Public Review Draft (March 2026) - Detailed Summary for Consultant Nephrologists

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CHAPTER 1: Definitions, Prevention, Case-Finding, Staging & CV Risk Assessment

1.1 Terminology

1.2 CKD Prevention - Paradigm Shift

1.3 Case-Finding and Diagnosis

• Test ALL adults and children with diabetes using both UACR and eGFR
• UACR on a spot urine sample (or point-of-care strip with automated UACR reading) is preferred
• T1D: Begin testing ≥5 years after diagnosis
• T2D: Begin testing at the time of diabetes diagnosis
• If eGFR ≥60 and UACR <30 mg/g with no other kidney damage markers: repeat annually
• If elevated: increase frequency per risk category

• T1D duration <5 years
• Active urinary sediment (RBCs, cellular casts, sterile pyuria)
• Well-controlled blood glucose with unexplained CKD
• Rapidly declining eGFR
• Rapidly rising or very high UACR/proteinuria/creatinine
• No diabetic retinopathy (especially in T1D)
• Systemic features (polyarthritis, gouty arthritis)

1.4 Staging

1.5 CV-Kidney Risk Prediction

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CHAPTER 2: Glycemic Monitoring and Targets

2.1 Glycemic Monitoring

• Remains recommended as the standard monitoring tool in CKD
• Monitor twice yearly when target is met; up to 4 times/year if target is unmet or therapy changes
• Accuracy declines with advanced CKD (G4-G5), particularly in dialysis patients where HbA1c has low reliability (due to altered RBC survival, erythropoiesis, iron deficiency, carbamylation)
• In G4-G5/dialysis: use glucose management indicator (GMI) from CGM data as a supplement

• Offer CGM to ALL people with T1D (PP 2.1.3)
• CGM may be offered to T2D patients, especially those on insulin and at hypoglycemia risk (PP 2.1.4)
• CGM and SMBG may help prevent hypoglycemia and improve glycemic control in CKD (PP 2.1.5)
• Real-time CGM with alerts for hypo/hyperglycemia offers additional advantages (PP 2.1.6)
• Specialist diabetes technology support is recommended to help navigate CGM selection (PP 2.1.7)

2.2 Glycemic Targets (Carried Forward - Not Updated in 2026)

• Lower target (<6.5-7.0%): younger patients, few comorbidities, mild-moderate CKD, long life expectancy, agents without hypoglycemia risk
• Higher target (<7.5-8.0%): multiple comorbidities, high hypoglycemia burden, advanced CKD, limited life expectancy
• HbA1c ≤6.0% is associated with increased all-cause mortality in CKD populations (avoid)
• Evidence base: HbA1c in the 6.5-8% range is associated with better survival, fewer CV events, reduced albuminuria progression

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CHAPTER 4: Pharmacotherapy

4.1 Comprehensive Diabetes and CKD Management

1. RAS inhibitor (ACEi or ARB)
2. SGLT2 inhibitor
3. Nonsteroidal MRA (nsMRA)
4. GLP-1 receptor agonist

• Personalized, risk-based approach; maximize cardiorenal protection as quickly as possible
• Multiple interventions can be initiated simultaneously when adverse effect profiles are non-overlapping
• Lipid management: initiate statin-based therapy for ASCVD risk reduction; for high-risk patients with T2D and CKD, target more intensive LDL-C goals
• Add non-statin lipid-lowering therapy (ezetimibe, PCSK9 inhibitors) when statin alone insufficient
• Measure Lp(a) at least once - elevated Lp(a) increases CV risk and guides preventive intensity
• Antiplatelet: low-dose aspirin for secondary CV prevention (Rec 4.1.4, Grade 1C)

