The overarching goal of the Washington University (WU) Center for Kidney Disease Research (CKDR) is to support centralized resources, facilities, and expertise shared by investigators at WU in order to delineate fundamental mechanisms of renal disease and to facilitate translation of such discoveries to its treatment. The CKDR consists of an Administrative Core and 3 Biomedical Research Cores.

If you wish to access any of the Core facilities please contact the applicable core director, Dr. Brennan, Dr. Jain, Dr. Hammerman, Dr. Miner or Dr. Morrison at the e-mail addresses included below.

ADMINISTRATIVE CORE

The administrative core serves to coordinate the interdisciplinary activities of all other Cores, and serves to seamlessly interface the WU renal investigators, core leadership and external collaborators (both national and international) and users of the specialized resources offered. Also, the administrative core oversees the solicitation, review and selection of pilot and feasibility projects.Aubrey R. Morrison, MBBS (TEL: 314 454 8495)


RENAL ORGANOGENESIS CORE

The Renal Organ Culture/Organogenesis Core provides users with materials, tools, technologies & access to special expertise in order to pursue more efficiently and effectively projects that require isolation, tissue processing, culture or transplantation of renal primordia. In addition the core provides access to special expertise relating to isolation and transplantation of embryonic pancreas. For additional information, please contact: Marc R. Hammerman, MD (TEL: 314 362 8233) or alternatively Rafi Kopan PhD (TEL: 341 747 5520)


RENAL DISEASE MODELS CORE

The Renal Disease Models Core: 1) provides expertise and advice for investigators wishing to study diverse aspects of renal development, function and disease; 2) generates non-genetic (injury) models of kidney disease in mice and rats; 3) generates transgenic and knockout mice for the study of genes involved in renal development, function, and disease; 4) provides a battery of renal chemistry assays of blood and urine to aid in the analysis of animal models of genetic and acquired kidney diseases; 5) provides equipment and support for analyzing renal development, morphology and histopathology by fluorescence, light, and transmission electron microscopy; and 6) maintains a repository of kidneys from animal models of kidney disease. For additional information, please contact: Jeffrey Miner PhD (TEL: 314 362 8235) or alternatively Andrey Shaw MD (TEL: 341 362 4614)


KIDNEY TRANSLATIONAL RESEARCH CORE

The Washington University Kidney Translational Research Core serves as a state-of-the-art accessible repository for clinical information and biological specimens. The core integrates diverse existing clinical datasets of kidney transplant and nontransplant patients at WU and Saint Louis Children’s Hospital (SLCH), and Saint Louis University Medical Center (SLU) creating a central database with standardized data elements. Services are provided for collecting, storing, de-identifying, and curating data. For additional information, please contact: Daniel C. Brennan, MD (TEL: 314 362 8351) or Sanjay Jain MD, PhD (TEL: 314 454-8728 or alternatively Helen Liapis MD or Rakesh Nagarajan MD, PhD or Mark Schnitzler PhD


Pilot and Feasibility Projects: 2007-2009

Project 1: Genetic cell ablation in the S1 proximal tubule; Feng Chen PhD
Project 2: Roles of GDNF-Ret Signaling in Kidney; Sanjay Jain MD, PhD
Project 3: Proteinuria: Causes and effects; George Jarad MD
Project 4: Proteomic screening for cardiac hypertrophic toxins in uremia; Anthony Muslin MD

Pilot and Feasibility Project 2009- : Vitamin D and Atherosclerosis

Carlos Bernal Mizrahi MD : Adhesion, migration, and foam cell formation in macrophages as well as hypertension are early events promoting vascular inflammation and atherosclerosis. Our preliminary data indicate that vitamin D receptor (VDR) signaling suppresses all of these events in humans and in mice. We hypothesize that vascular inflammation induced by vitamin D deficiency elevates blood pressure and promotes atherosclerosis. To test this hypothesis, we will evaluate the physiological and pathological vascular consequences of vitamin D deficiency in mice; and define the cellular and molecular mechanism(s) by which macrophage VDR signaling induces vascular inflammation and atherosclerosis. Carlos Bernal Mizrahi MD

