Diagnostic criteria (NICE CG182)
CKD is defined by EITHER (or both) present for >90 days:
eGFR <60
ml/min/1.73m² — confirmed on TWO readings at least 90 days apart
ACR ≥3 mg/mmol
On at least 2 of 3 samples — exclude UTI, menstruation, vigorous exercise
eGFR 60–89 alone does NOT diagnose CKD unless a structural abnormality, haematuria, or additional risk marker is present. Document as "reduced eGFR — monitor".
Always confirm with a repeat eGFR at least 90 days after the initial abnormal result to exclude acute kidney injury (AKI).
ACR (Albumin:Creatinine Ratio) Categories
| Category | ACR (mg/mmol) | Description | Dipstick equivalent | Action |
|---|---|---|---|---|
| A1 | <3 | Normal to mildly increased | Negative / trace | Reassure; annual check if risk factors |
| A2 | 3–30 | Moderately increased (microalbuminuria) | + (1+) | Confirm CKD; start ACEi/ARB if DM or hypertension |
| A3 | >30 | Severely increased (macroalbuminuria) | ++ or more | Nephrology referral if non-diabetic and ACR >70 |
Use early morning urine sample. ACR is preferred over PCR for CKD monitoring. PCR >50 mg/mmol ≈ ACR >30 mg/mmol.
Other markers that establish CKD diagnosis
- Persistent haematuria (non-urological) — refer urology to exclude malignancy first, then nephrology if confirmed non-urological
- Structural abnormalities: polycystic kidneys, reflux nephropathy, single kidney, congenital anomaly
- Electrolyte disorders from renal tubular disease (e.g. renal tubular acidosis)
- Renal biopsy-proven glomerulonephritis (GN) or tubulointerstitial nephritis
eGFR Staging (KDIGO / NICE CG182)
| Stage | eGFR (ml/min/1.73m²) | Description | Typical monitoring | Key action |
|---|---|---|---|---|
| G1 | ≥90 | Normal or high | Annual if markers present | Only CKD if additional markers present |
| G2 | 60–89 | Mildly decreased | Annual if markers present | Only CKD if markers present; document trend |
| G3a | 45–59 | Mildly–moderately decreased | Every 6–12 months | Optimise BP, lipids, DM, lifestyle |
| G3b | 30–44 | Moderately–severely decreased | Every 3–6 months | Add PTH/Ca/PO₄ monitoring; anaemia screen |
| G4 | 15–29 | Severely decreased | Every 3 months | Refer nephrology; begin RRT/conservative planning |
| G5 | <15 | Kidney failure | Monthly | RRT or conservative pathway; specialist care |
KDIGO Risk Heat Map — Progression Risk by G and A Stage
Monitoring frequency per year shown. Shading = low (green) → very high (dark red) risk of progression.
eGFR Stage
A1 — <3 mg/mmol
A2 — 3–30 mg/mmol
A3 — >30 mg/mmol
G1 (≥90)
Low — 1× if indicated
Moderate — 1×/yr
High — 1×/yr
G2 (60–89)
Low — 1× if indicated
Moderate — 1×/yr
High — 1×/yr
G3a (45–59)
Moderate — 1×/yr
High — 1×/yr
Very high — 2×/yr
G3b (30–44)
High — 1×/yr
Very high — 2×/yr
Very high — 2×/yr
G4 (15–29)
Very high — 3×/yr
Very high — 3×/yr
Refer — 3–4×/yr
G5 (<15)
Refer — 4+×/yr
Refer — 4+×/yr
Refer — 4+×/yr
Rapid Progression — Definition and Action
Refer to nephrology if: sustained decline in eGFR >5 ml/min/1.73m² within 1 year, OR >10 ml/min/1.73m² within 5 years — regardless of absolute eGFR value.
