American Society Of Nephrology Research Articles

A-113 Evaluation of Cystatin C Ordering Trends in a Quaternary Care Health System

Abstract Background Cystatin C is an alternative and adjunct kidney biomarker to creatinine in the estimation of glomerular filtration rate (eGFR). The National Kidney Foundation and American Society of Nephrology have called for increased use of cystatin C in the evaluation of kidney function. Our institution brought cystatin C testing in-house in August 2021. The goal of this study was to evaluate the utilization and longitudinal ordering trends of cystatin C within our quaternary care health system. Methods Cystatin C is measured on a Roche cobas® c502 using an assay traceable to IFCC-certified reference material. The electronic health record system (Epic) was queried using Epic SlicerDicer to identify ordering trends within our academic medical center between July 2021 and January 2024. The frequency of unique (one-time) cystatin C orders and concomitant orders with creatinine was also conducted. An in-depth analysis and chart review was performed over a one-month period to evaluate ordering locations, underlying clinical conditions, including previous diagnosis of kidney disease, and correlations between cystatin C and creatinine measurements. Results Between July 2021 and January 2024, 11,577 tests were performed from 8,415 unique patients. Cystatin C orders remained stable since April 2022, with an average 370 orders (363-378) per month. Eighty percent of cystatin C test requests were accompanied with creatinine testing during the same encounter. In a detailed analysis of a one month period, cystatin C testing was primarily performed in patients with an existing diagnosis of kidney disease (66%) and in the evaluation of renal function in patients with a cancer diagnosis (23%). Conclusions There has been sustained adoption of cystatin C by providers at our institution. The majority of orders have occurred in patients with an underlying renal diagnosis, as well as comorbid or chronic conditions that may affect kidney function.

ChatGPT Solving Complex Kidney Transplant Cases: A Comparative Study With Human Respondents.

ChatGPT has shown the ability to answer clinical questions in general medicine but may be constrained by the specialized nature of kidney transplantation. Thus, it is important to explore how ChatGPT can be used in kidney transplantation and how its knowledge compares to human respondents. We prompted ChatGPT versions 3.5, 4, and 4 Visual (4V) with 12 multiple-choice questions related to six kidney transplant cases from 2013 to 2015 American Society of Nephrology (ASN) fellowship program quizzes. We compared the performance of ChatGPT with US nephrology fellowship program directors, nephrology fellows, and the audience of the ASN's annual Kidney Week meeting. Overall, ChatGPT 4V correctly answered 10 out of 12 questions, showing a performance level comparable to nephrology fellows (group majority correctly answered 9 of 12 questions) and training program directors (11 of 12). This surpassed ChatGPT 4 (7 of 12 correct) and 3.5 (5 of 12). All three ChatGPT versions failed to correctly answer questions where the consensus among human respondents was low. Each iterative version of ChatGPT performed better than the prior version, with version 4V achieving performance on par with nephrology fellows and training program directors. While it shows promise in understanding and answering kidney transplantation questions, ChatGPT should be seen as a complementary tool to human expertise rather than a replacement.

EGFR inhibition with erlotinib induces membrane accumulation of aquaporin-2 via PDK1 and RSK activation