Pilot and Feasibility Project 2009- : In vivo analysis of claudin oligomerization and trafficking

Jianghui Hou PhD: Human mutations in claudin-16 and claudin-19 are responsible for the hereditary renal disease FHHNC (Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis). We have found that the two claudins co-localize in the thick ascending limb (TAL), interact and synergize to form a cation-selective protein complex. In the TAL of mouse kidney,claudin-16 and claudin-19 interaction is required for their assembly into tight junctions. This proposal will study claudin-16 co-oligomerization with claudin-19 and their trafficking in vitro and in vivo. Jianghui Hou PhD

Pilot and Feasibility Project 2009- : Evaluation of novel viruses as risk factors for post-renal transplant leukopenia

Steven J. Lawrence MD: Leukopenia may be an important complication during the first 6 months following renal transplantation. In addition to direct immunosuppressive effects, it can prompt clinicians to reduce anti-rejection immunosuppressive therapy, increasing the risk of graft rejection. Many causes of leukopenia are known, including viral infections and medications. However, a significant proportion of post-transplant leukopenia has no immediately recognizable etiology. In recent years, many new viral pathogens have been discovered, including BK polyomavirus, which is specifically pathogenic in renal transplant recipients. This proposal aims to evaluate the epidemiology of post-transplant leukopenia, and investigate novel virus infections as a risk factor for previously unexplained leukopenia.Steven Lawrence MD

Pilot and Feasibility Project 2009- : Using 153Gd to help determine how gadolinium chelates and renal insufficiency lead to nephrogenic systemic fibrosis (NSF)

Thaddeus Wadas PhD: Nephrogenic Systemic Fibrosis (NSF) occurs in patients with renal insufficiency that have been exposed to Gd-based magnetic resonance imaging (MRI) contrast media. Moreover, NSF is a chronic, progressive and systemic disease associated with high morbidity and mortality, and although the etiology of NSF is unknown, strong correlative evidence suggests it likely results from the production of a toxic metabolite following administration of Gd-chelate based MRI contrast agents. While initial reports established a linkage between Gd-chelate exposure and NSF, the identity and mechanism of production of this metabolite are unknown and effective NSF therapies remain elusive. The goals of the proposed research are to determine the nature of the toxic metabolite(s) through the use of 153Gd(Gd) chelates in metabolism studies involving mice with renal insufficiency; and to evaluate sodium thiosulfate (STS) as a potential therapy for NSF.Thaddeus Wadas, PhD