- Calculate rate of change from at least 3 eGFR readings over ≥18 months for reliability
- Consider AKI-on-CKD, obstructive uropathy, or renovascular disease as causes
- Review and stop nephrotoxic agents: NSAIDs, aminoglycosides, iodinated contrast, lithium
Blood Pressure Targets in CKD (NICE NG136 / CG182)
No diabetes — ACR <70 mg/mmol
≤140/90 mmHg
Clinic BP (or ≤135/85 on ABPM / home monitoring)
- Offer ACEi or ARB if ACR ≥30 mg/mmol — regardless of BP level
- If ACR <30 (non-proteinuric): treat as standard hypertension — A/C/D pathway (ACEi → CCB → thiazide-like)
- Do NOT combine ACEi + ARB — increased risk of AKI and hyperkalaemia (ONTARGET evidence)
No diabetes — ACR ≥70 mg/mmol (heavy proteinuria)
≤130/80 mmHg
Lower target — high CV and progression risk
- ACEi or ARB is mandatory first-line
- Up-titrate to maximum tolerated dose before adding second agent
- Likely non-diabetic GN — refer nephrology
With diabetes (T1DM or T2DM)
≤130/80 mmHg
Applies to ALL CKD stages if diabetes present
- ACEi or ARB: first-line if ACR ≥3 mg/mmol — regardless of BP
- SGLT2 inhibitor (dapagliflozin 10mg or empagliflozin): add if eGFR ≥20 AND ACR ≥22 mg/mmol (NICE TA739; DAPA-CKD / CREDENCE / EMPA-KIDNEY)
- Finerenone (Kerendia): consider in T2DM + ACR ≥30 already on ACEi/ARB (FIDELIO-DKD trial)
- Monitor K⁺ and creatinine 1–2 weeks after starting or up-titrating RASi
- Acceptable: up to 30% creatinine rise / eGFR fall ≤25% on ACEi/ARB — do NOT stop
Established CVD (IHD, stroke, PAD)
≤130/80 mmHg
Aligns with NG136 secondary prevention targets
- ACEi or ARB — especially if proteinuric or post-MI (HOPE trial support)
- Caution in elderly/frail: symptomatic hypotension → increased falls risk
- Apply clinical judgement in advanced CKD (eGFR <30) — balance benefit vs harm
- Consider cardiology and nephrology shared care if complex
Summary BP Targets by Population
| Patient group | BP target | First-line agent | Additional agents |
|---|---|---|---|
| CKD, no DM, ACR <30 | ≤140/90 | A/C/D pathway (no proteinuria) | CCB, thiazide-like diuretic |
| CKD, no DM, ACR 30–70 | ≤140/90 | ACEi or ARB (mandatory) | CCB, thiazide-like diuretic |
| CKD, no DM, ACR >70 | ≤130/80 | ACEi or ARB (mandatory) | Refer — likely GN |
| CKD + diabetes (any ACR) | ≤130/80 | ACEi or ARB + SGLT2i if eligible | Finerenone if ACR ≥30 |
| CKD + CVD/IHD/stroke/PAD | ≤130/80 | ACEi or ARB | As per CVD secondary prevention |
Lipid Management in CKD (NICE NG238, 2023)
Who to treat with a statin — NICE NG238 (2023)
Multiple independent triggers mandate atorvastatin 20mg — any ONE of the following is sufficient. In a CKD patient with diabetes, several triggers will apply simultaneously.
| Trigger | Population | Strength | Guideline |
|---|---|---|---|
| CKD G3a–G5 | Any — CKD is an independent CVD risk factor | Mandatory offer | NG238 CKD section |
| CKD G1–G2 + ACR ≥3 | Any — confirmed CKD via proteinuria | Mandatory offer | NG238 |
| T2DM age ≥40 | T2DM — QRISK3 ≥10% highly likely; offer without waiting for QRISK3 | Mandatory offer | NG238 rec 1.6 |
| T1DM age ≥40 | T1DM — all patients ≥40 years | Mandatory offer | NG238 rec 1.6.10 / NICE QS208 |
| T1DM + nephropathy (ACR ≥3) | T1DM any age — established diabetic nephropathy | Mandatory offer | NG238 rec 1.6.10 |
| T1DM + DM duration >10 yrs | T1DM any age — long-duration disease | Mandatory offer | NG238 rec 1.6.10 |
| T1DM age 18–39, no nephropathy | T1DM under 40 — earlier intervention discussion | Consider | NG238 rec 1.6.12 |
| QRISK3 ≥10% | General population primary prevention | Mandatory offer | NG238 |
| QRISK3 <10% | Lower-risk patients with patient preference | Do not rule out | NG238 — shared decision |
| Established CVD/ASCVD | Any — secondary prevention | High intensity 80mg | NG238 |
Common clinical error: T2DM patients aged ≥40 with early CKD (G1–G2, ACR <3) may be incorrectly deferred to QRISK3. Both the T2DM age trigger and the CKD trigger independently mandate the offer. T1DM patients aged ≥40 must also be offered a statin — this is a NICE quality standard (QS208) and is commonly under-prescribed (27% gap identified in recent NHS audit).
