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Assessing and Managing Kidney Function in Diabetic Patients (T1DM & T2DM)

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PART 1 - CLINICAL ASSESSMENT IN THE OPD

1A. History Taking

• Duration of diabetes (DKD rarely occurs before 5 years of T1DM; T2DM may already have nephropathy at diagnosis)
• Glycemic control - HbA1c trend over time
• Prior documentation of microalbuminuria or proteinuria
• Blood pressure history and current antihypertensive medications

• Nocturia (early), frothy urine (proteinuria), reduced urine output (late)
• Fatigue, pallor (anemia of CKD)
• Ankle/pedal edema (hypoalbuminemia, fluid retention)
• Nausea, vomiting, anorexia, metallic taste (uremic symptoms - late Stage 4-5)
• Pruritus, restless legs, muscle cramps
• Breathlessness (fluid overload, pericarditis)
• Visual disturbance (co-existing retinopathy)

• Hypertension, dyslipidemia, smoking, CAD, stroke
• BMI, weight change trend

• NSAIDs, aminoglycosides, contrast dye exposure (nephrotoxins)
• ACE inhibitor/ARB use and tolerance

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1B. Clinical Examination

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1C. Essential Investigations (OPD-Accessible)

Confirm an elevated UACR on 2-3 separate occasions over 3-6 months - single readings can be falsely elevated by exercise, fever, UTI, cardiac failure, marked hyperglycemia, or prostate disease. - Harrison's 22e, p. 3268

• T1DM: Screen for microalbuminuria 5 years after diagnosis, then annually
• T2DM: Screen at time of diagnosis and annually thereafter
• Once albuminuria is confirmed elevated, measure UACR 2-4 times per year

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PART 2 - STAGING KIDNEY DISEASE IN DIABETIC PATIENTS

CKD Staging by KDIGO (G + A Classification)

• Moderate risk: G1-G2/A2; G3a/A1
• High risk: G1-G2/A3; G3a/A2; G3b/A1
• Very high risk: G3a/A3; G3b/A2-A3; G4-G5/any A

Natural History of DKD (particularly T1DM, similar in T2DM)

1. Early (years 0-5): Glomerular hyperfiltration, renal hypertrophy, GFR may be supranormal
2. 5-10 years: GBM thickening, mesangial expansion; eGFR returns toward normal; normoalbuminuria
3. 10-15 years: Microalbuminuria (UACR 30-300 mg/g) appears; eGFR still normal
4. 15-20 years: Overt proteinuria (UACR > 300 mg/g); eGFR begins to decline
5. Advanced: Progressive GFR decline, hypertension, ESKD

Note: Up to 24% of T1DM and 50% of T2DM patients with CKD may be normoalbuminuric - a "non-proteinuric phenotype" with progressive GFR loss. This is why measuring both UACR and eGFR is essential. - Harrison's 22e, p. 3267

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PART 3 - STAGE-BY-STAGE TREATMENT

Foundational Treatments at ALL Stages

1. Glycemic control - HbA1c target 7.0% (KDIGO). Tight control prevents development or delays progression, especially in early CKD (stages 1-2 benefit most). Balance against hypoglycemia risk in advanced CKD. - Brenner & Rector, p. 2588
2. Blood pressure control - Target < 130/80 mmHg with proteinuria; < 140/90 mmHg without. First-line: ACE inhibitor or ARB if UACR ≥ 30 mg/g
3. Lifestyle modifications - Smoking cessation, moderate exercise (30-60 min/day), target BMI 18.5-24.9, low sodium diet (< 2.4 g/day), dietary protein 0.8 g/kg/day (ADA recommendation for DKD)
4. Statin therapy - For CV risk > 10% over 10 years (Stages 1-2); consider for all at Stage 3a+
5. Annual monitoring of UACR, eGFR, electrolytes, HbA1c, lipids, CBC

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Stage G1-G2 (eGFR ≥ 60, with albuminuria or structural damage)