In the canonical aquaporin-2 (AQP2) signaling pathway, vasopressin (VP) binds to its V2 receptor, which in turn activates adenylate cyclase and protein kinase A (PKA), resulting in AQP2 S256 phosphorylation and accumulation of AQP2 in the membrane. The epidermal growth factor receptor (EGFR) inhibitor erlotinib also increases AQP2 S256 phosphorylation and membrane accumulation, yet it does not increase cAMP or PKA activity. We hypothesize that the ribosomal s6 kinase (RSK), a downstream effector in the EGFR-MAPK/ERK pathway, is the terminal kinase phosphorylating AQP2 in this novel PKA-independent pathway activated by erlotinib, and that the phosphoinositide dependent kinase-1 (PDK1), a well-established activator of RSK, is indispensable for erlotinib-induced AQP2 activation. Using our LLC-AQP2 cell model, we show that erlotinib-induced AQP2 membrane accumulation and S256 phosphorylation are abolished by the specific RSK inhibitor BI-D1870. RSK knockdown with siRNA also blocked AQP2 S256 phosphorylation and membrane accumulation, as did RSK knockout with CRISPR/cas9 editing. Next, rat kidney slices were incubated in Hank’s buffer with or without BI-D1870 and treated with erlotinib. BI-D1870 inhibited AQP2 membrane accumulation in collecting duct principal cells, supporting the relevance of this pathway in kidney cells in situ. An in-vitro kinase assay using purified proteins demonstrated that RSK directly phosphorylates AQP2 at the S256 residue. Additionally, erlotinib consistently increased phosphorylation of RSK T359, a residue associated with RSK’s active state. In canonical RSK activation, a phosphorylation cascade results in PDK1 binding to and activating RSK. We found that PDK1 inhibition with an experimental compound PS-222 also blocked erlotinib-induced AQP2 membrane accumulation and S256 phosphorylation. This implicates PDK1 along with RSK in the novel erlotinib-induced pathway of AQP2 traffcking. Our data show that RSK and PDK1 are terminal effectors in the novel, PKA-independent pathway of AQP2 activation induced by erlotinib. Further elaboration of this new non-canonical pathway promises to uncover potential pharmacological targets for the treatment of water balance disorders. This work was supported by the National Institutes of Health (NIH) grant DK096586 (D. Brown). P. W. Cheung was supported was supported by NIH K-award DK115901. Richard Babicz is the recipient of the Ben J Lipps Research Fellowship (American Society of Nephrology). Additional support for the Program in Membrane Biology Microscopy Core came from the Boston Area Diabetes and Endocrinology Research Center (DK057521) and the Massachusetts General Hospital (MGH) Center for the Study of Inflammatory Bowel Disease (DK043351). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oxidative stress induced by menadione (vitamin K3) results in non-canonical AQP2 membrane traffcking in LLC-AQP2 cells

Oxidative stress affects a wide variety of cellular processes including morphology, protein traffcking, and cell death. Several studies show that reactive oxygen species (ROS) are able to pass through some water channels, and that ROS may modulate aquaporin expression and traffcking. However, a relationship between ROS status and the traffcking of aquaporin-2 (AQP2) has yet to be well-defined. To address this question, we first treated LLC-PK1 cells expressing cmyc-tagged AQP2 (LLC-AQP2 cells) for 30 min with menadione (MK3, 20 μM), an agent widely used to generate ROS in cell culture. Similar to vasopressin (VP), MK3 induced significant AQP2 accumulation in the plasma membrane of these cells. Using LLC-AQP2 cells expressing secreted soluble green fluorescent protein (ss-GFP), we revealed significantly increased vesicle exocytosis upon treatment with MK3. Surprisingly, MK3 did not affect rhodamine-labeled dextran endocytosis, suggesting that the MK3 effect is mainly due an increase in AQP2 exocytosis into the plasma membrane. Next, we studied the role of AQP2 c-terminal serine 256 phosphorylation in this process. MK3 treatment resulted in significant plasma membrane accumulation of the non-phosphorylatable AQP2 S256A mutant, whereas VP had no effect, as previously reported. To understand the contribution of protein kinase A (PKA) to MK3-mediated AQP2 traffcking, we used CRISPR-generated LLC-AQP2,koPKA cells that lack PKA isoforms. Interestingly, an increase in AQP2 membrane accumulation was still observed, suggesting that the MK3 effect is PKA-independent. By western blotting with anti-phospho-AQP2 antibodies, we found that MK3 did not affect phosphorylation of the critical S256 residue, but in contrast to VP, MK3 actually increased the phosphorylation level of S261 instead of reducing it. Finally, we showed that AQP2 accumulation in both LLC-AQP2 and LLC-AQP2 S256A cells was inhibited in the presence of glutathione (5 mM), an anti-oxidant or reducing agent. Interestingly, western blot analysis showed that glutathione abolished the MK3-induced increase of S261 AQP2 phosphorylation. In summary, our study shows that menadione (MK3) induces AQP2 membrane accumulation in LLC-AQP2 cells, suggesting a role of ROS in this process. This effect is largely due a change in AQP2 vesicle exocytosis. It does not require phosphorylation of the c-terminal S256 residue of AQP2, but MK3 does cause increased S261 phosphorylation. While incompletely understood at present, these data reveal that alternative, probably ROS-related, regulatory mechanisms can be involved in AQP2 traffcking and recycling. This work was supported by the National Institutes of Health (NIH) grant DK096586 (D. Brown). P. W. Cheung was supported was supported by NIH K-award DK115901. Richard Babicz is the recipient of the Ben J Lipps Research Fellowship (American Society of Nephrology). Additional support for the Program in Membrane Biology Microscopy Core came from the Boston Area Diabetes and Endocrinology Research Center (DK057521) and the Massachusetts General Hospital (MGH) Center for the Study of Inflammatory Bowel Disease (DK043351). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chronic kidney disease and the global public health agenda: an international consensus.

