Clinical Photography, Central Manchester University Hospitals NHS Foundation Trust, UK / Science Source
The history and findings in this case are suggestive of chronic kidney disease (CKD).
CKD affects between 8% and 16% of the population worldwide. Risk factors for CKD are numerous and include T2D, hypertension, and prediabetes. Diabetes is the leading cause of CKD. Up to 40% of patients with diabetes develop diabetic kidney disease, which can progress to end-stage renal disease (ESRD) requiring dialysis or kidney transplantation. In fact, diabetic kidney disease is the top cause of ESRD in the United States.
Diagnostic criteria for CKD include elevated urinary albumin excretion (albuminuria) and/or eGFR < 60 mL/1.73 m2 that persists for more than 3 months. The normal presentation of diabetic kidney disease includes long-standing diabetes, retinopathy, albuminuria without gross hematuria, and gradually progressive decline of eGFR. However, signs of diabetic kidney disease may be present in patients at diagnosis or without retinopathy in T2D. Reduced eGFR without albuminuria has been frequently reported in both type 1 diabetes (T1D) and T2D and is becoming increasingly common as the prevalence of diabetes rises in the United States.
Chronic kidney disease is usually identified through routine screening with serum chemistry profile and urine studies or as an incidental finding. Less often, patients may present with symptoms, such as gross hematuria, "foamy urine" (a sign of albuminuria), nocturia, flank pain, or decreased urine output. In advanced cases, patients may report fatigue, poor appetite, nausea, vomiting, a metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnea, and/or peripheral edema.
The American Diabetes Association (ADA) 2023 Standards of Care in Diabetes describes five stages of CKD. Stages 1-2 are defined by evidence of high albuminuria with eGFR ≥ 60 mL/min/1.73 m2, while stages 3-5 are defined by progressively lower ranges of eGFR. Of note, at any eGFR, the degree of albuminuria is associated with risk for cardiovascular disease, CKD progression, and mortality. Thus, as noted by the ADA Standards, both eGFR and albuminuria should be used to guide treatment decisions; additionally, eGFR levels are essential for modifying drug dosages or restrictions of use, and the degree of albuminuria should influence selection of antihypertensive agents and glucose-lowering medications.
According to the ADA 2023 Standards of Care in Diabetes, for people with non–dialysis-dependent CKD, dietary protein intake should be ∼0.8 g/kg body weight per day (the recommended daily allowance), as this level has been shown to slow GFR decline compared with higher levels of dietary protein intake, with evidence of a greater effect over time. Conversely, higher levels of dietary protein intake (> 20% of daily calories from protein or > 1.3 g/kg/d) have been associated with increased albuminuria, more rapid kidney function loss, and cardiovascular disease mortality. For patients on dialysis, higher levels of dietary protein intake should be considered, because malnutrition is a significant problem in some of these patients.
Urinary excretion of sodium and potassium may be impaired in patients with reduced eGFR. Thus, restriction of dietary sodium to < 2300 mg/d may help to control blood pressure and reduce cardiovascular risk, and restriction of dietary potassium may be necessary to control serum potassium concentration.
Intensive glycemic control with the goal of achieving near-normoglycemia has been shown to delay the onset and progression of albuminuria and reduced eGFR in patients with diabetes. Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of T1D while a variety of agents were used in clinical trials of T2D, supporting the conclusion that glycemic control itself helps prevent CKD and its progression. However, the presence of CKD affects the risks and benefits of intensive glycemic control and several glucose-lowering medications. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial of T2D, increased adverse effects of intensive glycemic control (hypoglycemia and mortality) were seen among patients with kidney disease at baseline. Moreover, it may take at least 2 years to see improved eGFR outcomes as an effect of intensive glycemic control. Therefore, in some patients with prevalent CKD and substantial comorbidity, target A1c levels may be less intensive.
According to guidance from the US Food and Drug Administration, eGFR should be monitored while taking metformin and metformin is contraindicated in patients with an eGFR < 30 mL/min/1.73 m2. Clinicians should assess the benefits and risks of continuing treatment when eGFR falls to < 45 mL/min/1.73 m2.
The ADA recommends that sodium–glucose cotransporter 2 inhibitors be given to all patients with stage 3 CKD or higher and T2D, regardless of glycemic control, as they have been shown to delay CKD progression and reduce heart failure risk independent of glycemic control. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) also have direct effects on the kidney and have been reported to improve renal outcomes compared with placebo. In patients for whom cardiovascular risk is a predominant problem, the ADA suggests using GLP-1 RAs for cardiovascular risk reduction.
Comprehensive guidance on the management of CKD in patients with T2D is available in the ADA 2023 Standards of Care in Diabetes.
Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia
Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
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