Q J Med 2002; 95: 371-377
© 2002 Association of Physicians
Natural history and prognostic factors of diabetic nephropathy in type 2 diabetes
1 From the Department of Medicine, Manchester Royal Infirmary, and 2 Department of Epidemiology, Stopford Building, Manchester University, Manchester, UK
Received 5 July 2001 and in revised form 21 March 2002
Background: The causes and mechanisms of increased mortality of patients with diabetic nephropathy are unclear, and its natural history is poorly understood.
Aim: To evaluate risk factors for mortality in type 2 diabetic patients with nephropathy.
Design: Retrospective study of clinical and biochemical parameters in diabetic nephropathic patients and controls sampled from a secondary care register.
Methods: We studied 170 type 2 diabetic patients (from 1987 to 1995) with nephropathy (proteinuria >0.5 g/24 h) and 170 non-nephropathic patients. Follow-up was until death or December 1997. Details of demographics, clinical and treatment history were obtained from medical records.
Results: Mean follow-up was 5.3 years. Of the patients with nephropathy at baseline, 63 (37%) died compared with 14 (8%) non-nephropathic patients (
2=53.8, p<0.0001). Age- and sex-adjusted all-cause mortality rates were 8.1 (6.4, 9.8) and 1.4 (0.5, 2.2) deaths per 100 person-years, respectively (rate ratio 5.8). Forty-four patients (57%) died from cardiovascular causes (rate ratio 5.4). Mortality was directly proportional to degree of proteinuria: 0.5–2 g/24 h, 4.6 (2.9–7.1); >2 g/24 h, 9.9 (7.3–13.5) per 100 patient-years. A 36% (5–78%) excess risk of mortality was observed for each log unit increase in proteinuria. Multivariate Cox regression analyses confirmed a five-fold excess risk for all-cause and cardiovascular mortality in patients with nephropathy compared with those without. This was independent of other risk factors including baseline age [5% (1–8%)/year], creatinine [2.5 (1.12–5.6)/10 µmol/l] and glycaemic control (HbA1c) [15% (1–31%) per 1% rise].
Conclusions: Proteinuria is a potentially preventable and reversible risk factor associated with high mortality in type 2 diabetic patients. Prevention of the development of overt nephropathy and improvement in diabetes control may reduce mortality in these patients.
Address correspondence to Dr E.B. Jude, Diabetes Centre, Tameside General Hospital, Fountain Road, Ashton-under-Lyne, Lancashire OL6 9RW. e-mail: ejude{at}man.ac.uk
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