Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD)Joint Steering Committee has declared 2021 the year of “Living Well with Kidney Disease” in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labelling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness program for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programs, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policymakers, applicable to both developed and developing countries

Gadolinium-chelated compounds have been widely used in clinical practice as contrast agents to improve magnetic resonance imaging quality. Gadolinium-based contrast agents (GBCA) had long been associated with the favorable safety profile being used as an alternative to an iodinated contrast agent in patients with renal dysfunction. Follow-up observations showed that the use of these agents in patients with severe renal excretory dysfunction, especially those receiving dialysis treatment, could result in the development of nephrogenic systemic fibrosis (NSF), which is known to be a fatal fibrosing disease affecting the skin and internal organs. Injunction on the use of GBCA for the risk group patients introduced by supervisory authorities allowed for decreasing the number of new NSF cases; at the same time, they had to refuse to carry out diagnostic magnetic resonance tomography in some patients, which could adversely affect diagnostic accuracy. The findings of the studies performed in the past decade show that the probability of NSF development depends not only on the kidney excretory function state but also on the chemical structure and characteristics of GBCA, which allows divide them into high and low-risk groups. At present, it is a well-known fact that most NSF cases reported previously were associated with the use of old linear GBCA (gadopentetate dimeglumine, gadodiamide and gadoversetamide). At the same time, more stable macrocyclic GBCA (gadobutrol, gadoteric acid, gadoteridol) could be safely used in individuals with acute renal injury, advanced chronic kidney disease and on dialysis. The strategy of NSF prophylaxis also changed. It is assumed that in the cases when only low-risk GBCA are used, kidney function screening using questionnaires or glomerular filtration rate test may be optional. Despite the changes in the safety concept concerning GBCA, there are still cases of unwarranted refusals to undergo contrast-enhanced magnetic resonance imaging in patients with severe kidney excretory function impairment. The goal of the present review is to raise awareness among nephrologists, radiologists and other medical specialists concerning the main aspects of using GBCA in patients at risk of developing NSF. The paper summarizes the main recommendations of the leading relevant international societies, as well as the results of the most representative studies and systematic reviews.

More than 850 million people worldwide suffer from various kidney diseases that are potentially irreversible and lead to end-stage kidney failure and disability. As before, the main method of treatment is to replace the lost kidney function with specialized methods of treatment: hemodialysis, peritoneal dialysis, hemodiafiltration and kidney transplantation. The number of available donor kidney transplants remains low. So dialysis remains the main method of treating kidney failure. About 80% of patients with the end-stage renal failure are treated with chronic programmed hemodialysis. The review briefly presents the history of the development of methods of extrarenal (extracorporeal) purification of the body's blood, the evolution of technical equipment and methodologies, and the change in ideas about existing methods as the evidence base accumulates. The article discusses the indications and contraindications of various methods of treatment of kidney failure. A comparative analysis is given and the path of development of various dialysis techniques is traced (low-flow intermittent hemodialysis, high-flow intermittent hemodialysis, extended/long-term intermittent hemodialysis, intermittent/extended hemodiafiltration). Currently, the most effective method of dialysis is hemodiafiltration as a result of a combination of diffusive and convective transport of solutes through the hemofilter membrane. The review considers the advantages of the hemodiafiltration method for hemodialysis (better elimination of uremic toxins, the effect on the blood lipid spectrum, better control of anemia, reduced doses of rEPO, better biocompatibility and hemodynamic stability, reduction of inflammation and oxidative stress products), a review of previously existing and recently conducted large randomized studies. Hemodiafiltration is considered to be the most effective method of dialysis associated with better patient survival. Modern criteria (international standards) for online hemodiafiltration (HDF OL) are evaluated. The article discusses the factors limiting the use of HDF OL in clinical practice. The latest data on the development and results of the first clinical studies of the use of extended dialysis using membranes with a "mid-cut-off point" is presented. The possibility of using extended dialysis as an alternative to HDF OL is discussed.

