Renal & Urinary

Chronic kidney disease: staging and outpatient management

Clinical Overview and When to Suspect CKD

— eGFR <60 mL/min/1.73 m² sustained ≥3 months, OR

— Markers of kidney damage (albuminuria ≥30 mg/g, urine sediment abnormalities, electrolyte/tubular disorders, histologic or imaging abnormalities, history of transplant) for ≥3 months.

— Diabetes ≥5 years, especially with retinopathy

— Long-standing hypertension, particularly poorly controlled or African American patients

— Age >60 with vascular disease

— Recurrent AKI episodes, NSAID overuse, lithium, calcineurin inhibitors, PPIs (chronic)

— Family history of polycystic kidney disease or Alport syndrome

— Autoimmune disease (lupus, vasculitis), monoclonal gammopathies, chronic HIV/HBV/HCV

— Obstructive symptoms, recurrent stones, or known solitary kidney

— USPSTF: insufficient evidence for general screening, but ADA and KDIGO recommend annual screening in diabetics (both types) and hypertensives with serum creatinine + eGFR + urine albumin-to-creatinine ratio (UACR)

— Type 1 DM: start screening 5 years after diagnosis; Type 2 DM: at diagnosis

— Repeat to confirm — a single abnormal value is not CKD until persistent ≥3 months

Board pearl: Use the 2021 race-free CKD-EPI creatinine equation (or creatinine-cystatin C combined for confirmation when eGFR is in the 45–59 range without albuminuria). Cystatin C avoids muscle-mass bias.

Definition (KDIGO 2024): abnormalities of kidney structure or function present for >3 months, with implications for health. Requires either:

Epidemiology: ~14% of US adults; diabetes (~38%) and hypertension (~26%) drive most cases. CKD is a coronary heart disease risk equivalent — most patients die of cardiovascular disease before reaching ESRD.

When to suspect in outpatient practice:

Screening (Step 3 ambulatory framing):

Step 3 management: A patient with eGFR 55 and UACR 45 mg/g found incidentally needs repeat testing in 3 months before labeling CKD; don't anchor on a single lab.

Presentation Patterns and Key History

— G1–G3a (eGFR ≥45): usually silent; may have hypertension or microscopic hematuria

— G3b (eGFR 30–44): early fatigue, nocturia (loss of concentrating ability), mild anemia symptoms

— G4 (eGFR 15–29): anorexia, pruritus, restless legs, metallic taste, volume overload, worsening hypertension

— G5 (eGFR <15): uremic symptoms — nausea/vomiting, pericarditis, encephalopathy, asterixis, uremic frost (rare)

— Diabetes duration, A1c history, retinopathy? (diabetic nephropathy almost always has concurrent retinopathy in T1DM)

— Blood pressure history, control, medications

— NSAIDs, PPIs, herbal supplements (aristolochic acid), IV contrast exposures, antibiotics (aminoglycosides, vancomycin)

— Recurrent UTIs, kidney stones, BPH symptoms → obstructive uropathy

— Family history: ADPKD (autosomal dominant), Alport (hearing loss, hematuria), sickle cell, Fabry

— Systemic symptoms: rash, arthralgias, hemoptysis → glomerulonephritis or vasculitis

— B symptoms, bone pain → myeloma cast nephropathy

— Recent infections → post-infectious GN, IgA nephropathy (synpharyngitic hematuria)

— HIV, HBV, HCV status; IV drug use; tattoo history

— Occupational exposures (heavy metals, solvents)

— Diet (protein load, potassium-rich foods, salt)

— Health literacy, transportation, insurance — predicts adherence to monthly–quarterly monitoring

— Advance care planning for older or G4/G5 patients

CCS pearl: On a CCS case of a newly identified eGFR of 38, order UACR, urinalysis with microscopy, renal ultrasound, CBC, CMP, lipids, A1c, PTH, 25-OH vitamin D, iron studies, and review the medication list before referring to nephrology. Advance the clock 3 months and reassess.

Asymptomatic until late — most CKD is detected via screening labs, not symptoms. Symptoms typically appear at eGFR <30 (Stage G4–G5).

