Chronic kidney disease (CKD) has emerged as a serious complication of lung transplantation. Not only is it a common occurrence but is one that is associated with significant morbidity and even mortality. There have been no prospective studies that addressed this problem. Therefore, we propose a concerted effort to more accurately define pretransplant kidney function and structure in candidates for lung transplants and to further characterize the evolution of kidney structure and function in the fist 4 years after transplantation. More specifically, we will determine the prevalence of CKD as assessed by measured GFR, urinary albumin excretion and careful histological evaluation of renal tissue obtained around the time of the lung transplantation. The longitudinal studies proposed will define the impact of lung transplantation on renal structure and function. Subjects who underwent a kidney biopsy at the time of transplantation will undergo a repeat kidney biopsy at 1 and 4 years. These studies will address whether current utilization of serum creatinine-based formulas and 24-hour creatinine clearance underestimate the prevalence of chronic kidney disease in candidates for lung transplantation and detailed renal histological examinationwill reveal progressive arteriolar hyalinosis, worsening glomerulosclerosis, and expansion of the cortical interstitial: all major contributors to renal fibrosis and renal death. In addition to our correlational studies of structure and function, we will assemble a repository of serial urinary samples that will be subjected to proteomic analysis in an attempt to detect potential biomarkers that may precede the functional and structural renal deterioration. The unprecedented planned detailed studies of kidney structure in lung transplant recipients and our ability to recruit and retain subjects in long-term studies of kidney structure will translate into a body of knowledge that will ultimately aid in designing interventional trials for a condition that lacks major therapeutic options.

Public Health Relevance

The proposed detailed studies of renal function and structure will carefully profile the evolution of renal deterioration after lung transplantation which will not only address a common problem but has a potential of aiding our understanding of chronic kidney disease,in the setting of other solid organ transplants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK013083-43
Application #
8381820
Study Section
Special Emphasis Panel (ZDK1-GRB-R)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
43
Fiscal Year
2012
Total Cost
$110,917
Indirect Cost
$34,253
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Kizilbash, Sarah J; Rheault, Michelle N; Bangdiwala, Ananta et al. (2017) Infection rates in tacrolimus versus cyclosporine-treated pediatric kidney transplant recipients on a rapid discontinuation of prednisone protocol: 1-year analysis. Pediatr Transplant 21:
Verghese, P S; Schmeling, D O; Filtz, E A et al. (2017) The impact of recipient BKV shedding before transplant on BKV viruria, DNAemia, and nephropathy post-transplant: A prospective study. Pediatr Transplant 21:
Ibrahim, H N; Berglund, D M; Jackson, S et al. (2017) Renal Consequences of Diabetes After Kidney Donation. Am J Transplant 17:3141-3148
Gross, Cynthia R; Reilly-Spong, Maryanne; Park, Taehwan et al. (2017) Telephone-adapted Mindfulness-based Stress Reduction (tMBSR) for patients awaiting kidney transplantation. Contemp Clin Trials 57:37-43
Serrano, Oscar Kenneth; Kandaswamy, Raja; Gillingham, Kristen et al. (2017) Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes From the University of Minnesota. Transplantation 101:2590-2598
Matas, Arthur J; Vock, David M; Ibrahim, Hassan N (2017) GFR ?25 years postdonation in living kidney donors with (vs. without) a first-degree relative with ESRD. Am J Transplant :
Ibrahim, Hassan N; Foley, Robert N; Reule, Scott A et al. (2016) Renal Function Profile in White Kidney Donors: The First 4 Decades. J Am Soc Nephrol 27:2885-93
Verghese, Priya; Gillingham, Kristen; Matas, Arthur et al. (2016) Post-transplant blood transfusions and pediatric renal allograft outcomes. Pediatr Transplant 20:939-945
Harindhanavudhi, Tasma; Parks, Alicia; Mauer, Michael et al. (2015) Podocyte structural parameters do not predict progression to diabetic nephropathy in normoalbuminuric type 1 diabetic patients. Am J Nephrol 41:277-83
Verghese, Priya S; Schmeling, David O; Knight, Jennifer A et al. (2015) The impact of donor viral replication at transplant on recipient infections posttransplant: a prospective study. Transplantation 99:602-8

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