Patients receiving hemodialysis (HD) treatment are one of the most promising groups for implementing the WHO HCV Infection Elimination Program. Until recently an obstacle to its elimination was the lack of antiviral drugs for the treatment of chronic hepatitis C in HCV genotypes 2 and 3 patients with low glomerular filtration rate. New opportunities have emerged with the introduction into clinical practice of direct antiviral drugs combination - glecaprevir and pibrentasvir (GLE/PIB). Eighteen dialysis patients with HCV (average age 49.4±12.4 years, HD duration 100.9±70.1 months) were treated with GLE/PIB. Thirteen (72.2%) of them had genotype 3 HCV, 4 (22.2%) had genotype 2, (one with the recombinant 2k/1b subtype) and 1 (5.6%) had genotype 1b. A sustained virological response was achieved at 12 and 24 weeks in all patients with a limited number of adverse events. In 17 of 18 patients after completion of antiviral therapy, there was a positive dynamics of transient liver elastography indicators, expressed to a greater extent in patients with initially increased activity of alanine aminotransferase. Thus, the use of the GLE/PIB pangenotype combination proved to be highly effective and safe in hemodialysis patients with HCV 2 or 3 genotypes, including the 2K/1b chimeric variant. Further analysis on a larger sample of patients with a longer follow-up period is required to clarify the possibility and degree of reduction of fibrosis severity after decreased inflammation activity in the liver.

Relevance: congenital and infantile nephrotic syndrome (CNS and INS respectively) are special groups of steroid-resistant nephrotic syndrome, in which progression to the end-stage kidney disease is unavoidable and therapy selection is rather difficult. Studies of the genetic causes of the CNS and INS existing in Russia had been performed on extremely small groups. Purpose: the study of genetic causes in CNS and INS in Russian children. Methods: an ambidirectional study based on the nephrology department of FSAI “National medical research center for children’s health” included 43 children with CNS and INS. All children underwent genetic testing of 57 genes target regions by the new generation sequencing. Pathogenic variants in these gene regions were found to be associated with nephrotic syndrome. Results: among the morphological variants, focal-segmental glomerulosclerosis prevailed (50%) regardless of the pathogenic variant. In 38 children, mutations were identified in the genes NPHS2 (37.2%), NPHS1 (13.9%), WT1 (9.3%), CUBN (7.0%), PLCE1 and LMX1B (4.7% each), SMARCAL1, CRB2, KANK2, COQ6, CFH (2.3% each). During therapy with cyclosporine A, 18.5% of 27 children showed a partial or complete unstable remission. Over the period of observation 15 children (34.9%) reached end-stage kidney disease, the average age was 4 years 11 month ± 3 years 3 month. Kidney transplantation was performed in 11 patients; the one-year graft survival rate was 82%. Conclusions: conducting a molecular genetic study in children with the onset of nephrotic syndrome in the first year of life is more informative to the choice of treatment tactics and evaluating of prognosis than the invasive method - nephrobiopsy. Kidney transplantation in these groups is rather perspective in cause of the low risk of recurrence.

Aid: hyperphosphatemia in hemodialysis patients remains one of the difficult challenges in correcting uremic syndromes associated with overall and cardiovascular mortality, adverse cardiovascular remodeling and calcification, although lowering of phosphatemia was never been shown to be associated with better outcomes. The stringent clinical trial conditions do not always correspond to real practice, where many factors can have opposite influence; their results should be applied with considering the specific circumstances, an analysis of real clinical practice is necessary. Methods: the treatment group included 240 patients who started sevelamer therapy. The control group was matched for baseline phosphatemia, age, duration of RRT. Results: for 17±3 months, 29 patients died in the treatment group (12%) compared to 46 patients (19%) in the control group, the hazard ratio was 0.616 (95%CI 0.389÷0.981). The decrease in phosphate levels was 0.19±0.09 vs. its increase by 0.03±0.07 mmol/l in the control group; effect size -2.73 (95%CI -2.74÷-2.73SD). The decrease in calcemia was 0.03±0.06 vs. growth 0.04±0.08 mmol/L in control (effect size -0.99 (95%CI -1.18÷-0.80SD). A decrease in PTH level by 46±84 vs. its increase by 188±114 pg/ml; effect size -2.33 (95%CI -2.56÷-2.10). In the multiple regression model for the whole group, the significance of entering the treatment group slightly changed compared to unadjusted (-43% risk). Each 0.1 mmol/L of higher calcemia added 20% risk, phosphatemia - 17%. Compared with the similar risks for ranges of 300-600 and >600 pg/ml (median 782) for ranges 150-300 and <150 pg/ml, the risks of death were 2 and 6.5 times higher. In separate analysis, the initially higher level of phosphate (for every 0.1 mmol/L) was associated with a higher (by 28%) the risk of death (similar in the treatment and control). To an even greater degree, the decrease in phosphate during therapy was associated with the risk: a decrease in phosphate by every 0.1 mmol/L in multiple regression was correlated with a 56% lower risk. For every 100 pg/ml above baseline PTH, therapy resulted in lesser decrease in phosphate levels by 0.01 mmol/L (p<0.001); for each decrease in PTH level by 100 pg/ml during therapy, a greater decrease in phosphate level by 0.08 mmol/L was obtained (p<0.001); for every 0.1 mmol/L higher baseline phosphate level, therapy produced a 0.02 mmol/L larger decrease. Conclusion: Sevelamer use was associated with reduction of mortality risk. The greater the severity of hyperparathyroidism and its resistance prevented effective reduction of phosphatemia during therapy with sevelamer, the better effect was observed at higher baseline phosphate levels.

