Fatigue by the Chalder Questionnaire and post-hemodialysis recovery in a population of predominantly African descent: The PROHEMO.

BACKGROUND/OBJECTIVE: A high prevalence of fatigue and a positive association between fatigue and post-hemodialysis recovery have been reported in predominantly white populations of maintenance hemodialysis (MHD) patients. The present study evaluates associations between self-reported fatigue by the 11-item Chalder Fatigue Questionnaire (CFQ-11) and the need for post-hemodialysis recovery in a predominantly African-descent MHD population. METHODS: A total of 233 patients (94% Black or Mixed-Race) participating in the "Prospective Study of the Prognosis of Patients on Maintenance Hemodialysis" (PROHEMO), Salvador, Brazil were recruited for this cross-sectional study. The CFQ-11 was used to measure fatigue: <4 for absent or mild, ⩾4 for moderate to severe. Patients were also asked if they needed some time to recover after the hemodialysis. Logistic regression was used to estimate odds ratio (OR) of the association with adjustments for age, sex, race, educational level, economic class level, diabetes, hearth failure, and hemoglobin. RESULTS: Mean age was 51.5 ± 12.5 years. Moderate to severe fatigue (⩾4 points) was observed in 70.8% (165/233), and absent or mild fatigue (<4 points) in 29.2% (68/233). Compared to patients with fatigue scores <4 (20.6%), the need for post-hemodialysis recovery was 2.5 times greater in patients with fatigue scores ⩾4 (52.7%). The covariate-adjusted logistic regression OR was 4.60, 95% CI: 2.27, 9.21. CONCLUSION: This study in MHD patients of predominantly African descent supports self-reported fatigue assessed by the CFQ-11 as a relevant predictor of the need for post-hemodialysis recovery. The results offer a rationale for investigating whether interventions to prevent fatigue reduce the need of post-hemodialysis recovery.

Chinese medicine Linggui Zhugan formula protects against diabetic kidney disease in close association with inhibition of proteinase 3-mediated podocyte apoptosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Linggui-Zhugan (LGZG) comprises four herbs and is a classic formula in traditional Chinese medicine. There is strong clinical evidence of its pleiotropic effects in the prevention of diabetes and its related complications. Although several classes of drugs are currently available for clinical management of diabetic kidney disease (DKD), tight glycemic and/or hypertension control may not prevent disease progression. This study evaluated the therapeutic effect of the ethnopharmacological agent LGZG on DKD. AIM OF THE STUDY: This study aimed to investigate the effects of LGZG formula with standard quality control on experimental DKD and its related metabolic disorders in animal model. Meanwhile, the present study aimed to investigate regulatory effects of LGZG on renal proteinase 3 (PR3) to reveal mechanisms underlying renoprotective benefits of LGZG. MATERIALS AND METHODS: LGZG decoction was fingerprinted by high-performance liquid chromatography for quality control. An experimental model of DKD was induced in C57 BL/6J mice by a combination of high-fat diet feeding, uninephrectomy, and intraperitoneal injection of streptozocin. The LGZG decoction was administrated by daily oral gavage. RESULTS: Treatment with LGZG formula significantly attenuated DKD-like traits (including severe albuminuria, mesangial matrix expansion, and podocyte loss) and metabolic dysfunction (disordered body composition and dyslipidemia) in mice. RNA sequencing data revealed a close association of LGZG treatment with marked modulation of signaling pathways related to podocyte injury and cell apoptosis. Mechanistically, LGZG suppressed the DKD-triggered increase in renal PR3 and podocyte apoptosis. In-vitro incubation of mouse immortalized podocytes with LGZG-medicated serum attenuated PR3-mediated apoptosis. CONCLUSION: Our data demonstrated that the LGZG formula protected against DKD in mice and was closely associated with its inhibitory effects on PR3-mediated podocyte apoptosis.

The validity of pathology codes for biopsy-confirmed kidney disease in the Danish National Patobank.

