Manish Ponda, MD, MS

Manish Ponda Dr. Ponda is an Assistant Professor of Clinical Investigation in Dr. Jan Breslow's Laboratory of Biochemical Genetics and Metabolism and an Attending Physician at The Rockefeller University Hospital. He graduated early and with honors from Harvard University, with a degree in biochemistry. Prior to entering medical school, he spent one year at the Massachusetts General Hospital Cancer Center as a bench scientist. After medical school, he completed training in Internal Medicine at NYU Medical Center and subspecialty training in Nephrology at the Albert Einstein College of Medicine. He joined The Rockefeller University in 2007 as a Clinical Scholar. He has developed research programs in vitamin D repletion and in understanding how kidney disease accelerates cardiovascular disease.

Vitamin D and Cholesterol

Vitamin D deficiency is an increasingly common diagnosis. This is concerning because low levels of vitamin D are associated with many diseases, including unhealthy cholesterol levels. While a vitamin D deficiency is easily "cured" by taking supplements, it is unclear whether oral vitamin D is beneficial beyond bone health. Clinical trials have yet to show a role for vitamin D repletion in reducing cardiovascular disease or improving the lipid profile.

In collaboration with Quest Diagnostics, Dr. Ponda utilized a clinical database to investigate the relationship between vitamin D status and cholesterol levels. A cross-sectional analysis found that higher vitamin D levels strongly correlated with a healthier lipid profile. However, when patients with low vitamin D levels were followed over time, those who increased their vitamin D levels to normal did not show any improvement in their lipid profile.

These results were corroborated by a double-blind, randomized, placebo-controlled trial led by Dr. Ponda, and supported by The Rockefeller University Hospital's Center for Clinical and Translational Science. In this study, 151 vitamin D deficient participants were given either oral vitamin D3 or placebo. There was no effect of vitamin D supplementation on cholesterol levels. In fact, individuals with a strong physiologic response to vitamin D therapy experienced increases in LDL (bad) cholesterol.

Dr. Ponda is now leading a new trial comparing the effect of oral vitamin D to ultraviolet light therapy. Sun exposure is the natural way of making vitamin D. Light therapy may explain why oral supplements fail to reproduce the benefits of naturally higher vitamin D levels.

Kidney Disease and Atherosclerosis

Kidney disease affects millions of people and results in premature death, mainly through accelerated cardiovascular disease. Even accounting for high blood pressure and diabetes that often accompany kidney disease, low kidney function still adds significant extra risk. There are many theories as to why and how kidney disease accelerates heart disease. Unfortunately, though, there is no current therapy targeting kidney-specific mechanisms. This is particularly concerning given that patients with the most advanced kidney disease are resistant to conventional therapy.

Dr. Ponda made the novel observation that kidney disease inhibits the regression of atherosclerosis. His current research focuses on the molecular mechanisms of this inhibition. He has identified a novel plasma factor that may play a role in human disease. He is currently characterizing this factor, with the goal of identifying a new therapeutic target. This work is supported by a 5-year NIH grant to Dr. Ponda.

Publications:

1. Ponda MP, Breslow JL. Vitamin D3 Repletion in Chronic Kidney Disease Stage 3: Effects on Blood Endotoxin Activity, Inflammatory Cytokines and Intestinal Permeability. Ren Fail. 2013 In Press

2. Ponda MP, Dowd K, Finkielstein D, Holt PR, Breslow JL. The Short-Term Effects of Vitamin D Repletion on Cholesterol: A Randomized Placebo-Controlled Trial. Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2510-5. PMID: 22947589

3. Ponda MP, Huang X, Odeh MA, Breslow JL, Kaufman HW. Vitamin D may not improve lipid levels: a serial clinical laboratory data study. Circulation. 2012 Jul 17;126(3):270-7. PMID: 22718799

4. Ponda MP, Barash I, Feig JE, Fisher EA, Skolnik EY. Moderate Kidney Disease Inhibits Atherosclerosis Regression. Atherosclerosis. 2010 May; 210(1):57-62 PMCID: PMC3175796

5. Ponda MP, Quan Z, Raff AC, Meyer T, Hostetter TH. Methylamine Clearance by Hemodialysis is Low. Nephrology, Dialysis and Transplantation. 2010 May; 25(5):1608-13 PMCID: PMC2910329

6. Quan Z, Ponda M, Melamed M, Raff A, Berman N, Scherer J, Bitzer M, Meyer T, Hostetter T. Derivatization of Methylamine and Ethylamine Followed by LC and Fluorescence Detection for Measurement of Urinary Clearance. Chromatographia. 2010 Mar; 71(5):411-18

7. Barash I, Ponda MP, Goldfarb DS, Skolnik EY. A Pilot Clinical Study To Evaluate Changes in Urine Osmolality and Urine cAMP In Response to Acute and Chronic Water Loading in Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol. 2010 Apr;5(4):693-7 PMID: 20167686

8. Ponda MP, Barash I. Lipid metabolism in dialysis patients-the story gets more complicated. Semin Dial. 2008 Sep-Oct;21(5):390-4. PMID: 18764791

9. Raff AC, Lieu S, Melamed ML, Quan Z, Ponda M, Meyer TW, Hostetter TH. Relationship of impaired olfactory function in ESRD to malnutrition and retained uremic molecules. Am J Kidney Dis. 2008 Jul;52(1):102-10. PMID: 18423810

10. Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, Susztak K. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008 Mar;14(3):290-8. PMID: 18311147

11. Ponda MP, Hostetter TH. Aldosterone antagonism in chronic kidney disease. Clin J Am Soc Nephrol. 2006 Jul;1(4):668-77. PMID: 17699271

12. Chen L, Haider K, Ponda M, Cariappa A, Rowitch D, Pillai S. Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase. J Biol Chem. 2001 Jun 15; 276(24):21737-44. PMID: 11278382

Book Chapters:

1. Abramowitz MK, Ponda MP, Hostetter TH. “Disorders of the Renin-Angiotensin-Aldosterone System” Renal and Electrolyte Disorders 7th Edition. 2010