Risk factors for diabetic nephropathy

Ari Kostadaras, M.D.

Diabetic nephropathy can occur in both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus.

Type 1 Diabetes: It has been suggested that 25 to 45 percent of these patients will, during their lifetime, develop clinically evident disease (the minimal criterion for which is a persistently positive urine dipstick for protein) the overall incidence of renal disease is substantially higher, since another 20 to 30 percent have subclinical microalbuminuria In addition to the importance of glycemic control, it is likely that more aggressive blood pressure reduction and the use of angiotensin converting enzyme inhibitors will further reduce the incidence of diabetic nephropathy. The peak onset of nephropathy in type 1 diabetes is between 10 and 15 years after the onset of the disease. Those patients who have no proteinuria after 20 to 25 years have a risk of developing overt renal disease of only about one percent per year.

Type 2 Diabetes: In Caucasians, the prevalence of progressive renal disease has generally been lower in type 2 diabetes than in type 1 disease. However, this observation did not apply to all groups with type 2 diabetes, some of whom have a more ominous renal prognosis. As an example, nephropathy develops in up to 50 percent of diabetic Pima Indians at 20 years, with 15 percent having progressed to end-stage renal disease by this time the time to proteinuria from the onset of diabetes and the time to end-stage renal disease from the onset of proteinuria were similar in type 1 and type 2 disease.

RISK FACTORS

Genetic susceptibility – Genetic susceptibility may be an important determinant of both the incidence and severity of diabetic nephropathy

Blood pressure – Studies have noted an association between subsequent development of nephropathy and higher systemic pressures, particularly if in the hypertensive range

The presence of these risk factors for hypertension is particularly important in patients with relatively poor glucose control (hemoglobin A1 concentration above 12 percent) are at increased risk of overt nephropathy within 20 years.

Glycemic control – Diabetic nephropathy is more likely to develop in patients with lesser degrees of glycose control, particularly if the hemoglobin A1c concentration is above 11 percent. Patients with type 1 diabetes whose hemoglobin A1c concentration is maintained below 8.1 percent are at much lower risk for renal disease.

Race – The incidence and severity of diabetic nephropathy are increased in blacks (3- to 6-fold compared to Caucasians), Mexican-Americans.

RELATION BETWEEN DIABETIC NEPHROPATHY AND RETINOPATHY Patients with nephropathy and type 1 diabetes almost always have other signs of diabetic microvascular disease, such as retinopathy and neuropathy. The retinopathy is easy to detect clinically and typically precedes the onset of overt nephropathy in these patients. By the time advanced retinopathy has occurred, there are usually histologic changes in the glomeruli and increased protein excretion that is at least in the microalbuminuric range. There are, however, some patients with advanced retinopathy who have little or no renal disease as assessed from renal biopsy and protein excretion.

In type 2 diabetics with marked proteinuria and retinopathy most likely have diabetic nephropathy, while those without retinopathy have a high incidence of non-diabetic glomerular disease.

OTHER RENAL DISEASES – Proteinuria in diabetes mellitus is occasionally due to a glomerular disease other than diabetic nephropathy. As examples, membranous nephropathy, minimal change disease, IgA nephropathy, Henoch-Schönlein purpura, thin basement membrane disease, and a proliferative glomerulonephritis have all been described.

The major clinical clues suggesting nondiabetic glomerular disease are

• Onset of proteinuria less than 5 years from the documented onset of diabetes (since the latent period for overt diabetic nephropathy is usually at least 10 to 15 years).

• The acute onset of renal disease. Diabetic nephropathy is a slowly progressive disorder characterized by increases in protein excretion and the serum creatinine concentration over a period of years.

• Presence of an active urine sediment containing red cells and cellular casts. Patients with only microscopic hematuria may have thin basement membrane disease, which may affect up to nine percent of the general population, with or without underlying diabetic nephropathy.

• In type 1 diabetes, the absence of diabetic retinopathy or neuropathy. In contrast, lack of retinopathy in type 2 diabetes does not preclude diabetic nephropathy, which remains the most likely diagnosis.

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