Utility of fractional excretion of magnesium in diagnosing renal magnesium wasting in pediatric nephrology practice.

BACKGROUND: Fractional excretion of magnesium (FEMg) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FEMg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice. METHODS: One hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FEMg, SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m2 or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values. RESULTS: Sixteen of all patients (13 %) had hypomagnesemia. All had FEMg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FEMg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FEMg, 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FEMg > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %). CONCLUSIONS: FEMg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice.

[Emergencies in nephrology]. / Notfälle in der Nephrologie.

Emergencies in nephrology are mainly acute life-threatening situations for patients. Furthermore, one needs to consider constellations that are so damaging to the kidneys that the need for permanent dialysis develops within a short period of time. Acute kidney failure as an immediate consequence is categorized using the Acute Kidney Injury Network (AKIN) stages and is pathophysiologically subdivided into pre-, intra- and post-renal. This leads to changes in volume status, acid base and electrolytes, while the terms nephrotic and nephritic describe the amount of kidney damage and help to choose diagnostic steps wisely. Patients that are already undergoing dialysis treatment or have received a kidney transplant are a further specific group in the case of emergencies.

Probiotic use in pediatric kidney transplant recipients: What are current practices, and are they evidence-based? A pediatric nephrology research consortium study.

BACKGROUND: Probiotics are living microorganisms that may confer health benefits to their host if administered in sufficient quantities. However, data on the use of probiotics in transplant recipients are scarce. METHOD: This multi-center survey of pediatric nephrologists aimed to examine variations in practice regarding the use of probiotics in pediatric kidney transplant recipients. The survey was conducted via a 10-item questionnaire (developed in Survey Monkey) administered to pediatric nephrologists participating in the Pediatric Nephrology Research Consortium meeting in April 2023. RESULTS: Sixty-four pediatric nephrologists completed the survey. Twenty-seven (42.2%) respondents reported having prescribed probiotics to pediatric kidney transplant recipients. The primary reason for probiotic use was the treatment of antibiotic-associated diarrhea (n = 20), with other reasons including recurrent Clostridium difficile infection (n = 15), general gut health promotion (n = 12), recurrent urinary tract infections (n = 8), and parental request (n = 1). Of those who prescribed probiotics, 48.1% held them during periods of neutropenia and 14.8% during central venous line use. Of the 64 respondents, 20 reported the lack of safety data as a concern for using probiotics in kidney transplant recipients. CONCLUSION: Pediatric nephrologists are increasingly prescribing probiotics to pediatric kidney transplant recipients; nevertheless, substantial practice variations exist. The paucity of safety data is a significant deterrent to probiotic use in this population.

Kidney Doppler ultrasonography in critical care nephrology.

Color pulsed-wave Doppler ultrasound (CPWD-US) emerges as a pivotal tool in intensive care units (ICUs) for diagnosing acute kidney injury (AKI) swiftly and non-invasively. Its bedside accessibility allows for rapid assessments, making it a primary imaging modality for AKI characterization. Furthermore, CPWD-US serves as a guiding instrument for key diagnostic-interventional procedures such as renal needle biopsy and percutaneous nephrostomy, while also facilitating therapy response monitoring and AKI progression tracking. This review shifts focus towards the integration of renal ultrasound into ICU workflows, offering contemporary insights into its utilization through a diagnostic standard-oriented approach. By presenting a flow chart, this review aims to provide practical guidance on the appropriate use of point-of-care ultrasound in critical care scenarios, enhancing diagnostic precision, patient management and safety, albeit amidst a backdrop of limited evidence regarding long-term outcomes.

Management dilemmas in pediatric nephrology: moving from friction to flourishing in "challenging" cases.