• ACE inhibitor or ARB: First line if UACR ≥ 30 mg/g; titrate to maximum tolerated dose. Monitor serum creatinine (up to 30% rise acceptable) and potassium after initiation. Do not combine ACE inhibitor + ARB
• SGLT2 inhibitor (e.g., dapagliflozin 10 mg, empagliflozin 10 mg): Recommended for T2DM with DKD and eGFR > 20 mL/min/1.73 m². Provides kidney and cardiovascular protection independent of glycemic lowering. Safe to initiate with eGFR ≥ 30
• Metformin: First-line glucose-lowering agent; safe when eGFR > 30 mL/min/1.73 m²
• Statin: If CVD risk > 10%

• Sodium restriction, protein 0.8 g/kg/day, weight management, smoking cessation
• Annual eye exam (dilated fundoscopy or retinal photography with remote reading)
• Annual foot examination (monofilament, vibration sense)
• Monitoring frequency: Annual

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Stage G3a (eGFR 45-59)

• Continue ACE inhibitor/ARB, SGLT2 inhibitor (if eGFR ≥ 30)
• GLP-1 receptor agonist (e.g., semaglutide): Improves kidney outcomes and reduces CV deaths in T2DM + CKD; add for additional glycemic, proteinuria, and cardiovascular benefit
• Finerenone (nonsteroidal mineralocorticoid receptor antagonist): Add to ACE inhibitor/ARB to further reduce albuminuria, slow eGFR decline, and reduce CV complications in T2DM. Requires monitoring potassium
• Statin: Consider for all patients at this stage
• Begin checking PTH; if rising, start phosphate restriction

• Every 6 months: eGFR, UACR, electrolytes, CBC
• Check serum phosphate, calcium, PTH, bicarbonate
• Metabolic acidosis: Treat with sodium bicarbonate supplementation if serum bicarbonate < 22 mEq/L

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Stage G3b (eGFR 30-44)

• Continue ACE inhibitor/ARB (check potassium closely)
• SGLT2 inhibitors: Dapagliflozin and empagliflozin can be continued (glucose-lowering efficacy decreases but kidney/CV benefit is preserved). Initiation of canagliflozin: maximum 100 mg/day
• Metformin: Reduce dose; use with caution at eGFR 30-44; stop if < 30
• Anemia: If hemoglobin < 10 g/dL, give IV iron supplementation; erythropoiesis-stimulating agents (ESAs) if iron-replete. Target hemoglobin 10-11.5 g/dL (do not exceed 13 g/dL)
• Bone/mineral: Phosphate binders if hyperphosphatemic; active vitamin D analogs (calcitriol, alfacalcidol) if PTH rising; monitor calcium
• Metabolic acidosis: Sodium bicarbonate supplementation

• Every 3-6 months
• Nephrology referral should be considered at eGFR < 30 or if UACR > 300 mg/g

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Stage G4 (eGFR 15-29)

• Continue RAAS blockade (with close potassium monitoring); loop diuretics now typically required for BP control and edema
• SGLT2 inhibitors: Initiation not recommended at eGFR < 20-25 mL/min/1.73 m² (glucose-lowering ineffective); may continue if already established with tolerated benefit
• Metformin: Stop (risk of lactic acidosis)
• Anemia: IV iron + ESA, hemoglobin target 10-11.5 g/dL
• Manage hyperkalemia (dietary potassium restriction, kayexalate, patiromer/sodium zirconium cyclosilicate)
• Phosphate binders, active vitamin D, sodium bicarbonate
• Statin: Continue if already on one

• Renal replacement therapy (RRT) planning: Educate patient about hemodialysis, peritoneal dialysis, and preemptive kidney transplantation options. AV fistula creation should be planned
• Protein intake 0.6-0.8 g/kg/day (low protein diet slows uremic toxin accumulation; do not go below 0.6 g/kg to avoid protein-energy wasting)
• Dietitian referral for phosphate, potassium, fluid management
• Monitoring: Every 1-3 months

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Stage G5 (eGFR < 15 or Dialysis)

• Initiate hemodialysis or peritoneal dialysis
• Preemptive kidney transplant preferred; T2DM on dialysis has very poor prognosis (majority die from CVD)
• Combined kidney-pancreas transplant should be considered for eligible T1DM patients

