Kidney International Supplements (2018) 8, 91-165 © 2018 KDIGO

In future update of clinical guidelines on dialysis adequacy prepared by the International Society of Nephrology, the main priorities are given to four topics: the choice of dialysis modality, conditions at dialysis start, vascular access, adequacy of hemodialysis with an emphasis on correction of water balance and dialysis duration. In Europe negative scenarios for the development of these problems have been avoided: the choice of dialysis modality is more available; neither early nor late start is widespread; vascular access is always held in attention; dialysis shorter than four hours is not used, and instrumental hydration assessments are being actively developed. New approaches to the intensification of dialysis, first of all with regard to the elimination of more and more high-molecular substances related to uremic toxins are used. The limiting factor for an increase in permeability of new membranes is the necessity to exclude (at least minimize) the albumin loss. To meet these requirements, the membrane must have a high retention onset (substances with a lower molecular weight are retained by less than 10%) and a medium cut-off (less than 10% of a substance with a higher molecular weight is lost through the membrane). Such membranes effectively remove substances with molecular weight of up to 50 kD, but as reliably as conventional high-flux membranes, eliminate substantial losses of albumin. Fundamentally important is that such membrane permeability provides throughout the dialyzer length the internal filtration, and then back filtration (equivalent to the replacement solution) with a convection volume of about half that of hemodiafiltration with conventional dialysis machines and without a separate system for preparing and introducing the replacement solution. Thereby, the risks of thrombosis of the system and a decrease in the diffusive clearance due to the hemoconcentration in the output part of the dialyzer and the circuit before infusion of replacement solution is reduced. The first clinical evidence confirmed the efficacy and safety of such a solution defined as expander dialysis.

Chronic HCV infection is a serious problem of kidney transplantation, limiting the effectiveness of this operation. Aim: to evaluate the efficacy and safety of direct-acting antiviral therapy (DAAT) in kidney graft recipients (KGR) with chronic hepatitis C (CHC). Methods: the study included 24 KGR with CHC who underwent DAAT. The mean age was 51.5±10.2 years (men 75%). The duration of post-transplant period at the beginning of therapy was 6.4±5.7 years, duration of HCV infection was 10.4±7.3 years. GFR was 58.9±18.9 ml/min/1.73 m2 (all above 30 ml/min/1.73 m2 by CKD-EPI). 50% of KGR had 1b genotype HCV. Level of HCV RNA reached 1.3×106 (6.8×104; 8.1×106) IU/ml). Half of the patients had F2 or F3 stage of fibrosis, liver cirrhosis (F4 on the METAVIR scale) was diagnosed in 8.3% of recipients. 5 patients received SOF 400 mg/day with DCV 60 mg/day and 15 mg/kg/day of RBV for 12 weeks, 14 patients received SOF+DCV for 12 weeks, and 5 patients for 24 weeks. The duration of follow-up period after the end of the therapy was 22.8±10.2 months. Results: aviremia was achieved in 100% pts after 8.3±3.4 weeks of DAAT. It was accompanied by a decrease in the levels of ALT (p<0.0001) and AST (p<0.001). Sustained virological response was observed in all patients after 12 and 24 weeks after the end of the therapy. The degree of liver fibrosis regressed from 11.7±5.1 kPa to 7.1±2.7 kPa (p<0,001) at 12 weeks after the end of therapy. During of DAAT, 2/3 of patients had a decrease of blood level of CNI: Cs - from 111.3±29.9 to 88.4±25.4 ng/ml (p<0.027), and Tac - from 7.5±1.3 to 5.3±1.5 ng/ml (p<0.001). Renal graft function remained stable, as well as the severity of proteinuria. There were no cases of serious complications of treatment, except for an episode of acute rejection. Conclusion: direct-acting antiviral agents are effective and save in renal transplant recipients with chronic HCV infection. The probability of reducing of the blood levels of CNI during treatment requires careful monitoring to avoid renal graft dysfunction.

