Nephrology Commons^™

Melatonin Attenuates Mitochondrial Damage In Aristolochic Acid-Induced Acute Kidney Injury, Jian Sun, Jinjin Pan, Qinlong Liu, Jizhong Cheng, Qing Tang, Yuke Ji, Ke Cheng, Rui Wang, Liang Liu, Dingyou Wang, Na Wu, Xu Zheng, Junxia Li, Xueyan Zhang, Zhilong Zhu, Yanchun Ding, Feng Zheng, Jia Li, Ying Zhang, Yuhui Yuan

Faculty, Staff and Students Publications

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro …

Relationship Between Femoral Artery Intima-Media Thickness And Atherosclerosis In Patients With Chronic Kidney Disease- A One Year Hospital-Based Cross-Sectional Study, Dr. Somashekhar Sogi, Dr. Ravi Sarvi, Dr. Pradeep Goudar, Dr. Mallikarjun Karishetti, Dr.V.V Hattiholi, Dr.Meenakshi Sarvi

Digital Journal of Clinical Medicine

Introduction: Chronic kidney disease (CKD) is one of the leading causes of morbidity and mortality worldwide. CKD and Peripheral arterial disease both independently increase the risk for cardiovascular disease (CVD) events and contribute significantly to morbidity and mortality. There is limited data about the co-relation between ultrasound measures of the femoral artery in peripheral vascular disease (PVD) & renal functional status. This research hence will help us in the establishment of a relationship between femoral intima-media thickness (fIMT) with CKD. Also, IMT assessment might help in earlier detection of atherosclerotic plaques & hence PVD.

Materials and methods: A cross sectional …

Targeted Exome-Based Predictors Of Patterns Of Progression Of Colorectal Liver Metastasis After Percutaneous Thermal Ablation, Iwan Paolucci, Yuan-Mao Lin, Yoshikuni Kawaguchi, Harufumi Maki, A Kyle Jones, Marco Calandri, Scott Kopetz, Timothy E Newhook, Kristy K Brock, Jean-Nicolas Vauthey, Bruno C Odisio

Faculty, Staff and Student Publications

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.

METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM.

RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway …

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

Faculty, Staff and Student 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 …

Case Report: Immune Checkpoint Inhibitor-Induced Multiorgan Vasculitis Successfully Treated With Rituximab, Sehrish Qureshi, Naszrin Arani, Vishnu Parvathareddy, Amanda Tchakarov, Maen Abdelrahim, Maria Suarez-Almazor, Jianjun Zhang, Don Lynn Gibbons, John Heymach, Mehmet Altan, Ala Abudayyeh

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. ICIs have a unique side effect profile, generally caused by inflammatory tissue damage, with clinical features similar to autoimmune conditions. Acute kidney injury from ICIs has been well studied; incidence ranges from 1% to 5%, with higher incidence when combination ICI therapies are used. Although the overall reported incidence of ICI-associated glomerulonephritis is less than 1%, vasculitis is the most commonly reported ICI-related glomerulonephritis. Other biopsy findings include thrombotic microangiopathy, focal segmental glomerulosclerosis, minimal change disease, and IgA nephropathy with secondary amyloidosis. We report a case in which a woman …

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

Faculty, Staff and Student 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 …

Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah

Faculty, Staff and Students Publications

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive …

Review Of Acute Kidney Injury And Progression To Chronic Kidney Disease In Pediatric Patients Undergoing Hematopoietic Cell Transplant, Kim T Vuong, Catherine Joseph, Joseph R Angelo

Faculty, Staff and Students Publications

While acute kidney injury (AKI) after hematopoietic cell transplant (HCT) has been well-described in pediatric patients, literature regarding the long term renal consequences of HCT-related AKI, the development of chronic kidney disease (CKD), and CKD care in pediatric patients post-HCT is limited. CKD affects almost 50% of patients after HCT with multifactorial etiology including infection, nephrotoxic medications, transplant-associated thrombotic microangiopathy, graft-versus-host disease, and sinusoidal obstruction syndrome. As renal function declines in CKD, eventually progressing to end stage kidney disease (ESKD), mortality increases and is more than 80% among patients requiring dialysis. Using society guidelines and current literature, this review summarizes …