Early detection is a key strategy to prevent kidney disease, its progression and related complications, but numerous studies show that awareness of kidney disease at the population level is low. Therefore, increasing knowledge and implementing sustainable solutions for early detection of kidney disease are public health priorities. Economic and epidemiological data underscore why kidney disease should be placed on the global public health agenda - kidney disease prevalence is increasing globally and it is now the seventh leading risk factor for mortality worldwide. Moreover, demographic trends, the obesity epidemic and the sequelae of climate change are all likely to increase kidney disease prevalence further, with serious implications for survival, qualityoflife and health care spending worldwide. Importantly, the burden of kidney disease is highest among historically disadvantaged populations that often have limited access to optimal kidney disease therapies, which greatly contributes to current socioeconomic disparities in health outcomes. This joint statement from the International Society of Nephrology, European Renal Association and American Society of Nephrology, supported by three other regional nephrology societies, advocates for the inclusion of kidney disease in the current WHO statement on major non-communicable disease drivers of premature mortality.

Sparsentan, a Dual Endothelin Type A and Angiotensin II Subtype 1 Receptor Antagonist for the Treatment of Immunoglobulin A Nephropathy: Latest Trial Results, Pharmacokinetic Considerations, and Binding Profile

Immunoglobulin A nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. In some patients, it can progress rapidly, leading to proteinuria, kidney failure, and death. Standard of care is traditionally with an angiotensin converting enzyme inhibitor (ACEi), or an angiotensin II (Ang II) receptor blocker (ARB). More recently, drugs targeting both endothelin 1 (ET-1) and Ang II receptors have been developed, as overactivation of such is implicated in IgAN. Sparsentan is a dual ET Type A (ETAR) and Ang II subtype 1 receptor (AT1R) antagonist. The PROTECT study compared sparsentan with the ARB irbesartan, in patients with IgAN and with proteinuria of ≥1 g/day despite stable dose of ACEi/ARB for ≥90 days. Data presented at the 2023 American Society of Nephrology (ASN) Kidney Week showed that use of sparsentan led to sustained (>110 weeks) decreases in proteinuria, and a significantly greater preservation of kidney function, compared with irbesartan. The ongoing SPARTAN study is investigating the use of sparsentan in recently diagnosed, treatment-naïve patients with IgAN. Preliminary data in 12 patients showed rapid and sustained proteinuria reductions, with little change from baseline in estimated glomerular filtration rate (eGFR), body weight, or total body water mean at Week 36. In both studies, sparsentan was generally well-tolerated with, in PROTECT, a comparable safety profile to irbesartan. Data presented at the congress also showed that sparsentan consistently occupies AT1R at levels exceeding ETAR occupancy. This balance is hypothesised to contribute to sparsentan’s limited risk of fluid retention.

Sudan's healthcare crisis: The struggle of kidney patients amidst conflict.

Conflicts, akin to other crises, disrupt lives and healthcare infrastructure, disproportionately affecting vulnerable individuals. The ongoing Sudanese conflict, initiated on April 15, 2023, between the Sudanese Armed Forces (SAF) and the Rapid Support Force (RSF), triggers significant population displacement, healthcare facility closures, and a scarcity of medical resources. Amid the intense conflict in Khartoum, reports of deceased individuals in the streets heighten concerns about public health, emphasizing the gravity of the situation. This crisis compounds the challenges faced by Sudan's already fragile healthcare system, impacting over 5 million displaced individuals, including those reliant on life-saving hemodialysis sessions. This commentary aims to illuminate the challenges confronting kidney dialysis patients in war-torn Sudan, emphasizing the impact on the Al-Goled hemodialysis center. This commentary relies on reports from the American Society of Nephrology (ASN), European Renal Association (ERA), and The International Society of Nephrology (ISN), along with recent journal articles discussing the consequences of ongoing conflicts. Personal observations in Al-Goled contribute to the insights, and data from the Al-Goled hemodialysis center in Sudan illuminate the struggles faced by kidney dialysis patients during the conflict, presented as a case study. Kidney dialysis patients, crucial for regular hemodialysis sessions, confront severe challenges due to the overwhelming conflict. With an estimated 8000 kidney failure patients in Sudan, disruptions in healthcare services, targeted attacks on medical staff, and a shortage of resources exacerbate their plight. The Al-Goled hemodialysis center, initially designed for 30 daily sessions, experiences a surge in demand, accommodating 85 patients daily-an alarming 183% increase. Limited resources, machine malfunctions, and a shortage of medications contribute to the loss of 13 patients' lives. The conflict in Sudan disproportionately impacts kidney dialysis patients, causing disruptions in essential healthcare services. The surge in demand at the Al-Goled center underscores the broader impact on healthcare institutions nationwide. Local efforts to source medical supplies face bureaucratic hurdles and complex exportation procedures, impeding support for kidney patients. Patients, once receiving 3 weekly sessions, now struggle to secure even one, jeopardizing their well-being. Urgent international intervention is needed to cease the conflict and ensure the safety of healthcare facilities, especially for vulnerable populations like kidney dialysis patients.

Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. Literature review and expert consensus. English language publications evaluating GFR assessment and racial disparities. We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

A Canadian Commentary on the NKF-ASN Task Force Recommendations on Reassessing the Inclusion of Race in Diagnosing Kidney Disease

In 2021, a committee was commissioned by the Canadian Society of Nephrology (CSN) to comment on the 2021 National Kidney Foundation (NKF)- American Society of Nephrology (ASN) Task Force recommendations on the use of race in glomerular filtration rate (GFR) estimating equations. The committee met on numerous occasions and agreed on several recommendations. However, the committee did not achieve unanimity, with a minority group disagreeing with the scope of the commentary. As a result, this report presents the viewpoint of the majority members. We endorsed many of the recommendations from the NKF-ASN Task Force, most importantly that race should be removed from the eGFR creatinine-based equation. We recommend an immediate implementation of the new CKD-EPI equation (2021), which does not discriminate among any group while maintaining precision. Additionally, we recommend that Canadian laboratories and provincial kidney organizations advocate for increased testing and access to cystatin C as the combination of cystatin C and creatinine in revised equations leads to more precise estimates. Lastly, we recommend that future research studies evaluating the implementation of the new equations and changes to screening, diagnosis, and management across provincial health programs be prioritized in Canada.

Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records

Randomised clinical trials showed that compared with placebo, SGLT2 inhibitors and GLP-1 receptor agonists reduced risk of adverse cardiovascular events. The evidence base for the older antihyperglycaemic drug classes (DPP-4 inhibitors and sulfonylureas) is generally less well developed. Because most randomised trials evaluated one antihyperglycaemic medication versus placebo, a head-to-head comparative effectiveness analysis of the newer drug classes (SGLT2 inhibitors vs GLP-1 receptor agonists) or newer (SGLT2 inhibitors or GLP-1 receptor agonists) versus older (DPP-4 inhibitors or sulfonylureas) drug classes on risk of major adverse cardiovascular events (MACE) is not available. In this study, we aimed to evaluate the comparative effectiveness of incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas on risk of MACE. We first specified the protocol of a four-arm randomised pragmatic clinical trial and then emulated it using the health-care databases of the US Department of Veterans Affairs. We built a cohort of metformin users with incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas between Oct 1, 2016 and Sept 30, 2021, and followed up until Dec 31, 2022. We used the overlap weighting approach to balance the treatment groups using a battery of predefined variables and a set of algorithmically selected variables from high-dimensional data domains. Both intention-to-treat and per-protocol analyses (the latter estimated the effect of maintained use of the antihyperglycaemic throughout follow-up) were conducted to estimate risk of MACE-defined as a composite endpoint of stroke, myocardial infarction, and all-cause mortality. The final cohort consisted of 283 998 new users of SGLT2 inhibitors (n=46 516), GLP-1 receptor agonists (n=26 038), DPP-4 inhibitors (n=55 310), or sulfonylureas (n=156 134). In intention-to-treat analyses, compared with sulfonylureas, SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors were associated with lower risk of MACE (hazard ratio [HR] 0·77 [95% CI 0·74-0.80], 0·78 [0·74-0·81), and 0·90 [0·86-0.93], respectively). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of MACE when compared with DPP-4 inhibitors (HR 0·86 [0·82-0·89] and 0·86 [0·82-0·90], respectively). The risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists yielded an HR of 0·99 (0·94-1·04). In per-protocol analyses, compared with sulfonylureas, SGLT2 inhibitors, GLP1 receptor agonists, and DPP-4 inhibitors were associated with reduced risk of MACE (HR 0·77 [95% CI 0·73-0·82], 0·77 [0·72-0·82], and 0·88 [0·83-0·93], respectively). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of MACE when compared with DPP-4 inhibitors (HR 0·88 [0·83-0·93] and 0·88 [0·82-0·93], respectively). The risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists yielded an HR of 1·01 (0·94-1·07). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with reduced risk of MACE compared with DPP-4 inhibitors or sulfonylureas. DPP-4 inhibitors were associated with reduced risk of MACE compared with sulfonylureas. There was no statistically significant difference in risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists. The results provide evidence of the real-world comparative effectiveness of the four most commonly used second-line antihyperglycaemics and could guide choice of antihyperglycaemic therapy. US Department of Veterans Affairs and the American Society of Nephrology.

