Nephrology Commons^™

From Infection To Encapsulation; A Case Report On Encapsulating Peritoneal Sclerosis, Clinical Challenges And Management, Sidra Memon Md, Jacob Seth Psomiadis Md, Syed Uzair Mahmood, Jennifer Hoffman Md

Advances in Clinical Medical Research and Healthcare Delivery

Encapsulating Peritoneal Sclerosis (EPS) is a rare but deadly sequlae of peritoneal dialysis resulting in intraperitoneal inflammation and fibrosis. The disease itself can present in a variety of ways and is associated with significant morbidity and mortality. Here we present the case of a man in his 50's with a history of chronic peritoneal aspergillus as well as end-stage renal disease on peritoneal dialysis that had multiple admissions for abdominal fluid collections as well as bowel obstruction. After a multidisciplinary approach, the patient was diagnosed with encapsulating peritoneal sclerosis and then started the recommended therapy of tamoxifen and prednisone.

National Liver Cancer Screening Trial (Tracer) Study Protocol, Amit G Singal, Neehar D Parikh, Fasiha Kanwal, Jorge A Marrero, Sneha Deodhar, Stephanie Page-Lester, Camden Lopez, Ziding Feng, Nabihah Tayob

Faculty, Staff and Students Publications

BACKGROUND: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. …

Asn Kidney Health Guidance On The Management Of Obesity In Persons Living With Kidney Diseases, T Alp Ikizler, Holly J Kramer, Srinivasan Beddhu, Alex R Chang, Allon N Friedman, Meera N Harhay, Elizabeth Yakes Jimenez, Brandon Kistler, Aleksandra Kukla, Kristin Larson, Lindamarie U Lavenburg, Sankar Dass Navaneethan, John Ortiz, Rocio I Pereira, David B Sarwer, Philip R Schauer, Evan M Zeitler

Faculty, Staff and Students Publications

No abstract provided.

Macrophage Iron Dyshomeostasis Promotes Aging-Related Renal Fibrosis, Lingzhi Wu, Hongchun Lin, Shaomin Li, Yuebo Huang, Yuxiang Sun, Shuangshuang Shu, Ting Luo, Tiantian Liang, Weiyan Lai, Jialing Rao, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Renal aging, marked by the accumulation of senescent cells and chronic low-grade inflammation, leads to renal interstitial fibrosis and impaired function. In this study, we investigate the role of macrophages, a key regulator of inflammation, in renal aging by analyzing kidney single-cell RNA sequencing data of C57BL/6J mice from 8 weeks to 24 months. Our findings elucidate the dynamic changes in the proportion of kidney cell types during renal aging and reveal that increased macrophage infiltration contributes to chronic low-grade inflammation, with these macrophages exhibiting senescence and activation of ferroptosis signaling. CellChat analysis indicates enhanced communications between macrophages and tubular …

First Interim Results From Fine-Real: A Prospective, Non-Interventional, Phase 4 Study Providing Insights Into The Use And Safety Of Finerenone In A Routine Clinical Settingfirst Interim Results From Fine-Real: A Prospective, Non-Interventional, Phase 4 Study Providing Insights Into The Use And Safety Of Finerenone In A Routine Clinical Setting, Susanne B Nicholas, Ricardo Correa-Rotter, Nihar R Desai, Lixin Guo, Sankar D Navaneethan, Kevin M Pantalone, Christoph Wanner, Stefanie Hamacher, Samuel T Fatoba, Andrea Horvat-Broecker, Antonio Garreta-Rufas, Alain Gay, Martin Merz, David C Wheeler

Center for Medical Ethics and Health Policy Staff Publications

Background: Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). The FINE-REAL study (NCT05348733) aims to evaluate the characteristics and treatment patterns of participants treated with finerenone in clinical practice.