BACKGROUND: The circumstances surrounding chronic kidney disease and its impact on families can be complex and difficult to navigate, leading to these cases being labeled "challenging." CASE PRESENTATION: We present the case of an adolescent with kidney failure due to unremitting systemic illness and multiple complications ultimately resulting in the family's request to forgo dialysis. Medical team members wrestled with meeting the family's needs among internal and external constraints. CONCLUSION: Past experiences, systemic inequities, differing perspectives, and consequential decision-making within individual belief systems can lead to friction between and among medical team members and families. As pediatric nephrologists, we must shift our focus from the "challenging" patient or family to addressing what is challenging their ability to flourishing.

Results from a cross-specialty consensus on optimal management of patients with chronic kidney disease (CKD): from screening to complications.

BACKGROUND: Chronic kidney disease (CKD) affects around 10% of the global population and has been estimated to affect around 50% of individuals with type 2 diabetes and 50% of those with heart failure. The guideline-recommended approach is to manage with disease-modifying therapies, but real-world data suggest that prescribing rates do not reflect this in practice. OBJECTIVE: To develop a cross-specialty consensus on optimal management of the patient with CKD using a modified Delphi method. DESIGN: An international steering group of experts specialising in internal medicine, endocrinology/diabetology, nephrology and primary care medicine developed 42 statements on aspects of CKD management including identification and screening, risk factors, holistic management, guidelines, cross-specialty alignment and education. Consensus was determined by agreement using an online survey. PARTICIPANTS: The survey was distributed to cardiologists, nephrologists, endocrinologists and primary care physicians across 11 countries. MAIN OUTCOMES AND MEASURES: The threshold for consensus agreement was established a priori by the steering group at 75%. Stopping criteria were defined as a target of 25 responses from each country (N=275), and a 4-week survey period. RESULTS: 274 responses were received in December 2022, 25 responses from Argentina, Australia, Brazil, Guatemala, Mexico, Singapore, South Korea, Taiwan, Thailand, Turkey and 24 responses from Egypt. 53 responses were received from cardiologists, 52 from nephrologists, 55 from endocrinologists and 114 from primary care physicians. 37 statements attained very high agreement (≥90%) and 5 attained high agreement (≥75% and <90%). Strong alignment between roles was seen across the statements, and different levels of experience (2-5 years or 5+ years), some variation was observed between countries. CONCLUSIONS: There is a high degree of consensus regarding aspects of CKD management among healthcare professionals from 11 countries. Based on these strong levels of agreement, the steering group derived 12 key recommendations focused on diagnosis and management of CKD.

Utilizing electronic medical records alert to improve documentation of neonatal acute kidney injury.

BACKGROUND: Neonatal acute kidney injury (AKI) is a common yet underdiagnosed condition in neonates with significant implications for long-term kidney health. Lack of timely recognition and documentation of AKI contributes to missed opportunities for nephrology consultation and follow-up, potentially leading to adverse outcomes. METHODS: We conducted a quality improvement (QI) project to address this by incorporating an automated real-time electronic medical record (EMR)-AKI alert system in the Neonatal Intensive Care Unit (NICU) at Le Bonheur Children's Hospital. Our primary objective was to improve documentation of neonatal AKI (defined as serum creatinine (SCr) > 1.5 mg/dL) by 25% compared to baseline levels. The secondary goal was to increase nephrology consultations and referrals to the neonatal nephrology clinic. We designed an EMR-AKI alert system to trigger for neonates with SCr > 1.5 mg/dL, automatically adding AKI diagnosis to the problem list. This prompted physicians to consult nephrology, refer neonates to the nephrology clinic, and consider medication adjustments. RESULTS: Our results demonstrated a significant improvement in AKI documentation after implementing the EMR-AKI alert, reaching 100% compared with 7% at baseline (p < 0.001) for neonates with SCr > 1.5 mg/dL. Although the increase in nephrology consultations was not statistically significant (p = 0.5), there was a significant increase in referrals to neonatal nephrology clinics (p = 0.005). CONCLUSIONS: Integration of an EMR alert system with automated documentation offers an efficient and economical solution for improving neonatal AKI diagnosis and documentation. This approach enhances healthcare provider engagement, streamlines workflows, and supports QI. Widespread adoption of similar approaches can lead to improved patient outcomes and documentation accuracy in neonatal AKI care.