Symptom clusters by stage:

Targeted history to elicit etiology:

Social and functional history (Step 3 flavor):

Physical Exam Findings and Volume Assessment

— Hypertension in >80% of CKD patients — frequently the driver and the consequence

— Resistant hypertension (≥3 agents including diuretic) should prompt evaluation for renovascular disease, primary aldosteronism, and OSA

— Orthostatic hypotension may signal autonomic neuropathy (diabetic) or overdiuresis

— JVP elevation, S3 gallop, bibasilar crackles, peripheral edema, ascites → volume overload

— Flat JVP, dry mucous membranes, orthostasis → overdiuresis or hypovolemia, especially after starting ACEi/ARB/SGLT2i

— Weight trends at each visit are the single most useful longitudinal data point

— LVH on exam (sustained apical impulse), pericardial friction rub in uremia

— Carotid/abdominal/femoral bruits → atherosclerotic disease; consider RAS in flash pulmonary edema

— Excoriations from uremic pruritus

— Calciphylaxis: painful violaceous plaques/necrosis on adipose-rich areas — high mortality, advanced CKD/ESRD

— Livedo reticularis → cholesterol emboli post-catheterization

— Asterixis, myoclonus in uremia

— Peripheral neuropathy (diabetic or uremic)

— Restless legs (also iron-deficiency related)

Key distinction: Bilateral small, echogenic kidneys on ultrasound + bland sediment + stable creatinine over months = chronic disease. Normal-sized kidneys in CKD suggest diabetes, amyloidosis, HIV-associated nephropathy, or ADPKD — etiologies that preserve or enlarge kidney size despite reduced function.

General appearance: sallow/yellow-brown complexion in advanced uremia; cachexia in protein-energy wasting; muscle wasting common in G4–G5.

Vital signs:

Volume status (critical for outpatient management):

Cardiovascular:

Skin:

Neuromuscular:

MSK: bone tenderness from renal osteodystrophy; proximal myopathy from vitamin D deficiency.

Eyes: AV nicking, retinopathy — diabetic or hypertensive — helps establish chronicity.

Diagnostic Workup — Initial Labs, Imaging, and Staging

— BMP/CMP: creatinine, BUN, electrolytes, bicarbonate, calcium, phosphate, albumin

— eGFR by 2021 CKD-EPI creatinine equation

— Urinalysis with microscopy — dysmorphic RBCs/casts → glomerular; WBC casts → interstitial; broad waxy casts → CKD

— Spot urine albumin-to-creatinine ratio (UACR) on first-morning void preferred — not 24-hour collection routinely

— CBC for anemia

— Lipid panel, A1c, fasting glucose

— Renal ultrasound in all new CKD: size, echogenicity, hydronephrosis, cysts, asymmetry

— G1: ≥90, G2: 60–89, G3a: 45–59, G3b: 30–44, G4: 15–29, G5: <15 or dialysis

— A1: <30 mg/g, A2: 30–300 mg/g, A3: >300 mg/g

— eGFR 45–59 without albuminuria (G3a A1) — confirm CKD before labeling

— Patients with extremes of muscle mass (amputees, bodybuilders, paraplegic, cachectic)

— Drug dosing decisions in transplant candidates

Board pearl: A bland urinalysis with heavy albuminuria in a diabetic = diabetic nephropathy presumptively. Active sediment (RBC casts, dysmorphic RBCs) = glomerulonephritis and warrants urgent nephrology referral, not a watchful-wait approach.

Confirm chronicity: persistence of eGFR <60 or markers of damage for ≥3 months. Compare with prior creatinine values if available.

Initial labs (every CKD workup):

CKD staging — GFR categories (G):

Albuminuria categories (A):

KDIGO heat map (risk): combine G and A to risk-stratify (green/yellow/orange/red). Example: G2A3 is high risk despite "normal" eGFR.

When to add cystatin C:

Iron studies, ferritin, TSAT, 25-OH vitamin D, intact PTH: check at G3b and beyond, or earlier if anemia.

SPEP/UPEP with immunofixation, free light chains: age >40 with unexplained CKD, especially with anemia, hypercalcemia, or bone pain.

