The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study
Open accessAbstract
Background Diabetic nephropathy has become the single most important cause of end-stage renal disease (ESRD) worldwide. Strategies to slow the rate of loss of renal function in these patients have been developed. We examined the risk factors that predict loss of kidney function (doubling of serum creatinine) or ESRD (dialysis or transplantation) in patients with type 2 diabetes in whom blood pressure was controlled. Methods We evaluated risk factors for doubling of serum creatinine or the development of ESRD in the Reduction of End Points in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study, which included 1513 patients with type 2 diabetes and nephropathy. Results Univariate analyses demonstrated a group of 23 risk factors that significantly predicted doubling of serum creatinine or ESRD. From these univariate analyses, a multivariate model was developed that demonstrated four independent risk factors: proteinuria, serum creatinine, serum albumin, and hemoglobin level. Proteinuria was the strongest and most consistent risk factor. The multivariate risk model was derived from only the placebo group and was similar to that derived for the total population, suggesting that the risk predictors for progression of kidney disease were independent of therapy. Conclusion After control of blood pressure in type 2 diabetic patients with nephropathy, proteinuria, degree of renal failure, serum albumin, and hemoglobin level are independent risk factors that predic…
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The kidney protective effect conferred by losartan exceeded the effect attributable to the small differences in blood pressure between the treatment groups.
“The kidney protective effect conferred by losartan also exceeded the effect attributable to the small differences in blood pressure between the treatment groups.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [14]
In the RENAAL trial, losartan significantly reduced the incidence of doubling of serum creatinine, kidney failure, and death, each by 16% compared with placebo, in combination with conventional antihypertensive treatment.
“In the RENAAL trial, losartan signi fi cantly reduced the incidence of doubling of serum creatinine, kidney failure, and death, each by 16% compared with placebo, in combination with ' conventional ' antihypertensive treatment.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [14]
Use of RAS blockade may be beneficial in patients with diabetes and CKD without hypertension.
“suggesting that use of RAS blockade may be bene fi cial in patients without hypertension. 12,14”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [14]
RCTs demonstrated decreased risk of CKD progression with a maximally dosed RAS inhibitor compared with placebo or an active antihypertensive drug comparator in patients with albuminuria.
“This recommendation is based on RCTs where findings demonstrated decreased risk of CKD progression, for which patients with albuminuria are at elevated risk, with a maximally dosed RAS inhibitor compared with placebo or an active antihypertensive drug comparator (42–44).”
Cites
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158 · see citing works
Levey, A. S., Bosch, J. P., Lewis, J. B., Greene, T., Rogers, N., Roth, D., & for the Modification of Diet in Renal Disease Study Group* (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-6-199903160-00002 · Cited by 15,079 · see citing works
Brenner, B. M., Cooper, M. E., de Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H.-H., Remuzzi, G., Snapinn, S. M., Zhang, Z., & Shahinfar, S. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011161 · Cited by 7,493 · see citing works
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A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease
Pfeffer, M. A., Burdmann, E. A., Chen, C.-Y., Cooper, M. E., de Zeeuw, D., Eckardt, K.-U., Feyzi, J. M., Ivanovich, P., Kewalramani, R., Levey, A. S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0907845 · Cited by 2,096 · see citing works
Self-citationKDIGO 2020 Clinical practice guideline for diabetes management in chronic kidney disease
de Boer, I. H., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.06.019 · Cited by 1,399 · see citing works
KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease
Rossing, P., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2022) · Kidney International · doi:10.1016/j.kint.2022.06.008 · Cited by 1,373 · see citing works
de Boer, I. H., Khunti, K., Sadusky, T., Tuttle, K. R., Neumiller, J. J., Rhee, C. M., Rosas, S. E., Rossing, P., & Bakris, G. (2022) · Diabetes Care · doi:10.2337/dci22-0027 · Cited by 919 · see citing works
Jones, D. W., Ferdinand, K. C., Taler, S. J., Johnson, H. M., Shimbo, D., Abdalla, M., Altieri, M. M., Bansal, N., Bello, N. A., Bress, A. P., et al. (2025) · JACC · doi:10.1016/j.jacc.2025.05.007 · Cited by 280 · see citing works
Sex differences in micro- and macro-vascular complications of diabetes mellitus
Maric-Bilkan, C. (2017) · Clinical Science · doi:10.1042/cs20160998 · Cited by 217 · see citing works
The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes
Hannon, T. S., & Arslanian, S. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12939 · Cited by 137 · see citing works
BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial
Leehey, D. J., Zhang, J. H., Emanuele, N. V., Whaley-Connell, A., Palevsky, P. M., Reilly, R. F., Guarino, P., & Fried, L. F. (2015) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.02850315 · Cited by 62 · see citing works
- Authors
- Keane, W. F., Brenner, B. M., de Zeeuw, D., Grunfeld, J.-P., McGill, J., Mitch, W. E., Ribeiro, A. B., Shahinfar, S., Simpson, R. L., Snapinn, S. M., Toto, R., & RENAAL Study Investigators
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Keane, William F.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 63
- Issue
- 4
- Pages
- 1499-1507
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2059346848
- Cited by
- 539
- References
- 3
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 19 · 2023: 22 · 2022: 31 · 2021: 17 · 2020: 27 · 2019: 13 · 2018: 15 · 2017: 20 · 2016: 28 · 2015: 27 · 2014: 32 · 2013: 21 · 2012: 32
- FWCI
- 21.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 02818-01A1, K24DK002818)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- end-stage renal disease, type 2 diabetes, diabetic nephropathy, losartan, angiotensin receptor blockers, risk factors, proteinuria, serum creatinine, serum albumin, hemoglobin, blood pressure control
- MeSH terms
- Aged, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Hemoglobins, Humans, Kidney Failure, Chronic, Male, Middle Aged, Predictive Value of Tests, Proteinuria, Risk Factors, Serum Albumin, Multivariate Analysis, Sex Distribution
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