Chronic Kidney Disease and Nephrology Care in People Living with HIV in Central/Eastern Europe and Neighbouring Countries-Cross-Sectional Analysis from the ECEE Network.

Chronic kidney disease (CKD) is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). The Central and East Europe (CEE) region consists of countries with highly diversified HIV epidemics, health care systems and socioeconomic status. The aim of the present study was to describe variations in CKD burden and care between countries. The Euroguidelines in the CEE Network Group includes 19 countries and was initiated to improve the standard of care for HIV infection in the region. Information on kidney care in HIV-positive patients was collected through online surveys sent to all members of the Network Group. Almost all centres use regular screening for CKD in all HIV (+) patients. Basic diagnostic tests for kidney function are available in the majority of centres. The most commonly used method for eGFR calculation is the Cockcroft-Gault equation. Nephrology consultation is available in all centres. The median frequency of CKD was 5% and the main cause was comorbidity. Haemodialysis was the only modality of treatment for kidney failure available in all ECEE countries. Only 39% of centres declared that all treatment options are available for HIV+ patients. The most commonly indicated barrier in kidney care was patients' noncompliance. In the CEE region, people living with HIV have full access to screening for kidney disease but there are important limitations in treatment. The choice of dialysis modality and access to kidney transplantation are limited. The main burden of kidney disease is unrelated to HIV infection. Patient care can be significantly improved by addressing noncompliance.

How sex and gender matter in infectious diseases - outcomes of the first Polish conference "A woman in an infectious diseases circle".

Occurrence of infectious disease in a woman is an interdisciplinary area of medicine. The common problem of lower recruitment of women to clinical trials leads to the necessity to rely in clinical practice on the exchange of practical experiences, specialist consultations and individualization of treatment. As the COVID-19 pandemic shows, there is a close relationship between infectious diseases and civilization diseases. People suffering from chronic diseases are both more susceptible to infection and the more severe course of an infectious disease. On the other hand, infection may accelerate or initiate the onset of a noncommunicable disease. Women, especially those living with HIV, are a group with an underestimated risk of high blood pressure or some cancers. Therefore, one of the main goals of the conference is to break the stereotypes of thinking about health, in which gender is the main determinant of some screening tests. Late presentation of women to medical care is a significant problem that is of great importance in the diagnosis and treatment of both communicable and non-communicable diseases. Women put family and professional responsibilities in the first place, and they are known to downplay their own health problems. It leads to the diagnosis of cardiovascular diseases or cancer at the stage of advanced changes, limiting the possibilities of effective therapy. Understanding gender attributed differences in the etiology and epidemiology of diseases allows for the improvement of patient care, as well as determines the right direction of reforms in the area of healthcare. It is essential to build models of care based on an interdisciplinary and patient-centered approach, with broad support from both stakeholders and NGOs. Each contact of the patient with the health care system should be seen as an opportunity for screening both in the area of civilization diseases, women's health, and infectious diseases corresponding to her lifestyle.

Discontinuation of tenofovir due to nephrotoxicity: insight into 12 years of clinical practice

INTRODUCTION: Chronic kidney disease is a significant cause of morbidity and mortality among patients infected with human immunodeficiency virus (HIV). Tenofovir disoproxil fumarate (TDF) is widely used as the part of combination antiretroviral therapy (cART) and may cause renal function impairment. AIM: The primary objective of this analysis was to determine the rate of reversibility of kidney dysfunction and factors correlated with eGFR improvement in patients treated with TDF. MATERIALS AND METHODS: All patients who discontinued TDF between 2003 and 2015 were screened and included in the study if the reason for withdrawal was nephrotoxicity. Kidney function (eGFR, proteinuria, haematuria) was assessed on treatment and one year after discontinuation. Factors associated with not achieving eGFR recovery one year after discontinuing TDF were assessed. RESULTS: A total of 69 patients out of 1625 screened discontinued TDF due to nephrotoxicity and were included in the analysis. At the end of the study period eGFR (CKD-EPI) improved in 52 (75,4%) patients. The eGFR difference was 11,7 ml/min/1,73m2 (95% CI: 6,0 ­ 14,5). Two factors were associated with kidney function improvement: the length of TDF treatment and baseline eGFR. Better recovery was observed in patients treated with shorter (difference: 15,6 ml/min/1,73m2, 95% CI: 5,99 ­ 23,0) and in those with impaired renal function at baseline (difference: 21 ml/min/1,73m2, 95% CI: 11,0 ­ 27,99). CONCLUSIONS: In majority of patients who discontinue TDF therapy, kidney function improves during oneyear period. The drug withdrawal in case of eGFR deterioration should not be postponed.