Background: This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases. Methods: Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated. Results: A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n = 368), tubulointerstitial disease (n = 67), renal vascular disease (n = 51), diabetic nephropathy (n = 51) and various renal disorders (n = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV. Conclusions: SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research.

Generating kidney organoids based on developmental nephrology.

Over the past decade, the induction protocols for the two types of kidney organoids (nephron organoids and ureteric bud organoids) from pluripotent stem cells (PSCs) have been established based on the knowledge gained in developmental nephrology. Kidney organoids are now used for disease modeling and drug screening, but they also have potential as tools for clinical transplantation therapy. One of the options to achieve this goal would be to assemble multiple renal progenitor cells (nephron progenitor, ureteric bud, stromal progenitor) to reproduce the organotypic kidney structure from PSCs. At least from mouse PSCs, all the three progenitors have been induced and assembled into such "higher order" kidney organoids. We will provide an overview of the developmental nephrology required for the induction of renal progenitors and discuss recent advances and remaining challenges of kidney organoids for clinical transplantation therapy.

Immune checkpoint inhibitor-associated nephritis - treatment standard.

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAE's) more frequently. Renal irAE's, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both CTLA-4 and PD1/PDL-1 blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs, and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management, and prognostication of ICI-AKI.

The Leicester, Leicestershire and Rutland quality improvement project and integrated chronic kidney disease system: implementation within a primary care network.

BACKGROUND: The optimisation of patients in primary care is a prime opportunity to manage patient care within the community and reduce the burden of referrals on secondary care. This paper presents a quality improvement clinical programme taking place within an NHS Primary Care Network as part of the wider Leicester Leicestershire Rutland integrated chronic kidney disease programme. METHOD: Patients are optimised to guidelines from the National Institute for Health and Care Excellence, by a primary care clinical team who are supported by nephrology consultants and nephrology pharmacists. Multidisciplinary team meetings take place with secondary care specialists and primary care staff. Learning is passed to the community clinicians for better patient treatment locally. RESULTS: A total of 526 patients were reviewed under this project.The total number of referrals to secondary care which were discharged following first outpatient appointment, reduced from 42.9% to 10%. This reduction of 32.9% represents the optimisation of patient cases through this quality improvement project. Patients can be optimised and managed within the community, reducing the number of unnecessary referrals to secondary care. CONCLUSION: This programme has the potential to offer significant improvement in patient outcomes when expanded to a larger patient base. Medicine management and the use of clinical staff are optimised in both primary and secondary care.

Nomenclature in Palliative and Kidney Supportive Care: Not Just at the End-of-Life.

The multidimensional view of disease is fundamental in the care of complex diseases such as chronic kidney disease (CKD). It is appropriate to define and unify concepts that allow the different professionals involved in care to provide a multidisciplinary approach tailored to the needs of each individual. Given the increasing incidence of CKD worldwide and the fact that the disease may progress at different rates, there is a need to establish personalized, comprehensive approaches for each patient and their families at an earlier stage. This approach goes beyond the simple control of uremic symptoms or congestion and consists of addressing not only symptomatic but also functional, social and coping problems at an early stage, facilitating decision making both in the CKD and in acute situations, potentially irreversible or interventions that do not improve life expectancy. To ensure excellence in care, it is important to assess indicators of palliative care and kidney support, such as the presence of advance and shared care planning, the inclusion of psychosocial, ethical, spiritual and bereavement care. This enables the provision of comprehensive, humanized, and high-quality care for patients and their families. Palliative and kidney care is not just about patients in the last days of life. Defining, unifying, and evaluating the concepts will allow them to be applied in a timely manner at each specific moment of the CKD trajectory.

Interventional nephrology in peritoneal dialysis: Best practice report of the Peritoneal Dialysis Project Group of the Italian Society of Nephrology.