Atorvastatin 20mg
Primary prevention — CKD, T2DM age ≥40, T1DM age ≥40 or with nephropathy, QRISK3 ≥10%
Atorvastatin 80mg
Secondary prevention — established ASCVD (IHD, stroke, PAD). Reduce to 40mg if not tolerated.
Evidence base
- SHARP trial: Simvastatin 20mg + ezetimibe 10mg in CKD — 17% reduction in major atherosclerotic events. Underpins ezetimibe combination use in CKD.
- CTT meta-analysis: Per 1 mmol/L LDL-C reduction → ~22% relative reduction in major vascular events including in CKD.
- AURORA / 4D trials: Rosuvastatin NOT beneficial in dialysis patients (G5D) — do NOT start statin in established dialysis patients without prior indication.
Dose Adjustments in Advanced CKD
| Statin | G1–G3b (eGFR ≥30) | G4 (eGFR 15–29) | G5 / dialysis |
|---|---|---|---|
| Atorvastatin | Standard dose ✓ | Standard dose ✓ | Standard dose — preferred ✓ |
| Rosuvastatin | Standard dose ✓ | Max 10mg/day | Avoid (no benefit in dialysis — AURORA) |
| Simvastatin | Standard dose ✓ | Use with caution | Max 10mg; prefer atorvastatin |
| Pravastatin | Standard dose ✓ | Standard dose ✓ | Standard dose — renally safe ✓ |
| Fluvastatin | Standard dose ✓ | Use with caution | Avoid |
Atorvastatin and pravastatin are hepatically cleared — safest in G4/G5. Avoid fibrates in CKD: fenofibrate contraindicated at eGFR <30 (risk of AKI); gemfibrozil + statin increases myopathy risk significantly.
Lipid Targets (NICE NG238, 2023)
<2.0 mmol/L
LDL-C target — secondary prevention (established ASCVD)
<2.6 mmol/L
Non-HDL-C — secondary prevention (NICE NG238 preferred metric)
>50% reduction
Non-HDL-C reduction target for primary prevention in CKD
NICE NG238 (2023) now uses non-HDL-C as the preferred monitoring metric — this does not require fasting. Non-HDL-C target: <2.6 mmol/L (secondary prevention) or >50% reduction from baseline (primary prevention).
Treatment Escalation
| Step | Treatment | Notes |
|---|---|---|
| 1st line | Atorvastatin 20mg (1°) or 80mg (2°) | Start and up-titrate to maximum tolerated dose |
| 2nd line | Add ezetimibe 10mg | NICE recommended if target not met; add to any statin dose |
| 3rd line | PCSK9 inhibitor (evolocumab / alirocumab) | Via specialist only — secondary prevention, LDL >2.0 despite statin + ezetimibe. No dose adjustment in CKD G3–G5 (minimal renal clearance) |
| Alternative | Inclisiran | Via specialist; limited G4/G5 data — use with caution |
Management by CKD Stage and ACR Category
G1–G2 + A1 eGFR ≥60, ACR <3 — Not CKD (unless markers present)
- Do not code as CKD — label as "reduced eGFR, monitor" if eGFR 60–89 without markers
- Identify and address modifiable risk: uncontrolled BP, DM, smoking, obesity, NSAIDs
- Annual check if diabetes, hypertension, CVD, or family history of CKD
- No routine nephrology referral required
G1–G2 + A2–A3 eGFR ≥60, ACR ≥3 — Confirmed CKD
- Code CKD on clinical system; add to disease register; annual QOF review
- ACEi or ARB: offer if DM or ACR ≥30 mg/mmol — regardless of BP
- SGLT2 inhibitor: T2DM + ACR ≥22 mg/mmol + eGFR ≥20 (DAPA-CKD / CREDENCE / EMPA-KIDNEY)
