ml / min / 1.73 m2 – in 16.4% of cases, which was associated with a high incidence of kidney function impairment.

Viral hepatitis of different etiologies as concomitant diseases were characteristic for most HIV-infected patients who were under our observation, regardless of the presence or absence of PU (31 out of 48 (64.6%) and 27 of 40 (67.5%) respectively). Of these, in the main group of 8 (16,7 ± 5,4)%, chronic HVV infection was detected, in 16 (33,3 ± 6,8)% – chronic HVV infection and in 7 (14, 6 ± 5.1)% – mixed hepatitis B + C. Hepatitis B was diagnosed in 4 – (10,0 ± 4,7)%, hepatitis C – in 17 (42,5 ± 7,8)% of patients, co-infection with hepatitis B and C viruses in 6 – (15 , 0 ± 5.6)% in the comparison group. Significant differences between the frequency of registration of viral hepatitis in the groups were also not detected (p> 0.05).

The laboratory characteristics of HCV-infected people and the presence of chronic HVV- and / or HCV-infection markers are presented in Table I. Hyperfermentemia (elevation of ALT and / or HLA) was observed in 6 out of 31 patients with CKD and the presence of markers of chronic HVV- and / or HCV infection AsAT in serum to 2.5-3.0 norms in 2 people and to 1.5-2.0 norms – in 4). Hyperfermentemia was combined with hyperbilirubinemia, elevated levels of alkaline phosphatase (LF) and γ-glutamyltranspeptidase (GGTP) in serum in 2 patients, with an increase in the concentration of bilirubin and GGPP – in 1 patient. The elevated levels of LF and bilirubin in serum were established only in 1 person in the absence of hyperfermentemia. The isolated increase in GGTP concentration in serum was detected in 9 out of 31 patients, which may be due to the use of hepatotoxic drugs and the use of alcohol.

Frequency of opportunistic infections of different etiologies in HIV-infected with proteinuria and in the comparison group

It should be noted that 5 out of 48 patients with CKD died during the two-year observation period. The cause of death in all cases was the development of severe inocurable opportunistic diseases.

There are statistically significant intergroup differences in clinical and laboratory parameters in patients with proteinuria and in its absence (Table III).

Statistically significant differences in the frequency of arterial hypertension among HIV-infected with CKD and control group were revealed. Thus, AG was more often registered in 15 patients with PU – (31,3 ± 6,7)% and only in one person – (2,5 ± 2,5)% in its absence (p <0,001). At the same time, among patients with proteinuria, 1st and 2nd grade of hypertension were determined in 9 and 10 persons – 37.5 and 20.8% respectively, 3rd degree was diagnosed in 22.9% of observations (n = 11) [8 ]. Accordingly, the levels of systolic and diastolic blood pressure were significantly higher in patients with PU (p <0.05).

A tendency to decrease the level of proteinuria with age increases (p> 0.05), which may be due to the more rare development of glomerular kidney damage in the older age group in the research of the relationship of markers of kidney damage with the sex and age of patients. To tell the truth, a small sample of patients over the age of 45 years old does not allow to interpret this result (Table IV).

We analyzed the factors that could affect the level of GFR and found that despite the lack of gender differences in the frequency of arterial hypertension (10 men – 32.3% and 6 women – 35.3%, p> 0.05), men (7 out of 10), in order to control the level of AT, more often took hypotensive drugs from the group of ACE inhibitors than women (2 out of 6).

Thus, there was not found significant difference between the risk factors for HIV infection, the duration of HIV infection, the age and the incidence of related viral hepatitis in the patients with markers of kidney damage and the control patients.

It was revealed that patients with proteinuria are more likely to be registered with hypertension and progressive course of the disease, which is confirmed by a decrease in the function of the kidneys, which deeper in women. In addition, we assume that frequent use by men in order to control the level of blood pressure of ACE inhibitors has led to a slowdown in the progression of CKD, which was reflected in a more stable kidney function.

Conclusions

1. The albuminuria/proteinuria is detected in HIV-infected patients with a high frequency (36.0%), which testifies to transient kidney damage, the presence of systemic inflammation syndrome, endothelial dysfunction, and the presence of CKD. The CKD was diagnosed, based on the main markers of kidney damage – persistent PU and GFR <60 ml / min / 1.73 m2 – in 16.4% of cases, which was associated with a high incidence of kidney function impairment.

2. People with PU revealed a high frequency of opportunistic diseases of viral etiology, which may be due to the involvement of the kidneys in the pathological process of cytomegalovirus infection and, accordingly, more frequent use of potentially nephrotoxic antiviral drugs.

3. It is found to be significantly more common in hypertension in the case of PU than in the absence of protein in the urine (p <0.001). In addition, hemoglobin and GFR levels in patients with persistent PU were lower in comparison with patients without this symptom, indicating a relationship between proteinuria and anemia and renal dysfunction.

4. There was a tendency to decrease the level of proteinuria with age (p> 0.05), which may be due to the lesser development of glomerular kidney damage in the older age group.

5. GFR in women is significantly lower than in men
(p> 0.05), which indicates a more significant renal dysfunction in women.

REFERENCES

1. Global Report. UNAIDS Global Report on the global AIDS epidemic 2015 New York: United Nations Program on HIV / AIDS, 2015. Access Mode: http://www.unaids.org/en/media/unaids/contentassets/docs/epidemiology2015gr2013 UNAIDS_Global_Report_2015_en. pdf .

