Diabetic Kidney Disease

The answer first

Diabetic kidney disease (DKD) is the chronic kidney injury caused by diabetes — structurally a combination of glomerular basement membrane thickening, mesangial expansion with Kimmelstiel-Wilson nodules, afferent and efferent arteriolar hyalinosis, and tubulointerstitial fibrosis. Clinically it is the leading single cause of end-stage kidney disease (ESKD) worldwide, responsible for around 40 to 50% of new dialysis patients in Australia, the UK and the US [2].

The two questions that dominate DKD management: [1]

1. Is this really DKD, or is there a superimposed or alternative process? Classic DKD in a patient with long-standing diabetes and retinopathy needs no biopsy. Atypical features — rapid decline, haematuria, active sediment, short diabetes duration, no retinopathy in T1DM — demand a renal biopsy to exclude a treatable glomerulonephritis.
2. How do I slow progression and reduce the cardiovascular death that kills most of these patients before they reach dialysis? [1]

The management mandate, in priority order: [1]

1. Start an SGLT2 inhibitor in every patient with T2DM and eGFR greater than or equal to 20 with albuminuria or eGFR-based CKD, irrespective of glycaemia — CREDENCE, DAPA-CKD and EMPA-KIDNEY are the three pillars of this mandate [3][4][5].
2. Maximise RAAS blockade — ACE inhibitor or ARB (never both) at maximally tolerated dose for any patient with albuminuria, the foundation laid by RENAAL, IDNT and ADVANCE [7][8][9].
3. Add finerenone in T2DM CKD with albuminuria on top of maximal RAAS blockade — FIDELIO-DKD [6].
4. Control blood pressure, glycaemia and lipids — the multifactorial Steno-2 model halves cardiovascular events over the long term [10].
5. Prevent and manage CKD complications — anaemia, CKD-MBD, acidosis, hyperkalaemia, volume overload.
6. Prepare for kidney replacement therapy early and offer a conservative care pathway where dialysis will not benefit.

The single most important exam principle: cardiovascular disease kills more DKD patients than kidney failure does. A stage 3 DKD patient is far more likely to die of an MI than reach dialysis. Statin and BP control are non-negotiable, and a DKD patient without a statin is a long-case fail. [1]

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References11Show ledgerHide ledger

1. [1]Stevens PE, Levin A Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline Ann Intern Med, 2013.PMID 23732715
2. [2]Alicic RZ, Rooney MT, Tuttle KR Diabetic Kidney Disease: Challenges, Progress, and Possibilities Clin J Am Soc Nephrol, 2017.PMID 28522654
3. [3]Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy N Engl J Med, 2019.PMID 30990260
4. [4]Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease N Engl J Med, 2020.PMID 32970396
5. [5]Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in Patients with Chronic Kidney Disease N Engl J Med, 2023.PMID 36331190
6. [6]Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes N Engl J Med, 2020.PMID 33264825
7. [7]Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy N Engl J Med, 2001.PMID 11565518
8. [8]Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes N Engl J Med, 2001.PMID 11565517
9. [9]Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial Lancet, 2007.PMID 17765963
10. [10]Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes N Engl J Med, 2003.PMID 12556541
11. [11]Tangri N, Stevens LA, Griffith J, et al. A predictive model for progression of chronic kidney disease to kidney failure JAMA, 2011.PMID 21482743