Renal/Urology · PANCE / PANRE

Chronic Kidney Disease (CKD)

Persistent decline in GFR or kidney damage for ≥3 months, staged by eGFR and albuminuria.

Also known as: CKD, chronic renal insufficiency, chronic renal failure

Overview

Abnormalities of kidney structure or function present for >3 months with implications for health. Defined by eGFR <60 mL/min/1.73 m² OR markers of kidney damage (albuminuria ≥30 mg/g, urine sediment abnormalities, electrolyte/structural abnormalities, biopsy findings, or kidney transplant) lasting ≥3 months.

Epidemiology

Affects ~14% of US adults. Diabetes and hypertension cause >70% of cases. Black, Hispanic, and Native American populations have higher incidence and progression rates.

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Risk factors

Diabetes mellitus (leading cause)
Hypertension (second leading cause)
Glomerulonephritis, polycystic kidney disease, recurrent AKI
Age >60, family history, obesity, smoking, nephrotoxin exposure
APOL1 high-risk genotype (African ancestry)

Pathophysiology

Progressive nephron loss triggers compensatory hyperfiltration in surviving glomeruli → glomerular hypertension, sclerosis, and tubulointerstitial fibrosis. Activation of the renin-angiotensin-aldosterone system, oxidative stress, and inflammatory cytokines accelerate decline. Loss of functional mass impairs erythropoietin production, vitamin D activation, acid-base homeostasis, and phosphate excretion.

Clinical presentation

Symptoms

Often asymptomatic until advanced (stage 4-5)
Fatigue, weakness, anorexia, weight loss
Pruritus, restless legs, muscle cramps
Foamy urine (albuminuria), nocturia, peripheral edema
Late: dyspnea, nausea, confusion, bleeding

Signs / physical exam

Hypertension (cause and consequence)
Pallor (anemia of CKD), volume overload (edema, elevated JVP, crackles)
Uremic features: sallow skin, asterixis, pericardial rub
Diabetic retinopathy, peripheral neuropathy supportive of diabetic etiology

Classic findings

Small echogenic kidneys on ultrasound (except in diabetes, amyloid, HIV-associated nephropathy, and PKD where kidneys may be normal or enlarged).

Differential diagnosis

Acute kidney injury — Abrupt onset (<3 months), often reversible; baseline labs critical to distinguish — small echogenic kidneys favor CKD
Diabetic nephropathy — Long-standing diabetes, retinopathy, gradual albuminuria progression; biopsy shows Kimmelstiel-Wilson nodules
Hypertensive nephrosclerosis — Long-standing HTN, minimal proteinuria, small bilateral kidneys, no active sediment
Glomerulonephritis (chronic) — Persistent proteinuria, hematuria, active sediment; biopsy diagnostic
Polycystic kidney disease — Family history, enlarged kidneys with cysts on imaging, extrarenal cysts
Obstructive uropathy — Hydronephrosis on US, history of stones, BPH, or pelvic malignancy
Multiple myeloma / monoclonal gammopathy — Anemia disproportionate to CKD stage, hypercalcemia, bone pain; SPEP/UPEP with free light chains

Diagnostic workup

Diagnostic criteria

CKD requires kidney damage OR eGFR <60 for ≥3 months. Staged G1-G5 by eGFR (G1 ≥90, G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, G5 <15) and A1-A3 by UACR (A1 <30, A2 30-300, A3 >300 mg/g).

Labs

Serum creatinine with eGFR (CKD-EPI 2021 race-free equation)
Urine albumin-to-creatinine ratio (UACR) on spot sample — preferred over dipstick
Urinalysis with microscopy
BMP (K, HCO3, Ca, phosphate), CBC (anemia), albumin
Stage 3-5: PTH, 25-OH vitamin D, iron studies, lipid panel

Imaging

Renal ultrasound — assess size, echogenicity, cysts, obstruction

Diagnostic algorithm

Stage	eGFR (mL/min/1.73 m²)	Description	Action
G1	≥90	Normal GFR with kidney damage	Treat comorbidities, slow progression
G2	60-89	Mild GFR decrease with damage	Estimate progression
G3a	45-59	Mild-moderate decrease	Evaluate and treat complications
G3b	30-44	Moderate-severe decrease	Evaluate and treat complications
G4	15-29	Severe GFR decrease	Prepare for RRT, transplant referral
G5	<15	Kidney failure	RRT if uremia present

KDIGO CKD staging by eGFR. Combine with albuminuria categories A1-A3 for full risk stratification.

Treatment

First-line

BP target <120/80 (KDIGO 2021); use validated office BP measurement
ACEi (lisinopril, ramipril, enalapril) or ARB (losartan, valsartan, irbesartan) — first-line for albuminuria or diabetes; reduces progression
SGLT2 inhibitor — dapagliflozin, empagliflozin, canagliflozin — for diabetic or non-diabetic CKD with eGFR ≥20 and UACR ≥200 (proven mortality and renal benefit)
Nonsteroidal MRA — finerenone — for type 2 diabetes with albuminuric CKD on maximal ACEi/ARB
Glycemic control: A1c 6.5-8% individualized; metformin safe down to eGFR 30
Statin therapy — atorvastatin, rosuvastatin — for all adults ≥50 with CKD or any age with diabetes/CVD

Second-line / adjunct

Anemia: iron repletion first; ESA (epoetin alfa, darbepoetin) when Hb <10 with caution to avoid >11.5
Mineral-bone disease: phosphate binders (sevelamer, lanthanum, calcium acetate), active vitamin D (calcitriol, paricalcitol), calcimimetics (cinacalcet, etelcalcetide)
Metabolic acidosis: sodium bicarbonate when HCO3 <22 (slows progression)
Hyperkalemia: dietary restriction, loop diuretic, potassium binder — patiromer, sodium zirconium cyclosilicate
Prepare for RRT at eGFR ~20: education, vascular access (AV fistula 6+ months in advance), transplant referral

Complications

Cardiovascular disease (leading cause of death in CKD)
Anemia (decreased EPO production)
CKD-mineral bone disease: hyperphosphatemia, low calcitriol, secondary hyperparathyroidism, renal osteodystrophy
Metabolic acidosis, hyperkalemia, hypocalcemia
Uremic complications: pericarditis, encephalopathy, platelet dysfunction
Progression to ESRD requiring dialysis or transplant

PANCE pearls

The 2021 CKD-EPI equation removed the race coefficient and is now the standard eGFR calculation in the US.
ACEi/ARB may cause an initial 30% Cr rise — this is acceptable and does not require discontinuation if K stable.
SGLT2 inhibitors are now first-line for CKD with proteinuria regardless of diabetes status (DAPA-CKD, EMPA-KIDNEY).
Avoid NSAIDs, gadolinium (eGFR <30), and excessive iodinated contrast in CKD.
Refer to nephrology at eGFR <30, rapid decline >5 mL/min/year, persistent UACR >300, or refractory complications.

References

KDIGO 2024 — KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (Kidney Int 2024)
KDIGO 2021 BP — KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD
DAPA-CKD — Dapagliflozin in Patients with Chronic Kidney Disease (Heerspink et al., NEJM 2020)
EMPA-KIDNEY — Empagliflozin in Patients with Chronic Kidney Disease (NEJM 2023)

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