- BP target ≤130/80 (DM or ACR ≥70) / ≤140/90 (non-DM, ACR <70)
- Atorvastatin 20mg for primary CVD prevention
- Annual monitoring: U&E, eGFR, ACR, HbA1c (if DM), BP, lipids
- Refer if ACR >70 without DM, haematuria, or uncertain diagnosis
G3a–G3b eGFR 30–59 — Moderate CKD
- Optimise all modifiable risk factors — BP, lipids, HbA1c (target 48–58 mmol/mol in T2DM with CKD), weight, smoking cessation
- ACEi or ARB: titrate to maximum tolerated dose; check K⁺ within 1–2 weeks (hold if K⁺ >6.0 mmol/L or creatinine rises >30% from baseline)
- SGLT2i (dapagliflozin 10mg): if eGFR ≥20 + ACR ≥22 with T2DM, or CKD alone with ACR ≥22 (DAPA-CKD non-diabetic subgroup)
- Finerenone: consider in T2DM + ACR ≥30 already established on maximum RASi (FIDELIO-DKD, FIGARO-DKD)
- Anaemia screen (G3b): Hb, ferritin, transferrin saturation (TSAT) — if Hb <110 g/L, investigate iron before ESA referral
- Bone and mineral: PTH, calcium, phosphate, bicarbonate — annually from G3b
- Dietary review: moderate protein (0.8g/kg/day); restrict high-K⁺ foods if K⁺ ≥5.5 mmol/L; moderate salt restriction (<6g/day)
- Medication safety: reduce/stop metformin at eGFR <30; avoid NSAIDs; nitrofurantoin ineffective and harmful at eGFR <45
- Nephrology referral if: progressive decline, ACR >70, resistant hypertension, suspected GN, haematuria + proteinuria
- Monitoring: every 6 months (G3a); every 3–6 months (G3b)
G4 eGFR 15–29 — Severe CKD
All G4 patients should be under nephrology — refer if not already done. Begin renal replacement therapy (RRT) planning or conservative pathway discussion.
- RRT planning: when eGFR approaches 15–20 — discuss HD vs PD vs pre-emptive transplant vs conservative care
- Renal anaemia: IV/oral iron to TSAT >20% + ferritin >100 µg/L; then ESA if Hb still <100 g/L (nephrology initiates)
- CKD-MBD (mineral bone disease): active vitamin D (alfacalcidol 0.25–0.5 mcg/day); phosphate binders (calcium carbonate, sevelamer) if PO₄ >1.5 mmol/L; PTH target 2–9× upper limit of normal
- Metabolic acidosis: sodium bicarbonate supplementation if HCO₃ <22 mmol/L (BICAR-ICU / BASE trial evidence — slows CKD progression)
- Continue ACEi/ARB if tolerated (K⁺ stable) — renoprotective benefit persists
- SGLT2i: can continue to eGFR ≥15 for cardiorenal protection (DAPA-CKD data)
- Medications to AVOID: metformin (eGFR <30), NSAIDs, rosuvastatin, nitrofurantoin, nephrotoxic contrast (without IV hydration + hold nephrotoxics 48hr)
- Immunisations: pneumococcal vaccine, annual influenza, hepatitis B series (for future dialysis access)
- AV fistula referral: if HD likely — ideally 6–12 months before projected need (KDOQI guidance)
- Review ALL medications for renal dose adjustment (use SPC / BNF / Renal Drug Database)
- Monitoring: every 3 months — U&E, FBC, Ca, PO₄, PTH, HCO₃, iron studies
G5 eGFR <15 — Established Kidney Failure
Specialist nephrology management. Primary care role: supportive care, medication safety, conservative pathway support, and advance care planning (ACP) if conservative route chosen.
