What is the most critical nephrology disease?

Diabetic Kidney Disease (DKD) Is the Most Important Nephrology Disease

Chronic kidney disease due to diabetes (diabetic kidney disease) is the most important nephrology disease as it is the leading cause of end-stage kidney disease worldwide, affects approximately 20-40% of people with diabetes, and is associated with significantly increased cardiovascular morbidity and mortality. 1, 2

Epidemiology and Impact

• DKD affects 20-40% of people with diabetes and is the single leading cause of end-stage kidney disease (ESKD) in the United States, accounting for approximately 35% of the ESKD population 1, 3
• CKD affects approximately 9% of the global population, with its impact substantial and rising due to the growing population of older adults and increasing incidence of obesity and diabetes 1
• DKD typically develops after a duration of 10 years in type 1 diabetes but may be present at diagnosis of type 2 diabetes 1, 2
• The presence of CKD markedly increases cardiovascular risk and healthcare costs in patients with both type 1 and type 2 diabetes 1, 2
• All-cause mortality in individuals with DKD is approximately 30 times higher than in diabetic patients without nephropathy, with most patients dying from cardiovascular disease before reaching ESKD 4

Pathophysiology and Diagnosis

• DKD is diagnosed by persistent albuminuria (>30 mg/24h or UACR >30 mg/g), persistent reduction in eGFR below 60 mL/min/1.73m², or both, for at least 3 months 1
• The typical presentation includes long-standing diabetes, retinopathy, albuminuria without gross hematuria, and gradually progressive loss of eGFR 1
• However, reduced eGFR without albuminuria has been increasingly reported in both type 1 and type 2 diabetes 1
• CKD is classified into five different stages based on GFR levels (Table 9 from 1):
  • Stage 1: Kidney damage with normal or increased GFR (≥90 mL/min/1.73m²)
  • Stage 2: Kidney damage with mild decrease in GFR (60-89 mL/min/1.73m²)
  • Stage 3: Moderate decrease in GFR (30-59 mL/min/1.73m²)
  • Stage 4: Severe decrease in GFR (15-29 mL/min/1.73m²)
  • Stage 5: Kidney failure (<15 mL/min/1.73m² or dialysis)

Screening and Early Detection

• Screening for albuminuria should be performed using urine albumin-to-creatinine ratio (UACR) in a random spot urine collection 1, 2
• Abnormal albuminuria is defined as:
  • Microalbuminuria: 30-299 mg/g creatinine
  • Macroalbuminuria: ≥300 mg/g creatinine 1
• Due to variability in urinary albumin excretion, two of three specimens collected within a 3-6 month period should be abnormal before confirming diagnosis 1
• Kidney function is best assessed with GFR according to the MDRD equation, which includes ethnicity and sex in its calculation 1

Cardiovascular Impact

• The risk of death from any cause, including cardiovascular disease, rises with progressive decrease of GFR, with a swift increase in events for GFR <60 mL/min/1.73m² 1
• Renal dysfunction is frequently observed in non-ST-elevation acute coronary syndromes and is associated with worse prognosis 1
• CKD complicates the management of and heightens mortality associated with many chronic conditions, such as cardiovascular disease and cancer 1

Management Approaches

• Optimal glycemic control is crucial to delay the onset of microalbuminuria and the progression of micro- to macroalbuminuria in patients with both type 1 and type 2 diabetes 1
• Blood pressure control, particularly with renin-angiotensin system blockade using ACE inhibitors or ARBs, is essential for slowing DKD progression 1
• For people with type 2 diabetes and CKD, a sodium-glucose cotransporter 2 (SGLT2) inhibitor is recommended to reduce CKD progression and cardiovascular events 1, 2
• Similarly, a glucagon-like peptide 1 receptor agonist with demonstrated benefit is recommended for people with type 2 diabetes and CKD to reduce cardiovascular risk and kidney disease progression 1
• Protein intake should be 0.8 g/kg body weight per day for people with non-dialysis-dependent stage G3 or higher CKD, and 1.0-1.2 g/kg/day for individuals on dialysis 1

Referral to Nephrology

• Individuals should be referred for evaluation by a nephrologist if they have continuously increasing urinary albumin levels, continuously decreasing eGFR, or if the eGFR is <30 mL/min/1.73m² 1, 2
• Consider referral when the GFR has fallen to <60 mL/min/1.73m² or if difficulties occur in the management of hypertension or hyperkalemia 1

Medication Considerations

• Metformin, a common diabetes medication, requires dose adjustment based on renal function and is contraindicated in patients with an eGFR below 30 mL/min/1.73m² 5
• For patients on metformin whose eGFR later falls below 45 mL/min/1.73m², assess the benefit-risk of continuing therapy 5
• Monitor for increased serum creatinine and potassium levels when ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists are used 1

Importance of Comprehensive Care

• Intensive outpatient clinic monitoring can improve the quality of patient care and slow the rate of progression to end-stage renal failure even in established diabetic nephropathy 6
• Management of metabolic and hemodynamic perturbations is crucial for prevention and delay of progression of DKD 4
• The average cost of managing one diabetic patient with ESKD is approximately $50,000 a year, highlighting the economic impact of this disease 3