My research interests include prevention of progression of renal diseases, diagnoses, and management of lipid disorders in renal disease, hypertensive nephrosclerosis, the role of angiotensin II converting enzyme inhibitors, and angiotensin II receptor blockers in renal disease. I am also interested in the impact of dialysis delivery on morbidity and mortality in patients on hemodialysis and cost effectiveness of prevention and treatment of renal disease.
Our current projects include The Hemodialysis Study, an NIH-sponsored multicenter clinical trial designed to determine whether high (Kt/V 1.6) versus standard (Kt/V 1.20) and/or high versus low flux dialyzers afford improved survival benefit in patients on maintenance hemodialysis. This is a long-term trial in which mortality is the primary outcome variable for which the study is powered. Our FDA sponsored Phase I trials of a-MSH is a series of studies evaluating the safety and tolerability of a-MSH in normal controls, subjects with ESRD on maintenance hemodialysis and in patients with acute renal failure. In addition, this is a pilot study of the efficacy of a-MSH to improve GFR in patients with non-oliguric ischemic acute renal failure. Also, methodology for fast GFR measurement is underway in our laboratory. This project includes both normals and subjects with the spectrum of GFR ranging from mildly abnormal to end-stage renal disease.
A disproportionate number of African-Americans suffer from renal insufficiency and end-stage renal disease (ESRD) as sequelae of essential hypertension. The African American Study of Kidney Disease and Hypertension (AASK) is a multicenter prospective randomized double-blinded controlled trial to determine the effects of blood pressure control and specific antihypertensive regimens on the progression of hypertensive nephrosclerosis. The AASK trial is the first large-scale, long-term trial to determine whether deterioration in renal function and the subsequent risk of ESRD can be reduced in high-risk patients with hypertensive nephrosclerosis. The AASK study also offers a unique opportunity to examine the relationships among lipid metabolism, the progression of renal impairment, and cardiovascular complications in African-Americans. We are currently assembling an ancillary proposal on lipid management and progression of renal disease as part of AASK, a study that will be performed in collaboration with Dr. Helen Hobbs. Our research group is also taking a similar approach to intervene for the treatment of progressive renal disease in patients with diabetes mellitus. We are part of an international multicenter group to study the renal-sparing effects of an angiotensin receptor antagonist in diabetic nephropathy. The goal of these ongoing research projects will be to decrease the rate of growth of the population of patients with ESRD due to hypertension and diabetes.
When patients require renal replacement therapy, it is unclear how their blood pressure should be managed. Nearly half of the deaths of patients on dialysis occur from cardiovascular complications. Some of these illnesses might be preventable with improved control of blood pressure, especially since the average pre-dialysis blood pressure in the USRDS database is ~150/88. Cross-sectional observations do not provide clear guidelines for management, since either low or dramatically elevated pre-dialysis blood pressures carry a high mortality risk. To determine the ideal blood pressure treatment, our research group, in collaboration with the Division of Cardiology, is performing a pilot prospective trial on cardiovascular outcomes in patients starting on a hemodialysis program. In this trial, new ESRD patients are being randomized to either usual or low pre-dialysis blood pressure goals. The primary endpoints include clinical events and echocardiographic features pertaining to cardiovascular function. Our clinical environment gives us a unique advantage to perform this and similar studies.
We have access to the UT Southwestern hemodialysis database that includes more than 300 dialysis patients, we average nearly 20 patients/month who initiate ESRD therapy from our practice, and we have formed a productive collaboration with the Cardiology division. The goal of this line of investigation is to improve the duration and quality of life of patients maintained on hemodialysis.
Eknoyan G, Hostetter T, Bakris GL, Hebert L, Levey AS, Parving HH, Steffes MW, Toto R. Proteinuria and other markers of chronic kidney disease: A position statement of the national kidney foundation (NKF) and the national institute of diabetes and digestive and kidney diseases (NIDDK). Am J Kidney Dis. 2003 Oct;42(4):617-22.
Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE, de Zeeuw D, Shahinfar S, Toto R, Levey AS; AIPRD Study Group. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003 Aug 19;139(4):244-52.
Toto RD. Anemia of chronic disease: past, present, and future. Kidney Int Suppl. 2003 Nov;(87):S20-3.
Chertow GM, Raggi P, McCarthy JT, Schulman G, Silberzweig J, Kuhlik A, Goodman WG, Boulay A, Burke SK, Toto RD. The effects of sevelamer and calcium acetate on proxies of atherosclerotic and arteriosclerotic vascular disease in hemodialysis patients. Am J Nephrol. 2003 Sep-Oct;23(5):307-14.
Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, Ribeiro AB, Shahinfar S, Simpson RL, Snapinn SM, Toto R; RENAAL Study Investigators. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int. 2003 Apr;63(4):1499-507.
Mohanram A, Toto RD. Outcome studies in diabetic nephropathy. Semin Nephrol. 2003 May;23(3):255-71.
Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002 Dec 19;347(25):2010-9.
Toto RD. Appropriate drug therapy for improving outcomes in diabetic nephropathy. Curr Diab Rep. 2002 Dec;2(6):545-52.
Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas-Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostand SG; African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002 Nov 20;288(19):2421-31.
Augustyniak RA, Tuncel M, Zhang W, Toto RD, Victor RG. Sympathetic overactivity as a cause of hypertension in chronic renal failure. J Hypertens. 2002 Jan;20(1):3-9.
Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP, Charleston J, Cheek D, Cleveland W, Douglas JG, Douglas M, Dowie D, Faulkner M, Gabriel A, Gassman J, Greene T, Hall Y, Hebert L, Hiremath L, Jamerson K, Johnson CJ, Kopple J, Kusek J, Lash J, Lea J, Lewis JB, Lipkowitz M, Massry S, Middleton J, Miller ER 3rd, Norris K, O'Connor D, Ojo A, Phillips RA, Pogue V, Rahman M, Randall OS, Rostand S, Schulman G, Smith W, Thornley-Brown D, Tisher CC, Toto RD, Wright JT Jr, Xu S; African American Study of Kidney Disease and Hypertension (AASK) Study Group. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA. 2001 Jun 6;285(21):2719-28.
Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol. 2000 Jan-Feb;20(1):12-7.