The aim of the study was to estimate the prognostic role of the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in hemodialysis patients with different substitution volumes during on-line hemodiafiltration (HDF). Materials and methods: During the 16 months of the prospective study, 68 patients on maintenance haemodialysis (HD) by the on-line HDF method were under observation. The NT-proBNP serum level was measured for all patients at the time of enrolment. Patients were divided into three groups depending on the substitution volume: <69 l/week; 69-83 l/week and >83 l/week (the mean values of the substitution volume for 16 months were used in statistical analysis for each patient). Results: New cardiovascular events (CVEs) were identified in 25.6% of patients, 47.4% of them were fatal. New CVEs developed more often in patients with CVEs before the start of observation (p<0.05). There was no significant difference in the serum NT-proBNP level and the substitution volume in patients with CVEs and those without them before the start of observation (p>0.05). In patients receiving on-line HDF, there was a lower frequency of CVEs as the quartile of the actual substitution volume increases (p<0.05). In the group with an actual substitution volume of more than 83 l/week, the NT-proBNP level was significantly lower than in the 69-83 l/week group (p<0.05), possibly leading to a more favourable prognosis. The frequency of CVEs in patients who did not reach the substitution volume corrected for body surface area (BSA) is higher than that in those who reach the required substitution volume (p>0.05). Conclusion: The risk of developing new CVEs on maintenance HD is higher in patients with a history of CVEs. The substitution volume of more than 83 l/week may reduce the frequency of CVEs in patients receiving maintenance HD using on-line HDF. There were no differences in NT-proBNP levels in patients with different substitution volume after correction for BSA. The need for accounting the individual BSA when calculating the target volume of substitution with on-line HDF remains unclear.

Comorbidity including chronic kidney disease (CKD) and anemia worsens the prognosis in patients with chronic heart failure (CHF). In patients chronic cardiorenal syndrome (CRS), hypoxia caused by CHF affects the formation of endogenous erythropoietin (eEPO). However, the predictive value of eEPO in patients with CHF, depending on CKD, have not been insufficiently studied. The aim of this study was to investigate the prognostic value of eEPO in patients with CHF. Materials and methods. 80 patients with CHF (48 women, mean age 70.1±9.7 years) were examined. CHF was carried out according to the recommendations for the diagnosis and treatment of CHF of the Russian Society of Heart Failure Specialists (OSSN) and the Russian Society of Cardiology (RKO, Clinical Guidelines. Chronic heart failure (CHF), 2016). CKD was diagnosed and classified according to the KDIGO guidelines (2012). Serum levels of eEPO, hypoxia-inducible factor-1 (HIF-1), N-terminal propeptide of type B natriuretic hormone (NT-proBNP) were assessed. The follow-up period was 12 months, the primary endpoint was death. Results. CKD was diagnosed in 49 (61.3%) patients with CHF. The eEPO level was significantly higher in the group of deceased patients with CHF than in the survivors - 16.92 (ICR 5.43; 64.57) and 5.76 (IQR 1.71; 8.85) mIU/ml, р=0.0004, as well as the level of NT-proBNP - 1126.3 (IQR 551.8; 2750.0) and 162.1 (IQR 135.0; 930.7) pg/ml, р<0.0001 and HIF-1 - 0.08 (IQR 0.06; 0.11) and 0.05 (IQR 0.04; 0.07) ng/ml, р=0.01. Multivariate regression analysis showed an independent relationship between the eEPO level and patient survival (R=0.37, ß=0.32, р=0.007). Conclusions. The level of eEPO in patients with chronic heart failure has an independent and closer relationship with the mortality of patients than the traditional marker of the severity and prognosis of CHF - NT-proBNP.