The procedure of peritoneal dialysis (PD) catheter placement is of utmost importance for a good outcome of peritoneal dialysis. Currently, catheters are mainly placed by surgeons and interventional nephrologists. Still, there is a lack of trained personnel in many dialysis units, which can impair the efficiency of PD units and reduce the patients' possibility to enter a PD programme. The Italian Society of Nephrology has endorsed a practical core curriculum for interventional nephrology in PD available on the Society website, which is here reported for the wider nephrology community. The topics addressed are the hernias of the abdominal wall, catheter placement with standard surgical open technique, basic video-laparoscopy, advanced video-laparoscopy, video-laparoscopic cholecystectomy and catheter placement, cuff-shaving and video-laparoscopy in catheter malfunction.

An Atypical Presentation of Fabry Disease in a Patient With Nephrotic Syndrome: A Case Report.

Fabry disease is a rare X-linked lysosomal storage disorder that leads to the accumulation of globotriaosylceramide (Gb3) across various tissues, stemming from a deficiency in alpha-galactosidase A (GLA). This condition is characterized by a spectrum of clinical manifestations that can significantly complicate diagnosis. Classical symptoms typically include neuropathic pain, angiokeratomas, and significant involvement of the renal and cardiac systems. However, atypical presentations may obscure the underlying diagnosis, emphasizing the importance of maintaining a high level of clinical suspicion. This case report details the diagnostic journey of a 24-year-old female who initially presented with nephrotic syndrome, a presentation not commonly associated with Fabry disease. Subsequent genetic testing revealed a pathogenic variant in the GLA gene, confirming Fabry disease and highlighting the critical need for genetic analysis in cases of unexplained renal pathology. This case underscores the variability of Fabry disease presentations and the pivotal role of comprehensive diagnostic strategies in uncovering this complex disorder.

Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) Erasmus+ project: The Renal Expert in Vascular Access (REVAC) module.

The Renal Expert in Vascular Access (REVAC) is one of the four modules of the Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) project, the first European-wide advanced training course in diagnostics and interventional nephrology, funded by Erasmus+ Knowledge Alliance, a European Commission program. The N-PATH primary goal was to train 40 young European nephrologists in both theoretical knowledge and practical skills related to interventional nephrology. The REVAC module focused on the crucial aspects of vascular access (VA) care in nephrology practice, as a complementary training path to the actual residency program. The aim was to provide nephrology fellows with comprehensive knowledge and skills related to VA management. The methodology was based on face-to-face meetings and online learning, modern facilities, experienced tutors, cutting edge simulators, augmented reality tools by means of a multidisciplinary international faculty and hands-on-courses. A feedback survey reported the experience of fellows who attended the REVAC module, confirming the positive impact on their ongoing nephrology training. We are confident that this project will revitalize their nephrology careers and will help training the next generation of nephrologists; they will be able to manage VA needs with the help of multi-disciplinary teams to safely optimize the care of hemodialysis patients.

Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from 2 phase 3, single-arm studies. Setting & Participants: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure: Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy - Fatigue score achieved by 26 weeks was maintained over 2 years. Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS.

This research tested a drug called ravulizumab for the treatment of atypical hemolytic uremic syndrome (aHUS). aHUS is a rare disease that causes clots in tiny blood vessels. This can damage the kidneys and other organs. We analyzed data from 2 clinical trials in which children and adults with aHUS received ravulizumab through a tube placed in a vein (intravenous line). They received ravulizumab every 4-8 weeks depending on their weight. We found that treating patients for 2 years with ravulizumab was associated with improved blood health, kidney function, and quality of life and was well tolerated. These results support ravulizumab as a long-term treatment for people with aHUS.

The potential of ChatGPT in medicine: an example analysis of nephrology specialty exams in Poland.

