Long-term outcome of kidney transplantation is limited by the development of allograft rejection due  to activation and  realization of Tand  B-cell immune response as well as the effects of other types of immune reactions mediated by various mechanisms. This article is dedicated to nowadays point of view upon the different immune and  morphological phenotypes of kidney transplant injury. Main focus is made on the pathways of microvascular inflammation in the case of donor-specific antibodies absence as the unique self-sustained phenotype of the kidney allograft injury.

New-onset diabetes mellitus  after  transplantation (NODAT) in kidney  transplant recipients promote the development of complications and  have  a negative impact on kidney  transplantation (KT) results.

Aim. Comparison of clinico-demographic characteristics and  KT results in recipients with and  without  NODAT.

Patients and methods.  Study included 439  patients 18+ years without  pre-transplantation diabetes who  underwent KT from  the  deceased donor in our  center from  01.01.2007 to 31.12.2016. All patients after  KT received calcineurin inhibitors and  mycophenolate, 322 received tacrolimus (TAK), 117cyclosporin A (CsA). Seventeen recipients received immunosuppression without  steroids.

Results. NODAT developed in 41 (9.3%) of 439 patients: 33 (10.2%) of 322 on TAK, and  8 of 117 (6.8%) on CsA, p=0.368. The groups with NODAT and  without NODAT did not differ in gender, proportion of patients with polycystic kidney disease, modality and duration of dialysis, features of immunosuppression, although there was  a tendency for older  age and  higher body  mass index  in patients with NODAT. In NODAT group there were significantly more patients with preexisting metabolic syndrome (31.7% versus 12.3%, p = 0.002), post-transplant surgical complications (21.9% vs. 8.5%, p= 0.012), fungal  infections (14.6% vs 5.0%, p=0.026), cardiovascular  complications (26.8% vs. 9.8%, p=0.003), patients who  died  with functioning graft  (17.1% % vs. 5.5%, p = 0.0012). Recipients and  transplants survival was significantly lower in NODAT group (p=0.008, p=0.022, resp.).

The Aim of the  study was  to assess the  association of T-cell  (CD3+),  monocyte/macrophage (CD68+), B-cell  (CD20+)  infiltrates in glomeruli with long-term kidney  allograft survival in patients with renal  allograft (RA) glomerulitis.

Patients  and methods.  97 RA recipients with biopsy-proven glomerulitis were enrolled in this retrospective study. 54,6% of patients were negative for donor-specific antibodies (DSA-) at the time of biopsy. DSA were detected in 25,8% of cases (DSA+). For 19,6% of patients DSA evaluation was  unavailable at  the  time  of biopsy. Morphological findings were assessed according to  the Banff 2013  criteria. After immunohistochemical staining for CD68+,  CD3+, CD20+  cells  quantitative assay of positive cells  in glomerular capillaries was performed. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the relationship between intraglomerular CD3+, CD68+,  CD20+ cells and risk of RA loss.

Results. CD68+ and CD3+ cells  were found in glomeruli in RA glomerulitis more frequently than  CD20+  cells. The level of intraglomerular CD68+  cells was higher in DSA+ group (p = 0,005), there was no difference in the level of CD3+ and  CD20+ cells between DSA subgroups. Infiltration of CD68+ ≥ 8 cells per glomerulus was associated with a lower RA survival (p _log-rank = 0,019) as well as infiltration of CD3+ ≥ 1 cell per glomerulus (p _log-rank = 0,029). The number of glomerular CD68+ (1 cell per glomerulus) was independent predictor of RA loss in multivariate Cox regression model (p ≤ 0,003).

Conclusion. RA glomerulitis could be realized by different immunological pathways including monocytes/macrophages actions that requires further investigations. Immunomorphological evaluation of immune cells subpopulations, in particular CD68+ cells, could be crucial for the evaluation of long-term RA prognosis and appropriate therapeutic approach.