420-P: Longitudinal Trajectories of Tubular Biomarkers in Type 1 Diabetes

Background: Tubular biomarkers may provide insight into progression of kidney tubulointerstitial pathology that is complementary to traditional measures of glomerular function and damage. Methods: We examined longitudinal tubular biomarker trajectories in the DCCT/EDIC Study of T1D. For each of 220 randomly-selected participants, biomarkers were measured at up to 7 time points over 26 years. Measurements comprised KIM-1 and sTNFR1 in plasma, EGF and MCP1 in timed urine, and a composite tubular secretion score calculated from the urinary clearances of 8 small molecules secreted by the proximal tubule. Biomarker trends were described and associations with intensive diabetes therapy and glycemia changes over time were tested. Results: Mean age was 28 years at baseline, 45% were women, and 50% were assigned to intensive versus conventional therapy during DCCT. At baseline, participants had a mean estimated glomerular filtration rate (eGFR) of 125 ml/min/1.73m2, and 90% had a urinary albumin excretion rate (AER) < 30 mg/24h. Mean changes in biomarkers over time (in percent per decade) were: KIM-1 27.3% (95% CI 21.4, 33.5), sTNFR1 16.9% (95% CI 14.5, 19.3), MCP1 18.4% (95% CI 8.9, 28.8), EGF -13.5% (95% CI -16.7, -10.1), EGF/MCP1 -26.9% (95% CI -32.2, -21.3), and tubular secretion score -0.9% (95% CI -1.8, 0.0), compared with -12.0% (95% CI -12.9, -11.1) for eGFR and 10.9% (95% CI 2.5, 20.1) for AER. Intensive versus conventional therapy was associated with slower rise in sTNFR1 (relative difference in change 0.94; 95% CI 0.90, 0.98). Higher time-updated HbA1c was associated with faster rises in sTNFR1 (relative difference in change 1.06 per 1% higher HbA1c; 95% CI 1.05, 1.08) and KIM-1 (1.09; 95% CI 1.05, 1.14). Conclusion: Among people with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in plasma sTNFR1 and KIM1 over time. Disclosure C.Limonte: None. I.Bebu: None. J.Seegmiller: None. M.Molitch: Consultant; Amryt Pharma Plc, Corcept Therapeutics, Janssen Pharmaceuticals, Inc., Sention, Takeda Pharmaceutical Co., Ltd. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.B.Karger: Consultant; Roche Diagnostics, Research Support; Kyowa Kirin Co., Ltd., Siemens, Speaker's Bureau; Siemens, American Society of Nephrology, American Kidney Fund, National Kidney Foundation. I.De boer: Advisory Panel; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Boehringer Ingelheim International GmbH, Otsuka America Pharmaceutical, Inc., Bayer Inc., Consultant; George Clinical, Gilead Sciences, Inc., Medscape, Research Support; Dexcom, Inc. Dcct/edic writing group: n/a. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK094176, U01DK094157)

