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Nephrology and Dialysis

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Vol 21, No 4 (2019)
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REVIEWS AND LECTURES

404-418 54
Abstract
Thrombotic microangiopathy (TMA) of the renal transplant is a clinical and morphological phenomenon characterized by specific damage of glomerular capillaries and medium-small arteries in the form of endothelial cells edema, expansion of the subendothelial space with a sharp narrowing of the vessels lumen, in some cases with blood clots. In the chronic TMA, a morphological picture of the "onion peel" is formed. TMA of a transplanted kidney develops de novo or as a recurrent pathology, may be systemic or localized in the transplant, but in all cases decreases the survival of the recipients and grafts. Morphological examination is necessary to confirm TMA of a renal transplant, but kidney biopsy does not always help to establish the etiology of TMA. The most common causes of de novo TMA are the toxicity of calcineurin inhibitors and antibody-mediated transplant rejection, and recurrent TMA is a relapse of atypical hemolytic-uremic syndrome (aHUS). Mutations in the genes of complement regulatory proteins play an important role not only in the recurrent aHUS after kidney transplantation (KT), but also in some cases of de novo TMA. To treat de novo TMA its causes should be eliminated. Plasma exchange and intravenous immunoglobulin are also used. In some cases of de novo TMA with uncontrollable activation of the complement system, resistant to standard therapy, it is advisable to use complement-blocking therapy. In all patients with recurrent aHUS after KT the first-line therapy is eculizumab. If a patient is diagnosed with aHUS and identified as high risk of relapse after KT through genetic testing and assessing of clinical features, prevention of disease recurrence with "endothelial protection regimen" and eculizumab is necessary. In general, the problem of TMA after KT requires further studies with the development of reliable predictors of its development and new approaches to prevention and treatment.

EDUCATIONAL MATERIALS

419-429 58
Abstract
The risk ratio (RR) and odds ratio (OR) are widespread methods of assessment of risk factor and outcome contingency. OR is an indirect evaluation of RR. It gives the representation polarity of absolute risk changes and its statistical significance, but often gives a distorted view of the risk multiplicity under the influence of the analyzed risk factor (as a rule, OR "overestimates" the RR). In a case of the marginal frequencies of outcomes less than 10% of the assessment of OR is very close to RR value. Therefore, often when conducting meta-analyzes of the risk factors for rare diseases, the OR is taken for OR, in other cases, the RR can be estimated from the OR with accurate data on the disease prevalence or the risk in the unexposed group. Although the RR is more obvious, the OR is most often used to assess the relationship of the risk factor and outcome. There are several explanations for this. OR is universal: unlike RR, OR can be assessed not only in a cohort study, but also in a case-control study. OR is much more convenient because it allows one to get inverse estimates not only concerning the risk factor, but also concerning the outcome. Univariate analysis, which does not take into account the influence of various confounders (factors which are not the direct purpose of the analysis), can lead to a biased assessment (an example is the Simpson paradox). To overcome this problem, multivariate analysis is used. One of the most commonly used types of multivariate analysis is logistic regression. As in the case of cohort studies, and case-control studies the relationship between risk factors and outcomes is assessed using the expression OR. The article presents a method for converting adjusted OR to RR (as well as the limits of the confidence interval) and provides examples. It should be remembered that both RR and OR, with a direct empirical assessment, are cumulative, do not imply censored observations, do not take into account the influence of covariates and the time of observation. If the subjects of the study have different observation times, the relationship between the risk factor and the outcome can be analyzed by calculating the intensity of events. This indicator is known as incidence density and represents the ratio of the number of events to the total time of observation of patients. The ratio of such assessments in the two groups can be interpreted as relative risk. The adjusted risk value for various factors can be obtained using the Poisson regression, which analyzes the influence of predictors on the intensity of the occurrence of events. Thus, despite the seeming simplicity of the OR and RR estimates, each of them has features of interpretation. It is necessary to possess basic knowledge about the OR and RR features to adequately and fully understand the information given in scientific publications and use it in clinical practice.
430-441 52
Abstract
Survival analysis is one of the most widely used methods of statistical analysis. With an imaginary simplicity, this analysis has certain pitfalls. There are different approaches, each of which requires compliance with certain assumptions and a peculiar clinical interpretation. The risk of death can be analysed by directly measuring the relative risk or indirectly assessing it using an odds ratio. However, these estimates are cumulative, do not involve censored observations and do not take into account the time of observation and the impact of covariates. The most common methods of analysis in a case of censored observation are the Kaplan-Meier procedure (which is empirically estimate the probability of surviving a certain time - survival function) and the Nelson-Allen (which is estimate the cumulative hazard function). Both of these methods do not require a priori information about the shape of survival function, however, they allow to estimate the impact on survival (or risk) of only one categorical predictor, cannot correct covariates and are based on the assumption of uninformative censoring. The use of these methods in a case of competing risks gives a deliberately biased assessment of survival. The most widely used method of survival analysis in the presence of competing risks is a cause-specific Cox proportional hazards model. The use of this method is advisable when the researcher aims to study the causal relationship of various factors and a certain outcome. However, it is important to interpret the results of such analysis correctly: it allows to assess the risk of a particular event among patients who have lived to a certain time-point and have not undergone any of the competing events. Because competing events are ignored (censored), it is not possible to directly assess the impact of covariates on their frequency. An alternative may be the increasingly popular Fine and gray competing risks regression model. This method simulates the impact of covariates on the cumulative incidence function and can be applied when the aim of the researcher is not to study the etiological associations, but to estimate the probability of each of the events - i.e. an individual forecast. Thus, the survival analysis can be performed using different methods. Each of them is not universal, and was designed for specific purposes, has its advantages, disadvantages and limitations. The use of the optimal approach in each case will provide the most objective analysis.