Methods: FINE-REAL is a prospective, single-arm, non-interventional study of patients initiated on finerenone as part of their routine care in accordance with country-approved labels. The study, initiated in June 2022, is expected to be completed by January 2028. The cutoff for this pre-specified interim analysis was June 13, 2023.

Results: Participants were …

Evaluation Of Short-Term Complications In Laparoscopic Peritoneal Dialysis Catheter Placement - A Single Tertiary Center Experience, Cristina Raluca Iorga, Iuliana Andreiana, Simona Hildegrad Stancu, Traian Constantin, Victor Strambu, Cristian Iorga

Journal of Mind and Medical Sciences

Background. Peritoneal dialysis is a form of kidney function replacement that is not as widespread as hemodialysis. However, it has recognized advantages, such as preservation of residual renal function, lack of vascular access, and the ability to be performed at home. On the other hand, it requires the correct insertion of a peritoneal dialysis (PD) catheter and maintaining its patency. Methods. We conducted a retrospective study of 126 patients with end-stage renal disease who underwent laparoscopic Tenckhoff catheter placement for peritoneal dialysis between January 2016 and December 2022. The study analyzed the frequency and type of complications registered within three …

Transjugular Random Renal Biopsy: A Review, Katelyn Gill, Dan F. Laney Iv, Hector Ferral

School of Medicine Faculty Publications

Random renal biopsy is considered the gold standard for the diagnosis of systemic renal disorders. Percutaneous biopsy remains a safe option for most patients; however, the percutaneous approach may be considered too risky in approximately 5-10% of patients. In these high-risk patients, transjugular renal biopsy (TJRB) may represent an underutilized alternative. TJRB is a technically difficult procedure with a learning curve of approximately 10 cases. When performed properly, TJRB is a safe alternative to percutaneous biopsy in patients with renal failure or who are at high risk of bleeding. This article aims to provide a comprehensive review of the indications, …

Genetically Conditioned Interaction Among Microrna-155, Alpha-Klotho, And Intra-Renal Ras In Male Rats: Link To Ckd Progression, Lisa M. Harrison-Bernard, L. Raij, R. X. Tian, E. A. Jaimes

School of Graduate Studies Faculty Publications

Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress-mediated injury. Additional mechanisms include deficiency of renal alpha-klotho, that inhibits Wnt/beta-catenin, an up regulator of intra-renal renin angiotensin system (RAS) genes. Alpha-klotho deficiency therefore results in upregulation of the intra-renal RAS via Wnt/beta-catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR-155, AT1R, alpha-klotho, and TNF-α. Hypertensive high salt DS (DS-HS), but not SHR developed proteinuria, plasminuria, and …

Employing Multi-Omics Analyses To Understand Changes During Kidney Development In Perinatal Interleukin-6 Animal Model, Ganesh Panzade, Tarak Srivastava, Daniel P. Heruth, Mohammad H. Rezaiekhaligh, Jianping Zhou, Zhen Lyu, Mukut Sharma, Trupti Joshi

Biomedical Sciences

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. Maternal obesity during pregnancy is linked to systemic inflammation and elevated levels of the proinflammatory cytokine interleukin-6 (IL-6). In our previous work, we demonstrated that increased maternal IL-6 during gestation impacts intrauterine development in mice. We hypothesized that IL-6-induced inflammation alters gene expression in the developing fetus. To test this, pregnant mice were administered IL-6 or saline during mid-gestation. Newborn mouse kidneys were analyzed using mRNA-seq, miRNA-seq and whole-genome bisulfite-seq (WGBS). A multi-omics approach was employed to quantify mRNA gene expression, miRNA expression and DNA methylation, using …

Assessment And Management Of Vitamin Status In Children With Ckd Stages 2-5, On Dialysis And Post-Transplantation: Clinical Practice Points From The Pediatric Renal Nutrition Taskforce., Caroline E. Anderson, Jetta Tuokkola, Leila Qizalbash, Matthew Harmer, Christina L. Nelms, Stella Stabouli, Barry Toole, Nonnie Polderman, An Desloovere, Jose Renken-Terhaerdt, Molly R Wong Vega, Evelien Snauwaert, Johan Vande Walle, Dieter Haffner, Fabio Paglialonga, Rukshana Shroff, Vanessa Shaw, Larry A. Greenbaum, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

