Internal Medicine Commons^™

Establishing Kidney Transplantation In A Low-Income Country: A Case In Tanzania, Francis F. Furia, Jaqueline G. Shoo, Paschal Ruggajo, Jonathan W. Jonathan W. Mngumi, Valentine Valentine, Mahmoud A. Muhiddin, Kim Kim, Isaack Mlatie, Moses Mulungu, Namala Mkopi

Internal Medicine, East Africa

Background

Sub-Saharan African countries, including Tanzania, have a high burden of chronic kidney diseases (CKDs) and limited capacity for the provision of services. Tanzania and other countries in the region have made signifcant improvements in the provision of services for patients with CKD, including hemodialysis. Few countries are ofering kidney transplantation services, which is the defnitive treatment for patients with CKD and kidney failure. This study was conducted to review the steps taken by Muhimbili National Hospital (MNH) to establish a kidney transplantation service in Tanzania.

Methods

This study was based on the review of the activities that were undertaken …

Impact Of Living Donor Liver Transplantation On The Improvement Of Hepatocellular Carcinoma Treatment, Yucel Yankol, Oswaldo Aguirre, Luis A Fernandez

Student and Faculty Publications

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, with increasing incidence. There are different treatment options, but only 30%-40% of HCC cases are diagnosed at an early stage for curative treatment. With the implementation of Milan Criteria for liver transplantation (LT) in HCC cases and its use for organ allocation with successful outcomes, LT has become an optimal treatment. Seeking new criteria for LT and developing updated algorithms for HCC treatment has become a hot topic nowadays. With the experience in living donor liver transplantation (LDLT), especially in Asian countries, LDLT was established and adopted with …

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Student and Faculty Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Spectrophotometric Analysis Of Purple Urine Secondary To Methylene Blue And Hydroxocobalamin Co-Administration, Jeremy Hardin, Henrik Galust, Richard Franklin Clark, Binh Ly, Raymond Theodore Suhandynata

Student and Faculty Publications

BACKGROUND: The development of purple urine after methylene blue (methylthioninium chloride) and hydroxocobalamin co-administration is a rare clinical entity that has not been fully elucidated. A 47-year-old male presented to the emergency department with hypotension, cyanosis, and depressed mental status. The patient was noted to have profound peripheral and central cyanosis, as well as chocolate-colored arterial blood. He was treated with both methylene blue and hydroxocobalamin and developed purple urine for approximately 1 week.

METHODS: Color chromatography was performed by placing the patient's urine directly onto absorbent filter paper. Urine spectrophotometry was performed utilizing the NanoDrop One/One C UV-Vis Spectrophotometer. …

Acute Kidney Injury After Percutaneous Coronary Intervention Guided By Intravascular Ultrasound, Minh Tran Duc, Thai Nguyen Quoc, Bach Yen T Nguyen, Ngoc Vu Quang, Nhuong Nguyen Duc, Hung Nguyen Duc, Lam Truong Hoai, Vu Nguyen Hoai, Hung Phan Kieu, Hieu Nguyen Trung

Faculty and Staff Publications

Purpose We investigated the impact of intravascular ultrasound guidance on reducing the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI). Methods Ninety-nine patients were enrolled in this prospective cohort who were not randomly assigned to angiography-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. The patients were hospitalized at the Vietnam National Heart Institute - Bach Mai Hospital between 2019 and 2020. Acute kidney injury incidence during hospitalization was the primary endpoint. Results A total of 99 patients were divided into two groups: the intravascular ultrasound-guided group (33 participants) and the angiography-guided group …

Rationale And Design Of The Nephrotic Syndrome Study Network (Neptune) Match In Glomerular Diseases: Designing The Right Trial For The Right Patient, Today, Howard Trachtman, Hailey Desmond, Amanda L Williams, Laura H Mariani, Sean Eddy, Wenjun Ju, Laura Barisoni, Heather K Ascani, Wendy R Uhlmann, Cathie Spino, Lawrence B Holzman, John R Sedor, Crystal Gadegbeku, Lalita Subramanian, Chrysta C Lienczewski, Tina Manieri, Scott J Roberts, Debbie S Gipson, Matthias Kretzler, Neptune Investigators

Student and Faculty Publications

Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges. The study has enrolled >850 pediatric and adult patients with proteinuric glomerular diseases who have contributed to deep clinical, histologic, genetic, and molecular profiles linked to long-term outcomes. The NEPTUNE Knowledge Network, comprising combined, multiscalar data sets, captures each participant's molecular disease processes at the time of kidney biopsy. In this editorial, we …

Qiditangshen Granules Alleviates Diabetic Nephropathy Podocyte Injury: A Network Pharmacology Study And Experimental Validation In Vivo And Vitro, Fei Gao, Ying Zhou, Borui Yu, Huidi Xie, Yang Shi, Xianhui Zhang, Hongfang Liu

Student and Faculty Publications

BACKGROUND: QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their pharmacological mechanism needs further exploration.