Purpose of the study was to assess the immunological parameters in patients with pneumonia and CKD in the background and to determine their significance in the development of acute kidney injury. Materials and methods: 120 patients with acute pneumonia were examined: 40 patients with pneumonia (group Pn) and 80 patients with pneumonia developed on the background of chronic kidney disease (group Pn+CKD); 20 healthy individuals were examined as a control group (CG). The number of leukocytes was increased in the group of Pn+CKD by 162.24% compared to the CG (p<0.001) although was 27.79% lower than in the group of Pn (p<0.001). In patients with Pn, the ratio of the number of neutrophils to lymphocytes increased significantly, and in the group of Pn+CKD, it remained unchanged, despite an increase in the absolute number of leukocytes. In patients with pneumonia with CKD in the background, the most pronounced increase in the proportion of T-lymphocytes was observed due to a subpopulation of CD8 and CD95 cells (p<0.001 compared with CG and the Pn group) and the prevalence of an increase in IgG (p<0.001). Among 120 patients with pneumonia included in the study, 97 patients (80.83%) were diagnosed with acute kidney injury (AKI): in 75 patients - the 1st stage, in 15 patients the 2nd stage and in 7 patients the 3rd one. In the group of patients with pneumonia without background renal pathology, AKI was diagnosed in 23 patients (57.5%), in the group of Pn+CKD - in 68 patients (85%, chi-square=10.80, p<0.01). Immune predictors of AKI development depending on the development of AKI and its severity were determined by a retrospective analysis of the studied parameters. Conclusion: pneumonia associated with CKD is associated with the depletion of the cellular component of nonspecific immunity, activation of acquired immunity due to chronic inflammation and chronic antigenic stimulation. In patients with pneumonia, background chronic kidney disease, high levels of reactive and antibody-producing lymphocytes, monocytes, immature granulocytes and IgG CICs and decreased levels of neutrophils and IgM CICs were predictors of AKI.

Physicians do not often correctly interpret the informativeness measures of biomarkers provided in scientific papers. The most common estimates are sensitivity (Se) the probability that the biomarker is positive in a case of disease, specificity (Sp) the probability that the marker is negative for patients who do not have a disease, the positive predictive value of a test result (PPV) the probability of a disease in a marker-positive patient, a negative predictive value (NPV) the probability that a marker-negative patient does not have a disease. Does the very high Se, Sp, PPV or NPV, as well as the revealed a statistically significant association between marker and outcome, mean that the marker is effective? Not always so. The statistical significance of the marker-outcome association is only a necessary condition, but not a sufficient one. The practical use of the marker depends on its frequency of occurrence (PM) and the prevalence of the disease (PD) in the population under study. The fact that some conventional indices of informativeness can be high even in the absence of a real association between marker and outcome (defined in such a case only by PM and PD) can be misleading. This leads us to an important conclusion: conventional indices of biomarker informativeness (Se, Sp, PPV and NPV) must be supplemented by statistics that measure the strength of the relationship between marker and outcome (odds ratio or risk ratio), as well as integral measures of marker informativeness (screening or predictive balance accuracy - SBA or PBA). The quantity of empirically evaluated diagnostic performance measures is directly determined by the study design: the case-control study enables to measure directly Se, Sp, SBA, and OR, the cohort study allows to evaluate PPV, NPV, PBA, OR, and RR. The population-based study provides investigators with any performance indices of diagnostic tests. It also should be kept in mind that Se, Sp and SBA (AUC) characterize only the screening informativeness of the marker. PPV, NPV and PBA characterize only the predictive informativeness of the marker. OR and RR quantify the strength of the association between marker and outcome.

Kaposi's sarcoma is a limphoangioproliferous tumor described for the first time in 1872 year by Moritz Kaposi. It is a relatively common malignancy after kidney transplantation, generally presents as characteristic dermatomucosal lesions. The frequency of Kaposi’s sarcoma in renal recipients appears to be significantly different in various geographical areas and is about 0.5% (from 0.06% to 4.1%). Visceral organ involvement is common in conjunction with skin lesions; however, isolated visceral Kaposi’s sarcoma is an uncommon disease among renal graft recipients. This report introduces a case of Kaposi’s sarcoma with lungs, lymph nodes, and small intestine involvements. A 53-years-old female renal graft recipient was admitted to our hospital with fever, cough, dyspnea, and diarrhea. The examination revealed pleural effusion and bilateral diffuse lesions in the lungs, intrathoracic and axillary lymphadenopathy, splenomegaly, pancytopenia. There were no specific skin manifestations for Kaposi’s sarcoma, so it was difficult to diagnose. However, the patient had a recurrent widespread maculopapular rash. These symptoms are clinical signs of HHV8-related viremic syndromes. Kaposi’s sarcoma was documented by histopathological evaluation of samples obtained from an axillary lymph node biopsy. Postmortem evaluation also indicated lung and small intestine involvements with Kaposi’s sarcoma. This case illustrates the complexity of diagnosing an isolated visceral form of Kaposi’s sarcoma and the need to exclude it in kidney graft recipients in the absence of dermatomucosal lesions.