Epidemiological characteristics and access to end-stage liver disease care for HIV-positive patients with HCV and/or HBV coinfections in Central/Eastern European and neighboring countries ­ data from the ECEE network

OBJECTIVES: There is currently an urgent need to harmonize hepatitis standards of care for HIV-positive patients across Europe. The HIV epidemic in Central and Eastern Europe has often been driven by injecting drug use, therefore a higher rate of co-infection with HCV and HBV is expected in this region. We have investigated the epidemiological prevalence and treatment availability for end-stage liver disease in HIV/HCV/HBV coinfections in countries represented in the ECEE Network Group. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care regarding HIV infection in the region. Information about HIV/HCV/HBV co-infections and the availability for end-stage liver disease treatment for HIV-positive patients were collected through on-line surveys. The respondents were ECEE members from 16 countries of the region. The information on co-infection prevalence was sourced from WHO, national HIV programmes, articles published in international journals, single clinic reports, and personal information in ten of the participating countries (62.5%). RESULTS: The HIV/HCV co-infection rate was from 3% to 99%. The range of reported of HIV/HBV coinfection percentages was 2.3% to 40%. HIV/HCV/HBV co-infection ranged from 0% to 9%. Regarding treatment for end-stage liver disease, liver transplantation was an available option for HIV-positive patients in only three countries (19%). CONCLUSION: Our findings revealed only a limited number of treatment options for the end-stage liver disease in HIV-positive patients for the vast majority of Central and Eastern European countries. There are gaps in epidemiological surveillance in this region. It appears there are many differences in the number of co-infected patients among Central and Eastern European and neighboring countries, but there is no unification of information sources.

Risk factors for kidney disease among HIV-1 positive persons in the methadone program.

BACKGROUND: Kidney injury is a serious comorbidity among HIV-infected patients. Intravenous drug use is listed as one of the risk factors for impaired renal function; however, this group is rarely assessed for specific renal-related risks. METHODS: Patients attending methadone program from 1994 to 2015 were included in the study. Data collected included demographic data, laboratory tests, antiretroviral treatment history, methadone dosing and drug abstinence. Patients' drug abstinence was checked monthly on personnel demand. We have evaluated two study outcomes: (1) having at least one or (2) three eGFR < 60 ml/min (MDRD formula). RESULTS: In total, 267 persons, with 2593 person-years of follow-up were included into analyses. At the time of analyses, 251 (94%) were on antiretroviral therapy (ARV). Fifty-two (19.5%) patients had 1eGFR and 20 (7.5%) 3eGFR < 60. In univariate analysis, factors significantly increasing the odds of impaired renal function were: female gender, detectable HIV RNA on ART, age at registration per 5 years older, atazanavir use and time on antiretroviral treatment per 1 year longer. In the multivariate model, only female gender (OR 4.7; p = 0.002), time on cART (OR 1.11; p = 0.01) and baseline eGFR (OR 0.71; p = 0.001) were statistically significant. CONCLUSIONS: We have demonstrated a high rate of kidney function impairment among HIV-1 positive patients in the methadone program. All risk factors for decreased eGFR in this subpopulation of patients were similar to those described for general HIV population with very high prevalence in women. These findings imply the need for more frequent kidney function monitoring in this subgroup of patients.

Non-AIDS defining bacterial infections in patients with HIV infection

OBJECTIVES: The use of effective combinated antiretroviral therapy has significantly improved the prognosis of patients with HIV infection. Although current antiretroviral regimens are very effective in inhibiting viral replication, its elimination is not a viable goal of treatment. Despite cART, non­AIDS-defining bacterial infections are still a serious problem. The spectrum of these infections, and in particular the proportion of particular bacterial pathogens, is not sufficiently described in the scientific literature. METHODS: In the study, HIV-infected patients followed at the HIV Out-Patient Clinic in Warsaw were registered in the clinic from 1 January 2007 to 31 July 2016. Survival analysis included 558 patients who met the study criteria. RESULTS: Among 251 (44.9%) of those with positive culture, the most common bacterial pathogen was Staphylococcus aureus (33%) and Escherichia coli (11.1%). The most common bacteria in the upper respiratory tract was Staphylococcus aureus (26.6%). In urine cultures the most common bacteria was Escherichia coli (9.5%). Staphylococcus aureus (2.3%) and Staphylococcus epidermidis (2.3%) were the most common bacterial cultures in the wound. In skin cultures the most common bacteria was Staphylococcus aureus (3.9%). The highest number of positive cultures was obtained from the upper respiratory tract -166 (66.1%). CONCLUSION: Non­AIDS-defining bacterial infections are a common clinical problem in HIV-infected patients despite the introduction of antiretroviral therapy and the pathogens that cause these infections are a very diverse group.

Factors associated with urinary tract infections among HIV-1 infected patients.