#5861 NEW-ONSET OR EXACERBATIONS OF GLOMERULONEPHRITIS FOLLOWING SARSCOV2 VACCINE: A REVIEW OF THE LITERATURE

Abstract Background and Aims Following vaccination against SarsCoV2 several cases of new-onset glomerulonephritis or exacerbations of glomerular diseases have been reported [1, 2]. No literature review has been published yet on the subject. Method We searched for single case or case series through the PubMed portal search and through the abstract search submitted to the EDTA and the American Society of Nephrology in 2021 and 2022 (last view on the 15th of December 2022). Results A total of 138 cases were analyzed, of which 127 complete for all the variables. The mean age was 52.6±20.75 years (min 12, max 99), M/F 67/63. The majority of patients received mRNA vaccine (BNT16b2 Pfizer (n = 70, 51%), mRNA-1273 Moderna (n = 42, 30.7%), followed by AZD1222 AstraZeneca (n = 10, 7.3%) and Ad26.COV2.S Johnson & Johnson (n = 4, 2.9%). A minority of cases were associate with Covaxin and Sinovac (Figure 1). Most cases were reported from the European continent (39.4%, n = 54), followed by North America (35.8%, n = 49) and Asia (21.9%, n = 30). A minority of cases were reported from Australia and Central/South America. The onset of glomerulonephritis occurred after a mean of 17.8 days±22.82 (min 1, max 89). In 37.4% of cases (n = 49), glomerulonephritis occurred after the first dose, in 61.8% after the second (n = 81), only 1 case after the third one. Regarding mRNA vaccine, in most cases, the disease occurred after the second dose (n = 78, 70.9% of cases, p<0.001). Gross hematuria as the initial symptom was significantly related to mRNA vaccination (27/27 cases). 30 cases (24.8%) showed nephrotic syndrome at onset. The most prevalent diagnosis was IgA nephropathy (n = 36, 26.3%), followed by vasculitis (n = 33, 24%), Minimal Change Disease (n = 26, 19%), and membranous nephropathy (n = 14, 10.2%) (Figure 2). Interesting, 6 cases (4.4%) of anti-GBM GN were reported. Compared to patients with glomerulonephritis, those with systemic vasculitis were older (59.84±19.43 vs 49.21±21.21 years), with a slightly shorter onset time (14.9±12.67 days, vs 16.6±24.14 days). Both vasculitis and glomerulonephritis generally occurred more frequently following mRNA vaccination. For vasculitis, ANCA-MPO was more frequent (n = 15, 45.45%), followed by ANCA PR3 (n = 10, 30.3%), and finally IgA vasculitis (n = 3,9%). Two cases (6.06%) were ANCA negative. New-onset glomerulonephritis accounted for 78.8% (n = 108), while relapses accounted for 21.2% (n = 29). There was no significant difference between the type of vaccine and de-novo or relapse glomerulonephritis. Patients were treated with steroid only (43.4%, n = 56), steroid and immunosuppressant (n = 21,16.3%), rituximab alone or in combination (n = 26, 20.15%), conservative therapy (24, 18.6%). 6 patients (4.4%) underwent dialysis, 2.9% (n = 4) received plasmapheresis. 80 patients (69%) responded effectively to therapy, achieving complete remission, 19% (n = 22) achieved partial remission, while 2.1% (n = 14) did not respond to therapy. Evolution towards ESKD occurred in 11 cases (8%). Conclusion New-onset glomerulonephritis or exacerbations of glomerular diseases that were in remission is a possible complication of SarsCov2 vaccination. Most patients received mRNA vaccine; more than half of the patient developed or worsened the GN after the second dose.

Shari Leventhal: Pitching in to Support CSE

Having worked at the American Society of Nephrology (ASN) for 20 years, Shari Leventhal has seen a lot of change in scholarly societies and scientific publishing. Beginning in the Communications department at ASN, Shari became a Managing Editor in 2012 for the Clinical Journal of the American Society of Nephrology (CJASN) and then the Executive Editor of the ASN portfolio of journals in March 2019. As she begins her term as the President of the Council of Science Editors, Shari spoke with Science Editor about her goals for CSE this year, the importance of accessibility, and the need to sometimes step up and get things done. Science Editor: How did you get involved in scientific editing and publishing, and what career path led to your current position? Shari Leventhal: My background was in communications, and I was working in public relations for ASN, but I didn’t really love the pressure of being put on the spot. My supervisor at the time was looking for a second Managing Editor to assume oversight for the clinical journal, and believed that my skill set would be the perfect fit to manage the journal. When she approached me with the opportunity, I was intrigued. I love managing multiple projects at once and improving efficiency. Additionally, I had worked with the Editor in Chief previously and liked him quite a bit. I thought that if I was going to move into scholarly publishing, he would be a great EIC to work with. SE: What […]