- RRT modalities: haemodialysis (in-centre or home HD), peritoneal dialysis (APD/CAPD), pre-emptive living or deceased donor renal transplant
- Conservative kidney management (CKM): appropriate for frail/elderly or those who decline RRT — focus on symptom control, ACP, DNACPR, end-of-life care coordination with palliative team
- Continue statin (atorvastatin preferred), antihypertensives, and ACEi/ARB if K⁺ stable and still passing urine
- Strict fluid balance, dietary K⁺ and phosphate restriction, low-sodium diet
- Monthly minimum: U&E, FBC, PO₄, Ca, bicarbonate, fluid status assessment
Medications to Avoid or Dose-Adjust in CKD
| Drug / Class | Threshold | Action required |
|---|---|---|
| Metformin | eGFR <30 | Stop. Reduce dose and review at eGFR 30–45. Risk of lactic acidosis. |
| NSAIDs (including OTC ibuprofen) | eGFR <30 (avoid any CKD) | Avoid — can precipitate AKI, worsen BP, and accelerate CKD progression |
| Nitrofurantoin | eGFR <45 | Stop — ineffective (cannot achieve therapeutic urine concentration) and toxic (peripheral neuropathy) |
| Direct oral anticoagulants (DOACs) | eGFR <30–15 (drug-specific) | Dose reduce (apixaban, edoxaban) or avoid (rivaroxaban <15); use warfarin or specialist advice |
| Digoxin | Any CKD | Renally cleared — use lower doses; monitor levels; target 0.6–1.0 nmol/L |
| Lithium | eGFR <30 | Specialist review — significant toxicity risk; nephrotoxic at higher levels |
| Iodinated contrast (IV) | eGFR <45 | Discuss with radiology; IV hydration; hold metformin + nephrotoxics 48hr post-procedure; eGFR check 48–72hr after |
| Rosuvastatin | eGFR <30 | Max 10mg; avoid in dialysis — switch to atorvastatin or pravastatin |
| Fenofibrate | eGFR <30 | Contraindicated — risk of AKI and rhabdomyolysis |
| Spironolactone | eGFR <30 | High hyperkalaemia risk — use with extreme caution; specialist advice |
| Trimethoprim | Any CKD | Raises serum creatinine by blocking tubular secretion (not true GFR fall) — be aware; avoid long-term in CKD |
Sick Day Rules — Patient Safety
"SADMAN" rule — Advise all CKD G3b+ patients to temporarily HOLD during intercurrent illness (vomiting, diarrhoea, fever, poor intake) and resume after 24–48hrs eating/drinking normally: Sulfonylureas · ACE inhibitors · Diuretics · Metformin · ARBs · NSAIDs
- Provide written sick day rules leaflet at diagnosis (Kidney Care UK leaflets available)
- Advise patient to check BP and resume medications once clinically well and eating/drinking normally
- AKI risk: elderly, CKD + diuretic + ACEi triple whammy — dehydration can precipitate rapid AKI
Referral Criteria to Nephrology (NICE CG182)
Urgent referral (within days / 2 weeks): Suspected accelerated hypertension · Pulmonary oedema from renal fluid overload · Rapidly rising creatinine (possible vasculitis, crescentic GN, or TMA) · Urine red cell casts on microscopy
| Criterion | Rationale | Urgency |
|---|---|---|
| eGFR <30 (G4–G5) | RRT planning, anaemia, bone disease management | Routine |
| Rapid eGFR decline >5 ml/min/yr or >10 ml/min/5yr | Potential reversible cause, accelerated progression | Soon |
| ACR >70 mg/mmol — non-diabetic | Likely GN or vasculitis; biopsy may be needed | Soon |
| ACR >30 + haematuria | IgA nephropathy, GN — requires investigation | Soon |
| Resistant hypertension (≥4 agents) | Secondary hypertension, renovascular disease | Soon |
| Suspected rare/genetic cause | FSGS, Alport syndrome, ADPKD, amyloid | Routine |
| Unexpectedly low eGFR age <40 | Atypical cause requiring specialist workup | Routine |
| Renal anaemia needing ESA initiation | First ESA prescription requires nephrology | Routine |
| AV fistula/PD catheter planning | G4 approaching dialysis — plan access early | Routine |
Monitoring Schedule Summary
| Stage | eGFR | Frequency | Core tests | Additional tests |
|---|---|---|---|---|
| G1–G2 + A1 | ≥60, ACR <3 | Annual if risk factors | eGFR, ACR, BP | — |
| G1–G2 + A2–A3 | ≥60, ACR ≥3 | Annual | U&E, eGFR, ACR, BP, lipids | HbA1c if DM, Hb |
| G3a | 45–59 | Every 6–12 months | U&E, eGFR, ACR, BP, Hb, lipids | HbA1c if DM |
| G3b | 30–44 | Every 3–6 months | + PTH, Ca, PO₄, HCO₃ | Iron studies, ferritin, TSAT |
| G4 | 15–29 | Every 3 months | Full renal panel + bone mineral | Hepatitis B serology; AV fistula referral |
| G5 | <15 | Monthly | U&E, FBC, PO₄, Ca, HCO₃ | Fluid status; RRT access; ACP |
Increase monitoring frequency if ACR worsens, BP uncontrolled, or eGFR declining. Always document the trend — a single value is far less meaningful than trajectory over time.