CASE REPORTS

442-449 68
Abstract
Vascular complications after renal transplantation occur with an incidence of 5% to 10%. Among them, transplant renal artery stenosis (TRAS) is the most common (up to 75%). The basic clinical and instrumental features of formed TRAS are refractory arterial hypertension (AH) and progressive kidney transplant (KT) dysfunction. Well-timed surgical correction of TRAS resulted in significant regression of renal transplant dysfunction and led to stabilization of the patient’s condition. The procedure of choice is percutaneous transluminal angioplasty (PTA) including balloon angioplasty and direct stenting of transplant renal artery (TRA). A clinical case of rapidly progressing allograft dysfunction in a patient with stable blood pressure is presented. Among possible causes of KT dysfunction, an accidental overdose of calcineurin inhibitors was excluded. Initially, TRAS as a possible cause of allograft dysfunction was not discussed. Color Doppler ultrasound of KT was performed within the diagnostic search. Direct Doppler signs of distal TRAS and multiple stenoses of segmental arteries were detected. Obtained data were confirmed by CT-scan angiography: severe TRAS (more than 85%) and multifocal atherosclerotic lesion of segmental arteries were diagnosed. After that PTA with TRA stenting was performed. KT function significantly improved in the early postoperative period and remained stable during the entire observation period. Successful PTA and active nephroprotective support before repeated contrast media introduction ensured KT safety prevented the start of hemodialysis. The patient was included in transplant list. Correct interpretation of peculiar doppler sings of TRAS in the absence of AH in a patient with rapidly progressing allograft dysfunction allowed to choose the right diagnostic search and optimal treatment strategy.
450-457 64
Abstract
Chronic HCV infection is characterized not only by severe hepatic complications, such as liver cirrhosis and hepatocellular carcinoma but also by equally serious extrahepatic manifestations. Mixed cryoglobulinemia (MC) is the most common extrahepatic complication of chronic HCV infection. Clinical manifestation of MC is cryoglobulinemic vasculitis (СV), often occurring with the development of membranoproliferative glomerulonephritis. Antiviral therapy remains an important component of the modern approach to the treatment of СV. However, the elimination of the virus is not always accompanied by clinical and immunological remission of vasculitis. This publication demonstrates a clinical case of severe СV associated with HCV infection, which debuted in 2004 with skin lesions, followed by the addition in 2009 cryoglobulinemic glomerulonephritis, and in 2014 lesions of the lungs, nervous system and joints. Corticosteroid therapy in 2009 and 2013 caused only short-term clinical remission of the disease. Hepatitis C (genotype 1) was characterized by low clinical activity with high viral load and was accompanied by an increase in the severity of liver fibrosis in dynamics. Antiviral treatment with interferon and ribavirin, used in inadequate doses of drugs due to the development of adverse events, was ineffective. Only the use of a combination of pathogenetic therapy using monoclonal antibodies to CD20 and antiviral treatment with modern direct-acting drugs (asunaprevir 200 mg/day and daclatasvir 60 mg/day) made it possible to achieve a sustained virological response and clinical remission of the disease by 2015. However, despite the elimination of cryoglobulins, which was first detected only 12 weeks after the completion of antiviral therapy, it was not possible to achieve full normalization of immunological parameters: for more than 4 years of follow-up, a high blood level of rheumatoid factor (RF) and a low concentration of the C4 component of the complement remained. The prognostic value of these disorders taking into account the possible risk of progression of the lymphoproliferation process remains unclear to date and requires further observation and analysis.
458-465 957
Abstract
Kidney transplantation among two identical twins precludes graft rejection. Despite this fact, according to recent reports, more than 70% of recipients received immunosuppression at the discharge and 33% therapy was continued a year after transplant. The key issues in planning a renal transplant from twins are confirmation of monozygosity, risk assessment for the donor and choice of immunosuppressive strategy. Same date of birth, gender, identical blood groups, and A-, B- DR- HLA antigens are mandatory, but insufficient to confirm monozygosity when planning transplantation. All of the above with a 16% probability may correspond to dizygotic twins. A type of DNA polymorphism consisted of tandemly arranged blocks of 2 to 10 nucleotides with a high level of heterozygosity, is widespread in the human genome. They are easy to genotype, and the identity of their variants in two twins proves monozygosity. In the presented case, before minimizing and further discontinuation of immunosuppression, donor and recipient were analyzed for short tandem DNA repeats. 1.5 years after transplant, of which the recipient does not receive immunosuppression for the last 9 months, the graft function is stable and there are no laboratory signs of rejection or IgA-nephropathy recurrence.

ABSTRACTS OF THE XIV CONFERENCE OF THE RUSSIAN DIALYSIS SOCIETY

 
466-495 55
Abstract
Chronic Kidney Disease
 
495-497 54
Abstract
Renal Replacement Therapy
 
517-518 56
Abstract
Chronic ambulatory peritoneal dialysis - CAPD
 
518-523 56
Abstract
Acute kidney injury
 
523-527 41
Abstract
Kidney transplantation


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ISSN 1680-4422 (Print)
ISSN 2618-9801 (Online)