4.2 RAS Blockade (ACEi/ARB)

• May be reasonable in diabetes + hypertension + no albuminuria (PP 4.2.1)
• May be considered in diabetes + albuminuria + normal BP (PP 4.2.2)
• Monitor BP, eGFR, and serum K+ within 2-4 weeks of initiation or dose increase
• Continue unless eGFR declines >30% within 4 weeks
• Hyperkalemia: attempt potassium management first; do not automatically stop RASi
• Reduce/discontinue if: symptomatic hypotension, uncontrolled hyperkalemia despite K-management, or to reduce uremic symptoms (eGFR <15)
• Contraindicated: ACEi + ARB combination or either with direct renin inhibitor (potentially harmful)
• Women of childbearing age: advise contraception; discontinue if pregnancy planned/confirmed

4.3 SGLT2 Inhibitors - UPGRADED to Grade 1A

• Tubulo-glomerular feedback restoration → afferent arteriolar vasoconstriction → reduction in intraglomerular pressure
• Osmotic diuresis + natriuresis → reduced ventricular preload/afterload → HF benefit
• Anti-inflammatory, anti-fibrotic, mitochondrial energetic effects
• Benefits are largely independent of glycemic control; glucose-lowering modest (~0.3-0.6% HbA1c), diminishing at lower eGFR

• Initiate: eGFR ≥20 ml/min/1.73m²
• Continue even if eGFR falls below 20 once initiated (unless not tolerated or KRT initiated)
• Early eGFR dip is expected, reversible, and hemodynamic - do NOT stop for acute dip ≤30%
• Dip >30%: evaluate for reversible contributors (hypovolemia, nephrotoxins)
• Withhold during prolonged fasting, major surgery, critical illness; restart when clinically stable
• Not applicable to kidney transplant recipients (insufficient data; immune-suppressed)

• Genital mycotic infections: most consistent adverse effect (2.27% vs 0.59% in CREDENCE)
• Euglycemic DKA: rare (<1 per 1,000 patient-years in T2D); higher risk with insulin deficiency, fasting, illness, perioperative period
• Fracture risk: not a class-wide effect (CANVAS anomaly; CREDENCE and others did not confirm)
• Lower limb amputation risk: noted in CANVAS; not confirmed in other trials

4.4 Nonsteroidal MRA (nsMRA) - UPGRADED to Grade 1A

• Select patients with consistently normal serum potassium; monitor K+ regularly after initiation
• Can initiate SGLT2i and nsMRA simultaneously in patients with T2D, RASi, persistent albuminuria, normal K+
• nsMRA also indicated in T2D + CKD with HFpEF/HFmrEF (LVEF ≥40%)
• Steroidal MRA: use only for HFrEF, hyperaldosteronism, or refractory hypertension
• Do NOT combine steroidal and nonsteroidal MRA
• Finerenone is the agent with the best evidence base (approved widely); esaxerenone has supporting data

• Suggest nsMRA in T1D + eGFR ≥25 + normal K+ + UACR ≥200 mg/g on max-tolerated RASi
• Higher albuminuria threshold than T2D (200 vs 30 mg/g) due to limited data in T1D

4.5 GLP-1-Based Therapies - UPGRADED to Grade 1A

• Avoid exenatide and lixisenatide at low eGFR (AKI risk; no proven CV benefit)
• Prefer agents with documented CV and CKD benefits: liraglutide, semaglutide, dulaglutide
• Oral semaglutide: now approved; reduces MACE in T2D with ASCVD/CKD (SOUL trial)
• Orforglipron (oral non-peptide GLP-1 RA): regulatory approval anticipated imminently
• GLP-1 RA + DPP-4i combination: contraindicated (additive mechanism, no additional benefit)

• HbA1c reduction: 0.81-3.73% depending on agent and baseline
• Body weight: -1 to -4.1 kg (FLOW: 4.1 kg loss)
• GLP-1 RA are more potent glucose-lowering and weight-loss agents than SGLT2i in CKD

• Obesity + T2D + CKD: preferentially use GLP-1 RA for intentional weight loss
• GLP-1 RA may be initiated/continued in dialysis patients to facilitate weight loss for transplant listing
• Sarcopenia risk: encourage structured resistance training when on GLP-1 RA in CKD
• Consult renal dietitian for nutritional guidance when combining GLP-1 RA with CKD diet