Prevalence of human immunodeficiency virus (HIV) infection remains high globally. Even though the number of new cases decreased over the last decade up to 23%, in 2019, 1.7 million acquired HIV-infection, and the overall number of persons, living with HIV, reached 38 million. As by June 2020, 26 million accessed antiretroviral therapy (ART), however despite decrease of mortality rate, observed since 2014, nearly 700 000 patients died from HIV-associated conditions in 2019 [1]. Prevalence of chronic kidney disease (CKD) in HIV-infected population in 2018 varied from about 1% in the Middle East region to 7.0-7.4% in Africa and North America, and in Europe estimated as 2.5% [2]. First description of collapsing glomerulopathy, also known as HIV-associated nephropathy (HIVAN) comes back to 1984 [3]; later on, other variants of kidney damage, associated with HIV-infection had been described, and during the last almost 25 years, several groups attempted to classify the pathological varieties of kidney diseases in HIV-infected individuals. Finally, the conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference published in the Kidney International in 2018 [4]. Proposed classification includes various immune complex diseases, classic collapsing focal segmental glomerulosclerosis/HIVAN and other podocytopathies, tubulointerstitial damage, including mictocystic changes, kidney damage, resulting from opportunistic infections, complications of ART, and even diabetic nephropathy and age-related nephrosclerosis. Given such diverse patterns, found in the setting of HIV, kidney biopsy remains the gold standard for the diagnostics of kidney disease in HIV-infected persons [5]. ART implementation associated with the lower incidence of classic HIVAN and decrease of CKD 5 progression risk, however the incidence of other variants, such as immune complex damage, tend to increase [6, 7]. For HIV-positive patients on ART, survival on dialysis is comparable to HIV-negative patients, and kidney transplantation in HIV-positive recipients on ART is associated with high recipient and allograft survival rates [4]. To conclude - kidney disease in HIV-infected persons is a broad topic, including epidemiology, clinical presentation, kidney pathology, and disease pathomorphism on ART, ART complications, outcomes and kidney replacement therapy for HIV-positive patients and many other problems. Unfortunately, these issues rarely covered in the “Nephrology and Dialysis” journal. In order to bridge the gap we prepared a special supplement, fully devoted to the different aspects of kidney disease, associated with HIV. The editorial board and the authors hope that readers, both practitioners and researches, will make use of these publications. Dr Elena V. Zakharova, Nephrology and Dialysis journal deputy-editor

The HIV-infection is a pandemic. Antiretroviral therapy (ART) markedly reduced mortality from acquired immunodeficiency syndrome and opportunistic infectious diseases. This led to an increase in the life expectancy of people infected with HIV. Nevertheless, the incidence of chronic kidney disease (CKD) that complicates HIV-infection increased. CKD is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and mortality. The etiology of kidney disease amongst PLWHIV includes HIV-related diseases, such as classic HIV-associated nephropathy or immune complex disease, CKD related to non-infectious comorbidities (NICMs), and antiretroviral toxicity. While it has long been recognised that HIV-infection is a risk factor for CKD, it is important to note that the pattern of kidney disease affecting PLWHIV has changed. Rather than the previously seen HIV-associated renal conditions, or acute kidney injury related to illnesses such as opportunistic infections, CKD now is often related to NICMs. Risk factors associated with CKD in HIV-infected populations include aging, hypertension, diabetes mellitus, and co-infection with hepatitis C virus, a low CD4 cell count, and a high HIV viral load. The cumulative toxic effect of antiretroviral drugs, which can lead to damage to several organs, including the kidneys, can result in a significant decrease in the quality of life of HIV-infected patients. CKD is also associated with increased hospital admissions, especially in elderly patients and patients with comorbid cardiovascular disease. CKD, once established, is often relentlessly progressive and can lead to end-stage renal failure, which is 2-20 times more likely to develop than the general population. Identifying patients with risk factors for CKD, and appropriate screening for the early detection of CKD are vital to improve patient outcomes. HIV-infection and CKD are two epidemic diseases with important social, clinical, and economic implications. The interplay between these two diseases represents an intersection between communicable and non-communicable diseases. This literature review is intended to assess the current problem of CKD in individuals living with the viral infection.

