Ochsner Health is a system that delivers health to the people of Louisiana, Mississippi and the Gulf South with a mission to Serve, Heal, Lead, Educate and Innovate.
The Department of Nephrology has a strong interest in clinical and translational research. We have a commitment to stimulate the medical students, residents and nephrology fellows interest in pursuing research conductive to peer-review publications. Every year we have most of our fellows, residents and rotating medical students present their research at major conferences, including Kidney Week (American Society of Nephrology), Spring Clinical Meeting (National Kidney Foundation) and the annual meeting of the Southern Society of Clinical Investigation, held yearly in New Orleans.
The Translational Kidney Research Program (TKRP) at the Department of Nephrology at Ochsner Medical Center (@OchsnerNephro) brings together basic and clinical science to bridge laboratory discovery to the advancement in diagnosis and treatment of human kidney disease. The program is based at the main campus of Ochsner Medical Center in New Orleans and is led by Dr. Juan Carlos Q. Velez. All nephrology fellows have the opportunity to participate in any of the research projects of the program. Currently, TKRP is focused on the following areas of investigation:
Overarching Goal: Our laboratory is interested in finding new ways to improve the currently available clinical tools for the diagnosis and treatment of acute kidney injury (AKI) in patients with cirrhosis. In particular, we are focused on hepatorenal syndrome type 1 (HRS-1), an ominous form of AKI in cirrhosis, as well as hyperbilirubinemia-associated toxic acute tubular injury.
Prospective Cohort (Pre-BRAKE) of AKI in Cirrhosis (Clinical arm)
Our research team has established a real-time electronic medical record-based prospective data collection for hospitalized patients with cirrhosis who develop AKI. The cohort (Pre-BRAKE) was established as a preliminary phase for the upcoming prospective pilot interventional study (BRAKE, Blood Pressure Rise in Acute Kidney Injury in End-Stage Liver Disease). Exploiting the existence of this cohort, we capture clinical data of patients with HRS-1 or other forms of AKI in cirrhosis, such as acute tubular injury (ATI). Urine specimens from subjects enrolled in the cohort are collected, examined (brightfield, phase contrast, darkfield), scored, utilized in the UCCP study (see below) and stored.
Prospective Pilot Study of Non-Contrast MRI to Assess Renal Perfusion in HRS (Clinical arm)
As an ancillary project of Pre-BRAKE, we are actively enrolling patients in the TRACE-HRS study (Tracking Renal Arterial Circulatory Effectiveness in HRS), a CRISP-funded project. The study involves measuring perfusion of the kidney cortex in cirrhotic subjects with HRS-1 or other forms of AKI by arterial spin labeling (ASL) MRI. The goal is to examine this technique as a diagnostic tool as well as to assess its value as predictor of response to vasoconstrictors in HRS-1. Urine specimens from subjects enrolled in this ancillary study are also collected, examined by microscopy (brightfield, phase contrast, darkfield), scored, utilized in the UCCP study (see below) and stored.
Role of Intrarenal Angiotensin-Mediated Hemodynamics in Animal Model of Cirrhosis (Translational arm)
Overarching Goal: Our laboratory is interested in determining the composition of urinary casts as a platform for future development of new diagnostic biomarkers for AKI. Our translational study is called UCCP (Urinary Cast Composition Project).
Utilizing urine specimens from the Pre-BRAKE cohort as well as from patients with AKI from other causes, our laboratory is currently studying new methodologies for urinary cast isolation and examination of its composition.
Overarching Goal: Our program is interested in identifying modifiable factors that increase the risk of acute kidney injury in patients with coronavirus disease 2019 (COVID-19). During the ongoing pandemic, our hospital managed one of the largest upsurges of COVID-19 in the United States. The initial experience of Ochsner Nephrology with COVID-19 and AKI has rapidly resulted in 3-peer-reviewed publications (JASN, Kidney360). We have established a prospective database of hospitalized patients with COVID-19 with or without AKI. Currently, we are conducting several ancillary projects:
Overarching Goal: Our laboratory is interested in understanding the role of the angiotensinase aminopeptidase A (APA) in kidney health and in development of glomerular disease. This is a translational study.
Dr. Velez and his collaborators at MUSC have demonstrated that aminopeptidase A (APA) plays an important role in modulating the intrarenal action of angiotensin II. In culture mouse podocytes and isolated rat glomeruli, it was shown that APA is the most robust enzyme responsible of cleaving angiotensin-related peptides in the glomerular compartment. APA degrades angiotensin II down to a heptapeptide Ang II to initiate the metabolism of angiotensin II, a potent vasoconstrictor and pro-fibrotic molecule implicated in the progression of proteinuric CKD. In addition, APA converts angiotensin I – the precursor of angiotensin II – into angiotensin 2-10, thereby shunting the pathway of conversion away from angiotensin II formation. Further, utilizing 3 model models of glomerular disease (angiotensin II chronic infusion, glomerulotoxic serum injection and 5/6 renal ablation) in APA knockout mice (APA-KO), our studies demonstrated that deficiency of APA is associated with exacerbated glomerular injury and augmented accumulation of intrarenal angiotensin II. Currently, our laboratory is pursuing the following next steps:
Overarching Goal: Our laboratory is interested in understanding the mechanism of steep rise in serum creatinine in individuals who develop precipitous AKI due to vancomycin. This is a translational study.
Based on our published case series as wells single center retrospective investigation, we have described a distinct form of AKI due to vancomycin characterized by a precipitous rise in serum creatinine out of proportion to the fall in glomerular filtration rate as seen clinically. We hypothesize that tubular secretion of creatinine is impaired due to competition for the organic anion transporters (OATs) in proximal tubular epithelia or by direct injury to those OATs. Currently, our laboratory is pursuing the following next steps:
Overarching goal: To test the impact of an innovative tool on nephrology-specific health literacy in patients with chronic kidney disease (CKD). The team has developed a wallet-sized laminated card that tracks the patient’s progress related to change in eGFR and proteinuria over time and provides an estimate of their risk to progress to ESKD. We aim to test the impact of this patient-centered educational tool after completion of the study. The tool may have significant impact of future patient care in CKD clinics.
Overarching Goal: To participate in practice-changing clinical trials in nephrology. We have previously participated in seminal industry-sponsored clinical trials: SUPER, AURORA, CONFIRM and PODOCYTE. Currently, we are involved in the following clinical studies:
DUPLEX (Retrophin). Sparsentan for the treatment of focal segmental glomerulosclerosis
VX19-147 (Vertex). Treatment with a molecule that interferes with the APOL1 gene in APOL1 high risk genotype-associated nephropathies
BMS11073 (Bristol Squibb Myers). Treatment of IgA nephropathy with a tyrosine kinase 2 inhibitor
FACT (Nephro-synergy). Corticotropin gel for the treatment of fibrillary glomerulonephritis