July Meeting Announcements

October 7-10, 2023, Academy of Nutrition and Dietetics, Food and Nutrition Conference and Expo (FNCE) 2023, Colorado Convention Center, Denver, CO. www.eatright.org/FNCE or call 800-877-1600 ext. 4862. October 14-16, 2023, American Nephrology Nurses Association (ANNA) Fall Meeting, Hilton Chicago, Chicago, IL. www.annanurse.org/events/2023-nephrology-nursing-practice-management-leadership-conference or call 888-600-2662. November 2-5, 2023, American Society of Nephrology (ASN) Kidney Week 2023, Pennsylvania Convention Center, Philadelphia, PA. www.asn-online.org/education or call 866-849-8868. April 13-16, 2024, International Society of Nephrology (ISN) World Congress of Nephrology 2024, Buenos Aires, Argentina. Visit www.theisn.org/wcn. April 14-17, 2024, American Nephrology Nurses Association (ANNA) 2024 Natl Symp Caribe Royale All Suite Hotel Convention Cent Orlando, FL. www.ananurse.org/events/2024-national-symposium or call 888-600-2662 May 14-18, 2024, National Kidney Foundation (NKF) Spring Clinical Meeting, Long Beach, CA. Visit www.kidney.org. or call 800-622-9010. May 23-26, 2024, 61st European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) Congress, Stockholmsmassan, Stockholm, Sweden, [email protected]. August 28-31, 2024, International Society on Renal Nutrition and Metabolism, 21st Congress of the International Society of Renal Nutrition and Metabolism, Hyderabad, India. www.icrnm2024.com. September 26-29, 2024, International Society for Peritoneal Dialysis, 40th Anniversary Congress, Dubai, UAE. www.ispd.org/dubai2024.

Editorial introductions.

Current Opinion in Nephrology and Hypertension was launched in 1992. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of nephrology and hypertension is divided into 12 sections that are each reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Agnes B FogoAgnes B FogoProfessor Agnes Borge Fogo completed her medical training at Vanderbilt University Medical School, USA. She has remained at Vanderbilt for residency in pathology and fellowship in renal pathology and experimental kidney disease models. Her main research interests are focused on potential regression of chronic kidney disease and tubular-glomerular crosstalk in this process, pursued with funding from the National Institutes of Health and other sources. She is also dedicated to diagnostic renal pathology and has created an online Atlas of Renal Pathology with the American Journal of Kidney Disease and the National Kidney Foundation. She has also authored two books on renal pathology. Prof. Fogo enjoys teaching renal pathology and received the Robert G. Narins award from the American Society of Nephrology in 2011 as well as the Roscoe R. Robinson award from the International Society of Nephrology in 2019, for her contributions in teaching. She is currently President of the ISN and the John L. Shapiro Professor of Pathology, Microbiology and Immunology, Professor of Medicine and Paediatrics and Director of the Renal/Electron Microscopy Laboratory at Vanderbilt University Medical Center, Nashville, Tennessee, USA. Navdeep TangriNavdeep TangriDr Tangri is an attending physician and Professor in the Division of Nephrology, Department of Internal Medicine, and the Rady Faculty of Community Health Sciences at the University of Manitoba, Winnipeg, Canada. Dr Tangri's research program is clinical, translational, and focused on improving clinical decision making for patients with advanced chronic kidney disease. He developed and validated the Kidney Failure Risk Equation to predict the need for dialysis in patients with CKD and is presently engaged in multiple validation and implementation exercises to increase the uptake of the KFRE. In addition, Dr Tangri is conducting a large prospective study on frailty, physical and cognitive function in advanced CKD, as well as leading a multinational randomized trial on the safety and efficacy of a new therapy in this population. He has published over 300 manuscripts, presented at multiple national and international scientific meetings, and is a recipient of the CIHR New Investigator Award and a CIHR Foundation grant.

TIGIT mediates experimental ischemia reperfusion and nephrotoxic acute kidney injury in mice

