Lowering of Microalbuminuria in Diabetic Patients by a Sympathicoplegic Agent: Novel Approach to Prevent Progression of Diabetic Nephropathy?
Abstract
Abstract.: There is convincing evidence for a specific BP-independent effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 ± 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 ± 5.1 yr) with baseline urinary albumin excretion rates (AER) >20 μg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 ± 7.1 mmHg in the third week of placebo and 91.1 ± 8.7 mmHg on moxonidine). There was a significant ( P < 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 μg/min (range, 15.9 to 117 μg/min) versus 29.0 (range, 9.03 to 85.8 μg/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for the finding.
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The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy
Lewis, E. J., Hunsicker, L. G., Bain, R. P., & Rohde, R. D. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311113292004 · Cited by 5,394 · see citing works
Sympathetic Overactivity in Patients with Chronic Renal Failure
Converse, R. L., Jacobsen, T. N., Toto, R. D., Jost, C. M. T., Cosentino, F., Fouad-Tarazi, F., & Victor, R. G. (1992) · New England Journal of Medicine · doi:10.1056/nejm199212313272704 · Cited by 1,132 · see citing works
Ruggenenti, P., Perna, A., Gherardi, G., Garini, G., Zoccali, C., Salvadori, M., Scolari, F., Schena, F. P., & Remuzzi, G. (1999) · The Lancet · doi:10.1016/s0140-6736(98)10363-x · Cited by 910 · see citing works
Cross-Over Trials in Clinical Research
Senn, S. J. (1994) · Technometrics · doi:10.1080/00401706.1994.10485798 · Cited by 777 · see citing works
Nephropathy in Patients with Type 2 Diabetes Mellitus
Ritz, E., & Orth, S. R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199910073411506 · Cited by 753 · see citing works
Self-citationParving, H. ‐., Oxenbøll, B., Svendsen, P. A., Christiansen, J. S., & Andersen, A. (1982) · European Journal of Endocrinology · doi:10.1530/acta.0.1000550 · Cited by 573 · see citing works
Prevention of diabetic renal disease with special reference to microalbuminuria
Mogensen, C. E., Keane, W. F., Bennett, P. H., Striker, G. E., Jerums, G., Parving, H.-H., Passa, P., Steffes, M. W., & Viberti, G. C. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91747-0 · Cited by 537 · see citing works
Relationship Between Insulin Sensitivity and Plasma Leptin Concentration in Lean and Obese Men
Segal, K. R., Landt, M., & Klein, S. (1996) · Diabetes · doi:10.2337/diab.45.7.988 · Cited by 493 · see citing works
Microalbuminuria: An Early Marker of Renal Involvement in Diabetes
Mogensen, C. E., Chachati, A.-S., Christensen, C., Close, C. F., Deckert, T., Hommel, E. E., Kastrup, J., Lefebvre, P., Mathiesen, E. R., Feldt‐Rasmussen, B., et al. (1985) · Uremia Investigation · doi:10.3109/08860228509088195 · Cited by 427 · see citing works
Reduction of Sympathetic Hyperactivity by Enalapril in Patients with Chronic Renal Failure
Ligtenberg, G., Blankestijn, P. J., Oey, P. L., Klein, I. H. H. T., Dijkhorst-Oei, L.-T., Boomsma, F., Wieneke, G. H., van Huffelen, A. C., & Koomans, H. A. (1999) · New England Journal of Medicine · doi:10.1056/nejm199904293401704 · Cited by 407 · see citing works
Renal Afferent Denervation Prevents Hypertension in Rats With Chronic Renal Failure
Campese, V. M., & Kogosov, E. (1995) · Hypertension · doi:10.1161/01.hyp.25.4.878 · Cited by 356 · see citing works
Markham, A., & Goa, K. L. (1997) · Drugs · doi:10.2165/00003495-199754020-00009 · Cited by 317 · see citing works
Amann, K., Rump, L. C., Simonaviciene, A., Oberhauser, V., Wessels, S., Orth, S. R., Groß, M.-L., KOCH, A., Bielenberg, G. W., van Kats, J. P., et al. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v1181469 · Cited by 190 · see citing works
Self-citationRenin-angiotensin blockade lowers MCP-1 expression in diabetic rats
Kato, S., Luyckx, V. A., Ots, M., Lee, K., Ziai, F., Troy, J. L., Brenner, B. M., & Mackenzie, H. S. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00643.x · Cited by 153 · see citing works
Ye, S., Nosrati, S. N., & Campese, V. M. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119191 · Cited by 104 · see citing works
Angiotensin-converting enzyme inhibitors and kidney protection: the AIPRI trial
Maschio, G., Alberti, D., Locatelli, F., Mann, J. F. E., Motolese, M., Ponticelli, C., Ritz, E., Janin, G., & Zucchelli, P. (1999) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199900001-00004 · Cited by 77 · see citing works
