A 60-year-old man comes to the office due to edema of his face and ankles for the past 2 weeks. He has had no chest pain or breathlessness. The patient has a 15-year history of type 2 diabetes mellitus, which is currently managed with exercise, dietary modification, and oral medications. A month ago, his hemoglobin A1c was 6.9%. Temperature is 37 C (98.6 F), blood pressure is 146/87 mm Hg, pulse is 75/min, and respirations are 15/min. Physical examination shows periorbital edema and bilateral pitting edema around the ankles. The remainder of the examination is normal. Laboratory results are as follows:
| Serum chemistry | |
| Sodium | 140 mEq/L |
| Potassium | 4.3 mEq/L |
| Bicarbonate | 20 mEq/L |
| Blood glucose | 120 mg/dL |
| Blood urea nitrogen | 37 mg/dL |
| Creatinine | 2.4 mg/dL |
| Total cholesterol | 300 mg/dL |
ECG is normal. Urine protein is 3,700 mg/24 hr. Estimated glomerular filtration rate is 28 mL/min/1.73 m2. Which of the following measures would have the greatest impact in slowing the progression of this patient's kidney disease?
Diabetic kidney disease | |
Clinical findings |
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Evaluation |
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Management/prevention |
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DM = diabetes mellitus; GFR = glomerular filtration rate; GLP-1 = glucagon-like peptide-1; SGLT2 = sodium-glucose cotransporter-2. | |
This patient has long-standing type 2 diabetes mellitus complicated by significant diabetic kidney disease (DKD). Initially, DKD is characterized by hyperfiltration (ie, increased glomerular filtration rate [GFR]); however, as the disease progresses, GFR decreases, manifesting as a rising serum creatinine level. Concurrently, glomerular protein losses lead to moderately increased albuminuria (urine protein excretion 30-300 mg/24 hr; previously termed microalbuminuria) and eventually severely increased albuminuria (>300 mg/24 hr). As in this patient, advanced DKD can present with frank proteinuria and nephrotic syndrome.
In patients with type 2 diabetes, intensive blood pressure control is associated with reduced progression of DKD; a blood pressure (BP) target of <130/80 mm Hg is recommended for most patients. ACE inhibitors or angiotensin II receptor blockers are the preferred antihypertensive drugs; these agents lower systemic and intraglomerular pressures, which may be renoprotective.
(Choices A and B) Intensive lipid control with statins can reduce the risk for coronary heart disease; however, lipid-lowering therapy has not clearly been shown to reduce the progression of nephropathy. Low-dose aspirin also may reduce the incidence of cardiovascular events but would not slow the progression of nephropathy.
(Choice D) Intensive glycemic management to a target hemoglobin A1c <7% can slow the progression of DKD; however, this patient has good overall glycemic control (A1c of 6.9%), and further lowering is associated with an increased risk for hypoglycemia and may actually increase the risk for cardiac events. Although sodium-glucose cotransporter 2 inhibitors also reduce the risk of DKD progression in patients with type 2 diabetes, these drugs are more effective when used in patients with an estimated GFR of ≥30 mL/min/1.73 m2.
(Choice E) A moderate restriction in protein intake (eg, <1 g/kg/day) in patients with type 2 diabetes may slow the progression of DKD, but the benefits are small. Very low protein intake is not advised because patients with diabetes often have some degree of protein wasting at baseline and additional, complex dietary requirements.
Educational objective:
Strict blood pressure control, particularly using ACE inhibitors or angiotensin II receptor blockers, can reduce the progression of diabetic kidney disease (DKD). Tight glycemic control with a target hemoglobin A1c <7% also can prevent progression of DKD; further lowering is associated with an increased risk of hypoglycemia and possibly cardiac events.