• GI effects (nausea, vomiting, diarrhea): dose-dependent; start low and titrate slowly
• No class-wide increase in pancreatitis, pancreatic cancer, or hypoglycemia (meta-analysis of 8 trials, n=60,080)
• Contraindicated: personal/family history of medullary thyroid cancer, MEN2
• Monitor retinopathy: especially in high-risk patients (older age, T2D duration ≥10 years)

4.6 Metformin - Now Repositioned (Grade 1B)

• Monitor eGFR more frequently when eGFR <60
• Kidney transplant recipients with T2D and eGFR ≥30: treat per T2D+CKD algorithm
• Monitor vitamin B12 after >4 years of metformin use

4.7 Type 1 Diabetes - Summary

• HbA1c target <6.5-8.0% (individualized)
• CGM offered to all T1D
• RASi for hypertension + albuminuria
• SGLT2i: Grade 1A for T2D, but no adequate T1D trials - remains a research need; not a Grade 1 recommendation in T1D
• nsMRA (4.7.1, Grade 2C): Suggest adding nsMRA in T1D + eGFR ≥25 + normal K+ + UACR ≥200 mg/g on max-tolerated RASi (higher threshold than T2D, reflecting limited evidence)
• Lifestyle recommendations (0.8 g protein/kg/day, sodium <2 g/day, ≥150 min moderate activity/week) apply to both T1D and T2D

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Treatment Algorithm Summary (T2D + CKD)

Foundational Baseline: Lifestyle + BP control + Statin + Low-dose Aspirin (if 2° prevention)

Step 1 - ALWAYS:
  → ACEi or ARB (if hypertension + albuminuria; Grade 1B)

Step 2 - SIMULTANEOUSLY or early:
  → SGLT2i (eGFR ≥20; Grade 1A) - primary cardiorenal protection
  → nsMRA (eGFR ≥25, normal K+, UACR ≥30 mg/g on max RASi; Grade 1A)

Step 3 - For high CV/kidney risk or glycemic targets not met:
  → GLP-1-based therapy (preferably semaglutide, liraglutide, or dulaglutide; Grade 1A)

Step 4 - If glycemic targets still not met (or cannot use SGLT2i/GLP-1):
  → Metformin (eGFR ≥30; Grade 1B)
  → Other glucose-lowering agents (insulin, DPP-4i, etc.) - no Grade 1A cardiorenal benefit

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Key Changes vs. KDIGO 2020

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Research Gaps Highlighted

• Long-term (>5 yr) safety of SGLT2i in T2D+CKD
• SGLT2i cardio-kidney benefits in T1D
• SGLT2i in kidney transplant recipients and eGFR <20 or dialysis
• Tirzepatide dedicated CKD trial outcomes (SURPASS-KIDNEY pending)
• Alternative glycemic biomarkers for advanced CKD/dialysis
• CGM target metrics specific to CKD
• Automated insulin delivery systems (closed-loop) in CKD
• nsMRA benefit data on top of SGLT2i (FIDELIO/FIGARO enrolled mostly pre-SGLT2i era patients)
• Cost-effectiveness analyses combining foundational therapies in resource-limited settings

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Important caveat: This is a Public Review Draft (March 2026). Recommendations may change based on feedback received before final publication. The document explicitly states it should not be used to define a standard of care at this stage.