• Continue ACE inhibitor/ARB if tolerated (loop diuretics usually needed)
• SGLT2 inhibitors: Continue if already established for non-glycemic kidney/CV benefit until dialysis initiation
• Anemia management: IV iron + ESA; target Hb 10-11.5 g/dL
• Insulin usually required as other agents have limited utility or are unsafe; adjust doses carefully (hypoglycemia risk increases as CKD clears less insulin)

• PEW occurs due to anorexia, systemic inflammation, dietary restrictions, catabolic losses during dialysis, and uremia
• Dialysis patients require 1.2-1.4 g protein/kg/day (increased to compensate for dialysis losses)
• Oral nutritional supplements or intradialytic parenteral nutrition (IDPN) may be needed
• Monitor serum albumin, prealbumin, body weight, muscle mass (sarcopenia screening)
• Low albumin is a strong predictor of mortality in dialysis patients

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PART 4 - CO-MANAGING RETINOPATHY AND OTHER MICROVASCULAR COMPLICATIONS

Diabetic Retinopathy

• T1DM: Begin screening 5 years after diagnosis, then annually
• T2DM: Screen at diagnosis, then annually
• Pregnancy: Screen before and during pregnancy; high risk of rapid progression
• Requires dilated fundoscopy or retinal photography; routine non-dilated exam is inadequate

• Prevention/early disease: Tight glycemic control (HbA1c 7%), BP < 140/80 mmHg, fenofibrate (lowers triglycerides and reduces retinopathy progression), smoking cessation
• Caution: Rapid improvement in glycemic control (including with GLP-1 agonists) can transiently worsen retinopathy - monitor closely
• Severe NPDR or PDR: Panretinal laser photocoagulation (PRP)
• Diabetic macular edema: Intravitreal anti-VEGF injections (bevacizumab, ranibizumab, aflibercept) are first-line; laser is second-line
• Advanced PDR with vitreous hemorrhage or traction: Vitrectomy

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Diabetic Peripheral Neuropathy

• Examine annually using 10-g monofilament, vibration sense (128 Hz tuning fork), and ankle reflexes
• Medications for painful neuropathy: duloxetine, pregabalin, gabapentin, amitriptyline
• Foot care education is essential; podiatry referral for active foot disease
• SGLT2 inhibitors and GLP-1 agonists have shown some benefit in reducing cardiovascular mortality which is the primary cause of death in DKD + neuropathy

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Diabetic Cardiovascular Disease

• ASCVD is the leading cause of death in diabetic individuals with nephropathy
• Treat dyslipidemia aggressively with statins; add ezetimibe or PCSK9 inhibitors if LDL target not met
• Aspirin for secondary prevention only (no benefit in primary prevention in DM)
• In T2DM + CKD + CVD or heart failure: SGLT2 inhibitors are strongly indicated

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PART 5 - SUMMARY MONITORING TABLE

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Key Drug Cutoffs at a Glance

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Recent evidence update (2025-2026): Two network meta-analyses (PMID 41147324, Lin et al. Diabetes Obes Metab 2026; PMID 40798873, Bramlage et al. Diabetes Obes Metab 2025) confirm SGLT2 inhibitors and GLP-1 receptor agonists (particularly semaglutide) provide superior renal and cardiovascular outcomes in T2DM + CKD compared to other antidiabetic drug classes. This reinforces the KDIGO 2022 guidelines hierarchy of treatment.

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• Comprehensive Clinical Nephrology 7e (Elsevier, 2023), Chapter 32 - Diabetic Kidney Disease
• Brenner & Rector's The Kidney (Elsevier), Chapter 59 - CKD Management by Stage (Table 59.2)
• Harrison's Principles of Internal Medicine 22e (2025), Chapters 322 and 417 - Diabetic Nephropathy
• Kanski's Clinical Ophthalmology 10e - Diabetic Retinopathy chapter
• National Kidney Foundation Primer on Kidney Diseases 8e - Management of Risk Factors and Complications