Metabolic acidosis is a modifiable risk factor for chronic kidney disease (CKD) progression. It develops in advanced CKD due to impaired excretion of the daily load of nonvolatile acid that is generated from metabolism of dietary nutrients. Subclinical acidosis develops prior to overt acidosis and may also adversely affect clinical outcomes. Treatment of both overt and subclinical acidosis with alkali supplements slows renal disease progression in clinical trials, but use of alkali supplements may be associated with unacceptable risks in some CKD patients. Lowering nonvolatile acid load through dietary manipulation may be a complementary strategy to mitigate acidosis and improve outcomes earlier in CKD when subclinical, but not overt, acidosis is present. Using intensive patient-oriented research, we will perform detailed, direct measures of dietary intake, renal acid excretion, glomerular filtration rate and subclinical acidosis in participants with early stage 3 CKD with and without diabetes, and in healthy controls, to determine independent risk factors for subclinical acidosis. Using this rich source of data, we will also validate estimates of nonvolatile acid load against gold- standard measures for future research applications. Finally, we will directly measure nonvolatile acid load in 1000 participants from the Chronic Renal Insufficiency Cohort (CRIC) study, a diverse CKD cohort, and examine its association with hard clinical outcomes over long term follow-up. We anticipate that these research aims will establish nonvolatile acid load as a modifiable risk factor in CKD that may exert adverse effects by directly contributing to subclinical acidosis, which, by definition, escapes detection in the vast majority of patients with CKD. In addition, this research will provide a rich training experience fr the PI, Dr. Julia Scialla, in physiologic and epidemiologic research. Dr. Scialla has prior trainin in clinical nephrology and epidemiology at Johns Hopkins University and a record of publication in this field which formed the basis of her research hypotheses. She will be mentored by Dr. Myles Wolf, an experienced, well-funded clinician-scientist with a broad range of skills in patient oriented research, including physiologic and epidemiologic studies. The PI will also benefit from additional advising by experts in renal epidemiology, nutrition and translational research. This Mentored Patient-Oriented Research Career Development Award will help Dr. Scialla achieve her immediate and long term goals by supporting: (1) new training in physiologic research;(2) advanced training in epidemiology;(3) the development of scientific expertise in early abnormalities of acid-base homeostasis;and (4) the generation of critical preliminary data and scientific collaborations to facilitate her transition to research independence.

Public Health Relevance

This research will evaluate the role of dietary intake in early abnormalities of acid-base balance in diabetic and non-diabetic CKD, as well as its subsequent impact on clinical outcomes, including progression of kidney disease, need for dialysis, development of cardiovascular disease and mortality. This work will help justify a randomized trial of dietary modification to lower nonvolatile acid load and improve outcomes, early in CKD, prior to the development of overt acidosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK095949-03
Application #
8661184
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2012-07-15
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
$168,454
Indirect Cost
$12,467
Name
University of Miami School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Scialla, Julia J; Asplin, John; Dobre, Mirela et al. (2016) Higher net acid excretion is associated with a lower risk of kidney disease progression in patients with diabetes. Kidney Int :
Scialla, Julia J (2015) The balance of the evidence on acid-base homeostasis and progression of chronic kidney disease. Kidney Int 88:9-11
Isakova, Tamara; Craven, Timothy E; Scialla, Julia J et al. (2015) Change in estimated glomerular filtration rate and fracture risk in the Action to Control Cardiovascular Risk in Diabetes Trial. Bone 78:23-7
Scialla, Julia J; Wolf, Myles (2015) When there will never be a randomized controlled trial. Kidney Int 88:220-2
Chen, Teresa K; Choi, Michael J; Kao, W H Linda et al. (2015) Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression. Clin J Am Soc Nephrol 10:2128-35
Scialla, Julia J; Parekh, Rulan S; Eustace, Joseph A et al. (2015) Race, Mineral Homeostasis and Mortality in Patients with End-Stage Renal Disease on Dialysis. Am J Nephrol 42:25-34
Tangri, Navdeep; Miskulin, Dana C; Zhou, Jing et al. (2015) Effect of intravenous iron use on hospitalizations in patients undergoing hemodialysis: a comparative effectiveness analysis from the DEcIDE-ESRD study. Nephrol Dial Transplant 30:667-75
Scialla, Julia J (2015) Epidemiologic insights on the role of fibroblast growth factor 23 in cardiovascular disease. Curr Opin Nephrol Hypertens 24:260-7
Suarez, Jonathan J; Isakova, Tamara; Anderson, Cheryl A M et al. (2015) Food Access, Chronic Kidney Disease, and Hypertension in the U.S. Am J Prev Med 49:912-20
Dobre, Mirela; Yang, Wei; Pan, Qiang et al. (2015) Persistent high serum bicarbonate and the risk of heart failure in patients with chronic kidney disease (CKD): A report from the Chronic Renal Insufficiency Cohort (CRIC) study. J Am Heart Assoc 4:

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