Introduction: frequency of development and risk factors for the formation of kidney pathology in HIV-infected patients need to be clarified. Aim of the study: the purpose of the study was to determine the occurrence of transient signs of kidney pathology, as well as the occurrence and risk factors of chronic kidney disease (CKD) in HIV-infected residents of St. Petersburg when they admitted the Center for AIDS and Other Infectious Diseases. Methods: the study included 840 patients with HIV-infection examined upon registration and after 3-4 months. Results: during the initial screening of patients, glomerular filtration rate (GFR) ≤90 ml/min/1.73 m2 (CKD-EPI 2009) ± the proteinuria more than 1.0 g/l was found in 155 (18.5%) patients. Significant kidney damage in the form of a decrease in GFR to <60 ml/min/1.73 m2 and/or proteinuria in a single urine test of more than 1.0 gram was detected in 44 patients (5.2%). The transitive nature of kidney pathology was recorded in only 17 people out of 155: after 3-4 months, the level of GFR in them was >90 ml/min/1.73 m2 (CKD-EPI 2009). The chronic kidney disease was diagnosed in 162 out of 840 (19.3%) examined patients based on the analysis of anamnestic data, GFR dynamics, urinalysis parameters, and ultrasound examination results. Chronic kidney disease of stages C3-5 was detected in 20 people (2.4%). Logistic regression modeling with reverse conditional inclusion of parameters in the group of patients included in the study (n=840) revealed a significant and independent relationship between the development of CKD stages C3-5 and more advanced stages of HIV-infection, patients’ age, cirrhotic transformation of the liver, when correcting the model for sex, history of drug use, the presence of HCVAb, the level of CD4+ T-lymphocytes <200 cells/μl when registering, and detection of opportunistic infections. Conclusions: basic screening examination (GRF, urine test) reveals high (18.5%) kidney involvement. As many as 19.3% of HIV-infected people suffer from CKD, 2.4% of them had CKD С3-5. The presence of CKD С3-5 associated with more advanced stages of HIV-infection, the patient’, age and the presence of liver cirrhosis.

In the era of combined antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection has become a manageable chronic disorder, rather than an acute condition that can rapidly progress to acquired immune deficiency syndrome (AIDS). Concurrent with the widespread use of cART, the prevalence of kidney disease in people infected with HIV-1 has been increasing and is expected to rise further as a result of population aging and improved patients’ survival. Despite such advances in the control of HIV-infection, kidney disease is among the causes of morbidity and mortality in human immunodeficiency virus (HIV)-1 positive individuals. A spectrum of renal diseases currently described in HIV-positive patients includes HIV-associated nephropathy (HIVAN), immunocomplex glomerular diseases in the setting of HIV (HIV-ICGD), thrombotic microangiopathy and a variety of diseases associated with abnormal immune systems and superinfections. HIV-associated nephropathy (HIV-AN) is one of the most important causes of end-stage renal disease (ESRD) in this population. Factors such as African American ancestry, APOL1 polymorphisms, comorbidities, high viral load, low CD4 count, advanced kidney disease, and nephrotic range proteinuria have been associated as risk factors for the development of HIVAN and its progression to ESRD. HIV-AN is hystopathologically characterized by collapsing focal segmental glomerulosclerosis with hypertrophy and proliferation of podocytes, tubuloreticular inclusions in endothelial cells, tubular microcysts, and tubulointerstitial infiltrate, consisting mainly of CD8+ T lymphocytes. The immunocomplex glomerular diseases described in patients in the setting of HIV-infections is a group of glomerulonephritis that includes IgA nephropathy, lupuslike nephritis with negative autoimmune serologies, and the absence of other clinical signs of lupus, membranous nephropathy, and membranoproliferative glomerulonephritis. In this review, we describe current trends in the development of HIVAN, and HIV-ICGD, pathophysiology, classification and clinical picture of diseases. An extensive review of the literature of kidney diseases developing in the context of HIV-infection has been conducted.

Thrombotic microangiopathy (TMA) is a syndrome representing a broad range of diseases and conditions, and characterized by microvasculature occlusion, thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ damage. Currently, classification distinguishes two primary forms of TMA - thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). Various secondary TMA forms are associated with pregnancy, organ transplantation, infections, autoimmune diseases, malignancies, drug exposure, and other conditions. The key feature of TTP pathogenesis is decreased activity of ADAMTS-13 metalloprotease, the classical clinical presentation is a tirade of microangiopathic hemolytic anemia, severe thrombocytopenia, and central nervous system damage. TTP may be innate or immune-mediated; the latter may be idiopathic or associated with underlying conditions, again like autoimmune diseases, drugs, pregnancy, malignancies, and infections. TMA associated with HIV-infection was described in 1984, and since that time, many cases and case series had been reported. Even though TMA is a relatively rare complication of HIV-infection, nowadays association between these conditions is well established. Endothelial damage, which is now considered a primary cause of platelet activation and microvasculature thrombosis, in HIV-infection may be a consequence of the direct viral invasion, or indirectly associated with cytokines and HIV-related proteins. HIV poses a risk of TTP 15-40 times higher compared to the non-infected persons, and the incidence of HIV-associated HUS is even higher. However, regardless of its form, TMA in HIV-infected patients known to be associated with 6-fold increased mortality. Although the majority of patients with HIV-associated TMA present with late stages of severe HIV-infection, in 28% of cases TMA turns to be the first presentation of the disease. We present here a case of immune-mediated TTP, associated with HIV-infection. In this particular case diagnosis of TTP was established on a clinical basis, however, its confirmation by almost zero ADAMTS-13 activity arrived post-mortem, while HIV-infection was discovered post-mortem only and confirmed by immune blotting.

