History and exam
Key diagnostic factors
common
hypertension
Hypertension is very common in patients with DKD and increases in prevalence as the stage of kidney disease increases.[55] In patients with type 1 diabetes mellitus, hypertension may present following symptoms of DKD, whereas in type 2 diabetes mellitus, hypertension is generally present before development of DKD.[55] It is a major risk factor for progression of DKD.[10][11]
signs of retinopathy
It is rare for patients with type 1 diabetes to develop DKD without retinopathy; however, kidney disease may be present without retinopathy in type 2 diabetes.[1]
Retinal findings include dot and blot hemorrhages, microaneurysms (background retinopathy), and/or neovascularization (proliferative retinopathy).[38]
edema
May be present in advancing DKD, which can also present with nephrotic syndrome.[37]
Other diagnostic factors
common
poor vision
Retinopathy may be present in patients with DKD.[38] Patients with retinopathy may be asymptomatic or have symptoms unrelated to retinopathy, such as fluctuation in vision. Visual disturbances may occur later in disease (e.g., floaters due to vitreous hemorrhage). Symptomatic patients may have either gradual vision loss (caused by macular edema) or acute vision loss (caused by vitreous hemorrhage).
numbness of the lower extremities
Peripheral neuropathy is a sign of advanced diabetes mellitus and may be present in a patient with DKD. Its presence should prompt further evaluation of kidney function to establish if DKD is also present.
It presents with impaired sensation in the feet, and loss of vibration, pain, temperature, and position sense in the lower extremities. Carpal tunnel syndrome may cause symptoms in the hands in patients with DKD. Charcot joints may also be present.[39]
pain of the lower extremities
Peripheral arterial disease is a sign of advanced diabetes mellitus and may be present in a patient with DKD.[56] Claudication in a patient with diabetes mellitus should prompt evaluation for prevention, screening, and diagnosis of DKD.
Reduced pulses may be detected on palpation.
Lower extremity discomfort may also signify painful neuropathy.
constitutional symptoms (advanced disease)
Fatigue and anorexia may be present in advanced disease. As patients become clinically uremic, encephalopathy, nausea and vomiting, dysgeusia (altered taste), bleeding, myoclonus, and pericarditis may be present.[37]
foot changes
Foot ulcers and Charcot joints may be present in DKD, as signs of other microvascular complications of diabetes mellitus.[57]
uncommon
orthostatic hypotension
Can occur if autonomic neuropathy is present.[58]
skin changes
Xerosis (abnormal dryness of the skin) is due to atrophy of eccrine and sebaceous sweat glands. Hyperpigmentation due to melanin deposition and sallow or yellow skin due to urochrome deposition is common in chronic kidney disease. Necrobiosis lipoidica and acanthosis nigricans may be found in DKD.[40]
muscular atrophy
Muscular atrophy may be present in DKD.[42]
pallor (as glomerular filtration rate declines)
Anemia due to lack of erythropoietin, iron deficiency, abnormalities of iron utilization, or other causes of anemia of chronic disease may cause pallor.[43]
bleeding tendency (advanced disease)
Platelet dysfunction manifests as easy bruising, bleeding gums, or epistaxis.[37]
Kussmaul respirations (advanced disease)
Risk factors
strong
sustained hyperglycemia
A higher mean elevated HbA1c increases the risk of developing DKD.[10] Duration of diabetes is usually >10 years.
hypertension
Uncontrolled hypertension causes more rapid decline in glomerular filtration rate.
Aggressive treatment of hypertension reduces the rate of progression of chronic kidney disease, including the incidence and degree of albuminuria.[11]
family history of hypertension and/or kidney disease
DKD is typically seen in patients with a family history of hypertension and/or kidney disease.[14]
The genetic predisposition is complex and is the subject of much current research.
obesity
Obesity is a key risk factor for development of type 2 diabetes and is also associated with development and progression of chronic kidney disease. In patients with type 2 diabetes mellitus, the risk of major renal events increases with increasing body mass index (BMI).[21] Weight loss in patients with overweight or obesity may play a role in reducing the risk of DKD development. In one study of patients with type 2 diabetes and severe obesity (BMI ≥35 kg/m²), compared with usual care, bariatric surgery was associated with lower overall incidence of microvascular disease, including a lower risk of nephropathy.[22]
smoking
Studies document a relationship between smoking and loss of glomerular filtration rate. The mechanisms underlying the adverse renal effects of smoking are still incompletely understood; however, the known association with cardiovascular risk makes control of this variable important.[12]
weak
physical inactivity
dyslipidemia
Statins decrease mortality and cardiovascular events in chronic kidney disease (CKD) but their efficacy in patients with end-stage renal disease and kidney or kidney-pancreas transplant recipients remains unproven.[25] Statins may decrease the rate of reduction in GFR and moderately decrease progressive increase in proteinuria in CKD.[26]
high protein, fat, and sodium intake
Diets with high protein, high saturated fat, high cholesterol, and high sodium are associated with progression of DKD.[4] High-protein diets should therefore be avoided.[1][4][27] Every patient should be assessed individually to weigh the benefits of a moderate-protein diet (and associated avoidance of aminoaciduria and hyperfiltration); low-protein diets (0.6 g/kg) should be avoided due to the risks of malnutrition and lack of evidence that they are effective in reducing progression of DKD.[28][29][30]
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