WU Renal Division 'Classic' Publications 1920-1979

Marshall EK Jr. The influence of diuresis on the hydrogen ion concentration of urine J. Pharmacology Experimental Therapeutics. 16:141-154, 1920/21.
Marshall EK Jr. The effect of loss of carbon dioxide on the hydrogen ion concentration of urine J. Biol. Chem. 51:3-10, 1922.
White HL, Schmitt FO Observations on kidney function in Necturus maculosus Science 62: 334, 1925.
White HL, Schmitt FO The site of reabsorption in the kidney tubule of necturus Am. J. Physiol 76:483—495, 1926.
Bulger HA, Dixon HH, Barr DP , Schregardus OJ. The functional pathology of hyper-parathyroidism. J. Clin. Invest. 9:143-90 1930.
Hartmann AF , Senn MJE, Studies in the metabolism of sodium-r-lactate II. Response of normal human subjects to the intravenous injection of sodium r-lactate J. Clin. Invest. 11:327-335, 1932
Hartmann AF, Senn MJE. JES Studies in the metabolism of sodium-r-lactate II. Response of human subjects with acidosis to the intravenous injection of sodium r-lactate J. Clin. Invest. 11:337-344, 1932
White HL Monaghan B. A comparison of the clearances of creatinine and various sugars Am. J. Physiol 106:16-27, 1933.
White HL, Heinbecker P. Pituitary regulation of water exchange in the dog and monkey. Am. J. Physiol 118:276-284, 1937.
White HL, Heinbecker P. Observations on inulin and diodrast clearance and on renal plasma flow in normal and hypohysectomized dogs Am. J. Physiol. 121:40-43, 1940.
White HL, Heinbecker P, Rolf D. Enhancing effects of growth hormone on renal function. Am J Physiol 157:47-51, 1949.
Bricker, N.S., Guild, W.R., Reardan, J.B., Merrill, J.P.: Studies on the functional capacity of a denervated homotransplanted kidney in an identical twin with parallel observations in the donor. J. Clin. Invest. 35: 1364-1380, 1956.
Bricker, N.S. and Patton, J.F.: Renal-function studies in polycystic disease of the kidneys: With observations on the effects of surgical decompression. N. Engl. J. Med. 256: 212-214, 1957.
Bricker, N.S., Straffon, R.A., Mahoney, E.P., Merrill, J.P. The functional capacity of the kidney denervated by autotransplatation in the dog. J. Clin. Invest. 37: 185-193, 1958.
Bricker, N.S., Dewey, R.R., Lubowitz, H., Stokes, J.N., Kirkensgaard, T.: Observations on the concentrating and diluting mechanisms of the diseased kidney. J. Clin. Invest. 38: 516-523, 1959.
Bricker NS, Kime SW Jr, Morrin PAF, Orlowski, T. The influence of glomerular filtration rate, solute excretion and hydration on the concentrating mechanism of the experimentally diseased kidney in the dog. J. Clin. Invest. 39: 864-875, 1960.
Bricker, NS, Orlowski T, Kime SWJr, Morrin PAF. Observations on the functional homogeneity of the nephron population in the chronically diseased kidney of the dog. J. Clin. Invest. 39: 1771-1776, 1960.
Reiss, E., Bricker, N.S., Kime, S.W., Jr., Morrin, PAF Observations on phosphate transport in experimental renal disease. J. Clin. Invest. 40: 165-170, 1961.
Morrin, P.A.F., Bricker, N.S., Kime, S.W., Jr., Klein, C. Observations on the acidifying capacity of the experimentally diseased kidney in the dog. J. Clin. Invest. 41 1297-1302, 1962.