METHODS: According to the active ingredients and targets of the QDTS in the TCMSP database, the network pharmacology of QDTS was investigated. The potential active ingredients were chosen based on the oral bioavailability and the drug similarity index. At the same time, targets for DN-related disease were obtained from GeneCards, OMIM, PharmGKB, TTD, and DrugBank. The TCM-component-target network and the protein-protein interaction (PPI) network were constructed with the Cytoscape and STRING platforms, respectively, and …

Heterogeneity In Intrahepatic Macrophage Populations And Druggable Target Expression In Patients With Steatotic Liver Disease-Related Fibrosis, Omar A Saldarriaga, Timothy G Wanninger, Esteban Arroyave, Joseph Gosnell, Santhoshi Krishnan, Morgan Oneka, Daniel Bao, Daniel E Millian, Michael L Kueht, Akshata Moghe, Jingjing Jiao, Jessica I Sanchez, Heidi Spratt, Laura Beretta, Arvind Rao, Jared K Burks, Heather L Stevenson

Student and Faculty Publications

BACKGROUND & AIMS: Clinical trials for reducing fibrosis in steatotic liver disease (SLD) have targeted macrophages with variable results. We evaluated intrahepatic macrophages in patients with SLD to determine if activity scores or fibrosis stages influenced phenotypes and expression of druggable targets, such as CCR2 and galectin-3.

METHODS: Liver biopsies from controls or patients with minimal or advanced fibrosis were subject to gene expression analysis using nCounter to determine differences in macrophage-related genes (n = 30). To investigate variability among individual patients, we compared additional biopsies by staining them with multiplex antibody panels (CD68/CD14/CD16/CD163/Mac387 or CD163/CCR2/galectin-3/Mac387) followed by spectral imaging …

Heterogeneity In Intrahepatic Macrophage Populations And Druggable Target Expression In Patients With Steatotic Liver Disease-Related Fibrosis, Omar A Saldarriaga, Timothy G Wanninger, Esteban Arroyave, Joseph Gosnell, Santhoshi Krishnan, Morgan Oneka, Daniel Bao, Daniel E Millian, Michael L Kueht, Akshata Moghe, Jingjing Jiao, Jessica I Sanchez, Heidi Spratt, Laura Beretta, Arvind Rao, Jared K Burks, Heather L Stevenson

Student and Faculty Publications

BACKGROUND & AIMS: Clinical trials for reducing fibrosis in steatotic liver disease (SLD) have targeted macrophages with variable results. We evaluated intrahepatic macrophages in patients with SLD to determine if activity scores or fibrosis stages influenced phenotypes and expression of druggable targets, such as CCR2 and galectin-3.

METHODS: Liver biopsies from controls or patients with minimal or advanced fibrosis were subject to gene expression analysis using nCounter to determine differences in macrophage-related genes (n = 30). To investigate variability among individual patients, we compared additional biopsies by staining them with multiplex antibody panels (CD68/CD14/CD16/CD163/Mac387 or CD163/CCR2/galectin-3/Mac387) followed by spectral imaging …

Hydrochlorothiazide And Prevention Of Kidney Stone Recurrence: A #Nephjc Editorial On The Nostone Trial, Renz Michael Pasilan, Nikita Pawar, Rasha Alawieh, Swapnil Hiremath, Jade Teakell

Faculty and Staff Publications

No abstract provided.

In-Center Dialysis Versus Extended Home Hemodialysis: More Evidence To Support Extended Dialysis, Osama El Shamy, Jade Teakell

Faculty and Staff Publications

No abstract provided.

Interstitial Lung Abnormalities After Hospitalization For Covid-19 In Patients With Cancer: A Prospective Cohort Study, Sungryong Noh, Christopher Bertini, Isabel Mira-Avendano, Maryam Kaous, Bela Patel, Saadia A Faiz, Vickie R Shannon, Diwakar D Balachandran, Lara Bashoura, Roberto Adachi, Scott E Evans, Burton Dickey, Carol Wu, Girish S Shroff, Joanna-Grace Manzano, Bruno Granwehr, Shannon Holloway, Kodwo Dickson, Alyssa Mohammed, Mayoora Muthu, Hui Song, Caroline Chung, Jia Wu, Lyndon Lee, Ying Jiang, Fareed Khawaja, Ajay Sheshadri

Student and Faculty Publications

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients.

METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and …

Rare Case Of Pediatric Post-Transplant Lymphoproliferative Disorder Presenting With Pleural Masses Complicated By Pleural Effusions, Erini Nessim Kostandy, David Wan, Essam Imseis

Student and Faculty Publications

Post-transplant lymphoproliferative disorder is a complication in organ transplant recipients characterized by uncontrolled proliferation of B-lymphocytes, occurring in 6% of pediatric patients, with risk factors including primary Epstein-Barr virus infection, intensity of immunosuppression, and cytomegalovirus infection. The clinical symptoms are often nonspecific, and it is associated with a high mortality rate if left untreated. We describe a rare case of post-transplant lymphoproliferative disorder who presented with pleural-based masses resulting in pleural effusions.

The Nephrocheck Bedside System For Detecting Stage 3 Acute Kidney Injury After Open Thoracoabdominal Aortic Repair, Panagiotis Doukas, Jan Paul Frese, Thorsten Eierhoff, Gabriel Hellfritsch, Ben Raude, Michael J Jacobs, Andreas Greiner, Alexander Oberhuber, Alexander Gombert

Student and Faculty Publications

Acute kidney injury (AKI) is a common complication after complex aortic procedures and it is associated with relevant mortality and morbidity. Biomarkers for early and specific AKI detection are lacking. The aim of this work is to investigate the reliability of the NephroCheck bedside system for diagnosing stage 3 AKI following open aortic surgery. In this prospective, multicenter, observational study,- https://clinicaltrials.gov/ct2/show/NCT04087161 -we included 45 patients undergoing open thoracoabdominal aortic repair. AKI risk (AKIRisk-Index) was calculated from urine samples at 5 timepoints: baseline, immediately postoperatively and at 12, 24, 48, and 72 h post-surgery. AKIs were classified according to the KDIGO …

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour And Sporadic Chromophobe Renal Cell Carcinoma, Ryosuke Jikuya, Todd A Johnson, Kazuhiro Maejima, Jisong An, Young-Seok Ju, Hwajin Lee, Kyungsik Ha, Woojeung Song, Youngwook Kim, Yuki Okawa, Shota Sasagawa, Yuki Kanazashi, Masashi Fujita, Seiya Imoto, Taku Mitome, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Haruka Hamanoue, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Kazuhide Makiyama, Masahiro Yao, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Hidewaki Nakagawa, Hisashi Hasumi

Student and Faculty Publications

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated.

METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated …

Apolipoprotein E Dyslipidemia And Nephrotic Syndrome: A Rare Connection, Sahana Tito, Avica Atri, Shivaraj Patil, Saima Dean, Sweta Carpenter

Einstein Health Papers

Severe hyperlipidemia warrants an extensive evaluation. We report a case of a 25-year-old man of Chinese descent seen in the cardiology-lipid clinic. He was found to have a serum low-density lipoprotein cholesterol of 12.12 mmol/L (468 mg/dL) and serum triglycerides of 2.29 mmol/L (203 mg/dL) during routine screening. Work-up revealed nephrotic-range proteinuria, and renal biopsy showed dilated glomerular capillary loops with lipid deposits, pathognomonic of lipoprotein glomerulopathy. Genetic studies showed apolipoprotein E3/E4 phenotype. He was treated with a high-intensity statin and fibrate therapy, which resulted in a marked improvement in dyslipidemia and proteinuria.

Following The Map For Improved Kidney Function In Hepatorenal Syndrome, Matthew R Thau, Pavan K Bhatraju

Faculty and Staff Publications

No abstract provided.

