Diabetes-related renal complications: Insights on the impact of diabetic kidney disease on mortality

Table 1 Diabetic kidney disease-staging, pathophysiology and treatment¹

Aspect	Details
Definition	DKD is defined as a clinical diagnosis of CKD occurring in people with diabetes, marked by persistent albuminuria and/or reduced eGFR (< 60 mL/minute/1.73 m²), in the absence of other primary renal diseases
Pathogenesis	Chronic hyperglycemia → glomerular hypertension, mesangial expansion, basement membrane thickening, podocyte loss → fibrosis and tubular atrophy
eGFR-based G-Stages	G1: ≥ 90, G2: 60-89, G3a: 45-59, G3b: 30-44, G4: 15-29, G5: < 15 or dialysis
Albuminuria stages (UACR)	A1: < 30 mg/g (normal-mild), A2: 30-300 mg/g (moderate), A3: > 300 mg/g (severe/proteinuria)
Risk stratification	Combine GFR and albuminuria (G-stage + A-stage) → KDIGO Heatmap: Low risk: G1-A1, moderate: G2-A2 or G3a-A1, high: G3b-A2 or G2-A3, very high: G4 or A3 with G3+
Diagnostic criteria	Requires two abnormal values (eGFR and/or UACR) ≥ 3 months apart. Exclude non-diabetic kidney disease by history, serology, or biopsy if atypical
Histological features	Nodular glomerulosclerosis (Kimmelstiel-Wilson lesions), mesangial expansion, interstitial fibrosis, arteriolar hyalinosis
First-line medications	ACE inhibitors/ARBs-for all DKD with albuminuria (A2 or A3). SGLT2 inhibitors-for eGFR ≥ 20-25, albuminuria A2-A3, or cardiovascular risk. Statins-if ≥ 40 years or cardiovascular risk. Metformin if eGFR ≥ 30 and tolerated
SGLT2 inhibitor evidence	CREDENCE (2019): Canagliflozin ↓ ESRD, doubling of serum creatinine. DAPA-CKD (2020): Dapagliflozin ↓ composite kidney outcome even in non-diabetics. EMPA-KIDNEY (2023): Empagliflozin ↓ progression in broad CKD population
GLP-1 receptor agonists	Reduce albuminuria and cardiovascular events (e.g., semaglutide, liraglutide). Not proven to slow eGFR decline directly
Finerenone (non-steroidal MRA)	Reduces albuminuria and progression of DKD in patients with T2DM and albuminuria (A2-A3), with preserved GFR ≥ 25
Glycemic target	HbA1c: 7.0% in most (individualize). Avoid < 6.5% in advanced DKD (risk of hypoglycemia due to reduced insulin clearance)
BP target	< 130/80 mmHg if albuminuria ≥ 30 mg/gStart with RAAS blockade
Dietary management	Protein: 0.8 g/kg/day (non-dialysis). Sodium: < 2.3 g/day. Limit potassium and phosphorus if advanced CKD
Monitoring frequency	eGFR/UACR: Every 6 months if stable; every 3 months if high risk. Electrolytes: With RAAS, MRA, or SGLT2i, HbA1c: Every 3-6 months
Referral to nephrology	GFR < 30 (G4), rapid GFR decline (> 5 mL/minute/year)
Renal replacement therapy	GFR < 15 with uremic symptoms or refractory metabolic derangements: Consider dialysis or transplant

¹This table summarizes diabetic kidney disease by outlining its definition, staging based on estimated glomerular filtration rate and albuminuria, key pathological features, and evidence-based management strategies. It highlights the pathophysiology linking chronic hyperglycemia to kidney damage, classifies disease severity using Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and presents treatment options including angiotensin-converting enzyme inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and mineralocorticoid receptor antagonists. The table also includes monitoring recommendations and referral criteria to optimize patient outcomes. References are provided from the latest KDIGO and American Diabetes Association guidelines, as well as pivotal clinical trials.

ACE: Angiotensin-converting enzyme; ADA: American diabetes association; ARBs Angiotensin II receptor blockers; BP: Blood pressure; CKD: Chronic kidney disease; DKD: Diabetic kidney disease; eGFR: Estimated glomerular filtration rate; GLP1: Glucagon-like peptide 1; HbA1c: Hemoglobin A1c; KDIGO: Kidney Disease: Improving Global Outcomes; MRA: Mineralocorticoid receptor antagonist; SGLT2: Sodium-glucose cotransporter 2; T2DM: Type 2 diabetes mellitus; UACR: Urine albumin-to-creatinine ratio.