Bricker, N.S., Biber, T., Ussing, H.H.: Exposure of the isolated frog skin to high potassium concentrations at the internal surface. I. Bioelectric phenomena and sodium transport. J. Clin. Invest. 22: 88-99, 1963.
Bricker, N.S., Klahr, S. & Rieselbach, RE . The functional adaptation of the diseased kidney. I. Glomerular filtration rate. J. Clin. Invest. 43: 1915-1921, 1964.
Ussing, H.H., Biber, T.U.L., Bricker, N.S.: Exposure of the isolated frog skin to high potassium concentrations at the internal surface. II. Changes in epithelial cell volume, resistance, and response to antidiuretic hormone. J. Gen. Physiol. 48: 425-433, 1965.
Slatopolsky E, Gradowska L, Kashemsant C, Keltner R, Manley C, Bricker NS. The control of phosphate excretion in uremia. J. Clin. Invest. 45: 672-677, 1966.
Shankel, SW, Robson, AM , Bricker, N.S.: On the mechanism of the splay in the glucose titration curve in advanced experimental renal disease in the rat. J. Clin. Invest. 46: 164-172, 1967.
Slatopolsky, E., Robson, AM ., Elkan, I., Bricker, N.S.: Control of Phosphate excretion in uremic man. J. Clin. Invest. 47: 1865-1874, 1968.
Schultze, R.G., Shapiro, H.S., Bricker, N.S .: Studies on the control of sodium excretion in experimental uremia. J. Clin. Invest. 48: 869-877, 1969.
Slatopolsky, E., Hoffsten, P., Purkerson, M., Bricker, N.S.: On the influence of extracellular fluid volume expansion and of uremia on bicarbonate reabsorption in man. J. Clin. Invest. 49: 988-998, 1970.
Schultze, R.G., Taggart, D.D., Shapiro, H., Pennell, J.P., Caglar, S., Bricker, N.S.: On the adaptation in potassium excretion associated with nephron reduction in the dog. J. Clin. Invest. 50: 1061-1068, 1971.
Bricker, N.S.: On the pathogenesis of the uremic state: An exposition of the "trade-off hypothesis". N. Engl. J. Med. 286: 1093-1099, 1972.
Bricker, N.S.: The time for reflection: A luxury of the past. Presidential address presented at the 65th Annual meeting of the American Society for Clinical Investigation, J. Clin. Invest. 52: 1526-1530, 1973.
Rodriguez, H. Walls, J , Yates, J., and Klahr, S. Effects of acetazolamide on the urinary excretion of cyclic AMP and on the activity of renal adenyl cyclase. J. Clin. Invest. 53: 122-130, 1974.
Hruska, K.A., Kopelman, R., Rutherford, W.E., Klahr, S. and Slatopolsky, E.Metabolism of immunoreactive parathyroid hormone in the dog: The role of the kidney and the effects of chronic renal disease. J. Clin. Invest. 56: 39-48, 1975.
Slatopolsky, E., Mercado, A., Morrison, A., Yates, J. and Klahr, S. Inhibitory effects of hypermagnesemia on the renal action of parathyroid hormone. J. Clin. Invest. 58: 1273- 1279, 1976.
Hammerman, MR . and Sacktor B. Transport of amino acids in renal brush border membrane vesicles. Uptake of L-proline. J. Biol. Chem. 252:591-595, 1977.
Freitag, J., Martin, K.J., Hruska, K.A., Anderson, C., Conrades, M., Ladenson, J., Klahr, S., and Slatopolsky, E. Impaired parathyroid hormone metabolism in patients with chronic renal failure. N. Engl. J. Med. 298: 29-32, 1978.
Needleman P, Wyche A, Bronson SD, Holmberg S, Morrison AR. Specific regulation of peptide-induced renal prostaglandin synthesis.J Biol Chem. 254:9772-9779, 1979.


