CLINICAL ASPECTS OF RENAL TRANSPLANTATION

В статье приведен литературный обзор, посвященный современным проблемам в трансплантологии почек. Нерешенными проблемами остаются оценка донора, низкая приверженность пациентов иммуносупрессивной терапии и развитие дисфункции трансплантата. Развивающиеся осложнения после трансплантации и иммуносупрессивной терапии требуют междисциплинарного подхода в лечении и наблюдении реципиентов донорской почки. Также необходимо широкое развитие трупного донорства для снижения числа потенциальных пациентов с хронической болезнью почек. The article presents a literature review of contemporary problems in kidney transplantation. Donor evaluation, low adherence of patients to immunosuppressive therapy and the development of graft dysfunction remain as unresolved problems. Developing complications after transplantation and immunosuppressive therapy require an interdisciplinary approach in the treatment and monitoring of recipients of donor kidney. It is also indispensable to the development of cadaveric donation to reduce the number of potential patients with chronic kidney disease.

Is It Time to Utilize Genetic Testing for Living Kidney Donor Evaluation?

Living donor kidney transplantation is an effective strategy to mitigate the challenges of solid organ shortage. However, being a living kidney donor is not without risk, as donors may encounter short- and long-term complications including the risk of developing chronic kidney disease, end-stage kidney disease, hypertension, and possible pregnancy-related complications. Although the evaluation of potential living donors is a thorough and meticulous process with the intention of decreasing the chance of complications, particularly in donors who have lifetime risk projection, risk factors for kidney disease including genetic predispositions may be missed because they are not routinely investigated. This type of testing may not be offered to patients due to variability and decreased penetrance of symptoms and lack of availability of appropriate genetic testing and genetic specialists. We report a case of a middle-aged woman with a history of gestational diabetes and preeclampsia who underwent an uneventful living kidney donation. She developed postdonation nonnephrotic range proteinuria and microscopic hematuria. Given the risk of biopsy with a solitary kidney, genetic testing was performed and revealed autosomal dominant Alport syndrome. Our case underscores the utility of genetic testing. Hopefully, future research will examine the incorporation of predonation genetic testing into living kidney donor evaluation.

Unnecessary Bureaucratic Barriers or Appropriate Patient Protection?

This chapter asserts that transplant centers have very strong motivations to encourage people to become living kidney donors. It analyzes the average age of transplant recipients today, the surgical and postsurgical complications when an organ finally becomes available, and the hospitals' financial incentive to help kidney patients get transplants. The chapter also discusses the importance of donors' physical and psychological health in order to make sure that they are not harmed by either the operation, and competent to make the very serious decision. Following the author's lengthy evaluation process that she described, the chapter illustrates the frustrating barriers to donation, and presents a program to evaluate donors more quickly and efficiently. The chapter cites Belfast City Hospital in Ireland, which recently instituted a one-day evaluation, as an example. Ultimately, the chapter argues that transplant centers should have an approach that might increase the efficiency of donor evaluation, decrease wait times, and increase the number of donors without sacrificing the benefits that come with careful and rigorous screening.

Prospective KIR genotype evaluation of hematopoietic cell donors is feasible with potential to benefit patients with AML

Donor KIR and recipient HLA combinations that minimize inhibition and favor activation of the NK repertoire are associated with improved outcomes after allogeneic hematopoietic cell transplantation (HCT) in patients with myeloid neoplasia. We prospectively evaluated a weighted donor ranking algorithm designed to prioritize HLA-compatible unrelated donors (URDs) with weak inhibitory KIR3DL1/HLA-Bw4 interaction, followed by donors with nontolerized activating KIR2DS1, and finally those with KIR centromeric B haplotype. During donor evaluation, we performed KIR genotyping and ranked 2079 URDs for 527 subjects with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Among all patients, 394 (75%) had at least 1 KIR-advantageous donor, and 263 (50%) underwent HCT. In patients with AML, KIR3DL1 weak inhibition provided protection from relapse. Compared with KIR3DL1-Weak Inhibiting donors, KIR3DL1-Noninteracting donors were associated with increased risk of relapse (HR, 2.97; 95% CI, 1.33-6.64; P = .008) and inferior event-free survival (EFS; HR, 2.14; 95% CI, 1.16-3.95; P = .015). KIR3DL1-Strong Inhibiting donors were associated with HR, 1.65 (95% CI, 0.66-4.08; P = .25) for AML relapse and HR, 1.6 (95% CI, 0.81-3.17; P = .1) for EFS when compared with the use of KIR3DL1-weak inhibiting donors. Donor KIR2DS1/HLA-C1 status and centromeric KIR haplotype-B content were not associated with decreased risk of AML relapse. There was no benefit to KIR-based donor selection in patients with MDS. This study demonstrates that donor KIR typing is feasible, and prioritization of donors with certain KIR3DL1 genotypes may confer a protection from relapse after HCT in patients with AML.

Long-term outcomes of kidney donors with fibromuscular dysplasia

Background Fibromuscular dysplasia (FMD) is a non-atherosclerotic systemic arterial disease that is not infrequently discovered during kidney donor evaluation. Current guidelines do not provide recommendations regarding the use of kidneys from donors with FMD and there is a paucity of data on the outcomes of these donors. Methods The Renal and Lung Living Donor Evaluation (RELIVE) study addressed long-term outcomes of 8922 kidney donors who donated between 1963 and 2007. We compared the development of hypertension, cardiovascular disease (CVD), proteinuria and reduced estimated glomerular filtration rate (eGFR) in 113 kidney donors with FMD discovered during donor evaluation versus 452 propensity score matched donors without FMD. Outcomes modeling with logistic and Cox regression analysis and Kaplan–Meier statistics were performed. Results Donors with FMD were older (51 versus 39 years), were more likely to be women (80% versus 56%) and had a higher systolic blood pressure at donation (124.7 versus 121.3 mmHg) (P < 0.05 for all). After a mean ± standard deviation follow-up of 15.5 ± 8.9 years, a similar proportion of donors with and without FMD were alive, and developed hypertension (22.2% versus 19.8%), proteinuria (20.6% versus 13.7%) and CVD (13.3% versus 13.5%). No donor with FMD developed an eGFR <30 mL/min/1.73 m2 or end-stage kidney disease. The multivariable risk of mortality, CVD and renal outcomes in donors with FMD was not elevated. Conclusions Kidney donors with FMD appear to do well, do not appear to incur increased risks of hypertension, proteinuria, CVD or reduced eGFR, and perhaps carefully selected candidates with FMD can safely donate as long as involvement of other vascular beds is ruled out.

Transfusion Practices for Pediatric Oncology and Hematopoietic Stem Cell Transplantation Patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III)

Purpose: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. Methods: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013-2016 at hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Transfusion practices were evaluated by diagnosis code and pre-transfusion laboratory values. Results: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% CI 37.9-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI 31.1-33.8%), followed by platelets (22.7%; 95% CI 21.5-23.9%). Patients in the 1 to <6-year old age range were most likely to be transfused and HSCT, acute myelogenous leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dL (10-90th percentile: 6.4-8.8 g/dL), with 45.7% of transfusions being given at 7-<8 g/dL. The median platelet count prior to platelet transfusion was 20x109/L (10-90th percentile: 8-51x109/L), and 37.9% of transfusions were given at platelet count of >20-50x109/L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between >1.4-1.7. Conclusion: Transfusion of blood components is common in hospitalized children with cancer. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for evidence- based practice in this population.