Cerebrospinal Fluid Biomarkers Provide Evidence For Kidney-Brain Axis Involvement In Cerebral Malaria Pathogenesis, Andrea L Conroy, Dibyadyuti Datta, Robert O Opoka, Anthony Batte, Paul Bangirana, Adnan Gopinadhan, Kagan A Mellencamp, Ayse Akcan-Arikan, Richard Idro, Chandy C John

Faculty, Staff and Students Publications

INTRODUCTION: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria.

METHODS: We evaluated 30 cerebrospinal fluid (CSF) markers …

Documented Adverse Drug Reactions And Discontinuation Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers In Chronic Kidney Disease, L Parker Gregg, Peter A Richardson, Michael A Herrera, Julia M Akeroyd, Shehrezade A Jafry, Glenn T Gobbel, Sheena Wydermyer, Jennifer Arney, Adriana Hung, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation.

METHODS: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …

Treatment Of Severe Covid-19 Infection With Remdesivir In Peritoneal Dialysis, Ryan Geffin, Shazia Raheem, Lavannya M Pandit, Andrew S Hunter, Michael W Holliday, Aditya V Rao, Maulin K Shah

Faculty, Staff and Students Publications

End-stage kidney disease (ESKD) has been shown to be correlated with an increased risk of COVID-19 infection and mortality. Remdesivir is an effective non-EUA U.S. Food and Drug Administration (FDA)-approved antiviral agent for the treatment of COVID-19 in hospitalized adult and pediatric patients, though a lack of data has prevented its use in patients with severe kidney disease including dialysis patients. Some observational studies report the use of remdesivir in hemodialysis patients, but there are no reports of patients treated with remdesivir on peritoneal dialysis. Dialysis modalities may affect drug pharmacokinetics, and safety and efficiency of remdesivir in peritoneal dialysis …

Cefepime Dosing In A Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With The Cardio-Renal Pediatric Dialysis Emergency Machine (Carpediem), Cynthia Toy, Grant Stimes, Megan Moore, Poyyapakkam Srivaths, Ayse Akcan Arikan

Faculty, Staff and Students Publications

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 …

Prophylactic Intravenous Prehydration With Sodium Bicarbonate Or Sodium Chloride In The Prevention Of Contrast Induced Acute Kidney Injury, Briana Lockett, Caroline Dong

Physician Assistant Capstones, 2020-current

Introduction: Iodinated contrast media is a crucial component in the diagnostic work up of many life-threatening illnesses. However, it has been reported to cause acute kidney injury after administration, especially in patients with pre-existing renal disease. Several prophylactic treatments have been studied in hopes of minimizing these adverse events. The current standard of care in this patient population is prophylactic intravenous volume administration with either sodium chloride or sodium bicarbonate. Objective: The goal of this literature review is to determine if prophylactic intravenous volume administration with either saline or sodium bicarbonate prior to contrast administration decreases the incidence of contrast …

Expression Of P-Stat3 And C-Myc Correlates With P2-Hnf4Α Expression In Nonalcoholic Fatty Liver Disease (Nafld), Mamoun Younes, Lin Zhang, Baharan Fekry, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

We studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 …

Chronic Kidney Disease In Public Renal Practices In Queensland, Australia, 2011–2018, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Vishal Diwan, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland.

METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years.

RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons …

Association Between Cause Of Kidney Failure And Fracture Incidence In A National Us Dialysis Population Cohort Study, Susan Ziolkowski, Sai Liu, Maria E Montez-Rath, Michelle Denburg, Wolfgang C Winkelmayer, Glenn M Chertow, Michelle M O'Shaughnessy

Faculty, Staff and Students Publications

Background: Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain.