Advances in the pharmacologic management of HIV-infection continue at a rapid pace. Currently, more than 30 antiretroviral drugs (ARVDs) and their combinations are available. The use of these drugs can suppress HIV viral load to an inconspicuous level and increase the life expectancy of HIV-infected people. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non-HIV-associated comorbidities, which may be observed earlier than in age-matched controls. Although most ARVDs are relatively free of renal toxicity, drug-related kidney damage can occur and may need to be distinguished from the progression of HIV-related kidney diseases, other infections (e.g., hepatitis C), or kidney diseases unrelated to HIV-infection and its treatment. The most common nephrotoxic effects associated with antiretroviral therapy (ART) include acute kidney injury, crystal-induced obstruction and kidney stone disease secondary to use of protease inhibitors (mainly indinavir and atazanavir), and proximal tubule damage related to the nucleotide analog reverse transcriptase inhibitor tenofovir. Finally, nonspecific metabolic complications might increase the risk of vascular chronic kidney disease (CKD) in patients on ART. Renal impairment usually develops under conditions of repeated treatment and may not always be attributed to a specific drug therefore, in patients with HIV receiving any ARVDs, renal function should be regularly monitored. Given the benefits of ART, fear of nephrotoxic effects is never a valid reason for not using it. Identification of patients with pre-existing chronic kidney disease, who are at increased risk of renal damage, enables appropriate dose modification, close monitoring, and avoidance or cautious use of potentially nephrotoxic medications. Given the prevalence of CKD, a wide range of possible interactions between HIV, ARVDs, CKD, and its treatments, nephrologists need to be aware of the possible effects of ART on the kidneys. The review addresses issues related to the mechanisms, risk factors, and clinical manifestations of renal damage with medications to assess the clinical situation during antiretroviral therapy and discusses measures to prevent their nephrotoxicity.

The article describes a clinical case of severe kidney injury in a 66-year-old HIV-infected man who received Tenofovir disoproxil fumarate (TDF), lamivudine and etravirine. The man was infected with HIV in 2008 during heterosexual transmission, received antiretroviral therapy (ART) with a change of medications due to adverse events (efavirenz-neurotoxicity, zidovudine - anemia, abacavir - dyslipidemia, atazanavir - cholestasis, microlithiasis): zidovudine + lamivudine + efavirenz + ritonavir → zidovudine + lamivudine + atazanavir + ritonavir → abacavir + lamivudine + atazanavir + ritonavir. In 2017, the following treatment regimens were prescribed: TDF, lamivudine, etravirine. Renal function at the time of therapy initiation was normal. In October 2019 the GFR (CKD-EPI) decreased to 58 ml/min/1.73 m2 (serum creatinine concentration 113 mmol/l), proteinuria, glucosuria appeared. The patient was referred to nephrologist, the ART was not changed. The patient did not visit a nephrologist. In February 2020, the patient was admitted to the nephrology department because of oliguria (diuresis 600 ml/24-h), severe renal injury - serum creatinine was 640 mmol/l (GFR 7 ml/min/1.73 m2), urea 29 mmol/L, dyselectrolytemia, daily protein excretion 0.6 g. A kidney biopsy was performed, which showed massive inflammation, total acute tubular necrosis, focal karyomegaly, multifocal formation of megamitochondria, numerous massive protein cylinders, single myoglobin cylinders (rhabdomyolysis); the development of complete sclerosis of 14% of the glomeruli. The presence and severity of tubulo-interstitial fibrosis were not evaluated due to the severity of inflammation. Diagnosis: chronic tubulointerstitial nephritis of iatrogenic (drug) origin with acute kidney injury. Infusion therapy and changeover of antiretroviral therapy (ART) for a solution of lamivudine 100 mg per day and lopinavir/ritonavir 800/200 mg per day led to a gradual partial improvement in nephrological parameters: renal function, electrolyte metabolism (in November 2020 - GFR 37 ml/min/1.73 m2), spot urine sample also improved.

