29th May 2025

Diabetic kidney disease (DKD)

Chronic hyperglycemia causes vascular calcification and endothelial damage, contributing to many of the complications seen in T2DM. In DKD, microvascular damage to the nephron arterioles and overstimulation of the local renin-angiotensin system, causing efferent arteriole constriction, leads to intraglomerular hypertension and glomerular hyperfiltration, manifesting as microalbuminuria. The hyperglycaemic environment also triggers intracellular pathways, including through activation of protein kinase C, causing an increase in the production of advanced glycation end products, which lead to oxidative stress and cellular damage. DKD affects all renal cell types, resulting in thickening of the glomerular and tubular basement membranes, mesangial expansion through both proliferation and hypertrophy, tubular hypertrophy and afferent arteriole thickening with endothelial effacement. Clinically, it presents as gradually deteriorating renal function, progressing towards end-stage renal failure. 

Unlike in T1DM, where DKD occurs after a long duration of the disease (usually >10 years), DKD may be present on diagnosis with T2DM as it may be undiagnosed for many years. DKD is defined by the presence of albuminuria and deterioration in the estimated glomerular filtration rate (eGFR) without another cause for renal impairment. Not all diabetics will develop DKD, the most notable risk factors are: 

• Chronically poor glycaemic control
• Hypertension
• Dyslipidemia 
• Family history
• Smoking
• Increasing age 
• Race – Afro-Caribbean, Mexican-American and Pima Indian are at an increased risk

DKD usually remains symptom-less until severe, when patients may experience peripheral oedema, anaemia, fatigue, haematuria and progression to end-stage renal failure.  Patients are screened on diagnosis using:

• Urinary albumin-creatinine ratio (ACR) – normal ACR is <3mg/mmol. Patients with DKD are categorised into microalbuminuria with an ACR of 3-30mg/g, or macroalbuminuria (overt nephropathy) with an ACR <30mg/mmol. The result should be repeatable on 2 separate occasions.
• eGFR – DKD patients will see a gradual deterioration in eGFR as seen in chronic kidney disease, it can be graded according to the regular CKD values:

Table 2: Staging of chronic kidney disease

Adapted from table in NICE CKD treatment summary: https://www.nice.org.uk/guidance/ng203/chapter/Recommendations#classification-of-ckd-in-adults

Definitive diagnosis can be made by renal biopsy but this is not routinely offered to patients and they are normally diagnosed using ACR and clinical assessment to rule out other causes of renal disease. When a biopsy is performed, characteristic changes include mesangial expansion, thickening of the basement membrane and nodular glomerulosclerosis.

Patients diagnosed with DKD (ACR >3mg/mmol) should be offered either an angiotensin-converting enzyme inhibitor (ACEi) (such as ramipril) or an angiotensin receptor blocker (ARB) (such as candesartan), titrated up to the highest dose the patient can tolerate. An SGLT-2 inhibitor should be added when ACR>30mg/mmol and may be considered earlier, they are effective in slowing the progression of DKD. Control of dyslipidaemia, good glycaemic control and smoking cessation are all important in preventing the progression of DKD.