BACKGROUND: Urinary tract infections remain an important yet underinvestigated clinical problem among HIV infected patients. Here we analyze factors associated with its occurrence and the spectrum of bacterial pathogens identified in the group of patients followed at the HIV Out-Patient Clinic in Warsaw. METHODS: Clinic database collected all medical information on patients routinely followed since 1994 to 2015. All patients with available urine culture were included into analyses, only the first culture was included. In statistical analyses logistic regression models were used to identify factors associated with positive culture. RESULTS: In total 608 patients had urine culture performed, 176 (28.9%) were females and 432 (71,1%) were males, 378 (62.2%) registered in care before/in 2007, 258 (42.4%) infected through homosexual contact. Median baseline lymphocyte CD4+ count was 385 (IQR:204-565) cells/µl and median nadir lymphocyte CD4+ count 197 (86-306) cells/µl. One hundred and eighteen patients were actively infected with HCV, as defined by positive real-time PCR. In total 141 (23.2%) patients had positive urine culture, the most common bacterial pathogen was E.coli (58.2%) and E. faecalis (12.8%). Patients with urinary tract infection were more likely to be female (51.8% vs. 22.1%, p<0.0001), infected through other than homosexual mode (80.1% vs. 50.7%, p<0.0001), with lower nadir CD4 count (139 vs. 221 cells/µl, p<0.0001) and lower baseline HIV RNA (4.02 vs. 4.35 log copies/ml, p = 0.01) and less likely to be HCV RNA positive (26.9% vs. 49.2%, p = 0.01). In multivariate regression model being registered before/in 2007 (OR = 2.10; [95%CI: 1.24-3.56]), infected through other than homosexual mode (2.05;[1.18-3.56]) and female gender (2.14;[1.33-3.44]) were increasing and higher nadir CD4+ count decreasing (0.92;[0.85-0.99]) the odds of urinary tract infection. CONCLUSIONS: We have identified that almost one third of patients had urinary tract infections with non-typical bacterial pathogens. Population with increased odds of urinary tract infections are women, patients infected through other than homosexual contacts and those registered before 2007.

Nephrology consultations incorporated into HIV care - non-compliance is an important issue.

Although infrequent, kidney disease is a potentially serious co-morbidity among human immunodeficiency virus (HIV)-infected patients. The spectrum of renal impairment is very wide from clinically insignificant to end stage renal disease and often requires nephrologist's consultation. Therefore, we established combined renal and HIV care in the HIV Out-Patient Clinic in Warsaw. Medical records of patients consulted by nephrologist from March 2014 to March 2015 were included in analyses. Patients changing medication without consulting the physician or persistently not coming for follow-up visits were defined as non-compliant. In statistical analyses, non-parametric tests and logistic regression models were used as appropriate. In total, 100 patients were consulted by a nephrologist during the study period. All patients were white Europeans, 88 (88%) male, 42 (42%) infected through men having sex with men and 16 (16%) through intravenous drug users. Fifteen (15%) patients had hepatitis C virus (HCV) infections and 11 (11%) confirmed with positive HCV RNA. The most common reasons for referral were proteinuria and increased serum creatinine. In 6 out of 31 patients (19.3% of those referred for increased creatinine level) elevated serum creatinine was due to illegal substances or diet supplements use. Fifty-seven (57%) of patients were non-compliant. In univariate logistic regression models, all tested factors were non-significant. In most cases, patients were referred to nephrologist due to possible link between laboratory abnormalities and antiretroviral treatment. In one out of five cases, elevated creatinine level was linked with substance/dietary abuse. Poor compliance is an important problem in integrated nephrological care, however we were not able to identify any factors associated with non-compliance.

Cysteine scanning reveals minor local rearrangements of the horizontal helix of respiratory complex I.

The NADH:ubiquinone oxidoreductase, respiratory complex I, couples electron transfer from NADH to ubiquinone with the translocation of protons across the membrane. The complex consists of a peripheral arm catalyzing the redox reaction and a membrane arm catalyzing proton translocation. The membrane arm is almost completely aligned by a 110 Å unique horizontal helix that is discussed to transmit conformational changes induced by the redox reaction in a piston-like movement to the membrane arm driving proton translocation. Here, we analyzed such a proposed movement by cysteine-scanning of the helix of the Escherichia coli complex I. The accessibility of engineered cysteine residues and the flexibility of individual positions were determined by labeling the preparations with a fluorescent marker and a spin-probe, respectively, in the oxidized and reduced states. The differences in fluorescence labeling and the rotational flexibility of the spin probe between both redox states indicate only slight conformational changes at distinct positions of the helix but not a large movement.

[Polyoma virus BK nephropathy in kidney allograft recipients]. / Sródmiazszowe zapalenie nerki przeszczepionej wywolane wirusem Polyoma BK.