Diagnostic Workup — Advanced and Confirmatory Studies

— ANA, anti-dsDNA, complements C3/C4 → lupus nephritis (low C3/C4)

— ANCA (MPO, PR3) → pauci-immune GN, GPA, MPA

— Anti-GBM antibody → Goodpasture

— Hepatitis B surface antigen, hepatitis C antibody, HIV → membranous, MPGN, HIVAN

— Anti-PLA2R antibody → primary membranous nephropathy (positive in ~70%)

— Cryoglobulins → HCV-associated MPGN

— ASO, anti-DNase B → post-streptococcal GN

— Serum/urine immunofixation, free light chain ratio → myeloma, MGRS, amyloid

— CT without contrast for stones, masses, or to characterize cysts (Bosniak)

— MRA or duplex ultrasound for renal artery stenosis when resistant HTN, flash pulmonary edema, or AKI after ACEi

— Avoid gadolinium at eGFR <30 (nephrogenic systemic fibrosis risk with older agents); newer macrocyclic agents are lower risk but use with caution

— Unexplained CKD with normal-sized kidneys and active sediment

— Nephrotic syndrome in adults (most need biopsy; exceptions: classic diabetic nephropathy)

— Rapidly progressive GN (rising Cr over weeks)

— Suspected lupus nephritis to guide immunosuppression

— Unexplained AKI without obvious cause

— Contraindications: uncontrolled HTN, bleeding diathesis, single kidney (relative), small echogenic kidneys (low yield, high risk)

Key distinction: Nephrotic (>3.5 g/day proteinuria, edema, hypoalbuminemia, hyperlipidemia) vs nephritic (hematuria, RBC casts, HTN, mild proteinuria, AKI). Diabetic nephropathy is the classic nephrotic-range proteinuria without active sediment picture — biopsy only if atypical (rapid decline, hematuria, absent retinopathy, short DM duration).

Serologic workup when glomerular disease is suspected:

Imaging beyond ultrasound:

Renal biopsy — indications:

Pre-biopsy checklist: BP <140/90, hold antiplatelets/anticoagulants per protocol, type & screen, hemoglobin, platelets, coags.

Risk Stratification and Referral Logic

— Low risk (green): G1–G2 with A1 → routine primary care, annual labs

— Moderate (yellow): G3a A1, G1–G2 A2 → labs every 6 months

— High (orange): G3a A2, G3b A1, G1–G2 A3 → every 3–6 months, consider nephrology

— Very high (red): G3b A2+, any G4–G5 → nephrology referral, every 1–3 months

— eGFR <30 (G4 or worse) — mandatory

— UACR >300 mg/g persistently

— Rapid eGFR decline (>5 mL/min/year or >25% drop)

— Refractory hypertension on ≥4 agents

— Refractory hyperkalemia, acidosis, anemia

— Suspected glomerular disease (active sediment, hematuria with proteinuria)

— Hereditary kidney disease

— Recurrent stones

— Difficult-to-manage CKD-MBD

— AV fistula maturation takes 3–6 months — place when eGFR 15–20 if hemodialysis chosen

— Avoid PICC lines and subclavian central lines in CKD patients to preserve future access veins ("save the veins" — wear a wristband, educate patient)

Step 3 management: Patient with eGFR 22, UACR 800, on ACEi/SGLT2i — refer to nephrology, refer to transplant evaluation, educate on modalities, place AV access referral, and avoid upper-extremity venipuncture/PICCs. Conservative (non-dialytic) management is appropriate to discuss in frail/elderly patients with limited life expectancy.

KDIGO risk categories drive monitoring frequency and referral:

Nephrology referral indications:

Kidney Failure Risk Equation (KFRE): 4-variable (age, sex, eGFR, UACR) predicts 2- and 5-year risk of kidney failure. 2-year KFRE ≥10% → start preparing for renal replacement (vascular access planning, transplant referral, modality education).

Pre-emptive transplant referral: eGFR <20 — refer to transplant center; living donor evaluation has best outcomes when done before dialysis.

Vascular access planning:

Modality education: hemodialysis (in-center vs home), peritoneal dialysis, transplant, conservative care — should occur at G4.