Annual CKD Review — Minimum Dataset
Biochemistry & urine
- eGFR (2 readings if new diagnosis)
- Urine ACR (early morning sample)
- U&E, creatinine, bicarbonate
- Hb, MCV, iron studies (ferritin, TSAT)
- Lipid profile (non-HDL-C preferred)
- HbA1c if diabetes
- PTH, Ca, PO₄ (G3b and above)
Clinical & lifestyle
- BP (clinic or ABPM/home reading)
- Weight and BMI
- Smoking status and cessation support
- QRISK3 / CVD risk assessment
- Medication review (renal dose adjustment)
- Sick day rules education
- Immunisation status (pneumococcal, flu, Hep B)
Key References
| Guideline / Trial | Topic | Key recommendation |
|---|---|---|
| NICE CG182 (2014, 2023) | CKD diagnosis, staging, management | Core UK CKD guideline |
| NICE NG136 (2019) | Hypertension — BP targets | ≤130/80 in high-risk groups |
| NICE NG238 (2023) | Lipid modification | Non-HDL-C targets; statin in CKD |
| NICE TA739 (2021) | Dapagliflozin in CKD | eGFR ≥20 + ACR ≥22 — regardless of DM |
| DAPA-CKD (2020) | SGLT2i in CKD | 39% reduction in kidney failure/death |
| CREDENCE (2019) | Canagliflozin in DKD | 30% reduction in renal composite endpoint |
| FIDELIO-DKD (2020) | Finerenone in T2DM + CKD | 18% reduction in renal progression |
| SHARP (2011) | Statins in CKD | 17% reduction in major atherosclerotic events |
The key conceptual shift: SGLT2 inhibitors were developed as glucose-lowering drugs for T2DM. We now know their kidney and heart protection is largely independent of glucose lowering. NICE now approves dapagliflozin for CKD even without diabetes — the indication is driven by eGFR + ACR thresholds, not HbA1c.
How SGLT2 Inhibitors Protect the Kidney
Mechanisms of renoprotection (beyond glucose lowering)
Haemodynamic effects
- Tubuloglomerular feedback (TGF) restoration: SGLT2 blockade increases sodium delivery to the macula densa → afferent arteriole constriction → reduces intraglomerular hypertension. This is the dominant renoprotective mechanism — analogous to how ACEi/ARB reduce efferent tone.
- Reduces hyperfiltration — the same mechanism that causes early diabetic nephropathy progression also occurs in non-diabetic CKD
- Modest BP reduction (~3–5 mmHg systolic) via osmotic natriuresis — additive to RASi
Metabolic & other effects
- Reduces tubular oxygen demand → less hypoxia-driven fibrosis in the tubular interstitium
- Anti-inflammatory and anti-fibrotic effects (reduces TGF-β, NF-κB signalling)
- Weight loss (~2–3 kg) reduces adipokine-driven renal inflammation
- Reduces uric acid (uricosuric effect) — relevant in gout-associated CKD
- Modest diuretic effect — reduces cardiac preload and proteinuria
The ~30% eGFR dip seen on starting SGLT2i is a haemodynamic effect (reduced hyperfiltration) — NOT nephrotoxicity. It is analogous to the creatinine rise with ACEi/ARB. Do not stop the drug for this reason unless eGFR falls below the licensed threshold (<20).
