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Discoveries & Distinctions

Dr. Grantham1958: Novel method devised to exchange fluid and electrolytes across the walls of an isolated segment of jejunum in a patient with renal insufficiency.
• Schloerb, P.R. The management of uremia by perfusion of an intestinal jejunal segment with observations of the dynamics of water and electrolyte exchange in the human jejunum. J. CIin. Invest. 37:1818-35

1968: Evidence that the processing of glomerular filtrate by tubule reabsorption requires high levels of energy-consuming sodium pump.
• Fanestil, D.D. Renal Na-K ATPase relationship to total functional renal mass. Nature 218(5137):176-7

1970: The first evidence that a physico-chemical change occurs in the apical membranes of collecting duct cells when water permeability is increased by vasopressin.
• Grantham, J.J. Vasopressin: effect on deformability of urinary surface of collecting duct cells. Science 168(3935):1093-5

1972:  Demonstration in single perfused renal tubules that basement membranes contribute tensile strength equivalent to that of tendon collagen.
• Welling, L.W. and Grantham, J.J. Physical properties of isolated perfused renal tubules and tubular basement membranes. J. Clin. Invest. 51:1063-1075

1973: Discovery that in plasma from uremic patients, proximal straight tubules secrete solutes and fluid, implicating a potential role for salt and fluid secretion in regulating water balance.
Grantham, J.J., Irwin, R.L., Qualizza, P.B., Tucker, D.R., and Whittier, F.C. Fluid secretion in isolated proximal straight renal tubules: Effect of human uremic serum. J. Clin. Invest. 52:2441-2450

1982: Polycystic Kidney Research Foundation established in Kansas City. Dr. Jared Grantham (above) teamed with Mr. Joseph Bruening to create the Polycystic Kidney Research Foundation (PKRF), headquartered in Kansas City, MO. By 2008, the PKRF was responsible for directly funding more than $3 million in national and international grants and in influencing federal support for PKD research to the extent of an additional $35 million per year.

1983: Innovative method to selectively anti-coagulate blood within extra-corporeal circuits that is currently in use world-wide.
• Pinnick, R.V., Wiegmann, T.B., Diederich, D.A. Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N. Engl. J. Med. 308(5):258-61.

1986: Dr. Grantham elected Secretary-Treasurer of the American Society of Nephrology.

1987: The first structural characterization of the human Goodpasture antigen opens the door to defining the structure of Type IV collagen in glomerular basement membranes.
• Wieslander, J., Kataja, M., Hudson, B.G. Characterization of the human Goodpasture antigen. Clin. Exp. Immunol. 69(2):332-40.

1988: Discovery that growth-promoting genes are highly expressed in the mural cells of renal cysts, indicating that cysts are in fact benign neoplastic structures.
• Cowley, Jr., B.D., Smardo, F.L., Grantham, J.J., and Calvet, J.P. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease. Proc. Natl. Acad. Sci. USA 84:8394-8398

1989: Discovery that cyclic AMP is a key intermediary in the sustained proliferation of cyst mural epithelial cells implicating vasopressin as an offensive growth factor in renal cystic disorders.
• Mangoo-Karim, R., Uchic, M., Lechene, C., and Grantham, J.J. Renal epithelial cyst formation and enlargement in vitro: Dependence on cyclic AMP. Proc. Natl. Acad. Sci. USA 86:6007-6011

1989: The Journal of the American Society of Nephrology founded on this campus by Dr. Grantham and Dr. Sullivan. Upon completion of their editorial terms in 1996, the journal had the highest impact factor of over 30 world-wide titles in Nephrology and Urology.

1992: Dr. Grantham received the Homer W. Smith Award from the American Society of Nephrology.

1993: Conclusive proof that cyclic AMP promotes fluid secretion into cysts dissected from kidneys of patients with polycystic kidneys.
• Ye, M., Grantham, J.J. The secretion of fluid by renal cysts from patients with autosomal dominant polycystic kidney disease. N. Eng. J. Med. 329:310-313

1993: Dr. Abrahamson received a MERIT award from the NIDDK, NIH covering the years 1993 - 2002.

1996: An innovative technology developed at KUMC was used to identify, isolate and characterize a powerful factor in the plasma of some patients with a devastating type of nephrotic syndrome.
• Savin, V.J., Sharma R, Sharma M, McCarthy ET, Swan SK, Lovell H, Warady B, Gunwar S, Chonko AM, Artero M, Vicenti F. Circulating factor increasing glomerular permeability in recurrent focal segmental glomerulosclerosis. N. Engl. J. Med. 334: 878-883.

1998: Doctors Grantham, Hudson and Calvet received a five year NIH Program Project Grant for studies of "Chronic Progressive Renal Diseases".

1998: Dr. Vincent Gattone patented the invention of the use of vasopressin V2 receptor antagonists for treatment of polycystic kidney disease. Clinical trials of the first such agent, tolvaptan, are ongoing at KU and other centers.