Aim: to study the incidence, predisposing factors, causes and outcomes of pregnancy-related acute kidney injury (AKI) in patients with chronic kidney disease (CKD). Methods: The study included 305 pregnancies in 291 women with CKD stages 1-4 (mean age 29.4 [25.8; 32.9] years; the duration of CKD 12.0 [5.0, 21.0] years). During pregnancy and after childbirth diuresis, creatinine level, and GFR were studied. The KDIGO criteria were used to identify AKI. Results: AKI on CKD developed in 35 of 305 (11.5%) pregnancies in 34 (11.7%) of 291 women (one patient had AKI in each of two pregnancies). A total of 37 episodes of AKI were recorded. The incidence of AKI on CKD stage 1 was 1.0%, stage 2 - 4.3%, stage 3A - 46.9%, stage 3B - 50.0%, and stage 4 - 71.4% (p<0.001). The risk of AKI on CKD increased with arterial hypertension, nephrotic proteinuria, CKD 3-4 stage, anemia, preeclampsia, placental insufficiency, cesarean section. The main cause of AKI (67.6% cases) was preeclampsia. In the AKI group, compared to pregnancies without AKI, gestational age at delivery and percentile birth weight were less - 35.3 [32.6; 37.1] vs 38.3 [37.3; 39.6] weeks, p<0.001, and 29.8 [12.4; 51.5] vs 44.5 [21.1; 66.6], p=0.014, respectively. In the follow-up, 35.3% of patients who had AKI on CKD during pregnancy progressed to stage 5 CKD and started dialysis, compared with 2.3% in women without AKI (p<0.001). Conclusion: AKI on CKD often occurs during gestation and impact negatively on pregnancy outcomes for the mother and fetus.

Background: rapid growth of patient’s population with chronic kidney disease stage 5, who are under the increased risk of bone damage due to mineral bone disease, increases the need for endoprosthetics in this population with high comorbidity. The study was focused on the practical application of endoprosthesis of large joints in dialysis patients. Aim: to evaluate efficacy and safety of total hip and knee joint arthroplasty in patients treated with chronic dialysis and to develop practical approach for the perioperative patient management considering concomitant bone and other disorders. Materials and methods: 25 patients treated with chronic dialysis (23 program hemodialysis, 2 peritoneal dialysis) were under our observation with median duration of RRT 74 months. We performed 34 operations: 28 total hip arthroplasty (THA), 5 total knee arthroplasty (TKA), 1 revision knee arthroplasty (RKA). We used endoprosthesis with different types of fixation and friction pair. All patients had signs and features of mineral bone disease and impaired mineral metabolism. In case of pronounced bone demineralization (Z score less than -3,5), the operation was postponed until improvement with alphacalcidol treatment. Other specific issue of patient’s management was prophylaxis of thrombotic complications using direct anticoagulants and antibiotic prophylaxis of a surgical infection. Operations were performed between two dialysis days. Results: good efficacy of hip and knee arthroplasty was demonstrated using multidisciplinary approach in a big hospital, with a low incidence of complications in ESRD patients with mineral bone disease. Three cases of thrombosis of the lower extremities, 1 periprosthetic fracture, 1 suppuration of the endoprosthesis were referred as the early complications of 34 surgical interventions. There were no cases of disturbance of dialysis mode and efficacy. Subsequent follow-up with median duration of 23 months showed improvement in the functional parameters of the joints and the absence of the need for revisions in the long-term period. Conclusions: patients with chronic kidney disease stage 5, receiving treatment with programmed dialysis, who need total arthroplasty can be effectively managed in the multidisciplinary hospitals with preliminary correction of bone and mineral disorders and adequate anticoagulant and antimicrobial prophylaxis.

Infantile nephrotic syndrome (NS) is a rare, genetically heterogeneous group of glomerulopathies with the onset of the disease at the age of 4-12 months. Aim: to study of clinical and pathological characteristics, genetic features and outcome in children with infantile NS. Materials and methods: we conducted a retrospective one-center follow up study of 8 children (4M/4F) aged 3.2 (IQR: 3.0; 6.1) years with infantile NS. Targeted next-generation sequencing covering 68 genes associated with steroid-resistant NS with confirmation by direct Sanger sequencing were applied. Results: renal biopsy revealed focal-segmental glomerulosclerosis (FSGS) in 7/7 (100%) of the affected children. Monogenic causes of infantile NS were identified in 4/8 (50%) of children. Mutations were found in 4/68 (5.9%) genes, including NPHS2, NPHS1, WT1 and ITGB4. Normal renal functions on the last follow up had 2/8 (25%) children with infantile NS. Conclusion: genetic analyses of infantile NS with next-generation sequencing technique expands diagnostic possibilities with the subsequent personalization of therapeutic approaches.

