Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

Splice-site variant in the RPS7 5'-UTR leads to a decrease in the mRNA level and development of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid aplasia. Pathogenic variants in ribosomal protein (RP) genes, GATA1, TSR2, and EPO, are considered to be the etiology of DBA. Variants in 5'-untranslated regions (UTRs) of these genes are poorly studied and can complicate the variant interpretation. We investigated the functional consequences NM_001011.4:c.-19 + 1G > T variant in the donor splice-site of the RPS7 5'-UTR. This variant was found in a family where two sons with DBA were carriers. Father, who also had this variant, developed myelodysplastic syndrome, which caused his death. Search for candidate causal variants and copy number variations in DBA-associated genes left RPS7 variant as the best candidate. Trio whole exome sequencing analysis revealed no pathogenic variants in other genes. Functional analysis using luciferase expression system revealed that this variant leads to disruption of splicing. Also, a decrease in the levels of mRNA and protein expression was detected. In conclusion, the established consequences of 5'-UTR splice-site variant c.-19 + 1G > T in the RPS7 gene provide evidence that it is likely pathogenic.

Trends in kidney transplantation rate across Europe: study from the ERA Registry.

BACKGROUND: The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. METHODS: The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. RESULTS: The total KT rate in the 40 participating countries increased with 1.9% annually  [95%  confidence  interval  (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). CONCLUSIONS: The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.

Recognizing Minor Leukemic Populations with Monocytic Features in Mixed-Phenotype Acute Leukemia by Flow Cell Sorting Followed by Cytogenetic and Molecular Studies: Report of Five Exemplary Cases.

Mixed-phenotype acute leukemia (MPAL), a rare and heterogeneous category of acute leukemia, is characterized by cross-lineage antigen expression. Leukemic blasts in MPAL can be represented either by one population with multiple markers of different lineages or by several single-lineage populations. In some cases, a major blast population may coexist with a smaller population that has minor immunophenotypic abnormalities and may be missed even by an experienced pathologist. To avoid misdiagnosis, we suggest sorting doubtful populations and leukemic blasts and searching for similar genetic aberrations. Using this approach, we examined questionable monocytic populations in five patients with dominant leukemic populations of B-lymphoblastic origin. Cell populations were isolated either for fluorescence in situ hybridization or for clonality assessment by multiplex PCR or next-generation sequencing. In all cases, monocytic cells shared the same gene rearrangements with dominant leukemic populations, unequivocally confirming the same leukemic origin. This approach is able to identify implicit cases of MPAL and therefore leads to the necessary clinical management for patients.

Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors.

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

Metal-Rich Phosphides Obtained from the Lead Flux: Synthesis, Crystal, and Electronic Structure of Sr5Pt12P9 and BaPt3P2.

Using a high-temperature ampoule technique and lead metal as a flux, we have grown single crystals and determined crystal structures from single-crystal X-ray diffraction data of two metal-rich phosphides, Sr5Pt12P9 (P 21/m, a = 6.1472(3) Å, b = 25.1713(13) Å, c = 6.4635(3) Å, ß = 99.604(2)°, Z = 2, R1 = 0.0326, wR2 = 0.0786) and BaPt3P2 (P 212121, a = 6.3605(6) Å, b = 6.8541(7) Å, c = 11.3493(12) Å, Z = 4, R1 = 0.0231, wR2 = 0.0501). Both compounds belong to their own structure types and feature 3D networks of Pt and P atoms, with the channels occupied by alkaline earth metal cations. Density functional theory calculations reveal Sr5Pt12P9 to be a metal, while BaPt3P2 is a narrow-gap semiconductor with a band gap of 0.24 eV. Bonding analysis shows that both compounds feature networks of prominent covalent localized Pt-P bonds, responsible for their structural stability, as well as additional weaker and, likely, less localized Pt-Pt interactions.

Hybrid Implants Based on Calcium-Magnesium Silicate Ceramics Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Dynamics of Reparative Osteogenesis in a Mouse Craniotomy Model.