Pharmacotherapy — Foundational Outpatient Regimen

— Indicated in all CKD with HTN or albuminuria ≥30 mg/g, especially diabetic

— Titrate to max tolerated dose; goal BP <130/80

— Expect 20–30% rise in creatinine and small K+ rise in first 2 weeks — acceptable; tolerate up to 30%. Recheck BMP at 1–2 weeks

— Hold if K+ >5.5 despite optimization, or Cr rises >30%

— Do not combine ACEi + ARB (ONTARGET — harm)

— Indicated at eGFR ≥20 with UACR ≥200 mg/g, regardless of diabetes status (DAPA-CKD, EMPA-KIDNEY)

— Reduces progression, CV death, HF hospitalization

— Expect transient eGFR dip (~4 mL/min) — continue

— Hold during acute illness/dehydration (sick day rules); risk of euglycemic DKA in T2DM

— Genital mycotic infections common, counsel on hygiene

— For T2DM + CKD with albuminuria, eGFR ≥25, K+ ≤4.8

— Reduces CV events and progression (FIDELIO-DKD, FIGARO-DKD)

— Monitor K+ at 4 weeks, then periodically

— FLOW trial: semaglutide reduces kidney and CV events in T2DM + CKD

— Add for T2DM patients especially with obesity/CVD

— Goal <120/80 SBP by SPRINT-style measurement per KDIGO 2021; pragmatically <130/80 in office

— ACEi/ARB first-line; add thiazide (or loop if eGFR <30), then dihydropyridine CCB

— Chlorthalidone effective even at eGFR 30 (CLICK trial)

Board pearl: A 30% rise in creatinine after starting ACEi is expected and acceptable — don't stop the drug. A >30% rise or K+ >5.5 warrants reassessment for renal artery stenosis or volume depletion.

Four pillars of modern CKD therapy (the "Fantastic Four" — converging with HFrEF):

1. RAAS inhibition (ACEi or ARB):

2. SGLT2 inhibitors (dapagliflozin, empagliflozin):

3. Nonsteroidal MRA — finerenone:

4. GLP-1 receptor agonists (semaglutide):

BP management:

Statin therapy: All CKD age ≥50 (not on dialysis) should receive moderate-intensity statin regardless of LDL (SHARP trial). Do not initiate de novo on dialysis.

Managing CKD Complications — Anemia, Bone-Mineral, Acidosis, Hyperkalemia

— Screen at G3 and beyond: CBC, ferritin, TSAT

— Iron repletion first: target ferritin >100 (>200 if on HD) and TSAT >20%

— Oral iron if not on HD; IV iron (sucrose, ferric carboxymaltose) if intolerant or HD

— ESAs (epoetin, darbepoetin) when Hb <10 g/dL after iron repletion; target Hb 10–11.5, do not exceed 11.5 (CHOIR, TREAT — increased stroke/CV events)

— HIF-PHIs (daprodustat): oral alternative for dialysis patients

— Always rule out other causes: B12/folate, occult bleed, hemolysis

— Monitor Ca, Phos, PTH, 25-OH vitamin D, alk phos starting G3b

— Phosphate control: dietary restriction first; phosphate binders (sevelamer, lanthanum, ferric citrate, calcium acetate) for persistent hyperphosphatemia

— Avoid calcium-based binders if hypercalcemia or vascular calcification

— Secondary hyperparathyroidism: activated vitamin D (calcitriol, paricalcitol) or calcimimetic (cinacalcet, etelcalcetide) for PTH >2× upper limit, after phos/Ca controlled

— Repair 25-OH vitamin D deficiency with cholecalciferol

— Goal serum bicarbonate ≥22 mEq/L

— Oral sodium bicarbonate 0.5–1 mEq/kg/day; correction slows CKD progression and improves nutrition

— Watch for sodium load worsening HTN/edema

— Dietary education (avoid bananas, oranges, potatoes, tomatoes, salt substitutes)

— Loop diuretic, optimize bicarbonate

— Patiromer or sodium zirconium cyclosilicate to enable continued RAAS inhibitor therapy

— Avoid SPS (Kayexalate) chronically — colonic necrosis risk

— Annual influenza, pneumococcal (PCV20 or PCV15+PPSV23), hepatitis B (higher-dose series in CKD, check titers), COVID-19, RSV (age-appropriate), shingles

CCS pearl: Don't reflexively stop the ACEi for K+ 5.4 — first restrict dietary K+, start/uptitrate loop diuretic, correct acidosis, and consider patiromer. Preserve renoprotective therapy whenever possible.