Methods: The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence …

Association Of Bradycardia And Asystole Episodes With Dialytic Parameters: An Analysis Of The Monitoring In Dialysis (Mid) Study, Qandeel H Soomro, Nisha Bansal, Wolfgang C Winkelmayer, Bruce A Koplan, Alexandru I Costea, Prabir Roy-Chaudhury, James A Tumlin, Vijay Kher, Don E Williamson, Saurabh Pokhariyal, Candace K Mcclure, David M Charytan, Mid Investigators

Faculty, Staff and Students Publications

BACKGROUND: Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain.

METHODS: The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence …

Letter To The Editor, Magdalene M Assimon, Patrick H Pun, Lily Wang, Sana M Al-Khatib, M Alan Brookhart, David J Weber, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

No abstract provided.

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

Faculty, Staff and Student 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 …

Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …

The Modifying Effect Of The Serum-To-Dialysate Potassium Gradient On The Cardiovascular Safety Of Ssris In The Hemodialysis Population: A Pharmacoepidemiologic Study, Magdalene M Assimon, Patrick H Pun, Sana M Al-Khatib, Maurice Alan Brookhart, Bradley N Gaynes, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

Background: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs).

Methods: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus < 4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study.

Results: …

[Nomenclature For Kidney Function And Kidney Diseases - Improving Assessment And Prognosis Through Precision And Comprehensibility], Kai-Uwe Eckardt, Isabelle Binet, Kirsten De Groot, Jürgen Floege, Jan C Galle, Isabelle Jordans, Andreas Kribben, Rainer Oberbauer, Hermann Pavenstädt, Alexander Rosenkranz, Marcus Säemann, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Kidney disease represents an increasing global health problem. Its mitigation requires effective communication between all stakeholders involved in assessment, diagnosis and therapy and individuals affected by kidney disease. However, as of today the nomenclature for kidney function and kidney disease is far from uniform. In 2019, the international non-profit organization Kidney Disease: Improving Global Outcomes (KDIGO) has implemented a consensus process to develop a glossary in English language to standardize the nomenclature for kidney function, kidney structure and kidney disease. Guiding principles for this process were (1) precision, (2) patient-centeredness and (3) consistency with KDIGO guidelines. The current position paper …

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …

The Lawnmower And The Pediatric Lower Extremity: A Catastrophic Combination, Alvaro Tamayo-Gutierrez, Hassan N Ibrahim

Faculty, Staff and Student 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

Faculty, Staff and Student 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.

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

Faculty, Staff and Student 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 …

Fatal Case Of Ebv-Negative Posttransplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis In An Adult Kidney Transplant Recipient, Sergio Mazzola Poli De Figueiredo, John C Johnson, Kirill A Lyapichev, Heather L Stevenson, Alfred Lea, Syed Hussain, Rupak D Kulkarni, Jeffrey H Fair, Muhammad Mujtaba, Mike L Kueht

Faculty, Staff and Student Publications

Renal transplantation usually requires the administration of lifelong immunosuppressive therapy to minimize rejection.1 However, while these immunosuppressants are vital to graft protection, they increase the risk of infection and malignancy. Posttransplant lymphoproliferative disorder (PTLD), a troublesome combination of both, covers a wide range of lymphomas, most commonly B-cell type and has been described in pediatric and adult patients.2 Risk factors for PTLD include Epstein-Barr virus (EBV) infection and immunosuppression and the prevalence of adult kidney transplant PTLD is estimated to be 0.5% to 4%, with the highest incidences occurring within the first year of transplant.2-5 …

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

Faculty, Staff and Student 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 …

Reno-Protective And Immune Effects Of Growth Differentiation Factor 15 In Obesity-Related Kidney Disease, Jessie T. Sullivan

Honors Thesis

According to the World Health Organization, worldwide obesity has tripled since 1975 and is still on the rise, putting people at a higher risk of some cardiovascular diseases and kidney disease. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied recently for its role in multiple biological processes and diseases. The member of the transforming growth factor beta (TGF-b) family has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases, stroke, diabetes, osteoarthritis, cancer, and kidney disease. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have …