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Overview

My research focuses on understanding the fundamental causes of the excess morbidity and mortality seen in patients with chronic and end-stage kidney disease in an effort to develop new targeted therapies. We have linked a protein modification known as carbamylation to several adverse outcomes such as resistance to erythropoietin and mortality in patients with kidney disease.  Similarly, using high throughput screening, we have identified a number of novel metabolite derangements associated with cardiovascular disease in dialysis patients.  We are now studying ways to correct these metabolic disturbances and determine, through clinical trials, if doing so results in improved patient outcomes.

References

  1. Berg AH, Drechsler C, Wenger J, Buccafusca R, Hod T, Kalim S, Ramma W, Parikh SM, Friedman DJ, Danziger J, Wanner C, Thadhani R, Karumanchi SA. Carbamylation of Serum Albumin as a Risk Factor for Mortality in Patients with Kidney Failure. Science Transl Med. 2013; 5(175):175ra29. PMID: 23467560. PMCID: PMC3697767.
  2. Kalim S, Tamez H, Wenger JW, Ankers E, Trottier CA, Deferio JJ, Berg AH, Karumanchi SA, Thadhani R. Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease. Clin J Am Soc Nephrol. 2013; 8(11):1927-34. PMID: 23970130. PMCID: PMC3817911.
  3. Kalim S, Clish CB, Wenger J, Elmariah S, Yeh RW, Deferio JJ, Pierce K, Deik A, Gerszten RE, Thadhani R, Rhee EP. A plasma long-chain acylcarnitine predicts cardiovascular mortality in incident dialysis patients. J Am Heart Assoc. 2013; 2(6):e000542. doi: 10.1161/JAHA.113.000542. PMID: 24308938. PMCID: PMC3886735.
  4. Kalim S, Thadhani R, Karumanchi SA, Berg AH. Protein carbamylation in kidney disease: pathogenesis and clinical implications. Am J Kidney Dis. 2014. PMID: 25037561.
  5. Drechsler C, Kalim S, Wenger JB, Suntharalingam P, Hod T, Thadhani RI, Karumanchi SA, Wanner C, Berg AH. Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease. Kidney Int. 2015. PMID: 25671766 PMCID: PMC4449819
  6. Kalim S, Ortiz G, Trottier CA, Deferio JJ, Karumanchi SA, Thadhani RI, Berg AH. The Effects of Parenteral Amino Acid Therapy on Protein Carbamylation in Maintenance Hemodialysis Patients. J Ren Nutr. 2015. PMID: 25753604 PMCID: PMC4469570.
  7. Kalim S, Clish CB, Deferio JJ, Ortiz G, Moffet AS, Gerszten RE, Thadhani R, Rhee EP. Cross-sectional examination of metabolites and metabolic phenotypes in uremia. BMC Nephrology. 2015;16(1):98. PMID: 26149577.