Research by Core Directors and Pilot/Feasibility PIs 1980-2008

Hammerman MR, Sacktor B, Daughaday WH. Myo-inositol transport in renal brush border vesicles and its inhibition by glucose. Am. J. Physiol. 239:F113-F120, 1980.
Winokur TS, Morrison AR. Regional synthesis of monohydroxy eicosanoids by the kidney. J. Biol. Chem. 256:10221-10223, 1981.
Benabe JE, Spry L, Morrison AR. Effects of angiotensin II on phosphatidyl inositol and phosphoinositide turnover in rat kidney: mechanism of prostaglandin release. J. Biol. Chem. 257: 7430-7434, 1982.
Hruska, K.A., Mills, S.C., Khalifa, S., and Hammerman, M.R. Phosphorylation of Renal Brush Border Membrane Vesicles. Effect on calcium uptake and membrane content of polyphosphoinositides. J. Biol. Chem. 258:2501-2507, 1983.
Hammerman MR, Gavin JR III. Binding of IGF II and multiplication stimulating activity-stimulated phosphorylation in basolateral membranes from dog kidneys. J. Biol. Chem. 259:13511-13517, 1984.
Shayman JA, Morrison AR. Bradykinin-induced changes in phospohatidylinositol turnover in cultured rabbit papillary collecting tubule cells. J. Clin. Invest, 76:978-984, 1985.
Hammerman MR, Gavin JR III. Binding of IGF I and IGF I-stimulated phosphorylation in canine renal basolateral membranes. Am. J. Physiol. 251:E32-E41, 1986.
Shayman JA, Morrissey JJ, Morrison AR. Islet activating protein inhibits kinin-stimulated inositol phosphate production, calcium mobilization, and prostaglandin E2 synthesis in renal papillary collecting tubule cells independent of cyclic AMP. J Biol Chem. 262:17083-17087, 1987.
Bortz JD, Rotwein P, DeVol D, Bechtel PJ, Hansen VA, Hammerman MR. Focal expression of insulin-like growth factor I in rat kidney collecting duct. J Cell Biol. 07:811-819, 1988.
Hammerman, M.R. The growth hormone-insulin-like growth factor axis in kidney Am. J. Physiol. 257:F503-F514, 1989.
Coyne DW, Mordhorst M, Morrison AR. Regulation of eicosanoid biosynthesis by phorbol ester in Madin Darby canine kidney cells. Am J Physiol. 259:F698-703, 1990.
Rogers SA, Ryan G, Hammerman MR. Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro. J. Cell. Biol. 113:1447-1454, 1991.
Miller SB, Martin DR, Kissane J, Hammerman MR Insulin-like growth factor I accelerates recovery from ischemic acute tubular necrosis in the rat. Proc. Natl. Acad. Sci. USA 89:11876-11880, 1992.
O'Shea M, Miller SB, Hammerman MR. Effects of IGF I on renal function in patients with chronic renal failure. Am. J. Physiol. 264:F917-F922, 1993.
Srivastava SK, Tetsuka T, Daphna-Iken D, Morrison AR. IL-1 beta stabilizes COX II mRNA in renal mesangial cells: role of 3'-untranslated region. Am J Physiol. 267 :F504-F508, 1994.
Sorenson CM, Rogers SA, Korsmeyer SJ, Hammerman MR. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am. J. Physiol. 268:F73-F81, 1995.
Muslin AJ, Tanner JW, Allen PM, Shaw AS. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell. 84:889-897, 1996.
Miner, JH, Patton, BL, Lentz, SI, Gilbert, DJ, Snider, WD, Jenkins,NA, Copeland,NG, Sanes, JR. The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1-5, identification of heterotrimeric laminins 8-11, and cloning of a novel alpha3 isoform. J. Cell. Biol., 137: 685-701, 1997.
Rogers SA, Lowell JA, Hammerman NA, Hammerman MR. Transplantation of developing metanephroi into adult rats. Kidney International 54:27-37, 1998.
Schnitzler MA, Hollenbeak CS, Cohen DS, Woodward RS, Lowell JA, Singer GG, Tesi RJ, Howard TK, Mohanakumar T, Brennan DC. The economics of HLA matching in cadaveric renal transplantation. N. Engl. J. Med. 341:1440-1446, 1999.
Huppert S, Le A, Schroeter EH, Mumm SJ, Saxena MT, Millner, and Kopan R. Embryonic lethality in mice homozygous for processing deficient Notch 1 allele Nature 405:966-970, 2000.
Chen F, Graef IA, Chenb L, Kuo A, Crabtree GR. Signals transduced by Ca+2/Calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 105:863-875, 2001.
Miner JH, Morello, R, Andrews K, Li C, Antignac C, Shaw A, Lee, B. Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. J. Clin. Invest.109:1065-1072, 2002.
Kim JM, Wu H, Green G, Winkler CA, Kopp J, Miner JH, Unanue E, Shaw, AS. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science 300: 1298-1300, 2003.
Jain S, Naughton CK, Yang M, Strickland A, Vij K, Encinas M, Golden J, Gupta A, Heuckeroth R, Johnson Jr EM, Milbrandt J. Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis. Development. 131:5503-5513, 2004.
Hardinger KL, Bohl DL, Schnitzler MA, Lockwood M, Storch GA, Brennan DC. A randomized, prospective, pharmacoeconomic trial of tacrolimus versus cyclosporine in combination with thymoglobulin in renal transplant recipients. Transplantation. 80:41-46, 2005.
Jarad G, Cunningham J, Shaw AS, Miner JH. Proteinuria precedes podocyte foot process effacement in Lamb2-/- mice, implicating the GBM as a barrier to albumin. J. Clin. Invest. 116, 2272-2279, 2006.
Rogers SA, Chen F, Talcott MR, Faulkner C, Thomas JM, Thevis M, Hammerman MR. Long-term engraftment following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic rhesus macaques. Xenotransplantation 14:591-602, 2007.
Akilesh S, Huber TB, Wu H, Wang G, Hartleben B, Kopp JB, Miner JH , Roopenian DC, Unanue ER, Shaw AS. Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc. Natl. Acad. Sci. 105: 967-972, 2008.
Siedlecki AM, Jin X, Muslin AS. Uremic cardiac hypertrophy is reversed by rapamycin, but not by lowering of blood pressure. Kidney Inernational 75:800-808, 2009.