2. HIV / AIDS Newsletters. http://ucdc.gov.ua/pages/diseases/hiv_aids/monitoring/information-bulletins

3. V.V. Pokrovskii HIV infection. T. N. Ermak, V.V. Belyaev, O.G. Yurin-M et al. Clinic, diagnostics and treatment.: GEOTAR-MED, 2003, p 488.

4. S. K. Gupta, J. A. Eustace, J. A. Winston et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: the recommendations of the HIV Medicine Association of the Infectious Diseases Society of America Clinical Infectious Diseases. 2005;80(11):1559-1585.

5. P. Campos, A. Ortiz, K. Soto HIV and Kidney Diseases: 35 Years of History and Consequences Clinical Kidney Journal. 2016;9(6):772-781doi: 10.1093 ckj sfw104

6. E. M. Shilov Nephrology Moscow.: GEOTAR Media, 2008, p 696.

7. Am. J. Kidney Dis. National Kidney Foundation (NKF). K / DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. NKF [online]. 2002;39:251-266.

8. Classification of arterial hypertension at the level of blood pressure (mm Hg) European Society of hypertension, European Society of Cardiologists, 2003. http://emergency.at.ua/news/classification_arterialnoji_gipertenziji/2009-12-05-31

 

The work is performed within the limits of the department’s scientific work “ Molecular-genetic and clinical-pathogenetic features of the combined the pathology of internal organs, the role of infectious, metabolic factors in its development, differentiated approaches to treatment”.

Authors’ contributions:

According to the order of the Authorship.

Conflict of interest:

The Authors declare no conflict of interest.

CORRESPONDING AUTHOR

Margarita O. Andrushchak

Hsei Bukovinian State Medical University,

2, Theatralna sq, 58002, Chernivtsi, Ukraine

tel: +380996019597

e-mail: margaritaassistent@gmail.com

Received: 11.03.2018

Accepted: 01.07.2018

Table I. Laboratory characteristics of HIV-positive people with CKD and presence of markers of chronic HVV- and / or HCV infection (n = 54)

Index

Median

Interquartile scale [25 %; 75 %]

АlАТ, оd/l

53,5

[39,4; 88,3]

АсАТ, od/l

45,0

[36,8; 70,6]

Total bilirubin, мcmole/l

27,0

[12,0; 49,0]

Alkaline phosphatase, mole/l

131,0

[94,6; 192,2]

GGTP, mole/l

72,5

[47,4; 139,7]

Total protein, g/l

75,0

[68,0; 80,5]

Table II. shows the frequency of opportunistic diseases of different etiologies in patients with and without proteinuria (comparison group).

Opportunistic

infections

Proteinuria

p

present (n=48)

absent (n=40)

Аbs.

M%±m%

Аbs.

M%±m%

Bacterial

5

10,4±4,4

6

15,0±5,6

>0,05

Viral

12

25,0±6,3

3

7,5±4,2

<0,05

Fungal

25

52,0±7,2

18

45,0±7,9

>0,05

Parasitic

5

10,4±4,4

6

15,0±5,6

>0,05

Tuberculosis

10

20,8±5,9

7

17,5±6,0

>0,05

As the table below shows, the opportunistic infections of viral etiology are significantly more common in patients with proteinuria (p <0,05) in the absence of significant differences in the frequency of other opportunistic diseases (p> 0,05). In both groups, the opportunistic infections of viral etiology were represented by cytomegalovirus infection and herpes zoster.

Table III. Clinical and laboratory characteristics of HIV-infected with proteinuria and in its absence

Index

Proteinuria

р

present (n=48)

absent (n=40)

Arterial hypertension,
n (M%±m%)

15 (31,3±6,7)

1 (2,5±2,5)

<0,001

АТ systolic, mm. m. c.

median [25 %; 75 %]

140 [110; 180]

115 [110; 130]

<0,05

АТ diastolic, mm. m. с.

median [25 %; 75 %]

95 [90; 105]

75 [70; 80]

<0,05

Cholesterol, мcmol/l

Median [25 %; 75 %]

4,0 [3,1; 5,0]

4,2 [3,3; 5,5]

>0,05

Hypercholesterolemia,
n (M%±m%)

9 (18,8±5,6)

8 (20,0±6,3)

>0,05

Hypercholesterolemia, g/l

median [25 %; 75 %]

110,0 [82,0; 130,0]

136,0 [112,0; 158,0]

<0,05

GKF, ml/m/1,73 m2

median [25 %; 75 %]

65,0 [35,0; 94,2]

104,0 [92,0; 122,0]

<0,05

Table IV. Sexual and age differences of HIV-infected patients with chronic kidney disease, median [25%; 75%]

Index

Patients with markers of kidney damage

Sexual difference

р

Age, years

р

male

(n=31)

female

(n=17)

19-24

(n=10)

25-44

(n=31)

45-55

(n=7)

Proteinuria, g/l

0,6

[0,4; 1,4]

1,1

[0,4; 2,8]

>0,05

1,1

[0,6; 2,6]

0,9

[0,4; 1,4]

0,5

[0,3; 0,9]

>0,05

GKF, ml/m/1,73 m2

84,0

[40,0; 100,0]

47,5

[26,0; 78,8]

<0,05

66,0

[40,3; 85,7]

72,0

[35,5; 106,0]

62,0

[28,3; 99,6]

>0,05

Note. p – the reliability of the difference between patients within the same indicator.