Background: In November 2022, OpenAI released a chatbot named ChatGPT, a product capable of processing natural language to create human-like conversational dialogue. It has generated a lot of interest, including from the scientific community and the medical science community. Recent publications have shown that ChatGPT can correctly answer questions from medical exams such as the United States Medical Licensing Examination and other specialty exams. To date, there have been no studies in which ChatGPT has been tested on specialty questions in the field of nephrology anywhere in the world. Methods: Using the ChatGPT-3.5 and -4.0 algorithms in this comparative cross-sectional study, we analysed 1560 single-answer questions from the national specialty exam in nephrology from 2017 to 2023 that were available in the Polish Medical Examination Center's question database along with answer keys. Results: Of the 1556 questions posed to ChatGPT-4.0, correct answers were obtained with an accuracy of 69.84%, compared with ChatGPT-3.5 (45.70%, P = .0001) and with the top results of medical doctors (85.73%, P = .0001). Of the 13 tests, ChatGPT-4.0 exceeded the required ≥60% pass rate in 11 tests passed, and scored higher than the average of the human exam results. Conclusion: ChatGPT-3.5 was not spectacularly successful in nephrology exams. The ChatGPT-4.0 algorithm was able to pass most of the analysed nephrology specialty exams. New generations of ChatGPT achieve similar results to humans. The best results of humans are better than those of ChatGPT-4.0.

Pyroglutamic acidosis in the setting of Staphylococcus aureus bacteremia treated with flucloxacillin-An uncommon cause of high anion gap metabolic acidosis.

Pyroglutamic acidosis (PGA) or 5-Oxoprolinuria is an uncommon and often overlooked cause of high anion gap metabolic acidosis (HAGMA). This case highlights the importance of systematically approaching HAGMA, and to consider PGA as a differential diagnosis when medications that disrupt the γ-glutamyl cycle such as flucloxacillin and paracetamol are present.

Organelle communication maintains mitochondrial and endosomal homeostasis during podocyte lipotoxicity.

Organelle stress exacerbates podocyte injury, contributing to perturbed lipid metabolism. Simultaneous organelle stresses occur in kidney tissues; therefore, a thorough analysis of organelle communication is crucial for understanding the progression of kidney diseases. Although organelles closely interact with one another at membrane contact sites, limited studies have explored their involvement in kidney homeostasis. The endoplasmic reticulum (ER) protein, PDZ domain-containing 8 (PDZD8), is implicated in multiple organelle tethering processes and cellular lipid homeostasis. In this study, we aimed to elucidate the role of organelle communication in podocyte injury using podocyte-specific Pdzd8-knockout mice. Our findings demonstrated that Pdzd8 deletion exacerbated podocyte injury in an accelerated obesity-related kidney disease model. Proteomic analysis of isolated glomeruli revealed that Pdzd8 deletion exacerbated mitochondrial and endosomal dysfunction during podocyte lipotoxicity. Additionally, electron microscopy revealed the accumulation of "fatty abnormal endosomes" in Pdzd8-deficient podocytes during obesity-related kidney diseases. Lipidomic analysis indicated that glucosylceramide accumulated in Pdzd8-deficient podocytes, owing to accelerated production and decelerated degradation. Thus, the organelle-tethering factor, PDZD8, plays a crucial role in maintaining mitochondrial and endosomal homeostasis during podocyte lipotoxicity. Collectively, our findings highlight the importance of organelle communication at the three-way junction among the ER, mitochondria, and endosomes in preserving podocyte homeostasis.

Implementation of a Co-Design Strategy to Develop a Dashboard to Support Shared Decision Making in Advanced Cancer and Chronic Kidney Disease.