Calcium-magnesium silicate ceramics, diopside, is a promising material for use in bone plastics, but until now the possibility of its use as a carrier of recombinant bone morphogenetic protein-2 (BMP-2) has not been studied, as well as the features of reparative osteogenesis mediated by the materials based on diopside with BMP-2. Powder of calcium-magnesium silicate ceramics was obtained by solid-state synthesis using biowaste - rice husks and egg shells - as source components. Main phase of the obtained ceramics was diopside. The obtained particles were irregularly shaped with an average size of about 2.3 µm and ~20% porosity; average pore size was about 24 nm, which allowed the material to be classified as mesoporous. Diopside powder adsorbs more than 150 µg of recombinant BMP-2 per milligram, which exceeds binding capacity of hydroxyapatite, a calcium-phosphate ceramic often used in hybrid implants, by more than 3 times. In vitro release kinetics of BMP-2 was characterized by a burst release in the first 2 days and a sustained release of approximately 0.4 to 0.5% of the loaded protein over the following 7 days. In vivo experiments were performed with a mouse model of cranial defects of critical size with implantation of a suspension of diopside powder with/without BMP-2 in hyaluronic acid incorporated into the disks of demineralized bone matrix with 73-90% volume porosity and macropore size from 50 to 650 µm. Dynamics of neoosteogenesis and bone tissue remodeling was investigated histologically at the time points of 12, 21, 48, and 63 days. Diopside particles were evenly spread in the matrix and caused minimal foreign body reaction. In the presence of BMP-2 by the day 63 significant foci of newly formed bone tissue were formed in the implant pores with bone marrow areas, moreover, large areas of demineralized bone matrix in the implant center and maternal bone at the edges were involved in the remodeling. Diopside could be considered as a promising material for introduction into hybrid implants as an effective carrier of BMP-2.

Relative expansion of CD19-negative very-early normal B-cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR-T cell therapy: implications for flow cytometric detection of minimal residual disease.

CD19-directed treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP-ALL is based on B-cell compartment study, CD19 loss could hamper MFC-MRD monitoring after blinatumomab or chimeric antigen receptor T-cell (CAR-T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B-lineage gating markers allows the identification of CD19-negative leukaemia, but it could also lead to misidentification of normal very-early CD19-negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19-negative normal BCPs in 106 children with BCP-ALL who underwent CD19 targeting (blinatumomab, n = 64; CAR-T, n = 25; or both, n = 17). It was found that normal CD19-negative BCPs could be found in bone marrow after CD19-directed treatment more frequently than in healthy donors and children with BCP-ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19-negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC-MRD more accurately in patients who have undergone CD19-targeted therapy, even in cases with normal CD19-negative BCP expansion.

Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

BACKGROUND: Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. METHODS: This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. RESULTS: The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. CONCLUSION: rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

Effect of Intrahippocampal Administration of α7 Subtype Nicotinic Receptor Agonist PNU-282987 and Its Solvent Dimethyl Sulfoxide on the Efficiency of Hypoxic Preconditioning in Rats.

We have previously suggested a key role of the hippocampus in the preconditioning action of moderate hypobaric hypoxia (HBH). The preconditioning efficiency of HBH is associated with acoustic startle prepulse inhibition (PPI). In rats with PPI > 40%, HBH activates the cholinergic projections of hippocampus, and PNU-282987, a selective agonist of α7 nicotinic receptors (α7nAChRs), reduces the HBH efficiency and potentiating effect on HBH of its solvent dimethyl sulfoxide (DMSO, anticholinesterase agent) when administered intraperitoneally. In order to validate the hippocampus as a key structure in the mechanism of hypoxic preconditioning and research a significance of α7nAChR activation in the hypoxic preconditioning, we performed an in vivo pharmacological study of intrahippocampal injections of PNU-282987 into the CA1 area on HBH efficiency in rats with PPI ≥ 40%. We found that PNU-282987 (30 µM) reduced HBH efficiency as with intraperitoneal administration, while DMSO (0.05%) still potentiated this effect. Thus, direct evidence of the key role of the hippocampus in the preconditioning effect of HBH and some details of this mechanism were obtained in rats with PPI ≥ 40%. The activation of α7nAChRs is not involved in the cholinergic signaling initiated by HBH or DMSO via any route of administration. Possible ways of the potentiating action of DMSO on HBH efficiency and its dependence on α7nAChRs are discussed.