Introduction. Kidney transplant (KTx) with reduced functional reserve is more sensitive to the  toxic effects of calcineurin inhibitors (CNI). Immunosuppressive (IST) approach included m-TOR inhibitors in case of KTx from the ECD lead to decreasing levels of cyclosporine (CsA) in the blood. Despite of presence international pilot studies we having not yet strong recommendation for real  combination of CsA and  Everolimus. In this  article we presented 5-yeras results of the  first Russian experience of systematic use Everolimus as basic IST in KTx from  ECDs. 

Patients  and methods.  The group of recipients (n=41) was formed during the operation; received a bilateral kidney transplants from the same ECDs. Comparison group (n=19) received standard IST consisting of CsA, MMF and  steroids. Study group included 22 recipients who received an another kidney  from the same ECD and  IST, based on early (starting from the 90th  day after  transplantation) conversion from MMF to Everolimus-1.5mg/day (target concentration-3-6ng/mL). Simultaneously with the appointment Everolimus, dosing occurred immediately Neoral decrease by 50% and  then, in accordance with the target concentration (C0-30-50ng/ml). Implementing a program of gradual minimization of the dose steroids in patients of the study group.

Results. Both groups were comparable in terms of level of serum creatinine and glomerular filtration rate of up to 3 months after transplantation. As a result of the introduction of a new scheme of ICN in the study group, for the 60-month observation GFR study group was 46±15 ml/min/1.73m², the control is reduced to 28±7  ml/min/1.73m²;P<0.05.

Conclusion. Early administration of Everolimus is strongly recommended in all cases of the use of grafts for KTx obtained from the ECDs. This approach helps to minimize of nephrotoxity of CNT, provides the prevention of chronical transplant nephropathy, the  stable renal  function, and  contributes to the  survival and  renal  transplant recipients.

Background: The progression of diabetic nephropathy (DN) often accompanies by a combination with non-diabetic glomerulopathies (NDGP), which can significantly affect the prognosis and treatment of patients. However, the information about such influences, in particular, on the severity of tubulointerstitial fibrosis, one of the main pathomorphological prognostic criteria, on the renal parenchyma is not enough. AIM: To investigate the significance of NDGP for fibrotic processes kidney parenchyma in patients with diabetic nephropathy (DN).

Patients (materials) and methods: Single-center retrospective analysis based on medical records of 51 patients (32 men, mean age: 49±13 years) with DN who underwent renal  biopsy between 2002  and 2016. All patients were diagnosed as cases of DN -gr.№1, those were divided  on “pure”  DN-gr.№2 and  DN-gr.№3 with NDGP.

Results:  Out of the 51 DN gr. №1 patients, 30 (60. %) had  gr. № 2, 21 (40. %) had  gr. №3.  IgA nephropathy (IgAN)-20 % was the most common GN followed  by focal  segmental glomerulosclerosis (FSGS)-35%, and  HCV –associated GN was the most common secondary GN. Patients with “pure”  DN had  lower estimated glomerular filtration  rates (eGFR)  and  higher value  of systolic blood pressure  (SBP), glomerulosclerosis ( GS),  peritubular capillarirtis ( PTC) and  myofibroblasts quantity ( SMApositive cells). No significant between-group differences were observed with respect to majority of laboratory and morphological features. The activity of myofibroblasts positively  correlated with tubular atrophy, focal sclerosis, the stage of diabetes and GS in gr. №2 in comparison with gr. № 3.

Conclusions: The fibrosis of tubulointerstitium in the kidney of patients with DN accoppanied the pathomorphological markers such as SMA and  PTC . There wasn’t  significant evidences about the differences of fibrotic processes in the renal  parenchyma in patients with and  without NDHD.

The quantification of specific urinary  proteins in high-grade proteinuria can  be  of importance for the  evaluation of mophrological lesions, response to therapy and  prognosis.