Background: Shared decision making (SDM) is the process by which patients and clinicians exchange information and preferences to come to joint healthcare decisions. Clinical dashboards can support SDM by collecting, distilling, and presenting critical information, such as patient-reported outcomes (PROs), to be shared at points of care and in between appointments. We describe the implementation strategies and outcomes of a multistakeholder collaborative process known as "co-design" to develop a PRO-informed clinical dashboard to support SDM for patients with advanced cancer or chronic kidney disease (CKD). Methods: Across 14 sessions, two multidisciplinary teams comprising patients, care partners, clinicians, and other stakeholders iteratively co-designed an SDM dashboard for either advanced cancer (N = 25) or CKD (N = 24). Eligible patients, care partners, and frontline clinicians were identified by six physician champions. The co-design process included four key steps: (1) define "the problem", (2) establish context of use, (3) build a consensus on design, and (4) define and test specifications. We also evaluated our success in implementing the co-design strategy using measures of fidelity, acceptability, adoption, feasibility, and effectiveness which were collected throughout the process. Results: Mean (M) scores across implementation measures of the co-design process were high, including observer-rated fidelity and adoption of co-design practices (M = 19.1 on a 7-21 scale, N = 36 ratings across 9 sessions), as well as acceptability based on the perceived degree of SDM that occurred during the co-design process (M = 10.4 on a 0 to 12 adapted collaboRATE scale). Capturing the feasibility and adoption of convening multistakeholder co-design teams, min-max normalized scores (ranging from 0 to 1) of stakeholder representation demonstrated that, on average, 95% of stakeholder types were represented for cancer sessions (M = 0.95) and 85% for CKD sessions (M = 0.85). The co-design process was rated as either "fully" or "partially" effective by 100% of respondents, in creating a dashboard that met its intended objective. Conclusions: A co-design process was successfully implemented to develop SDM clinical dashboards for advanced cancer and CKD care. We discuss key strategies and learnings from this process that may aid others in the development and uptake of patient-centered healthcare innovations.

Failure to Thrive With Severe Hypokalemia Yields Cystinosis Diagnosis in a 19-Month-Old Female Child: A Case Report.

Cystinosis is a rare, genetically inherited disease that affects lysosomal storage of cysteine. It is the most common cause of Fanconi syndrome. Mutations have led to early-onset end-stage renal disease as well as other systemic organ failures. In this case, we report a 19-month-old female child who presented acutely to the outpatient clinic with nausea, vomiting, and diarrhea. The patient was previously diagnosed with unspecified renal tubular acidosis and treated with oral electrolytes. Early labs during her acute presentation showed severe hypokalemia and electrolyte imbalance, which necessitated a transfer to a pediatric ICU. Through confirmatory testing, a diagnosis of cystinosis was made. This case is an example of the recognition and treatment of a rare inherited disease.

Time Series AI Model for Acute Kidney Injury Detection Based on a Multicenter Distributed Research Network: Development and Verification Study.

Background: Acute kidney injury (AKI) is a marker of clinical deterioration and renal toxicity. While there are many studies offering prediction models for the early detection of AKI, those predicting AKI occurrence using distributed research network (DRN)-based time series data are rare. Objective: In this study, we aimed to detect the early occurrence of AKI by applying an interpretable long short-term memory (LSTM)-based model to hospital electronic health record (EHR)-based time series data in patients who took nephrotoxic drugs using a DRN. Methods: We conducted a multi-institutional retrospective cohort study of data from 6 hospitals using a DRN. For each institution, a patient-based data set was constructed using 5 drugs for AKI, and an interpretable multivariable LSTM (IMV-LSTM) model was used for training. This study used propensity score matching to mitigate differences in demographics and clinical characteristics. Additionally, the temporal attention values of the AKI prediction model's contribution variables were demonstrated for each institution and drug, with differences in highly important feature distributions between the case and control data confirmed using 1-way ANOVA. Results: This study analyzed 8643 and 31,012 patients with and without AKI, respectively, across 6 hospitals. When analyzing the distribution of AKI onset, vancomycin showed an earlier onset (median 12, IQR 5-25 days), and acyclovir was the slowest compared to the other drugs (median 23, IQR 10-41 days). Our temporal deep learning model for AKI prediction performed well for most drugs. Acyclovir had the highest average area under the receiver operating characteristic curve score per drug (0.94), followed by acetaminophen (0.93), vancomycin (0.92), naproxen (0.90), and celecoxib (0.89). Based on the temporal attention values of the variables in the AKI prediction model, verified lymphocytes and calcvancomycin ium had the highest attention, whereas lymphocytes, albumin, and hemoglobin tended to decrease over time, and urine pH and prothrombin time tended to increase. Conclusions: Early surveillance of AKI outbreaks can be achieved by applying an IMV-LSTM based on time series data through an EHR-based DRN. This approach can help identify risk factors and enable early detection of adverse drug reactions when prescribing drugs that cause renal toxicity before AKI occurs.