Synthesis of macrocyclic peptidomimetics via the Ugi-click-strategy.

The Ugi-click-strategy was employed for the synthesis of 12-28 membered 1,2,3-triazole derived macrocyclic peptidomimetics. The Ugi reaction with acid components bearing acetylenic fragments and azidoisocyanides provided the corresponding peptidomimetics in up to 97% isolated yield. The subsequent CuAAC click reaction with these bifunctional substrates containing both acetylene and azide groups was investigated to reveal the influence of the structure of Ugi products on the direction of the click-cyclization. It was demonstrated that this approach allows efficient synthesis of either monomeric (12- and 13-membered) or dimeric (24-, 26- and 28-membered) macrocycles prepared in up to 85% yield. The scope and limitations of this method are discussed.

Natalia Tomilina - personality and profession.

Natalina Tomilina, a pioneer of Russian nephrology, is a clinician, researcher, teacher, organizer, leader, and a real pioneer, who has worked in nephrology from the very beginning of its development in Russia and continues to inspire new generations of Russian nephrologists. Her interests are very broad: from the physiology and pathophysiology of water and electrolyte balance and tubular dysfunctions to the management of transplant rejection, and from nephropathology to the treatment of idiopathic glomerulonephritis and ANCA-associated vasculitis…. to name a few. She implemented peritoneal dialysis, started first ICU for kidney patients in Russia, opened the door for the international communications, initiated a registry of the patients receiving RRT, and she never stopped seeing patients with kidney problems. In the interview on can find not only the story of her professional life, but also standpoint and philosophy of a great personality. Answering the question about emigration she said: "I never wanted to leave - I have to work at home, where I know and understand almost everything about my patients. Don't talk about prosperity, prosperous life sooner or later becomes boring. Prosperity is not the main point, and this is not prosperity, what gives you satisfaction. I feel that one should live in the place where he or she has an opportunity for personal fulfillment ad maximum". Her personal fulfillment is 100 % indeed.

What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Women's Day.

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to have an impact on women, with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Women and kidney disease: reflections on World Kidney Day 2018: Kidney Health and Women's Health: a case for optimizing outcomes for present and future generations.

Chronic kidney disease (CKD) affects ∼10% of the world's adult population: it is one of the top 20 causes of death worldwide and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day coincide in 2018, thus offering an opportunity to reflect on the importance of women's health, and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply these learnings more broadly. Girls and women, who make up ∼50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for the diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest and that may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing and on the fetus. Women have different complications on dialysis than men and are more likely to be donors than recipients of kidney transplants. In this editorial we focus on what we do and do not know about women, kidney health and kidney disease and what we might learn in the future to improve outcomes worldwide.

What we do and do not know about women and kidney diseases; questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Women's Day
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Chronic kidney disease affects ~ 10% of the world's adult population: It is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health, and specifically their kidney health, on the community and the next generations as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those insights more broadly. Girls and women, who make up ~ 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in terms of access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women, with profound consequences for child bearing and on the fetus. Women have different complications on dialysis than men and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.
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What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman's Day.

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to have an impact on women, with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

What we do and do not know about women and kidney diseases - questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

What we do and do not know about women and kidney diseases; questions unanswered and answers unquestioned: reflection on World Kidney Day and International Woman's Day.

Chronic Kidney Disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly.Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants.In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Women and Kidney Disease: Reflections on World Kidney Day 2018.

World Kidney Day and International Women's Day 2018 are commemorated on the same day (March 8), an opportunity to highlight the importance of women's health, and particularly, their kidney health. On its 13th anniversary, World Kidney Day promotes affordable and equitable access to health education, health care, and prevention for all women and girls in the world. In this article, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.