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The Chronic Kidney Disease Section focuses on the mechanisms of diabetic kidney disease. Our work has focused on adults with type 2 diabetes, but recent studies indicate that youth who develop type 2 ... The Chronic Kidney Disease Section focuses on the mechanisms of diabetic kidney disease. Our work has focused on adults with type 2 diabetes, but recent studies indicate that youth who develop type 2 diabetes may have a far more aggressive course of diabetic kidney disease than their adult counterparts. Accordingly, we wish to study persons with youth onset type 2 diabetes and compare their kidney structure and transcriptomic profile with those of the adults we have already studied and to also compare them with youth onset type 1 diabetes. Therefore, we have established a collaboration with Dr. Peter Bjornstad at the University of Colorado, who is the only researcher to acquire kidney tissue in youth with youth-onset type 2 diabetes and to establish a detailed clinical phenotype in the same individuals. Dr. Bjornstad has presently conducted over 100 studies of intrarenal hemodynamic function combined with state-of-the-art functional magnetic resonance imaging in youth, including those with type 1 or type 2 diabetes. The goal of this project is for the first time to comprehensively detail morphometric, molecular, metabolic and energetic patterns of early diabetic kidney disease in youth. Tissue obtained from these biopsies will be sent to the University of Michigan where they will undergo quantitative morphometry and RNA sequencing studies performed either in single cell preparations or in the glomerular and tubulointerstitial compartments after microdissection. In this modification, we will acquire the services to obtain an additional 5 research kidney biopsies from the University of Colorado. The morphometric and transcriptiomic work will be performed at the University of Michigan. Data and results from these studies will be shared with NIDDK and NIDDK investigators will be authors on all publications emanating from this work. We wish to examine the underlying mechanisms responsible for the development of diabetic kidney diseasein persons with youth onset disease. We do not have access to this patient population locally, but we cancompare findings in our adult population with those from this youth onset population. By adding a second component to the study, on the same patients, makes it pertinent to use the samevendor for ensuring consistency and reproducibility of our study. Furthermore, it would be difficult tocompare the results from the first part of the study with the second part without using the same vendor.Prior work done, allows this vendor access to unique proprietary information.

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INTRODUCTION THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME). The Nat... INTRODUCTION THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME). The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Office of Acquisitions (OA) on behalf of the on behalf of the National Institute of Digestive, Diabetes & Kidney Diseases intends to award a purchase order without providing for full and open competition (Including brand-name) to COLORADO UNIV HLTH SCI CTR for Kidney Biopsies in Diabetic Kidney Disease. NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE The intended procurement is classified under NAICS code 541380 with a Size Standard of $16.50. REGULATORY AUTHORITY The resultant contract will include all applicable provisions and clauses in effect through the current Federal Acquisition Circular. This acquisition is conducted under the procedures as prescribed in FAR subpart 13—Simplified Acquisition Procedures at an amount not exceeding the simplified acquisition threshold ($250,000). STATUTORY AUTHORITY This acquisition is conducted under the authority of 41 U.S.C. 253(c) under provisions of the statutory authority of FAR Subpart 6.302- FAR 6.302-1—Only one responsible source and no other supplies or services will satisfy agency requirements 41 U.S.C. 253(c)(1). PERIOD OF PERFORMANCE Base Year Plus Four Option Years Place of Performance National Institutes of Health National Institute of Digestive, Diabetes & Kidney Diseases 1550 E. Indian School Road Phoenix, AZ 85014 DESCRIPTION OF REQUIREMENT The prevalence of youth-onset type 2 diabetes is increasing in parallel with the rise in obesity in the US, and world-wide. Almost 40% of people with diabetes will develop diabetic kidney disease, and 50% of youth-onset type 2 diabetes will develop early diabetic kidney disease during young adulthood. The initial metabolic and molecular derangements underlying the development of early diabetic kidney disease are poorly understood. Renal hypoxia, potentially stemming from a mismatch between increased renal energy demand and impaired substrate utilization, is emerging as a unifying early pathway in the development of diabetic kidney disease and a potential therapeutic target. Compared to type 1 diabetes and adult-onset type 2 diabetes, youth-onset type 2 diabetes has a more aggressive phenotype with a greater degree of insulin resistance, mitochondrial dysfunction, and higher prevalence of diabetic kidney disease, increasing the risk for early renal hypoxia and arguing for dedicated studies in youth. The unique pathological and molecular features of diabetic kidney disease in youth-onset type 2 diabetes and how it differs from type 1 diabetes remains poorly understood. For a complex disease such as diabetic kidney disease, an integrative biological approach is required to advance the field, yet no studies to-date have integrated renal biopsy data with intrarenal hemodynamic function by clearance