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Assessment of Volume Status

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1. Physiological Framework

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2. History

• Fatigue, weakness, thirst, postural dizziness
• Oliguria, abdominal/chest pain
• Confusion or obtundation (severe)

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3. Physical Examination

3A. Hypovolemia Signs

• Hypotension + tachycardia
• Peripheral vasoconstriction, cold extremities
• Peripheral cyanosis
• Oliguria/anuria
• Altered mental status

3B. Hypervolemia Signs

3C. Jugular Venous Pressure - Clinical Technique

• Position patient at 30-45° recumbent
• Identify internal jugular vein pulsation (biphasic, non-palpable)
• Measure vertical height above the sternal angle
• Normal: ≤4 cm; elevated: >4 cm; flat: suggests hypovolemia
• JVP correlates with right atrial pressure: add 5 cm to give estimated RAP in cmH₂O

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4. Laboratory Assessment

4A. Urine Studies

4B. Serum Studies

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5. Hemodynamic Monitoring (ICU/Advanced Setting)

5A. Static (Filling Pressure) Parameters

5B. Dynamic (Fluid Responsiveness) Parameters - Preferred

Passive Leg Raise (PLR) Test

• Technique: Patient supine at 45°, then bed tilted to Trendelenburg (horizontal trunk, legs elevated at 45°)
• Mechanism: Autotransfusion of ~300 mL from lower limbs to central circulation
• Positive response: Increase in cardiac output (or pulse pressure) within 1 minute = fluid responsive
• Can be used in spontaneously breathing patients (unlike SVV/PPV)
• Harrison's 22nd: "The PLR test can predict responsiveness to additional IV fluid by providing the patient with an endogenous volume bolus."

Pulse Pressure Variation (PPV) / Stroke Volume Variation (SVV)

• Requires mechanical ventilation in volume-controlled mode, no arrhythmias
• >12% SV variation = volume-responsive state
• Reflects cyclic changes in venous return during positive-pressure ventilation
• Harrison's 22nd: "A >12% SV variation suggests a volume-responsive state. This measurement requires that the patient be in a volume cycle mode of ventilation, without breath-to-breath variations in intrathoracic pressure and without arrhythmias."

5C. Point-of-Care Ultrasound (POCUS)

• B-lines (≥3 per zone, bilateral): pulmonary edema/congestion
• Pleural effusions: bilateral suggest cardiac/renal overload; unilateral consider exudate

• Hyperdynamic LV with small cavity = hypovolemia ("kissing walls")
• Dilated, poorly contracting LV = cardiogenic state
• Serial LV assessment during fluid bolus guides resuscitation

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6. Integrated Approach by Clinical Context

Context 1: Suspected Hypovolemia (e.g., Prerenal AKI, Diarrhea, Sepsis)

Clinical history → physical exam (JVP, orthostatic vitals)
→ Urine Na⁺ + osmolality + FENa
→ BUN:creatinine ratio, serum electrolytes
→ POCUS (IVC, cardiac)
→ PLR test (or fluid challenge with response monitoring)
→ If ICU + ventilated: assess PPV/SVV

Context 2: Suspected Hypervolemia (e.g., Heart Failure, CKD, Nephrotic Syndrome)

Clinical history (dyspnea, orthopnea, edema, weight gain)
→ JVP elevation, S3, pulmonary crackles, peripheral edema
→ BNP/NT-proBNP (elevated in cardiac/volume overload)
→ Chest X-ray (vascular congestion, effusions, cardiomegaly)
→ POCUS (lung B-lines, IVC dilation, LV function)
→ Echocardiogram for LVEF and filling pressures

Context 3: Uncertain Volume Status (Common in CKD/AKI)

• Physical exam may be unreliable (chronic edema, reduced skin turgor from uremia)
• BUN:creatinine ratio may be spuriously elevated from catabolism, not pre-renal state
• POCUS is most useful: IVC + lung assessment combination

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7. Summary Table: Clinical Tools for Volume Assessment

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Key Harrison's 22nd Principle: Physical examination signs like skin turgor and dry mucous membranes are "less than ideal markers" in adults. The most clinically reliable bedside findings for hypovolemia are decreased JVP, orthostatic tachycardia (>15-20 bpm), and orthostatic hypotension (>10-20 mmHg) (Harrison's 22nd - Fluid and Electrolyte Disorders, Chapter on Hypovolemia). For resuscitation guidance, dynamic parameters (PLR, PPV/SVV) and POCUS are preferred over static filling pressures (CVP) (Harrison's 22nd - Initial Treatment of Shock).