GSK1278863 induced an effective EPO response and stimulated non-EPO mechanisms for erythropoiesis in anemic non-dialysis-dependent and dialysis-dependent patients with CKD.

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While the effect of early referral to a nephrologist on QoL appeared centre dependent, a smooth transition onto dialysis was associated with significantly better early QoL, independent of other variables.

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Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

The pathogenetic relationship of kidney damage and an aberrant clone of the B-cell line producing nephrotoxic monoclonal immunoglobulin underlies the concept of “monoclonal gammopathy of renal significance” (MGRS). Herein the aberrant clone does not reach the criteria necessary for initiating antitumor therapy according to oncohematological indications. MGRS is a new nosology in modern nephrology and oncohematology. Monoclonal protein’s pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most health-care facilities; iii) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. In order to overcome these limitations, leading oncohematologists and nephrologists of the Russian Federation on behalf of professional communities at the end of 2019 published a conciliation document: “Monoclonal gammopathy of renal significance: Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment”. Consensus document comprises the opinion of experts – leading nephrologists and hematologists of Russian Federation – on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia “Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy”, 15–16 of March 2019, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia. Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses which we present here.

INTRODUCTION:Renal injury associated with monoclonal gammopathies (MG) is an area of interest of practical onconephrology. Prevalence, spectrum and renal outcome as far as approaches to treatment in this pathological entity, particularly in Russian population, still remain unclear and need refinement. AIM: Analysis of the prevalence, spectrum, treatment approaches and renal outcome in kidney injury associated with monoclonal gammopathies (MG).PATIENTS AND METHODS:Patients with MG and renal injury proven by kidney biopsies from 01.01.2011 till 01.05.2018 were enrolled into this one-center prospective study (n=119). Cases of MG of undetermined significance and non-amyloid kidney lesions were estimated as MG of renal significance (MGRS). Treatment approaches, haematological and renal responses were analysed. Worsening of kidney function was estimated as eGFR decrease >25 % from initial value or initiation of renal replacement treatment (RRT), improving – as eGFR increase >25 % from the initial value or the discontinuation of RRT. Other cases were determined as stable kidney function. Kidney outcome was determined in RRT initiation or eGFR<15 ml/min/1,73m2 at the end of follow-up. Long-term kidney outcome was estimated by Kaplan-Meier survival analysis. The median follow-up period was 12 (2; 27) months.RESULTS.Prevalence of kidney injury associated with MG among all performed kidney biopsies was 7,5 %, MGRS – 0,94 %. Multiple myeloma (MM), AL-amyloidosis and lymphoproliferative disorder (LPD) were diagnosed in 39, 55 and 10 patients, respectively. Prevalence of kidney injury types was the following: Al-amyloidosis (53 %); cast nephropathy (12 %); light chain deposition disease (12 %); C3-glomerulopathy (3 %); proliferative glomerulonephritis (GN) with monoclonal immunoglobulin deposits (3 %); cryoglobulinemic GN (2 %); thrombotic microangiopathy (2 %); podocytopathy (2 %); acute tubular necrosis – 2 %; immunotactoid GN (1 %); fibrillary GN (1 %); proximal tubulopathy (1 %), combination of different types (6 %). Patients mostly were treated with bortezomib and dexamethasone. Autologous stem cell transplantation was performed in 13 patients. Haematological response was achieved in 48,8 %, 45,4 % and 46,7 % of patients with MM, AL-amyloidosis and MGRS, respectively. Worsening of kidney function was registered in 11,1 % of MM and in 37,2 % of AL-amyloidosis; improving or stable kidney function was in 88,9 % and 62,7 % MM and AL-amyloidosis patients, respectively. In MGRS improving (20 %) and stable kidney function (80 %) were detected. Four-years cumulative renal survival in MM, AL-amyloidosis, MGRS and LPD groups was 63 %, 54 %, 80 % and 39 %, respectively, and does not differ between 4 groups.CONCLUSION:MG-associated kidney disease represented by diverse clinical and morphological patterns is standard problem in routine clinical practice. It is associated with inferior renal outcome and requires a practical implementation of highly-specialized interdisciplinary approach to diagnostics and treatment.