The Confusion Explained — Two Separate Indications
SGLT2 inhibitors in T2DM vs CKD — they overlap but are NOT the same
INDICATION 1 — T2DM management
NICE NG28 (T2DM guideline) / NG238
- Goal: glucose lowering, weight, CV/renal protection
- Drugs: dapagliflozin, empagliflozin, canagliflozin, ertugliflozin
- Threshold: eGFR ≥45 for glucose-lowering effect (some benefit ≥30)
- Add to metformin (or first-line if high CV/renal risk)
- Driven by HbA1c + CVD/renal risk stratification
- Stop if eGFR <45 for glucose-lowering indication (less effective)
INDICATION 2 — CKD protection (with or without DM)
NICE TA739 — Dapagliflozin only
- Goal: slow CKD progression, reduce kidney failure, reduce CV death
- Drug: dapagliflozin 10mg only (only SGLT2i with NICE approval for non-DM CKD)
- Threshold: eGFR ≥20 AND ACR ≥22 mg/mmol
- Add to ACEi/ARB (maximum tolerated dose — mandatory background therapy)
- Driven by eGFR + ACR — NOT HbA1c
- Continue down to eGFR 15 for organ protection (even though glucose effect minimal)
The practical point: A patient with CKD G3b (eGFR 35) and ACR 40 mg/mmol but NO diabetes should be offered dapagliflozin 10mg under TA739 for renoprotection. Their eGFR is below the glucose-lowering threshold — but that doesn't matter. The CKD indication persists to eGFR ≥20.
Eligibility Decision — Which Drug, Which Patient
| Patient scenario | eGFR | ACR | SGLT2i indicated? | Drug & dose | NICE basis |
|---|---|---|---|---|---|
| T2DM — glucose lowering only, no CKD | ≥45 | Any | Yes — glucose | Dapa/Empa/Cana 10mg | NG28 |
| T2DM + CKD (ACR ≥22) | ≥20 | ≥22 | Yes — dual indication | Dapagliflozin 10mg preferred | TA739 + NG28 |
| T2DM + CKD but eGFR 20–44 | 20–44 | ≥22 | Yes — CKD indication | Dapagliflozin 10mg | TA739 (glucose effect minimal but renoprotection continues) |
| CKD without diabetes (ACR ≥22) | ≥20 | ≥22 | Yes — CKD only | Dapagliflozin 10mg | TA739 (DAPA-CKD non-DM subgroup) |
| CKD without diabetes, ACR <22 | Any | <22 | No — below threshold | Not indicated | TA739 threshold not met |
| CKD any cause, eGFR <20 | <20 | Any | Stop / do not start | Discontinue if started; switch or omit | Licensed lower limit eGFR 20 |
| T1DM + CKD | Any | Any | No (off-label) | Not NICE-approved for T1DM CKD | TA739 excluded T1DM; increased DKA risk |
| Heart failure with CKD (HFrEF or HFpEF) | ≥20 | Any | Yes — HF indication | Dapa or Empa 10mg | TA679 / TA902 (HF indication — separate to CKD TA) |
Key Trial Evidence — What Each Trial Actually Showed
| Trial | Drug | Population | Primary result | % with DM | UK relevance |
|---|---|---|---|---|---|
| DAPA-CKD (2020) | Dapagliflozin 10mg | eGFR 25–75, ACR 200–5000 mg/g (≈22–556 mg/mmol); all on max RASi | 39% ↓ in kidney failure, sustained eGFR decline ≥50%, or CV/renal death | 67% DM / 33% no DM | Basis of TA739 — non-DM arm drove the non-diabetic CKD indication |
| CREDENCE (2019) | Canagliflozin 100mg | T2DM + eGFR 30–90 + ACR ≥34 mg/mmol; on max RASi | 30% ↓ in composite renal/CV endpoint | 100% DM | T2DM + DKD only — no NICE TA for non-DM CKD; less used in UK primary care |
| EMPA-KIDNEY (2022) | Empagliflozin 10mg | eGFR 20–45 (any ACR) OR eGFR 45–90 + ACR ≥22 mg/mmol; ~46% no DM | 28% ↓ in kidney disease progression or CV death | 54% DM / 46% no DM | Supports broader non-DM use but currently NO separate NICE TA for empagliflozin in CKD (non-DM) |
| EMPEROR-Reduced / Preserved | Empagliflozin 10mg | Heart failure (HFrEF + HFpEF) | 25–21% ↓ in CV death/HF hospitalisation | Mixed | Basis for empagliflozin HF indication (TA679/TA902) — often co-exists with CKD |
