Diabetic kidney disease

1. Define the terms diabetic nephropathy (DN) and diabetic kidney disease (DKD).

The terms DN and DKD are used interchangeably to describe a set of characteristic clinical and pathologic findings. The main clinical findings of DKD are the presence of albuminuria, progressive chronic kidney disease (CKD), and less commonly microscopic hematuria. Diabetes is the most common cause of the nephrotic syndrome. Proteinuria is first detected by screening for albumin in the urine. A normal urine albumin level is less than 30 mg/day. Abnormal urine protein is defined in two stages. Moderately increased albuminuria (formerly known as microalbuminuria) is defined as 30 to 300 mg/day. Severely increased albuminuria (formerly known as macroalbuminuria) is defined as greater than 300 mg/day and is also known as overt proteinuria or overt nephropathy. The pathologic features of DKD are outlined in question 4.

2. How is DN from type 1 diabetes mellitus (DM) similar/different from type 2 DM?

See Table 31.1 . Of note, young adults diagnosed with type 2 DM before the age of 20 are at a higher risk for DN, retinopathy, peripheral neuropathy, and hypertension than patients with type 1 DM who are diagnosed at the same age.

3. What is the natural history of the progression of DN to end-stage renal disease (ESRD)?

This question is most clearly answered in patients with nephropathy from type 1 DM, given the readily identifiable onset of DM. The earliest change of kidney function in DM is kidney hypertrophy and glomerular hyperfiltration occurring in the first 1 to 2 years after diagnosis. The degree of hyperfiltration correlates with the risk of developing nephropathy. The onset of albuminuria is on average 15 years after the diagnosis of DM and increases in severity over time. Patients with type 1 DM who have not developed nephropathy after 25 years have a very low risk of developing nephropathy. End-stage kidney disease (ESKD) occurs 20 to 30 years after the onset of diabetes.

Due in part to the unknown time of onset for patients with type 2 DM, moderately increased albuminuria can be seen as early as at the time of diagnosis. In addition, it does not always progress as it does in type 1 DM, because some patients develop diabetes-related loss of kidney function without albuminuria. Patients with DN and type 2 DM are at increased risk of both ESKD and death from cardiovascular disease. Due to increased comorbidities, most patients will die before reaching the need for dialysis.

4. How and when should physicians screen for DKD?

After DM is diagnosed, consideration for screening of DKD must commence. Screening consists of annual measurements of creatinine and urine albumin-to-creatinine ratio (ACR). It should begin 5 years after diagnosis in type 1 DM and at the time of diagnosis in type 2 DM. Moderately increased albuminuria (ACR between 30 mg/g and 300 mg/g) that persists for more than 3 months means the patient is at risk for progression to overt nephropathy.