[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.

Targeting the Kidneys at the Nanoscale: Nanotechnology in Nephrology.

Kidney diseases, both acute and chronic, are a substantial burden on individual and public health, and they continue to increase in frequency. Despite this and an intense focus on the study of disease mechanisms, few new therapeutic approaches have extended to the clinic. This is in part due to poor pharmacology of many, if not most, therapeutics with respect to the sites of kidney disease within the glomerulus or nephron. Considering this, within the past decade, and more pointedly over the past 2 years, there have been substantial developments in nanoparticle systems to deliver therapeutics to the sites of kidney disease. Here, we provide a broad overview of the various classes of nanomaterials that have been developed to improve therapeutic development for kidney diseases, the strategy used to provide kidney accumulation, and briefly the disease models they focused on, if any. We then focus on one specific system, polymeric mesoscale nanoparticles, which has broadly been used over 13 publications, demonstrating targeting of the tubular epithelium with 26-fold specificity compared with other organs. While there have been several nanomedicines that have advanced to the clinic in the past several decades, including mRNA-based coronavirus disease vaccines and others, none have focused on kidney diseases specifically. In total, we are confident that the rapid advancement of nanoscale-based kidney targeting and a concerted focus by clinicians, scientists, engineers, and other stakeholders will push one or more of these technologies into clinical trials over the next decade.

Nephrology workforce in China: describing current status and evaluating the optimal capacity based on real-world data.

OBJECTIVE: This study aims to characterize the current status of the nephrology workforce in China and evaluate its optimal capacity based on real-world patient mobility data. METHODS: Data on nephrologists in China were collected from two prominent online healthcare platforms using web crawlers and natural language processing techniques. Hospitalization records of patients with chronic kidney disease (CKD) from January 2014 to December 2018 were extracted from a national administrative database in China. City-level paths of patient mobility were identified. Effects of nephrology workforce on patient mobility were analyzed using multivariate Poisson regression models. RESULTS: Altogether 9.13 nephrologists per million population (pmp) were in practice, with substantial city-level variations ranging from 0.16 to 88.79. The ratio of nephrologists to the estimated CKD population was 84.57 pmp. Among 6 415 559 hospitalizations of patients with CKD, 21.3% were cross-city hospitalizations and 7441 city-level paths of patient mobility with more than five hospitalizations were identified. After making adjustment for healthcare capacity, healthcare insurance, economic status, and travel characteristics, the Poisson regression models revealed that the number of nephrologists in both the source city (incidence rate ratio [IRR] 0.99, per 1 pmp increase) and destination city (IRR 1.07, per 1 pmp increase) were independently associated with patient mobility. An IRR plateau was observed when the number of nephrologists exceeded 12 pmp in the source city, while a rapidly increasing IRR was observed beyond 20 pmp in the destination city. CONCLUSIONS: The nephrology workforce in China exhibits significant geographic variations. Based on local healthcare needs, an optimal range of 12-20 nephrologists pmp is suggested.

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.

Which patients with CKD will benefit from genomic sequencing? Synthesizing progress to illuminate the future.

PURPOSE OF REVIEW: This review will summarize and synthesize recent findings in regard to monogenic kidney disorders, including how that evidence is being translated into practice. It will add to existing key knowledge to provide context for clinicians in consolidating existing practice and approaches. RECENT FINDINGS: Whilst there are long established factors, which indicate increased likelihood of identifying a monogenic cause for kidney disease, these can now be framed in terms of the identification of new genes, new indications for genomic testing and new evidence for clinical utility of genomic testing in nephrology. Further, inherent in the use of genomics in nephrology are key concepts including robust informed consent, variant interpretation and return of results. Recent findings of variants in genes related to complex or broader kidney phenotypes are emerging in addition to understanding of de novo variants. Phenocopy phenomena are indicating a more pragmatic use of broader gene panels whilst evidence is emerging of a role in unexplained kidney disease. Clinical utility is evolving but is being successfully demonstrated across multiple domains of outcome and practice. SUMMARY: We provide an updated framework of evidence to guide application of genomic testing in chronic kidney disease (CKD), building upon existing principles and knowledge to indicate how the practice and implementation of this can be applied today. There are clearly established roles for genomic testing for some patients with CKD, largely those with suspected heritable forms, with these continuing to expand as new evidence emerges.