studies and renal energetics by state-of-the-art functional magnetic resonance imaging in youth with type 1 and 2 diabetes. The goal of this project is for the first time to comprehensively detail morphometric, molecular, metabolic and energetic patterns of early diabetic kidney disease in youth. Dr. Petter Bjornstad and his team at Children’s Hospital of Colorado and University of Colorado School of Medicine are experts in early diabetic kidney disease in youth with type 1 and 2 diabetes. Dr. Bjornstad is an NIH and JDRF funded translational researcher, and Co-Chair of the Renal Working Group of the multicenter NIH-funded Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY). He is also the PI of ongoing NIH and JDRF funded studies in youth with type 1 and 2 diabetes measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) by iohexol and p-aminohippurate clearance studies, renal oxygenation and furosemide-suppressible oxygen consumption by blood oxygen level dependent (BOLD) MRI, renal perfusion by pseudo-continuous arterial spin labeling (ASL) MRI, insulin secretion and sensitivity by hyperglycemic and hyperinsulinemic-euglycemic clamps. Dr. Bjornstad holds an IND (#140129) with FDA to use pharma-grade p-aminohippurate to quantify ERPF in pediatric studies. To date, Dr. Bjornstad’s team has performed more than 100 study visits with GFR, ERPF and MRI measurements in youth with and without diabetes. To more comprehensively define the pathophysiology of early diabetic kidney disease, Dr. Bjornstad’s team has added morphometric and transcriptomic analyses of kidney tissue from research kidney biopsies to their ongoing studies. To our knowledge, Dr. Bjornstad’s group is the only investigative team successfully performing these studies in adolescents with diabetes, and their expertise and infrastructure will ensure feasibility. He has performed 6 kidney biopsies since mid-September 2019, with 3 more scheduled in November 2019. We are anticipating as many as 75 biopsies over the coming months with 2-3 scheduled each month. Transcriptomics technologies offer an organizational and methodological platform to identify key genes and pathways involved in early diabetic kidney disease. The maturation of various integrative biology approaches is already contributing to research capabilities, and this is expected to expand. However, crucial components of the future success of these endeavors are deep clinical phenotyping and access to renal tissue. Molecular pathways identified in this study will be validated in model systems (e.g. human organoids and murine models) and leveraged as starting points for future drug development. Finally, data generated from this project will be used to direct and design a longitudinal multicenter center study that will define pathological and molecular features of early diabetic kidney disease and its progression in youth with diabetes. Objective of Requirement To acquire kidney tissue from research participants with youth onset type 1 or type 2 diabetes. Tissue from these biopsies will undergo quantitative morphometry and RNA sequencing studies performed either in single cell preparations or in the glomerular and tubulointerstitial compartments after microdissection. Specific objectives of this work are to: To characterize structural and transcriptomic features of early diabetic kidney disease in youth with diabetes. To identify distinct structural and transcriptomic differences of kidney disease, if they exist, between youth with T1D and youth with T2D. To define the structure-function relationship between renal energetics, tissue integrity and gene expression in youth with diabetes. Salient/Required Features and Specifications The procurement of kidney tissue from well-characterized participants with youth onset type 1 or type 2 diabetes for morphometric and transcriptomic evaluation will enhance the NIDDK research goals of establishing the underlying mechanisms of diabetic kidney disease in youth onset individuals and exploring the underlying structural injury that occurs in these high-risk cohorts. Task Areas: Recruit and enroll eligible youth with type 1 and type 2 diabetes for research kidney biopsies and for measurement of renal hemodynamics and functional magnetic resonance imaging. We anticipate 2-3 kidney biopsies to be performed each month. Perform ultrasound-guided percutaneous kidney biopsies in eligible participants and prepare the biopsy specimens according to the protocol established by the Kidney Precision Medicine Project. Ship tissue specimens to the University of Michigan for morphometric and transcriptomic analysis as soon as possible after collection. Morphometric results are available in 4-6 weeks. Transcriptomic results are batched so could take longer. Participate in telephone conference calls every 3 months and email progress reports monthly to evaluate the progress of this research and to examine the quality and utility of the tissue samples. Provide clinical, hemodynamic, morphometric, and transcriptomic data to NIDDK as it becomes available and at provide a final dataset at completion of the project. Publish results with NIDDK investigators as authors. CLOSING STATEMENT This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: descriptive literature, delivery timeframe, warranties and/or other information that demonstrates that the offer meets all the foregoing requirements, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.” A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement. All responses to this notice shall be submitted electronically by 9:00 am Eastern Standard Time, on Tuesday, February 18, 2020 to the Contract Specialist, Amber Harris, at amber.harris@nih.gov . Assessment of Capability Lowest Price Technically Acceptable