Longitudinal Associations Between Dietary Fructose And Sodium And Systolic And Diastolic Blood Pressure Among Us Black And White Adults In The Cardia Study, Rana Elhamzawy, Dragana Komnenov, Daniel Domin

Medical Student Research Symposium

Longitudinal associations between dietary fructose and sodium and systolic and diastolic blood pressure among US Black and White adults in the CARDIA study

Authors: Rana Elhamzawy, Daniel Domin, Dragana Komnenov

Hypertension is one of the leading risk factors for major adverse cardiovascular events (MACE). Likewise, suboptimal dietary habits, including high fructose and sodium intake, are major contributors to mortality. High dietary fructose alone predisposes to salt-sensitivity of blood pressure, which is an independent, significant cardiovascular risk factor. We previously showed in our rat model of fructose-salt-sensitive hypertension that even a short term (4 weeks) feeding with 20% fructose and 4% …

The Effects Of Different Antihypertensives, Steroids, And Beta Blockers On Covid-19 Outcomes In A Ckd And Non-Ckd Cohort In Detroit, Michigan, Vidhya Nadarajan, Maham Ahmed, Katerina Furman, Zoya Gurm, Priyanka Kale, Zaina Khoury, Paul Kim, Sara Koussa, Dana Labuda, Margo Mekjian, Pooja Polamarasetti, Charlotte Thill, Sophie Wittenberg, Sorabh Dhar, Dragana Komnenov

Medical Student Research Symposium

Initial studies during the COVID-19 pandemic reported angiotensin converting enzyme 2 inhibitors (ACE2i) could be associated with worse disease course due to potential increase in ACE2 receptors which SARS-CoV2 virus uses for cellular entry. Subsequent studies refuted such concerns, reporting that continued use of ACEis and angiotensin receptor blockers (ARBs) in hypertensive individuals is protective. However, there remains a paucity of data evaluating effects of various antihypertensive medications, steroids, and beta blockers in chronic kidney disease (CKD) populations and in individuals with normal kidney function. This study was designed to evaluate the potential risks associated with antihypertensive medications and COVID-19 …

Spatial Molecular And Cellular Determinants Of Stat3 Activation In Liver Fibrosis Progression In Non-Alcoholic Fatty Liver Disease, Jingjing Jiao, Jessica I Sanchez, Omar A Saldarriaga, Luisa M Solis, David J Tweardy, Dipen M Maru, Heather L Stevenson, Laura Beretta

Student and Faculty Publications

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice.

METHODS: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and …

Impacts Of Dietary Lysine And Crude Protein On Performance, Hepatic And Renal Functions, Biochemical Parameters, And Histomorphology Of Small Intestine, Liver, And Kidney In Broiler Chickens, Mohamed A Mousa, Ahamed S Asman, Reham M J Ali, Ramy K A Sayed, Kamlah A Majrashi, Khloud G Fakiha, Rashed A Alhotan, Shaimaa Selim

Student and Faculty Publications

The present study aimed to investigate the effects of increasing dietary lysine (Lys) levels with an adequate dietary crude protein (CP) content, as well as the effects of a reduction in dietary CP content with the recommended amino acid (AAs) level, on the performance, blood biochemical parameters, and histomorphology of the duodenum, liver, and kidney in broiler chickens. A total of 500 broiler chickens were randomly distributed into five dietary treatment groups, following a completely randomized design, where, at the beginning, the control group (C) was fed a diet containing the standard CP and Lys levels: 23% CP with 1.44% …

Rapid Onset Hydralazine-Induced Antineutrophil Cytoplasmic Antibody (Anca) Associated Vasculitis Presenting With Hemoptysis And Kidney Failure: Case Report, Rachel E. Easter, Andinet Gizaw, Natalie Klein

Internal Medicine Publications

Hydralazine-induced vasculitis can be challenging to recognize and diagnose as presenting symptoms vary and can mimic other conditions or diseases, however, swift intervention and treatment is key in halting progression of the disease and providing patients with the best possible outcomes. A 71-year-old African American female presented to the emergency department with weakness, fatigue, anemia, blood-streaked sputum, fever, chills, and severe myalgias. Hydralazine was prescribed to treat resistant hypertension eight months prior to presentation. Hydralazine was discontinued on hospital day (HD) 4. Pertinent laboratory values showed elevated inflammatory markers, positive antinuclear antibody (ANA), negative rheumatoid factor (RF), normal complement levels, …

Multi-Task Learning For Post-Transplant Cause Of Death Analysis: A Case Study On Liver Transplant, Sirui Ding, Qiaoyu Tan, Chia-Yuan Chang, Na Zou, Kai Zhang, Nathan R Hoot, Xiaoqian Jiang, Xia Hu