Incorporating genetics services into adult kidney disease care.

Studies have shown that as many as 1 in 10 adults with chronic kidney disease has a monogenic form of disease. However, genetic services in adult nephrology are limited. An adult Kidney Genetics Clinic was established within the nephrology division at a large urban academic medical center to increase access to genetic services and testing in adults with kidney disease. Between June 2019 and December 2021, a total of 363 patients were referred to the adult Kidney Genetics Clinic. Of those who completed genetic testing, a positive diagnostic finding was identified in 27.1%, a candidate diagnostic finding was identified in 6.7% of patients, and a nondiagnostic positive finding was identified in an additional 8.6% of patients, resulting in an overall yield of 42.4% for clinically relevant genetic findings in tested patients. A genetic diagnosis had implications for medical management, family member testing, and eligibility for clinical trials. With the utilization of telemedicine, genetic services reached a diverse geographic and patient population. Genetic education efforts were integral to the clinic's success, as they increased visibility and helped providers identify appropriate referrals. Ongoing access to genomic services will remain a fundamental component of patient care in adults with kidney disease.

Patient-Reported Outcomes as Endpoints in Clinical Trials of Kidney Transplantation Interventions.

Patient-reported outcomes (PROs) that assess individuals' perceptions of life participation, medication adherence, disease symptoms, and therapy side effects are extremely relevant in the context of kidney transplantation. All PROs are potentially suitable as primary or secondary endpoints in interventional trials that aim to improve outcomes for transplant recipients. Using PRO measures (PROMs) in clinical trials facilitates assessment of the patient's perspective of their health, but few measures have been developed and evaluated in kidney transplant recipients; robust methodologies, which use validated instruments and established frameworks for reporting, are essential. Establishing a core PROM for life participation in kidney transplant recipients is a critically important need, which is being developed and validated by the Standardized Outcomes in Nephrology (SONG)-Tx Initiative. Measures involving electronic medication packaging and smart technologies are gaining traction for monitoring adherence, and could provide more robust information than questionnaires, interviews, and scales. This article summarizes information on PROs and PROMs that was included in a Broad Scientific Advice request on clinical trial design and endpoints in kidney transplantation. This request was submitted to the European Medicines Agency (EMA) by the European Society for Organ Transplantation in 2016. Following modifications, the EMA provided its recommendations in late 2020.

Optimising transitions of care for acute kidney injury survivors: protocol for a mixed-methods study of nephrologist and primary care provider recommendations.

INTRODUCTION: Acute kidney injury (AKI) affects nearly 20% of all hospitalised patients and is associated with poor outcomes. Long-term complications can be partially attributed to gaps in kidney-focused care and education during transitions. Building capacity across the healthcare spectrum by engaging a broad network of multidisciplinary providers to facilitate optimal follow-up care represents an important mechanism to address this existing care gap. Key participants include nephrologists and primary care providers and in-depth study of each specialty's approach to post-AKI care is essential to optimise care processes and healthcare delivery for AKI survivors. METHODS AND ANALYSIS: This explanatory sequential mixed-methods study uses survey and interview methodology to assess nephrologist and primary care provider recommendations for post-AKI care, including KAMPS (kidney function assessment, awareness and education, medication review, blood pressure monitoring and sick day education) elements of follow-up, the role of multispecialty collaboration, and views on care process-specific and patient-specific factors influencing healthcare delivery. Nephrologists and primary care providers will be surveyed to assess recommendations and clinical decision-making in the context of post-AKI care. Descriptive statistics and the Pearson's χ2 or Fisher's exact test will be used to compare results between groups. This will be followed by semistructured interviews to gather rich, qualitative data that explains and/or connects results from the quantitative survey. Both deductive analysis and inductive analysis will occur to identify and compare themes. ETHICS AND DISSEMINATION: This study has been reviewed and deemed exempt by the Institutional Review Board at Mayo Clinic (IRB 20-0 08 793). The study was deemed exempt due to the sole use of survey and interview methodology. Results will be disseminated in presentations and manuscript form through peer-reviewed publication.