| FIDELIO-DKD / FIGARO-DKD | Finerenone (not SGLT2i) | T2DM + CKD + ACR ≥30 on max RASi | 18–13% ↓ in renal and CV composites | 100% DM | Finerenone is an MRA — can be added ON TOP of SGLT2i in T2DM+CKD (complementary mechanisms) |
Practical Prescribing in Primary Care
Starting dapagliflozin for CKD — step by step
- Check eligibility: eGFR ≥20 AND ACR ≥22 mg/mmol AND on maximum tolerated ACEi or ARB (this is a prerequisite in TA739)
- Check contraindications: Type 1 diabetes (high DKA risk), recurrent genital mycotic infections, active foot ulcers or amputation risk, severe hepatic impairment
- Baseline bloods: eGFR, U&E, glucose/HbA1c (even in non-DM — baseline reference), urinalysis
- Dose: Dapagliflozin 10mg once daily (same dose regardless of DM status — do NOT use 5mg; that is the lower glucose-lowering dose, not used in CKD indication)
- Expected eGFR dip: Up to ~5 ml/min/1.73m² in first 2–4 weeks — this is expected and haemodynamic. Recheck at 4–6 weeks. Continue unless eGFR <20.
- Sick day rules: Add dapagliflozin to SADMAN list — hold during acute illness to reduce euglycaemic DKA risk (even in non-DM, there is a very small DKA risk under metabolic stress)
- Monitoring at 4–6 weeks: eGFR, K⁺, urine ACR, BP — document response
- Long-term monitoring: Annual eGFR, ACR, U&E alongside standard CKD review
Side effects to counsel on
Common / expected
- Genital mycotic infections (thrush) — counsel on hygiene; treat with topical antifungal
- Increased urinary frequency initially (osmotic diuresis)
- Mild BP reduction — monitor for dizziness/postural hypotension, especially in elderly on diuretics
- Mild eGFR dip in first 4 weeks (haemodynamic — expected, not harmful)
Rare but serious
- Euglycaemic DKA — rare in non-DM but possible under metabolic stress (surgery, prolonged fasting, acute illness). Blood glucose may be normal. Counsel: hold during illness, before surgery. Suspect if unwell + high ketones.
- Fournier's gangrene (necrotising fasciitis of genitalia) — very rare; seek urgent surgical review if perineal pain/swelling
- Lower limb amputation risk — associated with canagliflozin (not clearly with dapagliflozin); caution in peripheral arterial disease
One-Page Quick Reference — SGLT2i in CKD
eGFR ≥20
Minimum eGFR to START or continue for CKD protection (TA739)
ACR ≥22 mg/mmol
Minimum proteinuria threshold to qualify (regardless of DM status)
10mg daily
Dapagliflozin — only licensed SGLT2i for non-DM CKD in UK (TA739)
| Question | Answer |
|---|---|
| Does the patient need diabetes to qualify? | No — TA739 covers CKD with or without T2DM |
| Which drug has NICE approval for non-DM CKD? | Dapagliflozin 10mg only (empagliflozin does not yet have a separate UK CKD-without-DM TA) |
| Must they already be on an ACEi/ARB? | Yes — TA739 requires maximum tolerated RASi as background therapy |
| What if eGFR drops after starting? | Expected — haemodynamic dip ≤5 ml/min. Only stop if eGFR <20. |
| Can it be used in T1DM + CKD? | No — not NICE-approved; high DKA risk in T1DM |
| Can it be combined with finerenone? | Yes — in T2DM + CKD, all three (ACEi/ARB + SGLT2i + finerenone) can be used together (FLOW-like combination); complementary mechanisms |
| Can it be used in heart failure + CKD? | Yes — dual indication; single dapagliflozin 10mg covers both HF (TA679) and CKD (TA739) |
| When to add to sick day rules? | Always — add to SADMAN list; hold during acute illness or perioperative period |