Student and Faculty Publications

Organ transplant is the essential treatment method for some end-stage diseases, such as liver failure. Analyzing the post-transplant cause of death (CoD) after organ transplant provides a powerful tool for clinical decision making, including personalized treatment and organ allocation. However, traditional methods like Model for End-stage Liver Disease (MELD) score and conventional machine learning (ML) methods are limited in CoD analysis due to two major data and model-related challenges. To address this, we propose a novel framework called CoD-MTL leveraging multi-task learning to model the semantic relationships between various CoD prediction tasks jointly. Specifically, we develop a novel tree distillation …

Dysregulated Coagulation System Links To Inflammation In Diabetic Kidney Disease, Mengyun Xiao, Donge Tang, Shaodong Luan, Bo Hu, Wenyu Gong, Wolfgang Pommer, Yong Dai, Lianghong Yin

Student and Faculty Publications

Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease worldwide. Despite extensive research, the exact mechanisms responsible for its development remain incompletely understood. Notably, patients with diabetes and impaired kidney function exhibit a hypercoagulable state characterized by elevated levels of coagulation molecules in their plasma. Recent studies propose that coagulation molecules such as thrombin, fibrinogen, and platelets are interconnected with the complement system, giving rise to an inflammatory response that potentially accelerates the progression of DKD. Remarkably, investigations have shown that inhibiting the coagulation system may protect the kidneys in various animal models and clinical trials, suggesting …

Refractory Thrombocytopenia During Liver Transplantation Requiring Splenectomy, Ivana Wrobleski Wilder, Alexander Reskallah, Catherine M Pivalizza, John S Bynon, Evan G Pivalizza

Student and Faculty Publications

Although thrombocytopenia is common in end-stage liver disease, severe, refractory thrombocytopenia during liver transplantation is rare, and if immune based, usually presents months or years later. This case describes an adult woman in whom preoperative evaluation had not determined an immune-related cause of thrombocytopenia. Clot strength was dramatically impaired as measured by thrombelastography during the transplant. Following a lack of response to repeat platelet transfusions, splenectomy was performed after graft reperfusion with rapid temporal restoration of clot strength. This case shows a severe manifestation of perioperative thrombocytopenia during liver transplantation and clinically guided management when measured clot strength is too …

Pathologic Predictors Of Response To Treatment Of Immune Checkpoint Inhibitor-Induced Kidney Injury, Ala Abudayyeh, Liye Suo, Heather Lin, Omar Mamlouk, Noha Abdel-Wahab, Amanda Tchakarov

Student and Faculty Publications

Background: Immune-related adverse events are a management challenge in patients receiving immune checkpoint inhibitors (ICIs). The most common renal immune-related adverse event, acute interstitial nephritis (AIN), is associated with patient morbidity and mortality. AIN, characterized by infiltration of renal tissue with immune cells, may be analogous to kidney transplant rejection. We evaluated clinical variables and pathologic findings to identify predictors of renal response and overall survival (OS) in patients with ICI-induced AIN. Design, setting, participants, and measurements: We reviewed the records and biopsy specimens of all 35 patients treated for ICI-induced AIN at our institution, between August 2007 and August …

The Kidney In Heart Failure: The Role Of Venous Congestion, Alvaro Tamayo-Gutierrez, Hassan N Ibrahim

Student and Faculty Publications

Heart failure can lead to renal impairment, an interaction now termed "cardiorenal syndrome." The prevalent physiological explanation for the renal impairment that accompanies heart failure centers around the forward failure hypothesis, which emphasizes the role of left ventricular dysfunction in causing edema, and the backward failure hypothesis, which singles out venous congestion as the dominant mechanism of edema and reduced glomerular filtration rate. In this review, we provide an appraisal on venous congestion, an extremely important contributor that has received little attention. We also summarize the pharmacology of loop diuretics, explain current understanding of diuretic resistance, and address controversies regarding …

Hypertension Management In Patients With Chronic Kidney Disease, Sean A Hebert, Hassan N Ibrahim

Student and Faculty Publications

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.

Hepatic Circadian And Differentiation Factors Control Liver Susceptibility For Fatty Liver Disease And Tumorigenesis, Baharan Fekry, Aleix Ribas-Latre, Rachel Van Drunen, Rafael Bravo Santos, Samay Shivshankar, Yulin Dai, Zhongming Zhao, Seung-Hee Yoo, Zheng Chen, Kai Sun, Frances M Sladek, Mamoun Younes, Kristin Eckel-Mahan

Student and Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon-Like Receptor Like 1 (ARNTL, or Bmal1) and the liver-enriched nuclear factor 4 alpha (HNF4α) are robustly co-expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α- either by isoform switching, or loss of expression- results in an increased …