Children with chronic kidney disease (CKD) are at risk for vitamin deficiency or excess. Vitamin status can be affected by diet, supplements, kidney function, medications, and dialysis. Little is known about vitamin requirements in CKD, leading to practice variation.The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric kidney dietitians and pediatric nephrologists, was established to develop evidence-based clinical practice points (CPPs) to address challenges and to serve as a resource for nutritional care. Questions were formulated using PICO (Patient, Intervention, Comparator, Outcomes), and literature searches undertaken to explore clinical practice from assessment to management of vitamin status in …

Evaluation Of Vancomycin Dose Needed To Achieve 24-Hour Area Under The Concentration-Time Curve To Minimum Inhibitory Concentration Ratio Greater Than Or Equal To 400 Using Pharmacometric Approaches In Pediatric Intensive Care Patients, Dawoon Jung, Omayma A Kishk, Adnan T Bhutta, Ginny E Cummings, Hana M El Sahly, Manpreet K Virk, Brady S Moffett, Jennifer L Morris Daniel, Amy Watanabe, Nicholas Fishbane, Karen L Kotloff, Kenan Gu, Varduhi Ghazaryan, Jogarao V S Gobburu, Ayse Akcan-Arikan, James D Campbell

Faculty, Staff and Students Publications

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

DESIGN: Prospective population pharmacokinetic study of vancomycin.

SETTING: Critically ill patients in quaternary care PICUs.

PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the …

Design And Cohort Characteristics Of Track, A Prospective Study Of Hyperkalaemia Management Decision-Making, Judith Hsia, Nitin Shivappa, Ameet Bakhai, Jordi Bover, Javed Butler, Pietro Manuel Ferraro, Linda Fried, Markus P Schneider, Navdeep Tangri, Wolfgang C Winkelmayer, Meredith Bishop, Hungta Chen, Anna-Karin Sundin, Marc P Bonaca

Faculty, Staff and Students Publications

BACKGROUND: Guideline-recommended hyperkalaemia management includes dietary potassium (K

METHODS: This study enrolled participants within 21 days of an episode of hyperkalaemia in four European countries (UK, Spain, Germany, Italy) and the USA. During the 12-month follow up, data collected will include participant and healthcare provider characteristics (specialty and practice setting), hyperkalaemia treatment objectives and strategies, rationale for management decisions and indicators of response and patient-reported perceptions of their hyperkalaemia treatment.

RESULTS: The enrolled cohort includes 1330 participants, mean age 68 years, of whom 31% were women. At baseline, 6% reported heart failure, 55% chronic kidney disease, 29% both and 9% …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

Removal Of Common Antimicrobial Agents By Sustained Low- Efficiency Dialysis, Joanna Q. Hudson Pharmd, Bcps, Fasn, Fccp, Madelyn N. Hilgers Bs, Pharmd Candidate, Elvira O. Gosmanova Md

Faculty Publications

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin–tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for …

Unveiling The Impact Of Phosphate On Skeletal Muscle Dysfunction In Chronic Kidney Disease, Hiram Garcia, Sowmya Duddu, Erik Hinojosa, Model Zerfu, Nathaniel L. Alvarez, Mohammad Razzaque, Alex Zuo

Research Colloquium

Background: Chronic Kidney Disease (CKD) is characterized by progressive decline in renal function that ultimately culminates in the inability of the kidneys to effectively maintain homeostasis. The kidneys are a key regulator of phosphate, with other organs assisting in regulation including the skeletal system. In CKD, reduced kidney function leads to hyperphosphatemia. While its impact on the skeletal system is moderately studied, its effects on skeletal muscle are less reviewed. In our literature review, we aim to describe the effects of phosphate in the context of patients who have CKD while providing clinical context for this deserving population. We describe …