The aim of our study was to analyze whether the urinary  excretion of high and  low molecular proteins associated with the  degree of glomerular, tubulointerstitial and  vascular fibrosis.

Patients and methods. The study included 97 patients with biopsy proven primary immune glomerulopathies: membranous nephropathy (n =22), minimal change disease (n=13), focal segmental glomerulosclerosis (n =30), IgA nephropathy (n=32). Measurements of total  protein, immunoglobulin G (IgG),  transferrin (Trf), α1-microglobulin (α1-МG), β2-microglobulin (β2-MG)  were performed by nephelometric method in morning urine samples. The results were standardized for urine creatinine (Cr) concentration.

Results. There were a correlation between proteinuria and  specific proteins: β2-MG (r=0.24, р=0.025), α1-МG (r=0.38, р<0.001), Trf (r=0.78, р<0.001), IgG (r=0.67, р<0.001), as well as the  positive correlation between high and  low molecular proteins. Low molecular proteins (β2-МG,  α1-МG)  correlated with global  glomerular sclerosis (r=0.28, р=0.010 and  r=0.21, р=0.049 respectively) while levels of proteinuria and high molecular weight proteins did not. Urinary excretion β2-microglobulin was also significantly higher in patients with moderate-to-severe tubulointerstitial and vascular fibrotic lesions.

Conclusion. β2-microglobulin was suggested to be candidate integrative biomarker of renal  fibrosis in primary glomerulopathies.

The aim. To assess the effect of enrichment of calcium and  magnesium in drinking water on the level of arterial pressure (BP), myocardial remodeling processes, and  autorhythmic contractile activity of the  portal vein (PV) of spontaneously hypertensive SHR rats  and control WKY rats.

Material and methods. One group of SHR rats  received drinking water enriched with calcium (120 mg/L)  and  magnesium (45 mg/L)  from a 6-week-old age within 2 months. Two other groups of SHR and  WKY rats  received St. Petersburg tap water with a low content of Са²⁺ (8 mg/L) and Mg²⁺  (3 mg/L). All groups received a standard diet. At the end of the observation period, rats  were assessed with blood pressure, myocardial mass index, urea level (UR), total cholesterol (Chol), total calcium (totalCa) and  albumin (Alb) in blood. A contractile activity of PV was investigated by the method of myography (in vitro). The total and maximal amplitude and frequency of contractions of PV, as well as the work done by PV was determined.

Results. In SHR rats, the enrichment of drinking water of Са²⁺ and Mg²⁺, prevented the progressive rise BP to the level characteristic of the SHR, resulting in its stabilization at 18% lower than in the SHR of the mineral deficient group. Theincreaseinthecontent of Са²⁺ and  Mg²⁺  in drinking water did not affect the degree of myocardial hypertrophy, as well as on the level of UR, totalCa and Alb of blood, but led to a decrease in the level of total cholesterol compared to animals that received low-mineralized water. The options of the autorhythmic contractile activity depended on the mineralization of drinking water. The addition of Са²⁺ and  Mg²⁺ to the drinking water of SHR rats  resulted in a decrease in both  the amplitude of contractions of PV and  the work performed by PV as compared with rats  of mineral deficient groups.

Conclusion. The researches have  shown the important role of mineral composition of drinking water in processes of regulation of a level of arterial pressure. In spontaneously hypertensive SHR rats, the  antihypertensive effect of drinking water enrichment with Са²⁺  and  Mg²⁺   has  been revealed. The increase in the  intake of exogenous calcium and  magnesium with water modifies the autorhythmic contractile activity of the portal vein of spontaneously hypertensive SHR rats, normalizing it to a level characteristic of normotensive WKY rats.

Objective: to compare the  indicators of iron metabolism, the  level of hypoxia  induced factor (HIF-1α) and  erythropoietin (EPO) in children with anemia in CKD Stage 1-5.

Patients  and methods:  three groups of patients: I – 32 children under dialysis with CKD Stage 1-5 without therapy, II – 18 children up to dialysis CKD Stage 2-5 receiving treatment with iron and ESP, group III – 30 dialysis  patients with CKD Stage 3-5 receiving treatment with iron and  ESP. Serum levels of EPO and  HIF-1α was determined by solid-phase chemiluminescent enzyme-linked immunosorbent assay method (sandwich) using a test system Biomerica EPO ELISA kit to determine the level of HIF-1α, Cloud-Clone Corp.

Results: In the I group, a statistically significant increase in the level of HIF-1α (0,089 ± 0,011ng / ml) was found compared with the mean normal (0,043 ng / ml) (p = 0.0001). In the II group, an increased level of EPO (63,01 ± 14,84 MIU / ml) was found in comparison with normal (17,56 MIU / ml) (p = 0,0088), an increase in HIF-1α (0,138 ± 0,025 ng / ml) compared with normal (0,043 ng / ml) (p = 0.005). A comparative study of EPO and  HIF-1α in children with CKD showed a statistically significant increase in EPO and  HIF-1α in the  II group before dialysis  (on therapy) compared to group I before dialysis  (without  therapy). A correlation between GFR and  HIF-1α was established in group II patients.

Conclusion: A direct correlation between the level of GFR and HIF-1α in the blood was revealed in patients of group II with CKD Stage 2-5 before dialysis, receiving preparations of erythropoietin and  iron. In the I group, before dialysis  (without  therapy) and  III group of dialysis  patients receiving ESP and  iron, the  binding strength of GFR and  HIF-1α is not significant.

AL-amyloidosis is a disease associated with the clonal plasma cell proliferation and aberrant immunoglobulin light chain secretion. Deposition of insoluble polymers composed of monoclonal light chain lead  to disruption of tissue architecture and  organ dysfunction. Infiltrative amyloidogenesis often results in restrictive cardiomyopathy, leading to progressive heart failure, and kidney  involvement with nephrotic proteinuria and  dysfunction. Diagnostic is based on findings of tissue amyloid  deposition and  confirmation of monoclonal light chain nature. Here we reported course, diagnostic and  successful treatment of primary AL-amyloidosis case  with unusual disease presentation with lungs and  pleura involvement, resulting further in heart and  kidneys injuries.

ITG (immunotactoid glomerulopathy) cases in patients with multiple myeloma (MM) are extremely rare. We present a clinical case of a patient with MM Gκ who developed nephrotic syndrome, macrohematuria and acute kidney injury. Kidney biopsy revealed microtubules in glomerular basement membrane 19 nm in diameter, organized in bundles. The patient was treated with bortezomib, cyclophosphamide and  dexamethasone (BorCyDex) and  achived complete remission after  6 cycles of therapy with a complete renal  function recovery. Repeated renal  biopsy has  revealed a complete resorption of the deposits. Later the patient has  received autologous hematopoietic stem cells  transplantation (auto-HSCT). After 2 years, an immunochemical relapse of MM has  developed. Nephropathy signs have appeared 4 years after  auto-HSCT, ITG was diagnosed again on kidney biopsy during MM relapse with microtubules 11-12 nm in diameter. A special characteristic of our case was excessive glomerular infiltration by the lymphoid cells  with capillary lumen  obstruction. We consider the build-up of lymphoid cells  in the glomerulal capillaries lumen  as a special variant  of renal  tumor lesion  in MM. Lymphoid cells  had  signs of plasmatization. Bundles of microtubules, similar to the deposits in kidneys, were revealed in some of lymphoid cells. The data obtained confirm that microtubules are formed in plasma cells that situated in the lumen  of glomerular capillary vessels and later migrate into renal structures.

In 2017, 20 years have  passed since the launch of the Dialysis Department of St. Petersburg City Hospital No. 15 – one  of the largest dialysis  centers in St. Petersburg.