Genetic Loci And Prioritization Of Genes For Kidney Function Decline Derived From A Meta-Analysis Of 62 Longitudinal Genome-Wide Association Studies, Mathias Gorski, Humaira Rasheed, Alexander Teumer, Laurent F Thomas, Sarah E Graham, Gardar Sveinbjornsson, Thomas W Winkler, Felix Günther, Klaus J Stark, Jin-Fang Chai, Bamidele O Tayo, Matthias Wuttke, Yong Li, Adrienne Tin, Tarunveer S Ahluwalia, Johan Ärnlöv, Bjørn Olav Åsvold, Stephan J L Bakker, Bernhard Banas, Nisha Bansal, Mary L Biggs, Ginevra Biino, Michael Böhnke, Eric Boerwinkle, Erwin P Bottinger, Hermann Brenner, Ben Brumpton, Robert J Carroll, Layal Chaker, John Chalmers, Miao-Li Chee, Miao-Ling Chee, Ching-Yu Cheng, Audrey Y Chu, Marina Ciullo, Massimiliano Cocca, James P Cook, Josef Coresh, Daniele Cusi, Martin H De Borst, Frauke Degenhardt, Kai-Uwe Eckardt, Karlhans Endlich, Michele K Evans, Mary F Feitosa, Andre Franke, Sandra Freitag-Wolf, Christian Fuchsberger, Piyush Gampawar, Ron T Gansevoort, Mohsen Ghanbari, Sahar Ghasemi, Vilmantas Giedraitis, Christian Gieger, Daniel F Gudbjartsson, Stein Hallan, Pavel Hamet, Asahi Hishida, Kevin Ho, Edith Hofer, Bernd Holleczek, Hilma Holm, Anselm Hoppmann, Katrin Horn, Nina Hutri-Kähönen, Kristian Hveem, Shih-Jen Hwang, M Arfan Ikram, Navya Shilpa Josyula, Bettina Jung, Mika Kähönen, Irma Karabegović, Chiea-Chuen Khor, Wolfgang Koenig, Holly Kramer, Bernhard K Krämer, Brigitte Kühnel, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Terho Lehtimäki, Man Li, Wolfgang Lieb, Lifelines Cohort Study, Lars Lind, Cecilia M Lindgren, Ruth J F Loos, Mary Ann Lukas, Leo-Pekka Lyytikäinen, Anubha Mahajan, Pamela R Matias-Garcia, Christa Meisinger, Thomas Meitinger, Olle Melander, Yuri Milaneschi, Pashupati P Mishra, Nina Mononen, Andrew P Morris, Josyf C Mychaleckyj, Girish N Nadkarni, Mariko Naito, Masahiro Nakatochi, Mike A Nalls, Matthias Nauck, Kjell Nikus, Boting Ning, Ilja M Nolte, Teresa Nutile, Michelle L O'Donoghue, Jeffrey O'Connell, Isleifur Olafsson, Marju Orho-Melander, Afshin Parsa, Sarah A Pendergrass, Brenda W J H Penninx, Mario Pirastu, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Olli T Raitakari, Myriam Rheinberger, Kenneth M Rice, Federica Rizzi, Alexander R Rosenkranz, Peter Rossing, Jerome I Rotter, Daniela Ruggiero, Kathleen A Ryan, Charumathi Sabanayagam, Erika Salvi, Helena Schmidt, Reinhold Schmidt, Markus Scholz, Ben Schöttker, Christina-Alexandra Schulz, Sanaz Sedaghat, Christian M Shaffer, Karsten B Sieber, Xueling Sim, Mario Sims, Harold Snieder, Kira J Stanzick, Unnur Thorsteinsdottir, Hannah Stocker, Konstantin Strauch, Heather M Stringham, Patrick Sulem, Silke Szymczak, Kent D Taylor, Chris H L Thio, Johanne Tremblay, Simona Vaccargiu, Pim Van Der Harst, Peter J Van Der Most, Niek Verweij, Uwe Völker, Kenji Wakai, Melanie Waldenberger, Lars Wallentin, Stefan Wallner, Judy Wang, Dawn M Waterworth, Harvey D White, Cristen J Willer, Tien-Yin Wong, Mark Woodward, Qiong Yang, Laura M Yerges-Armstrong, Martina Zimmermann, Alan B Zonderman, Tobias Bergler, Kari Stefansson, Carsten A Böger, Cristian Pattaro, Anna Köttgen, Florian Kronenberg, Iris M Heid

Student and Faculty Publications

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine …