Research Updates in Kidney and Urologic Health
UTI Vaccine on the Horizon
Urinary tract infection (UTI) is the most common
kidney and urologic problem, affecting millions of people each year.
Among infections, only respiratory infections are more common than
UTIs. Women are disproportionately affected and have a 1 in 5 chance
of getting at least one UTI during their lifetime. Some women suffer
recurrent UTIs, as many as three or more a year.
Researchers funded by the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) have provided important clues to the reasons why some women are especially prone to UTIs. This knowledge has been valuable in the development of new therapies to treat and even prevent UTIs. One of the most promising lines of research is the development of a vaccine to prevent UTIs.
In the late seventies, researchers noted the presence of an antibody in the vaginal secretions of women who were not susceptible to recurrent UTIs. Women with recurrent UTIs were much less likely to have the antibody.1 In the following decade, researchers attempted to develop parenteral vaccines, which were effective but caused postvaccine reactions,2 and oral vaccines, which were not effective at building immunity.3
More recently, NIDDK-funded researchers have conducted studies to find ways to increase the production of immunoglobulin A on the lining of the urinary tract of women who lack this normal immunological response to urinary pathogens.4 A recent phase II trial with 96 women tested a vaccine delivered through a vaginal suppository. Women who received the vaccine were more likely to stay infection-free for 8 weeks than the women who received placebo.5 Researchers are looking at patient characteristics, such as their human leukocyte antigen phenotype, to determine why some patients respond to the vaccine while others do not.6 As researchers learn more, the likelihood of an effective vaccine increases.
1. Stamey, T. A., Wehner, N., Mihara G., & Condy, M. (1978). The immunologic basis of recurrent bacteriuria: Role of cervicovaginal antibody in enterobacterial colonization of the introital mucosa. Medicine, 57(1):47–56.
2. Grischke, E. M., & Ruttgers, H. (1987). Treatment of bacterial infections of the female urinary tract by immunization of patients. Urology International, 42(5):338–341.
3. Schulman, C. C., Corbusier, A., Michiels, H., & Taenzer, H. J. (1993). Oral immunotherapy of recurrent urinary tract infections: A double-blind, placebo-controlled, multicenter study. Journal of Urology, 150(3):917–921.
4. Uehling, D. T., Hopkins, W. J., & Balish, E. (1995). Vaginal mucosal immunization in recurrent UTIs. Infections in Urology, 8(2):57–61.
5. Uehling, D. T., Hopkins, W. J., Balish, E., Xing, Y., & Heisey, D. M. (1997). Vaginal mucosal immunization for recurrent urinary tract infection: Phase II clinical trial. Journal of Urology, 157(6):2049–2052.
6. Hopkins, W. J., Heisey, D. M., & Uehling, D. T. (1999). Association of human leucocyte antigen phenotype with vaccine efficacy in patients receiving vaginal mucosal immunization for recurrent urinary tract infection. Vaccine, 17(2):169–171.
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Healthy People 2010 To Include Goals for Stopping the Rise in Kidney Disease
The third Healthy People report, Healthy People 2010, will be the first in the series to include a chapter on kidney disease.
It was drafted by the Kidney, Urologic, and Hematologic Diseases Interagency Coordinating Committee, led by scientists from the National Institute of Diabetes and Digestive and Kidney Diseases. The committee solicited comments from representatives of private organizations
and State and Federal agencies.
The 10 objectives of the new kidney disease chapter focus on detection and treatment to preserve renal function in patients at risk for
end-stage renal disease (ESRD), as well as minimizing cardiovascular complications in patients with chronic renal failure and ESRD. The objectives also aim to decrease the racial and gender disparities in kidney transplantation rates.
In 1979, the Surgeon General issued the first Healthy People report, which established the strategy of setting national goals and monitoring progress as a way to improve the Nation's health. The report made the case for focusing on prevention as the way to achieve health goals.
In 1990, an alliance of 350 national membership organizations and 300 State health, mental health, substance abuse, and environmental agencies—the Healthy People Consortium—released Healthy People 2000, an agenda with 319 health objectives organized into 22 priority areas such as physical activity and fitness, nutrition, cardiovascular disease and stroke, sexually transmitted diseases, and substance abuse. The Federal Government, States,
and communities use the Healthy People 2000 objectives as a way to measure progress in
their programs. Congress has specified Healthy People 2000 as the standard for measuring progress in the Indian Health Service, the Maternal and Child Health Block Grant, and the Preventive Health Services Block Grant.
Healthy People 2010 will be released in January 2000. Anyone interested in the report can find more information on the Healthy People web site at www.health.gov/healthypeople. Also, a draft of the chapter on chronic kidney disease can be found at www.niddk.nih.gov/federal/kuhdic/kidsub/2010.htm.
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NIDDK Researchers Seek Model for Reversing
Kidney Damage
The 1990s have seen significant advances
in the understanding and treatment
of chronic renal failure in general and diabetic nephropathy in particular. At the beginning of the decade, scientists knew that antihypertensive drugs could slow the progressive decline of renal function caused by diabetic nephropathy. In 1993, the Collaborative Study Group, funded
in part by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), found that captopril, an angiotensin-converting enzyme (ACE) inhibitor, protected renal function in patients with type 1 diabetes better than other medicines that provided the same level of blood pressure control.1 Subsequent studies have shown that the protection conferred by ACE inhibitors extends to patients with other types of renal disease,2 although it is not clear in large populations whether the protection of renal function
goes beyond that attributable to lowering the blood pressure.3 Still, in all of these studies, the treatment merely slows the progression of the disease; it does not reverse or stop it.
More recently, NIDDK-funded researchers have been exploring possible ways to actually reverse the damage done by diabetic and other nephropathies. In July 1998, one group of researchers reported observing the reversal of the lesions of diabetic nephropathy after transplantation of the pancreas.4 While the study is based on only eight cases and improvement was not observed until
10 years after transplantation, the study provides hope of the reversibility of renal disease in patients with type 1 diabetes.
The researchers explain that diabetic nephropathy results from a buildup of extracellular material in the mesangium and membranes of
the glomerulus that decreases filtration surface. In people who do not have diabetes or hyperglycemia, the volume of this extracellular material stays constant throughout their adult lives, reflecting a balance between the production of extracellular material and its removal. In some people with diabetes, hyperglycemia causes a buildup of this extracellular material until diabetic nephropathy becomes evident. But many people with diabetes do not develop nephropathy, and the researchers theorize that some genetic mechanism is responsible for the different renal reactions to hyperglycemia.5
In the patients who achieved 10 years of good glycemic control after receiving a pancreas transplant, the volume of extracellular material had decreased, indicating a shift in the balance between the buildup and removal of this substance in and around the glomeruli.
The researchers point out that neither the mechanism that reverses extracellular buildup after pancreas transplantation nor the genetic mechanism that protects some people with diabetes from nephropathy is well understood. In their commentary, Fioretto, Kim, and Mauer assert that further research in this area will result in greater understanding of the mechanisms that protect and restore renal function and in powerful tools for treating a range of renal diseases.5
1. Lewis, E. J., Hunsicker, L. G., Bain, R. P., & Rohde,
R. D., for the Collaborative Study Group. (1993). The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. New England Journal of Medicine, 329(20):1456–1462.
2. Maschio, G., Alberti, D., Janin, G., Locatelli, F., Mann, J. F. E., Motolese, M., Ponticelli, C., Ritz, E., & Zucchelli, P. (1996). Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. New England Journal of Medicine, 334(15):939–949.
3. Giatras, I., Lau, J., & Levey, A. S. (1997). Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: A meta-analysis of randomized trials. Annals of Internal Medicine, 127(5):337–345.
4. Fioretto, P., Steffes, M. W., Sutherland, D. E. R., Goetz, F. C., & Mauer, M. (1998). Reversal of lesions of diabetic nephropathy after pancreas transplantation. New England Journal of Medicine, 339(2):69–75.
5. Fioretto, P., Kim, Y., & Mauer, M. (1998). Diabetic nephropathy as a model of reversibility of established renal lesions. Current Opinion in Nephrology and Hypertension, 7(5):489–494.
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