[Introduction to renal pathology]. / Einführung in die Nierenpathologie.

In recent decades, nephropathology has developed worldwide as a subspeciality of pathology, which requires special methodological and technical equipment to process the material and specific clinical and pathological expertise to interpret the findings. These special requirements mean that nephropathology is not available at all pathology institutes, but is carried out on a large scale in a few highly specialised centres. The history of nephropathology, or in a narrower sense the specialised histopathological examination of kidney biopsies, began in 1958 with the first use or performance of a kidney biopsy [1]. It thus replaced the practice of urinalysis, which had been common since the Middle Ages, as a diagnostic tool for kidney diseases. Specialised techniques such as immunofluorescence or immunohistology but also electron microscopy are required to assess specific renal changes, for which the examination of renal biopsies is one of the few remaining routine applications today. In Germany and German-speaking countries, the discipline developed thanks to the work of outstanding people in the field of pathology who were primarily involved in this discipline and had the necessary technical and human resources in their laboratories to ensure that these biopsies could be analysed.

Onco-nephrology: Physicians' Expectations About a New Subspecialty.

INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.

Podocentric view of glomerular proteinuria: Focused on cytoskeletal changes and toward promising targeted therapies and challenges.

Among renal cells, podocytes (glomerular epithelial cells) are the most critical to prevent plasma proteins from excessive loss by forming their sophisticated foot processes (FP) and slit diaphragms (SD). A general finding in the glomeruli of patients with nephrotic syndrome is the foot processes "effacement" resulted from dysregulated actin cytoskeleton reorganization. Ultrastructural analysis in patients with nephrotic syndrome has demonstrated that such changes tend to be dynamic and can sometimes be reversible. In a more molecular sense, injured podocytes can no longer maintain their tight regulation and "retract" their FP, but not "efface" them. Past studies have revealed multiple exquisite mechanisms and arrays of proteins participating in the regulation of cytoskeletal rearrangement, and these mechanisms serve as potential targets to treat. A major challenge to develop specific therapies is the targeted mechanism has to be crucial and specific enough for podocyte-oriented kidney diseases, and it would be even better to manifest in most of the glomerulonephritis. Studies have shown many approaches targeting different mechanisms, but none of them has been proved to be effective in clinical medicine. Up to the present, Abatacept (Orencia) is the first (and the only) clinical targeted therapy demonstrating limited success. It inhibits the co-stimulatory response of B7-1 (CD80) induced in various types of glomerulonephritis. Future clinical studies have to be expanded to substantiate this highly specific targeted therapy because the Abatacept effect is not generally accepted even within the nephrology community. Nevertheless, there are ongoing searches for specific treatment targeting podocytes through various approaches.

Artificial intelligence with kidney disease: A scoping review with bibliometric analysis, PRISMA-ScR.

BACKGROUND: Artificial intelligence (AI) has had a significant impact on our lives and plays many roles in various fields. By analyzing the past 30 years of AI trends in the field of nephrology, using a bibliography, we wanted to know the areas of interest and future direction of AI in research related to the kidney. METHODS: Using the Institute for Scientific Information Web of Knowledge database, we searched for articles published from 1990 to 2019 in January 2020 using the keywords AI; deep learning; machine learning; and kidney (or renal). The selected articles were reviewed manually at the points of citation analysis. RESULTS: From 218 related articles, we selected the top fifty with 1188 citations in total. The most-cited article was cited 84 times and the least-cited one was cited 12 times. These articles were published in 40 journals. Expert Systems with Applications (three articles) and Kidney International (three articles) were the most cited journals. Forty articles were published in the 2010s, and seven articles were published in the 2000s. The top-fifty most cited articles originated from 17 countries; the USA contributed 16 articles, followed by Turkey with four articles. The main topics in the top fifty consisted of tumors (11), acute kidney injury (10), dialysis-related (5), kidney-transplant related (4), nephrotoxicity (4), glomerular disease (4), chronic kidney disease (3), polycystic kidney disease (2), kidney stone (2), kidney image (2), renal pathology (2), and glomerular filtration rate measure (1). CONCLUSIONS: After 2010, the interest in AI and its achievements increased enormously. To date, AIs have been investigated using data that are relatively easy to access, for example, radiologic images and laboratory results in the fields of tumor and acute kidney injury. In the near future, a deeper and wider range of information, such as genetic and personalized database, will help enrich nephrology fields with AI technology.

Onconephrology: The intersections between the kidney and cancer.

Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. This intersection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, paraneoplastic glomerulonephritis, and the interactions of chronic kidney disease with cancer. Data clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. This highlights the imperative for collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer. In response to this need, specific training programs in onconephrology as well as dedicated onconephrology clinics have appeared. This comprehensive review covers many of the critical topics in onconephrology, with a focus on acute kidney injury, chronic kidney disease, drug-induced nephrotoxicity, kidney disease in stem cell transplantation, and electrolyte disorders in patients with cancer.

Renal supportive care, palliative care and end-of-life care: Perceptions of similarities, differences and challenges across Australia and New Zealand.

Renal supportive care (RSC) is an approach integrating nephrology and palliative care to improve quality of life for people with chronic kidney disease (CKD). RSC practice varies across services; therefore, understanding clinicians' perspectives is important to the evolution and definition of RSC. AIM: To understand renal clinicians' views and experiences of RSC, palliative care and end-of-life care. METHOD: A cross-sectional online survey was undertaken across Australia and New Zealand between February and May 2018. Participants were asked about end-of-life care, RSC, palliative care and an ideal model of RSC. RESULTS: Estimated response rate 13% included 382 clinicians; doctors (32%), nurses (68%); of whom 84% access specialist palliative care and 59% RSC. A lack of agreed treatment goals (86%) and late or rushed treatment decision making (85%) was associated with challenging end-of-life experiences. Variable concepts of RSC were described, with RSC being considered the same as: usual care for all CKD patients (40%), conservative (30%) or palliative care (22%). The term RSC was generally distinct from (77%) and more acceptable than palliative care (80%) with preferential RSC referral for symptoms (86% vs 69%, P < .01) and complex treatment decision making (82% vs 58%, P < .01). Aspirations for RSC included improving symptoms and quality of life (89%), with an ideal model comprising: symptom management (98%), improved nephrology and community service integration (96%) and clinician education (94%). CONCLUSION: This study revealed challenges for renal clinicians in providing end-of-life care and variation of views and experiences of RSC. It represents opportunities to develop RSC aligned with clinician priorities to improve patient care.

Research progress on advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor and the third most common urinary disease. It was estimated that RCC affected over 350,000 individuals in 2013, and there are nearly 140,000 deaths annually due to this disease. The initial masses in RCC patients are mostly confined to a single organ. However, due to the metastatic spread of cancer cells through the circulatory system, more than 30% of RCC patients relapse after surgery. The appearance of distant metastases often means that patients enter the advanced stage of cancer with low quality of life and a short expected survival time. This review aims to describe the extant research on advanced RCC, including its pathophysiology, heterogeneity, diagnosis, treatment, and prospects. We try to highlight the most suitable means of treating advanced RCC patients, focusing on comprehensive personalized treatments.

El riñón del niño prematuro: riesgos a largo plazo / The kidney of the premature child: long-term risks

Resumen: El recién nacido prematuro se enfrenta a las condiciones extrauterinas con sistemas aún inmaduros, tanto anatómica como fisiológicamente. El riñón termina de desarrollarse a finales del tercer trimes tre del embarazo, por lo que está especialmente expuesto a alterar su desarrollo normal en caso de nacer en forma prematura. Esta situación puede condicionar, entre otras consecuencias, una menor masa renal funcional y cambios microvasculares que representan un riesgo elevado de hipertensión arterial y daño renal crónico en el largo plazo. En el presente artículo se analiza la evidencia existente actual sobre estos riesgos en los prematuros y se ofrece un esquema de seguimiento de estos niños desde el punto de vista nefrológico.

Abstract: The premature newborn faces extrauterine conditions with some systems still immature, both ana tomically and physiologically. The kidney finishes developing at the end of the third trimester of pregnancy, so it is especially exposed to alter its normal development if preterm birth occurs. This si tuation may condition, among other consequences, a lower functional renal mass and microvascular changes comprising a high risk of chronic kidney disease in the long term and arterial hypertension. This article analyzes the current evidence on these risks in premature infants and offers a nephrology follow-up scheme of these children.

The predictive value of crescents in the disease progression of lupus nephritis based on the 2018 International Society of Nephrology/Renal Pathology Society Revision System: a large cohort study from China.