Self-citationNielsen, F. S., Hansen, H. P., Jacobsen, P. K., Rossing, P. R., Smidt, U., Christensen, N. J., Pévet, P., VIVIEN‐ROELS, B., & Parving, H. ‐. (1999) · Diabetic Medicine · doi:10.1046/j.1464-5491.1999.00127.x · Cited by 71 · see citing works
Nephrotoxicity of increased glomerular protein traffic
Abbate, M. (1999) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/14.2.304 · Cited by 66 · see citing works
Wenzel, R. R., Spieker, L. E., Qui, S., Shaw, S., Lüscher, T. F., & Noll, G. (1998) · Hypertension · doi:10.1161/01.hyp.32.6.1022 · Cited by 64 · see citing works
Imidazoline-guanidinium and α2-adrenergic binding sites in basolateral membranes from human kidney
Lachaud-Pettiti, V., Podevin, R., Chrétien, Y., et al. (1991) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(91)90142-5 · Cited by 61 · see citing works
Current strategies for retarding progression of renal disease
Hs, M., & Brenner, B. M. (1998) · American Journal of Kidney Diseases · doi:10.1053/ajkd.1998.v31.pm9428469 · Cited by 59 · see citing works
Chrisp, P., & Faulds, D. M. (1992) · Drugs · doi:10.2165/00003495-199244060-00008 · Cited by 55 · see citing works
Insulin stimulates epinephrine release under euglycemic conditions in humans
Tack, C. J., Lenders, J. W. M., Willemsen, J. J., van Druten, J. A. M., Thien, T., Lutterman, J. A., & Smits, P. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90251-7 · Cited by 28 · see citing works
Attenuated renal response to moxonidine and rilmenidine in one kidney‐one clip hypertensive rats
Li, P., Penner, S. B., & Smyth, D. D. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb13052.x · Cited by 24 · see citing works
Moxonidine: a review of safety and tolerability after seven years of clinical experience.
Schachter, M. (1999) · PubMed · Cited by 24 · see citing works
The AB/BA Design with Normal Data
Senn, S. J. (2002) · doi:10.1002/0470854596.ch3 · Cited by 15 · see citing works
Future Management of High Blood Pressure
Johnston, C. I. (1996) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199627003-00008 · Cited by 6 · see citing works
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Grassi, G., Mark, A., & Esler, M. (2015) · Circulation Research · doi:10.1161/circresaha.116.303604 · Cited by 616 · see citing works
Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome
Thorp, A. A., & Schlaich, M. P. (2015) · Journal of Diabetes Research · doi:10.1155/2015/341583 · Cited by 425 · see citing works
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Schlaich, M. P., Socratous, F., Hennebry, S., Eikelis, N., Lambert, E. A., Straznicky, N., Esler, M. D., & Lambert, G. W. (2009) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008040402 · Cited by 408 · see citing works
Management of Glomerular Proteinuria: A Commentary
Wilmer, W. A., Rovin, B. H., Hebert, C. J., Rao, S. V., Kumor, K., & Hebert, L. A. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000100145.27188.33 · Cited by 217 · see citing works
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Schlaich, M., Straznicky, N., Lambert, E., & Lambert, G. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70033-6 · Cited by 171 · see citing works
Sympathetic Overactivity in Chronic Kidney Disease: Consequences and Mechanisms
Kaur, J., Young, B., & Fadel, P. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081682 · Cited by 168 · see citing works
Adamczak, M., Zeier, M., Dikow, R., & Ritz, E. (2002) · Kidney International · doi:10.1046/j.1523-1755.61.s80.28.x · Cited by 95 · see citing works
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- Authors
- STROJEK, K., GRZESZCZAK, W., GÓRSKA, J., LESCHINGER, M. I., & RITZ, E.
- Affiliations
- Medical University of Silesia (PL)
- Eli Lilly (Germany) (DE)
- Heidelberg University (DE)
- Corresponding author
- STROJEK, KRZYSZTOF
- GÓRSKA, JUTA
- ORCID
- STROJEK, KRZYSZTOF
- Venue
- Journal of the American Society of Nephrology
- Published
- 2001-03
- Volume
- 12
- Issue
- 3
- Pages
- 602-605
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2119431414
- Cited by
- 112
- References
- 27
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2022: 2 · 2021: 6 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 7 · 2013: 6 · 2012: 5
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- moxonidine, microalbuminuria, type 1 diabetes, albuminuria, renal protection, sympathetic nervous system, diabetic nephropathy, urinary albumin excretion rate
- MeSH terms
- Adult, Albuminuria, Animals, Blood Pressure, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Female, Humans, Imidazoles, Male, Sympatholytics, Cross-Over Studies
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