Original Investigation
Pathogenesis and Treatment of Kidney Disease
Relative Incidence of ESRD Versus Cardiovascular Mortality in Proteinuric Type 2 Diabetes and Nephropathy: Results From the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) Database

https://doi.org/10.1053/j.ajkd.2011.09.017Get rights and content

Background

Previous studies have shown that patients with chronic kidney disease, including those with diabetic nephropathy, are more likely to die of cardiovascular disease than reach end-stage renal disease (ESRD). This analysis was conducted to determine whether ESRD is a more common outcome than cardiovascular death in patients with type 2 diabetic nephropathy, significant proteinuria, and decreased kidney function who were selected for participation in a clinical trial.

Study Design

Retrospective analysis of the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database derived from 2 prospective randomized controlled clinical trials (IDNT [Irbesartan Diabetic Nephropathy Trial] and RENAAL [Reduction of Endpoints in Non–Insulin-dependent Diabetes With the Angiotensin II Antagonist Losartan]).

Setting & Participants

3,228 adult patients with type 2 diabetic nephropathy from IDNT and RENAAL were combined to establish the DIAMETRIC database. This is the largest global source of clinical information for patients with type 2 diabetic nephropathy who have decreased kidney function and significant proteinuria.

Intervention

Angiotensin receptor blocker versus non–angiotensin receptor blocker therapy to slow the progression of type 2 diabetic nephropathy (in the prospective trials).

Outcomes & Measurements

Incidence rates of ESRD, cardiovascular death, and all-cause mortality.

Results

Mean follow-up was 2.8 years; 19.5% of patients developed ESRD, approximately 2.5 times the incidence of cardiovascular death and 1.5 times the incidence of all-cause mortality. ESRD was more common than cardiovascular death in all subgroups analyzed with the exception of participants with low levels of albuminuria (albumin excretion <1.0 g/g) and well-preserved levels of kidney function (estimated glomerular filtration rate >45 mL/min/1.73 m2) at baseline.

Limitations

All participants were included in a prospective clinical trial.

Conclusions

Patients with type 2 diabetic nephropathy, characterized by decreased kidney function and significant proteinuria, are more likely to reach ESRD than die during 3 years' mean follow-up. Given the rapidly increasing number of cases of type 2 diabetes worldwide, this has implications for predicting future renal replacement therapy requirements.

Section snippets

DIAMETRIC Database

We conducted a retrospective analysis of the DIAMETRIC database. The database was established in 2009 and is composed of patients with type 2 diabetes and nephropathy and significant proteinuria. The present analysis of the DIAMETRIC database consists of 3,228 patients randomly assigned in the IDNT (Irbesartan Diabetic Nephropathy Trial) and RENAAL (Reduction of Endpoints in Non–Insulin-dependent Diabetes With the Angiotensin II Antagonist Losartan) trial. The detailed design, rationale, and

Results

Table 2 lists baseline characteristics of the 3,228 evaluable patients. These patients had been followed up for a mean of 2.8 ± 1.0 years.

Table 3 lists crude event rates for primary and secondary end points. In all, 628 (19.5%) patients developed ESRD compared with the 260 (8.1%) cardiovascular deaths before ESRD, a nearly 2.5-fold difference. All-cause mortality prior to ESRD was 409 (12.7%) patients. An additional 328 patients had a doubling of baseline creatinine level that fell short of ESRD

Discussion

Patients with proteinuria and decreased kidney function due to type 2 diabetic nephropathy who were included in the DIAMETRIC database were 2.5 times more likely to develop ESRD than have a cardiovascular death. Only in the subgroup of patients with relatively well-preserved kidney function (eGFR >45 mL/min/1.73 m2) and initial ACR ≤1.0 g/g is this not the case, reflecting the low incidence of ESRD in this group within the follow-up period. Factors predicting the highest incidence rate ratio

Acknowledgements

We thank Ms Jill Keegan for assistance in preparing this manuscript.

Support: The RENAAL trial was sponsored by Merck & Company. Drs de Zeeuw and Cooper received financial support from Merck & Co for their participation in the steering committee of the RENAAL trial. Dr Shahinfar was an employee of Merck at the time of the conduct of the RENAAL trial. IDNT was sponsored by Bristol Myer Squibb Institute for Medical Research and Sanofi-Synthelabo. Dr Atkins received research grants from Bristol

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    Originally published online November 4, 2011.

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