Introduction: despite advances in the study of the immunopathogenesis of HIV-infection, many aspects of diagnosis of the characteristics of the cellular immune response and the cytokine profile in HIV-infected patients with CKD remain unanswered. Answering these questions can provide a more complete understanding of the mechanisms of kidney damage in HIV-infection. The study aimed to determine the role of immune factors based on the study of the cellular and cytokine immune response in the pathogenesis of kidney damage in HIV-infection. Material and methods: the study involved 30 HIV-infected patients with chronic kidney disease (mean age 31.7±6.2 years). The comparison group consisted of 10 patients with HIV-infection without renal pathology. The control groups of 24 and 15 healthy individuals were used to analyze the immune status and normal cytokine profile, respectively. The study of the cellular composition of lymphocytes of a typical immunogram was performed on a BD FACSCanto II flow cytometer. The determination of the concentration of cytokines in blood serum was carried out by the method of solid-phase ELISA on a multichannel photometer Infinite F50. Results: in patients with HIV-infection kidney damage (presence of proteinuria, decreased GFR) developed against a background of a decrease in the blood content of the T-helper subpopulation of lymphocytes (CD3+/CD4+) (0.2×109/l and 0.4×109/l, respectively, p=0.015) with an increase in the number of cytotoxic T cells (CD3+/CD8+), IFN-γ, IL-10, IL-13, TGF-β and TNF-α. A correlation analysis was found beteween the helper population of T-lymphocytes and the cytokine profibrotic action levels IL-13 that controls the humoral immune response (r=0.671, p=0.034), and TNFα (r=-0.733, p=0.025) that regulates secretion TGFβ. In patients with a decreased level of CD4+ lymphocytes of less than 200 cells/μl and an increase in the concentration of HIV RNA in the blood of more than 100,000 copies/ml in HIV-infected patients with kidney damage, a statistically significant increase in TNFα was observed (with a level of CD4+ lymphocytes of more and less than 200 cells/μl - 19.0 pg/ml and 24.2 pg/ml, respectively, p=0.017; with HIV RNA levels of more and less than 100,000 copies/ml, 24.4 pg/ml and 19.7 pg/ml, respectively, p=0.012) A direct correlation was established between TNFα (r=0.683, p=0.042) and proteinuria, and the inverse with glomerular filtration rate (r=-0.755, p=0.031). Conclusion: in HIV-infected patients with CKD, changes were revealed in the parameters of typical immunograms and cytokine status. Kidney damage developed against the background of a more pronounced drop in the blood T-helper subpopulation of lymphocytes with a predominance of pro-inflammatory and immunosuppressive reactions. The leading role of TNFα in combination with depression of the immune system and high viral load in the formation of kidney damage in HIV-infection has been established.

Chronic kidney disease is a serious complication of HIV-infection. Its progression inevitably leads to end-stage renal disease (ESRD). The prevalence of ESRD in HIV-positive patients is 2-20 times higher than in the general population. Until 1996, hemodialysis was dominant in the ESRD treatment in HIV infected patients, while kidney transplantation was considered a contraindication due to the potential risks of chronic immunosuppression exacerbating HIV-related immune dysfunction. In the small number of HIV-positive patients transplanted at that time, outcomes were generally poor. Interest in kidney transplantation in HIV-infection aroused with the beginning of antiretroviral therapy (ART). The very first experience in this field under the new conditions showed good outcomes, confirmed later in a multicenter trial funded by US National Institute of Health. Contemporary studies have now demonstrated that renal transplantation is a safe and effective treatment of ESRD in HIV patients, with patient and allograft survival rates similar to those in uninfected patients. According to a meta-analysis summarizing data from 27 cohort studies covering 1,670 kidney transplantations in HIV-positive patients from 2003 to 2018, the one-year patients’ survival rate was 97%, the graft survival rate was 91%, and three-year survival rates were 94% and 81%, respectively. To date, criteria have been formulated for donor and potential recipient’s selection. It is generally recognized that a potential recipient should be treated with ART for at least 6 months before surgery, have an undetectable viral load and a CD4 cell count >200 per μl. Opportunistic infections use to be exclusion criteria, but several centers allow some of them as potentially curable. The experience in transplantation in HIV-infection has identified unique challenges including high rates of acute rejection, delayed graft function, and significant drug-drug interactions. This article discusses current experience in the field of kidney transplantation in HIV-infection and presents two of our clinical cases illustrating the long post-transplant course.