The aim of the study. To compare the effectiveness of screening techniques for protein-energy wasting (PEW) in haemodialysis patients (HD). Patients and methods. A total of 645 haemodialysis patients were examined (300 men, 345 women age 56.8±12.8 years. All patients received treatment HD for 8.4±5.3 years. The assessment of nutritional status in order to diagnose PEW was carried out using the method of the Russian Ministry of Health (RMH) and the method proposed by the International Society of Renal Nutrition and Metabolism (ISRNM). Malnutrition Universal Screening Tool (MUST), Nutritional Risk Screening (NRS), Nottingham screening tool (NST), Malnutrition Screening Tool (MST), Malnutrition-Inflammation Score (MIS) were used for screening PEW. Results. When diagnosing PEW by RMH method of screening MUST, NRS, NST, MST showed an index of diagnosis of PEW, not exceeding 36%, the index of accuracy of diagnosis of PEW using MIS was 53%. When diagnosing PEW by the ISRNM method, all screening methods showed an index of accuracy of the diagnosis of PEW in the range of 53-61%. In the diagnosis of PEW by the MR method, the screening technique of the PEW "MEGASCRIN" demonstrated a sensitivity of 92% with a specificity of 72.5%, the overall accuracy index was 76%. At the same time, when diagnosing PEW using the ISRNM method, the "MEGASCRIN" PEW screening method demonstrated a sensitivity of 71% with a specificity of 92.5%, an overall accuracy index of 81%. Conclusion. The screening technique of the "MEGASCRIN" PEW in haemodialysis patients demonstrated acceptable predictive value and can be recommended for routine use when screening PEW in haemodialysis patients, regardless of the method for diagnosing PEW in the future.

Atypical hemolytic-uremic syndrome (aHUS) is an ultra-rare disease associated with uncontrolled activation of an alternative pathway of complement. Anti-complementary protection of the endothelium is disturbed by the development of systemic complement-mediated thrombotic microangiopathy. The unfavorable prognosis of overall and renal survival with aHUS without using complement-blocking antibodies (Eculizumab) is obvious. Here we present a clinical case of a patient with aHUS manifested at the age of 18 months (on the 4th day after revaccination with an attenuated oral polio vaccine). The onset of the disease was characterized by the development of microangiopathic hemolysis, thrombocytopenia and acute renal damage. A genetic study identified the heterozygous genotype of factor H (c.3653G>A (p.Cys1218Tyr)) and 2 heterozygous genetic variants (polymorphisms) in the same gene (c.2016A>G; c.2808G>T). Multigenic thrombophilia was also detected. It was represented by homo- and heterozygous genotypes of several genes (PAI: 4G/4G; MTHFR: 677 C/T; MTRR: 66 A/G; MTR: 2756 A/G; FGB: 455 G/A; ITGA2: 807 T/T). Despite the achievement of hematological remission of thrombotic microangiopathy on the background of plasma therapy, kidney function has not recovered. The severity of the condition was caused by dialysis-related renal failure (anuria), severe hypertension, and development of dilated cardiomyopathy with signs of congestive heart failure (reduction in ejection fraction to 42%). Renal biopsy revealed a mixed (glomerular and vascular) type of lesion specific for thrombotic microangiopathy involving interstitial tissue and tubules. The delayed initiation of therapy with Eculizumab allowed us to stop dialysis for more than 10 months. Up to date, this is the longest period after which a patient with aHUS did not require a renal replacement therapy. The treatment with Eculizumab, with the already existing chronic kidney damage, provided a significant improvement in their function, maintaining stable remission and improving the quality of life of the patient with aHUS. Early initiation of Eculizumab therapy in this patient could have prevented irreversible renal sclerosis. Due to the confirmed CFH genetic mutation, the girl needs lifelong therapy with Eculizumab. Its cancellation can provoke aHUS relapse with the risk of life-threatening complications.