Small Gtp-Binding Protein Gdp Dissociation Stimulator Influences Cisplatin-Induced Acute Kidney Injury Via Perk-Dependent Er Stress, Yuxue Yang, Ting Xiong, Ti Wang, Xiwei Chen, Ziwei Ma, Bangyun Zuo, Dong Ning, Ruilong Song, Xuesong Liu, Daxin Wang

Children’s Nutrition Research Center Staff Publications

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK …

Recommendations For Clinical Trial Design In Acute Kidney Injury From The 31st Acute Disease Quality Initiative Consensus Conference A Consensus Statement, Alexander Zarbock, Lui G Forni, Jay L Koyner, Samira Bell, Thiago Reis, Melanie Meersch, Sean M Bagshaw, Dana Y Fuhmann, Kathleen D Liu, Neesh Pannu, Ayse Akcan Arikan, Derek C Angus, D'Arcy Duquette, Stuart L Goldstein, Eric Hoste, Michael Joannidis, Niels Jongs, Matthieu Legrand, Ravindra L Mehta, Patrick T Murray, Mitra K Nadim, Marlies Ostermann, John Prowle, Emily J See, Nicholas M Selby, Andrew D Shaw, Nattachai Srisawat, Claudio Ronco, John A Kellum

Faculty, Staff and Students Publications

PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus.

METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived …

Fluid Overload In Pediatric Acute Respiratory Distress Syndrome After Allogeneic Hematopoietic Cell Transplantation, Colin J Sallee, Julie C Fitzgerald, Lincoln S Smith, Joseph R Angelo, Megan C Daniel, Shira J Gertz, Deyin D Hsing, Kris M Mahadeo, Jennifer A Mcarthur, Courtney M Rowan, Pediatric Acute Lung Injury Sepsis Investigators (Palisi) Network

Faculty, Staff and Students Publications

The aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children posthematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) postallogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated …

The Role Of Complement In Kidney Disease: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Marina Vivarelli, Jonathan Barratt, Laurence H Beck, Fadi Fakhouri, Daniel P Gale, Elena Goicoechea De Jorge, Marta Mosca, Marina Noris, Matthew C Pickering, Katalin Susztak, Joshua M Thurman, Michael Cheung, Jennifer M King, Michel Jadoul, Wolfgang C Winkelmayer, Richard J H Smith, For Conference Participants

Faculty, Staff and Students Publications

Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. Although complement activation plays a causal role in atypical hemolytic uremic syndrome and C3 glomerulopathy, over the past decade, a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022, Kidney Diseases: Improving Global Outcomes (KDIGO) convened a Controversies Conference, "The Role of Complement in Kidney Disease," to address the expanding role of complement dysregulation in the …

Mitochondrial Complex I Promotes Kidney Cancer Metastasis, Divya Bezwada, Luigi Perelli, Nicholas P Lesner, Ling Cai, Bailey Brooks, Zheng Wu, Hieu S Vu, Varun Sondhi, Daniel L Cassidy, Stacy Kasitinon, Sherwin Kelekar, Feng Cai, Arin B Aurora, Mckenzie Patrick, Ashley Leach, Rashed Ghandour, Yuanyuan Zhang, Duyen Do, Phyllis Mcdaniel, Jessica Sudderth, Dennis Dumesnil, Sara House, Tracy Rosales, Alan M Poole, Yair Lotan, Solomon Woldu, Aditya Bagrodia, Xiaosong Meng, Jeffrey A Cadeddu, Prashant Mishra, Javier Garcia-Bermudez, Ivan Pedrosa, Payal Kapur, Kevin D Courtney, Craig R Malloy, Giannicola Genovese, Vitaly Margulis, Ralph J Deberardinis

Faculty, Staff and Student Publications

Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human …