Abstract Background: We unexpectedly found upregulated expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on kidney CD4 T cells after ischemia reperfusion (IR) using RNA-Seq. However, TIGIT role in kidney T cells and during acute kidney injury (AKI) is poorly understood. Methods: Effect of TIGIT on murine kidney T cells was assessed at baseline and after IR injury by flow cytometry and single cell RNA sequencing (scRNA-Seq). B6 wild type (WT) and TIGIT knockout (KO) mice were subjected to IR and cisplatin-induced AKI. TIGIT expression was assessed in AKI patients using the Kidney Precision Medicine Project (KPMP) scRNA-Seq dataset. Results: We found increased kidney CD4+TIGIT+ central memory (10.0±2.3 vs 0.9±0.1%, p=0.001) cells compared to CD4+TIGIT− cells in WT mice. TIGIT KO mice had reduced serum creatinine (SCr) after IR (24h Scr, 1.1±0.2 vs 2.7±0.1 mg/dL; p≤0.001) and cisplatin (72h Scr, 0.8±0.1 vs 1.4±0.1 mg/dL; p=0.0002) injury compared to WT mice. TIGIT KO kidneys had reduced necrotic tubules in outer medulla after IR (48.8±4.7% vs 73.0±1.5%; p=0.001) and cisplatin (11.5±3.0% vs 31.3±4.0%; p=0.008) injury than WT kidneys. Gene set enrichment analysis of scRNA-Seq data showed enrichment of inflammatory genes in Th17 cells from WT kidney and oxidative phosphorylation and mTORC1 signaling genes in TIGIT KO kidney. Human KPMP data demonstrated significant TIGITexpression in kidney T/NK cells from AKI patients compared to controls (p≤0.0001). Conclusions: TIGIT mediates both IR and nephrotoxic AKI in mice and its expression increases in kidney T cells from AKI patients. TIGIT is a promising novel therapeutic target for AKI, and also relevant due to increasing efforts to develop TIGIT blockade to treat cancers. American Society of Nephrology, Johns Hopkins University Ed Kraus Award, National Kidney Foundation of Maryland and Delaware

Editorial introduction

Editorial introduction

Reimagining Nephrology Fellowship Education to Meet the Future Needs of Nephrology: A Report of the American Society of Nephrology Task Force on the Future of Nephrology.

The American Society of Nephrology (ASN) Task Force on the Future of Nephrology was established in April 2022 in response to requests from the American Board of Internal Medicine and the Accreditation Council for Graduate Medical Education regarding training requirements in nephrology. Given recent changes in kidney care, ASN also charged the task force with reconsidering all aspects of the specialty's future to ensure that nephrologists are prepared to provide high-quality care for people with kidney diseases. The task force engaged multiple stakeholders to develop 10 recommendations focused on strategies needed to promote: ( 1 ) just, equitable, and high-quality care for people living with kidney diseases; ( 2 ) the value of nephrology as a specialty to nephrologists, the future nephrology workforce, the health care system, the public, and government; and ( 3 ) innovation and personalization of nephrology education across the scope of medical training. This report reviews the process, rationale, and details (the "why" and the "what") of these recommendations. In the future, ASN will summarize the "how" of implementing the final report and its 10 recommendations.

Engagement in Free Open Access Medical Education by US Nephrology Fellows.

As free open access medical education (FOAMed) use increases, it is important to characterize how and why learners are using this educational material in nephrology. We describe the frequency, purpose, and type of FOAMed usage across US nephrology fellows. In this cross-sectional survey, items were emailed to all US adult and pediatric nephrology fellows via the American Society of Nephrology (ASN) Fellow Survey in May 2022. The eight-item survey, developed to measure FOAMed engagement, had previously undergone instrument validation. The results were analyzed by descriptive statistics. In total, 43% (359/842) adult nephrology fellows and 51% (45/88) pediatric nephrology fellows completed the survey. Seventy-four percent (300/404) of fellows reported using FOAMed, and 72% (215/300) started using FOAMed within the past 2 years. Of FOAMed users, 41% (122/300) reported viewing FOAMed and 33% (99/300) reported applying knowledge gained from these resources daily or weekly. Common purposes for FOAMed engagement included searching Twitter to learn about others' opinions in the field (43%; 130/300), reading blogs to answer clinical questions (35%; 105/300), and listening to podcasts for the most up-to-date information (39%; 116/300). Compared with traditional educational resources, fellows preferred using FOAMed for staying up to date on nephrology topics (75%) and answering clinical questions (37%). Among all fellows, the greatest barriers to FOAMed use were unfamiliarity with FOAMed (27%; 111/404), validity concerns (22%; 90/404), and a lack of a local community of FOAMed users (22%; 87/404). Seventy-four percent of nephrology fellows used FOAMed resources in a variety of ways, and of them, 33% of fellows clinically applied knowledge gained from these resources. Reasons for engaging with FOAMed varied across resources.

Deprescribing the Kt/V Target for Peritoneal Dialysis in the United States: The Path Toward Adopting International Standards for Dialysis Adequacy.

Deprescribing the Kt/V Target for Peritoneal Dialysis in the United States: The Path Toward Adopting International Standards for Dialysis Adequacy.