Washington University George M. O'Brien Center for Kidney Disease Research Organogenesis Forum

October 4, 2007 Marc R Hammerman MD Chromalloy Professor of Renal Diseases in Medicine, Washington University School of Medicine: Hammerman MR. Organogenesis of kidney and endocrine pancreas: The window Opens. Organogenesis 3:59-66, 2007.

January 16, 2008 David KC Cooper MD PhD Professor of Surgery, Thomas E Starzl Research Institute, University of Pittsburgh School of Medicine: Cooper DKC. Xenotransplantation of organs and islets - how close are we to clinical trials? Organogenesis 4: 1-10, 2008

April 30, 2008 Sanjay K Nigam MD Nancy Kaehr Professor in Pediatric Research, University of California San Diego School of Medicine: Nigam SK, Wu W, Bush KT. In vitro kidney development, tissue engineering and systems biology. Organogenesis 4: 137-143, 2008

June 6, 2008, Emanuele Cozzi MD, PhD Director European Union XENOME project, Professor of Surgery and Immunology University of Padua ITALY Cozzi E, Bosio E, Seveso M, Rubello D, Ancona E. Xenotransplantation as a model of integrated, multidisciplinary research Organogenesis 5:288-296, 2009

September 17, 2008, Fadi G Lakkis MD Scientific Director, Thomas E. Starzl Transplantation Institute, Frank and Athena Sarris Chair in Transplantation Biology, University of Pittsburgh School of Medicine Lakkis FG, Dellaporta SL, Buss LW. Allorecognition and Chimerism in an Invertebrate Model Organism. Organogenesis 4:236-240, 2008

October 22, 2008, Mario Thevis PhD Professor for Preventive Doping ResearchGerman Sport University Cologne Institute of Biochemistry GERMANY Thevis M, Schanzer W. Illicit organogenesis  – modifying organs using performance-enhancing drugs. Organogenesis 4: 264-271, 2008

November 18, 2008, Dale Abrahamson PhD University Distinguished Professor and Chair, Department of Anatomy, University of Kansas Medical Center Development of Kidney Glomerular Endothelial Cells and Their Role In Basement Membrane Assembly. Organogenesis 5:275-287, 2009

January 21, 2009, Cathy Mendelsohn PhD Associate Professor of Urology, Genetics and Development and Pathology, Columbia Univ. P & S
Using Mouse Models to Understand Normal and Abnormal Urogenital Tract Development. Organogenesis 5:306-314, 2009

January 28, 2009, Feng Chen PhD Assistant Professor of Medicine and Cell Biology and Physiology, Washington University School of Medicine Plumbing the Depths of Obstructive Nephropathy Using Murine Models. Organogenesis 5:297-305, 2009

April 29, 2009, Greg Dressler PhD Collegiate Professor of Pathology, University of Michigan
The Specification and Maintenance of Renal Cell Types by Epigenetic Factors. Organogenesis 5:73-82, 2009

July 15, 2009, Melissa Little PhD Professor & HMRC Principal Research Fellow, Institute for Molecular Bioscience, University of Queensland, Australia Repair and Regeneration of the Kidney

August 19, 2009, Sanjay Jain MD PhD Assistant Professor of Medicine and Pathology, Washington University School of Medicine The Many Faces of RET Dysfunction in Kidney

October 21, 2009, Michael S. Goligorsky MD PhD Professor, Medicine & Pharmacology Alvin I. Goodman Chair in Nephrology New York Medical College The Decline and Fall of Blood Vessels

March 24, 2010, Jordan Kreidberg MD PhD Associate Professor of Pediatrics, Boston Childrens' Hospital Harvard Medical School

May 12, 2010, Frank Costantini PhD Professor of Genetics and Development, Columbia University Medical Center

June 9, 2010, S. Steven Potter PhD Professor of Pediatrics, Cincinnati Children's Medical Center