Polyomavirus BK (BKV) infection is a fast growing problem in modern transplantation medicine. Interstitial nephritis is the most important pathology caused by the virus leading to graft failure and the need for dialysis treatment. Ethiopathogenesis of the disease is multifactorial with immunosuppressive treatment playing main role. Many cases of BKV infection have been misdiagnosed and mistreated as steroid-resistant acute rejection. In such cases the infection was spreading what inevitably led to graft failure. Now it is known that the only way to control the disease is close monitoring and decreasing the net state of immunosuppression.

[Human herpes virus 6 infection in renal transplant recipient--case report]. / Zakazenie ludzkim wirusem herpes typu 6 u biorcy alloprzeszczepu nerki--opis przypadku.

Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus of emerging clinical significance in immunocompromised patients. Little is known about clinical impact and relevance of HHV-6 variant A infection in renal transplant recipients. We describe the case of a 44-year-old woman who underwent second allogenic kidney transplantation (Tx). On day 6 after Tx she presented with high fever. She developed thrombocytopenia, anemia, diarrhea, liver dysfunction and graft failure. Renal graft biopsies that followed revealed acute rejection. Apart from the introduction of anti-rejection therapy, empiric gancyclovir, as well as antibacterial treatment was initiated. To determine the serostatus of HHV-6 and load of HHV-6A and -6B DNA in paired sera samples an enzyme-linked immunosorbent assay, indirect immunofluorescence assay and real time quantitative polymerase chain reaction (PCR) assay based on the exonuclease format (TaqMan) was devised. HHV-6A was the sole pathogen, the DNA of which was retrospectively detected in patient's serum. HHV-6 IgM seroconversion was demonstrated. No other viral (e.g. cytomegalovirus (CMV)) or other pathogens were detected in the blood, urine, and stool. Following therapy with gancyclovir, viral load declined to undetectable levels. Gradual improvement in clinical status of the patient was observed. HHV-6 infection may be associated with specific clinical manifestations and should be considered in a transplant recipient who presents with a clinical syndrome resembling CMV infection, where CMV assays are negative. This case confirm symptomatic HHV-6 infection and suggests that HHV-6 variant A reactivation may potentially trigger graft rejection.

[Cytokines and growth factors serum level and renal allograft function (preliminary report)]. / Cytokiny i czynniki wzrostu w surowicy u biorców nerki allogenicznej a losy przeszczepu (doniesienie wstepne).

Long-term cyclosporine nephrotoxicity, subclinical rejections are risk factors of chronic allograft nephropathy. In a prospective, randomized study 44 pts. were randomized either to a reduced dose of CyA and daclizumab (group A, n = 22) or to a normal dose of CyA without daclizumab (group B, n = 22). Both groups were treated with MMF and prednisone. Number of rejection episodes was the primary endpoint. The secondary endpoints were renal function; histological parameters related to CyA; serum level of TGF-beta, PDGF-BB, blockade of CD25 molecule and surface expression of CD3, CD4, CD8, CD69, CD11a, CD49d, CD28, CD152 molecules in the subpopulations of T cells in the peripheral blood. A low incidence of clinically suspected rejection episodes were observed (19% in group A and 12.4% in group B; NS). The protocol biopsies at 3 month emerged 7 subclinical rejection episodes (4 in group A and 3 in group B). Serum creatinine level did not differ between examined groups. Chronic histopathologic changes related to CyA progressed significantly at the 3 month biopsies in both groups (with no differences between groups). Serum TGF-beta, PDGF did not differ between groups. Expression of CD25, CD152 molecule was significantly lower in group A than in group B. Immunosuppression regiment with low CyA dose with daclizumab, MMF, prednisone seems to be efficient and safe in low-risk rejection kidney allograft recipients.

[The usefulness of tubular and glomerular proteinuria measurement in non-invasive diagnosis of vascular changes accompanying chronic allograft nephropathy]. / Ocena przydatnosci oznaczania bialek wydalanych z moczem w rozpoznawaniu stopnia zaawansowania zmian naczyniowych towarzyszacych przewleklej nefropatii alloprzeszczepu nerkowego.

Chronic allograft nephropathy (CAN) is the most important cause of late renal allograft loss. The standard diagnosis of CAN is based on pathological examinations according to Banff'97 scheme. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria in non-invasive recognition of vascular changes accompanying CAN (AH--arteriolar hyaline thickening, CV--vascular fibrous intimal thickening). beta 2- and alpha 2-microglobulin (beta 2-m and alpha 2-m), albumin (alb), immunoglobulin G (IgG), total protein (tp) and creatinine (cr) concentration were measured in the second time urine specimen in 66 renal allograft recipients. Then the subsequent renal biopsies were done. The aim of statistical analysis (MANOVA, Stepwise Discriminant Analysis, SDA) was to diagnose CV and AH changes based on results of urine analysis listed above and the patient's age, time after transplantation and serum creatinine level (scr). Results obtained with statistical analysis were in 90.91% and 87.69% identical with CV and AH pathological diagnoses, respectively.