Objective: This study analyzed the associations of different crescents' fraction and clinical features in a Chinese lupus nephritis cohort based on the 2018 revision of ISN/RPS classification system.Methods: A total of 288 lupus nephritis patients with complete clinicopathological data and well follow-up was enrolled. The fraction of glomeruli with cellular or fibrocellular crescents based on the new system was reevaluated. The association between crescents fractions and the outcomes were further analyzed.Results: The median follow-up period was 76.5 months. Cellular or fibrocellular crescents were present in 146 (50.7%) of the total individuals. The percentage of crescents were significantly associated with severe clinical renal injury indices and other renal pathological parameter. According to the survival receiver operating characteristic (survival ROC) curve, the optimal cutoff level of cellular or fibrocellular crescents for predicting the composite events was 7.39%. By multivariable Cox hazard analysis, the presence of crescents was predictive of survival from the composite events with a hazard ratio [HR] of 2.5 (95% CI 1.190-5.431; p = .02). Furthermore, when we used absent, present in less than 7.39% of glomeruli, and present in greater than or equal to 7.39% of glomeruli as cutoffs in all the patients, a gradation appeared, with adjusted HRs of 2.9 (95% CI 1.326-6.313; p = .008) for crescents in greater than or equal to 7.39% of glomeruli, in reference to no crescents.Conclusion: We proposed that the crescents were not uncommon and had important clinical significance in lupus nephritis. The cutoff point of crescents as prognosticator might be nearly 7.39%.

Critical Care Nephrology: Core Curriculum 2020.

The intensive care unit (ICU) is a common source of high-acuity nephrology consultations. Although advanced chronic kidney disease is associated with increased ICU mortality, the prognosis of acute kidney injury (AKI) requiring renal replacement therapy is far worse, with short-term mortality rates that often exceed 50%. As such, it is essential that practicing nephrologists be comfortable caring for critically ill patients. This Core Curriculum article emphasizes the developments of the last decade since the last Core Curriculum installment on this topic in 2009. We focus on some of the most common causes of AKI in the critical care setting and use these AKI causes to delve into specific topics most relevant to critical care nephrology, including acute respiratory distress syndrome, extracorporeal membrane oxygenation, evolving concepts in fluid management, and shock. We conclude by reviewing the basics of palliative care nephrology and dialysis decision making in the ICU.

Acute kidney injury electronic alerts: mixed methods Normalisation Process Theory evaluation of their implementation into secondary care in England.

OBJECTIVE: Around one in five emergency hospital admissions are affected by acute kidney injury (AKI). To address poor quality of care in relation to AKI, electronic alerts (e-alerts) are mandated across primary and secondary care in England and Wales. Evidence of the benefit of AKI e-alerts remains conflicting, with at least some uncertainty explained by poor or unclear implementation. The objective of this study was to identify factors relating to implementation, using Normalisation Process Theory (NPT), which promote or inhibit use of AKI e-alerts in secondary care. DESIGN: Mixed methods combining qualitative (observations, semi-structured interviews) and quantitative (survey) methods. SETTING AND PARTICIPANTS: Three secondary care hospitals in North East England, representing two distinct AKI e-alerting systems. Observations (>44 hours) were conducted in Emergency Assessment Units (EAUs). Semi-structured interviews were conducted with clinicians (n=29) from EAUs, vascular or general surgery or care of the elderly. Qualitative data were supplemented by Normalization MeAsure Development (NoMAD) surveys (n=101). ANALYSIS: Qualitative data were analysed using the NPT framework, with quantitative data analysed descriptively and using χ2 and Wilcoxon signed-rank test for differences in current and future normalisation. RESULTS: Participants reported familiarity with the AKI e-alerts but that the e-alerts would become more normalised in the future (p<0.001). No single NPT mechanism led to current (un)successful implementation of the e-alerts, but analysis of the underlying subconstructs identified several mechanisms indicative of successful normalisation (internalisation, legitimation) or unsuccessful normalisation (initiation, differentiation, skill set workability, systematisation). CONCLUSIONS: Clinicians recognised the value and importance of AKI e-alerts in their practice, although this was not sufficient for the e-alerts to be routinely engaged with by clinicians. To further normalise the use of AKI e-alerts, there is a need for tailored training on use of the e-alerts and routine feedback to clinicians on the impact that e-alerts have on patient outcomes.