1999: Doctors Grantham, Calvet, Robin Maser, Kenneth Peterson, Matthew Buechner and Xiangyi Lu were granted one of the Magnet Centers for Polycystic Kidney Research by the National Institutes of Diabetes, Digestive and Kidney Diseases. The Center grant was re-funded for an additional five years in 2004 under Dr. Calvet's directorship.

2000: The Kidney Institute received a grant from the National Institutes of Health for $1.9 million dollars, matched by another $1.9 million, for construction on the KUMC campus of research laboratories sufficient to house most of the principal investigators who work on kidney-related research problems.

2001: Demonstration that cyclic AMP stimulates net fluid secretion in inner medullary collecting ducts adding further support to the possibility that in the regulation of fluid balance, salt and water may be added to the urine all along the renal tubule system.
• Wallace DP, Rome LA, Sullivan LP, Grantham JJ. cAMP-dependent fluid secretion in rat inner medullary collecting ducts. Am J Physiol Renal Physiol 280:F1019-F1029

2001: Dr. Hudson received a MERIT award from the National Institutes of Health. This prestigious award provided approximately a half-million dollars a year for research of kidney disease over a period of seven years.

2002: Dr. Dubose was elected to the Council of the American Society of Nephrology and later served as President.

2003: Dr. Hudson received the Homer W. Smith Award from the American Society of Nephrology.

2003: Dr. Grantham received the Lillian Jean Kaplan Prize for research contributions that improve the understanding of polycystic kidney disease.

2004: Discovery that a small, sustained reduction in the cellular calcium level will transform normal renal cells into a proliferative phenotype responsive to the mitogenic action of cyclic AMP.
• Yamaguchi T, Wallace DP, Magenheimer BS, Hempson SJ, Grantham JJ, and Calvet JP. Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J. Biol. Chem. 279:40419-30

2006: Demonstration in individual patients that cystic kidneys enlarge symmetrically at a relatively constant rate over a life-span.
• Grantham, JJ. Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr, Wetzel LH, Baumgarten DA, Kenney PJ, Harris PC, Klahr S, Bennett WM, Hirschman GN, Meyers XM, Zhang X, Zhu F, Miller JP; CRISP Investigators. Volume progression in polycystic kidney disease. N. Engl. J. Med. 354:2122-30

2009: Dr. Grantham received the Jean Hamburger Award from the International Society of Nephrology.

2011: Dr. Calvet received the Lillian Jean Kaplan Prize for research contributions that improve the understanding of polycystic kidney disease.

2011: Dr. Grantham received the John P. Peters Award from the American Society of Nephrology.

2011: Dr. Alan Yu, MB, BChir was recruited to KUMC as Professor of Internal Medicine and to be the Director of the Division of Nephrology and Hypertension, and the Director of the Kidney Institute.

2012: Results from the TEMPO 3:4 clinical trial were published in the NEJM, which showed that tolvaptan slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD. KUMC was one of the clinical sites testing tolvaptan. Dr. Grantham was an author on this paper.

  • Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Ron T Gansevoort, Jared J Grantham, Eiji Higashihara, Ronald D Perrone, Holly B Krasa, John Ouyang, Frank S Czerwiec, TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med (2012) 367(25):2407-18.

2015: The PKD Center was awarded a P30 program grant from NIDDK under Dr. Calvet. The Center supported four biomedical research cores – Gene Targeting (Dr. Chris Ward, Director), Epigenetics (Dr. Xiaogang Li, Director), Biomarkers and Biomaterials (Dr. Darren Wallace, Director), and Clinical Research (Dr. Alan Yu, Director). The Center also supported several pilot and feasibility grants.

2017: With the passing of Dr. Jared Grantham, the Kidney Institute was re-named the Jared Grantham Kidney Institute.

2018: Based on the results of the TEMP 3:4 trial and the subsequent REPRISE trial, the US Food and Drug Administration (FDA) approved Jynarque (tolvaptan) to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Drs. Yu and Mustafa were authors on this paper summarizing the guidelines for tolvaptan use.

  • Fouad T Chebib, Ronald D Perrone, Arlene B Chapman, Neera K Dahl, Peter C Harris, Michal Mrug, Reem A Mustafa, Anjay Rastogi, Terry Watnick, Alan S L Yu, Vicente E Torres. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. J Am Soc Nephrol (2018) 29(10):2458-70.

2020: The PKD Center was awarded a U54 program grant from NIDDK under Dr. Calvet. This Center supported three biomedical research cores – Biomarkers and Biomaterials (Dr. Darren Wallace, Director), Rodent Models (Drs. Pamela Tran and Stephen Parnell, Co-Directors), and Clinical Research (Dr. Alan Yu, Director and Dr. Reem Mustafa, Associate Director). The PKD Center, together with centers at the University of Maryland and the University of Alabama-Birmingham formed a national PKD Research Resources Consortium to provide services and reagents to the national PKD research community.

2021: Dr. Reena Rao patented the invention of the use of vasopressin V2 receptor antagonists for treatment of renal cell carcinoma.

KU School of Medicine

University of Kansas Medical Center
The Jared Grantham Kidney Institute
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3901 Rainbow Boulevard
Kansas City, KS 66160