Redesigning Kidney Disease Care to Improve Value Delivery.

This article describes the articulation, development, and deployment of a machine learning (ML) model-driven value solution for chronic kidney disease (CKD) in a health system. The ML model activated an electronic medical record (EMR) trigger that alerted CKD patients to seek primary care. Simultaneously, primary care physicians (PCPs) received an alert that a CKD patient needed an appointment. Using structured checklists, PCPs addressed and controlled comorbid conditions, reconciled drug dosing and choice to CKD stage, and ordered prespecified laboratory and imaging tests pertinent to CKD. After completion of checklist prescribed tasks, PCPs referred patients to nephrology. CKD patients had multiple comorbidities and ML recognition of CKD provided a facile insight into comorbid burden. Operational results of this program have exceeded expectations and the program is being expanded to the entire health system. This paradigm of ML-driven, checklist-enabled care can be used agnostic of EMR platform to deliver value in CKD through structured engagement of complexity in health systems.

Zishen Qingre Tongluo Formula Improves Renal Fatty Acid Oxidation and Alleviated Fibrosis via the Regulation of the TGF-ß1/Smad3 Signaling Pathway in Hyperuricemic Nephrology Rats.

Hyperuricemia, an independent risk factor for ensuing chronic kidney disease (CKD), contributed to tubulointerstitial fibrosis and insufficiency of renal fatty acid oxidation. Many studies have shown that renal fatty acid oxidation dysfunction is related to the TGF-ß1/Smad3 signaling pathway. We experimented the effects of Zishen Qingre Tongluo Formula (ZQTF) on the adenine/yeast-induced HN rats and uric acid-induced renal mouse tubular epithelial cells (mTECs), determined whether this effect was related to the TGF-ß1/Smad3 signaling pathway, and further investigated the relationship between this effect and renal fatty acid oxidation. Rats were given intraperitoneally with adenine (100 mg/kg) and feed chow with 10% yeast for 18 days and then received ZQTF (12.04 g/kg/day) via intragastric gavage for eight weeks. The TGF-ß1/Smad3 signaling pathway and renal fatty acid oxidation protein were detected by using western blotting, real-time PCR, and immunohistochemistry staining. mTECs induced by UA were used to investigate the relationship between the TGF-ß1/Smad3 signaling pathway and renal fatty acid oxidation. After treatment with ZQTF, levels of UA, 24 h UTP, BUN, and Scr were significantly decreased and histologic injuries were visibly ameliorated in HN rats. Western blotting, real-time PCR, and immunohistochemistry staining revealed that PGC-1α, PPARγ, and PPARα significantly increased, and fibronectin, collagen 1, and P-Smad3 significantly decreased in HN rats and UA-induced mTECs after ZQTF treatment. SIS3 (a specific inhibitor of Smad3) treatment significantly increased the expressions of PGC-1α, PPARγ, and PPARα and decreased the expressions of fibronectin, collagen 1, and P-Smad3 in UA-induced mTECs. Our study demonstrated that ZQTF exhibited renoprotective effects by promoting renal fatty acid oxidation via the regulation of the TGF-ß1/Smad3 signaling pathway. Thus, the present results indicated that ZQTF was a novel antifibrotic strategy for hyperuricemic nephropathy.