Summary of the International Conference on Onco-Nephrology: an emerging field in medicine.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Hemolytic uremic syndrome in a developing country: Consensus guidelines.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. The aim of the consensus meeting was to formulate guidelines for the diagnosis and management of HUS in children, specific to the needs of the country. METHODS: Four workgroups performed literature review and graded research studies addressing (i) investigations, biopsy, genetics, and differential diagnosis; (ii) Shiga toxin, pneumococcal, and infection-associated HUS; (iii) atypical HUS; and (iv) complement blockade. Consensus statements developed by the workgroups were discussed during a consensus meeting in March 2017. RESULTS: An algorithm for classification and evaluation was developed. The management of Shiga toxin-associated HUS is supportive; prompt plasma exchanges (PEX) is the chief therapy in patients with atypical HUS. Experts recommend that patients with anti-FH-associated HUS be managed with a combination of PEX and immunosuppressive medications. Indications for eculizumab include incomplete remission with plasma therapy, life-threatening features, complications of PEX or vascular access, inherited defects in complement regulation, and recurrence of HUS in allografts. Priorities for capacity building in regional and national laboratories are highlighted. CONCLUSIONS: Limited diagnostic capabilities and lack of access to eculizumab prevent the implementation of international guidelines for HUS in most developing countries. We propose practice guidelines for India, which will perhaps be applicable to other developing countries.

Big science and big data in nephrology.

There have been tremendous advances during the last decade in methods for large-scale, high-throughput data generation and in novel computational approaches to analyze these datasets. These advances have had a profound impact on biomedical research and clinical medicine. The field of genomics is rapidly developing toward single-cell analysis, and major advances in proteomics and metabolomics have been made in recent years. The developments on wearables and electronic health records are poised to change clinical trial design. This rise of 'big data' holds the promise to transform not only research progress, but also clinical decision making towards precision medicine. To have a true impact, it requires integrative and multi-disciplinary approaches that blend experimental, clinical and computational expertise across multiple institutions. Cancer research has been at the forefront of the progress in such large-scale initiatives, so-called 'big science,' with an emphasis on precision medicine, and various other areas are quickly catching up. Nephrology is arguably lagging behind, and hence these are exciting times to start (or redirect) a research career to leverage these developments in nephrology. In this review, we summarize advances in big data generation, computational analysis, and big science initiatives, with a special focus on applications to nephrology.

Contribution of Electron Microscopy to the Clinicopathologic Diagnosis in Childhood Glomerular Renal Diseases.

Background: Electron microscopy (EM) provides another diagnostic assessment of glomerular lesions in addition to light and fluorescent microscopy. Objectives: We evaluated the contribution of diagnostic EM in childhood glomerular diseases. Patients and methods: Forty-eight renal biopsies which were assessed by EM between 2000 and 2014 were evaluated. Results: There were 21 (44%) females and 27 (56%) males, ages ranged between 6 and 204 months. EM findings were compatible with light and immunofluorescence microscopy in 65%, made additional contributions to diagnosis in 31% (especially in focal segmental glomerulosclerosis, Alport disease, membranoproliferative glomerulonephritis, dense deposit disease, thin basement membrane disease, and nephronophthisis), and was non-contributory in 4%. Conclusion: Electron microscopic evaluation supports other histopathological diagnoses in most cases, contributes additional diagnostic information in pediatric glomerular disease, especially in FSGS, thin glomerular basement membrane nephropathy, Alport disease, MPGN, and dense deposit disease, and its utilization should clinically justify the increase in cost and testing time.

Addressing the Need for Clinical Trial End Points in Autosomal Dominant Polycystic Kidney Disease: A Report From the Polycystic Kidney Disease Outcomes Consortium (PKDOC).

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Expansion of multiple cysts throughout both kidneys is thought to lead to progressive loss of kidney function and kidney failure in some patients. In recent years, much has been learned about the pathophysiology of ADPKD. However, to date, only one therapy has been approved in the United States and in other regions for the treatment of ADPKD. Feasible end points and a clear regulatory pathway may stimulate further development in this area and ultimately lead to more treatments for ADPKD successfully reaching the market. In July 2016, the PKD Outcomes Consortium under the auspices of the Critical Path Institute and the PKD Foundation convened a PKD Summit to facilitate a discussion among patients, regulators, pharmaceutical sponsors, and academic clinical trialists regarding trial end points and the regulatory path to approval of new drugs for ADPKD. Following the summit, participants continued the dialogue using regularly scheduled teleconferences. This article addresses key considerations related to the design of clinical trials in ADPKD based on these discussions.