Anemia of CKD:

CKD-MBD (mineral and bone disorder):

Metabolic acidosis:

Hyperkalemia:

Vaccinations:

Special Populations — Elderly and Hepatic Considerations

— eGFR naturally declines ~1 mL/min/year after age 40; eGFR 50 in an 85-year-old without albuminuria may represent normal aging, not progressive CKD

— Use UACR and trajectory to determine pathology vs senescence

— Avoid overtreatment of HTN in frail elderly — SPRINT excluded nursing home patients; aim 130–140 SBP if frailty, falls, polypharmacy

— Higher bleeding risk on anticoagulation; reassess CHA2DS2-VASc vs HAS-BLED regularly

— Deprescribing: NSAIDs, PPIs (long-term), sulfonylureas (hypoglycemia), digoxin

— Metformin: continue if eGFR ≥30; do not initiate at eGFR <45; hold for contrast, sepsis, dehydration

— DOACs: apixaban preferred at low eGFR; avoid dabigatran <30; rivaroxaban dose-adjust

— Gabapentin/pregabalin: dose-reduce — frequent cause of altered mental status

— LMWH: enoxaparin 1 mg/kg daily (not BID) at CrCl <30; consider anti-Xa monitoring

— Antibiotics: dose-adjust aminoglycosides, vancomycin, beta-lactams, fluoroquinolones

— Opioids: avoid morphine and meperidine (active metabolites); use hydromorphone or fentanyl

— Cirrhosis can falsely lower creatinine (low muscle mass) — eGFR overestimates true function; use cystatin C-based eGFR

— Avoid NSAIDs absolutely; cautious diuretic use

— Hepatorenal syndrome is a diagnosis of exclusion in cirrhosis with AKI — different pathway, terlipressin/midodrine-octreotide-albumin

— Hold metformin and SGLT2i day of contrast; restart after 48 h if Cr stable

— IV isotonic saline pre/post contrast at eGFR <30 or AKI risk

— Statins, ACEi do not need to be held routinely

Board pearl: A nursing-home patient with eGFR 35, A1c 6.2 on glipizide having confusion at night — stop the sulfonylurea (hypoglycemia in CKD) and reassess A1c goal (7.5–8 acceptable in frail elderly).

Elderly CKD patients:

Drug dosing pearls in CKD:

Hepatic disease + CKD (hepatorenal physiology):

Pre-procedure/contrast:

Special Populations — Pregnancy, Pediatrics, Transplant

— Pre-conception counseling essential; baseline eGFR <40 or proteinuria >1 g/day → high-risk pregnancy

— Discontinue ACEi/ARB, SGLT2i, MRAs, statins, finerenone before conception

— Safe antihypertensives: labetalol, nifedipine, methyldopa, hydralazine

— Target BP ~135/85 (CHAP trial)

— Aspirin 81–162 mg daily from 12 weeks to reduce preeclampsia risk

— Watch for superimposed preeclampsia — proteinuria worsens, distinguishing from baseline disease is difficult; use uric acid, sFlt-1/PlGF ratio

— Multidisciplinary care: nephrology, MFM, transplant team if applicable

— Pregnancy after transplant: wait 1–2 years post-transplant, stable function, mycophenolate switched to azathioprine

— Most common etiologies: congenital anomalies of kidney and urinary tract (CAKUT), reflux nephropathy, FSGS

— Growth failure is a hallmark; growth hormone may be indicated

— Special eGFR equations (Schwartz, CKiD)

— Transition to adult nephrology is a high-risk handoff — structured transition programs reduce graft loss

— Lifelong immunosuppression (typically tacrolimus + mycophenolate + prednisone)

— Drug interactions: azoles, macrolides, diltiazem raise tacrolimus levels; rifampin/phenytoin lower it

— Cancer surveillance: skin (NMSC), cervical, lymphoma (PTLD)

— Infection prophylaxis: TMP-SMX for PJP (6–12 months), valganciclovir for CMV, isoniazid if latent TB

— Vaccinate before transplant; avoid live vaccines after

— Cardiovascular disease is leading cause of death with functioning graft

— Comprehensive screen including 24-hour urine, GFR measurement, imaging, psychosocial

— Donor long-term ESRD risk slightly elevated but absolute risk low

Step 3 management: Pregnant CKD patient on lisinopril 20 mg presenting for prenatal visit at 8 weeks — stop lisinopril today, start labetalol, initiate aspirin 81 mg at 12 weeks, refer MFM, monitor UACR and BP closely.

CKD in pregnancy:

Pediatric CKD:

Kidney transplant recipients:

Living donor evaluation:

Complications and Adverse Outcomes

— CKD is a CHD risk equivalent; most CKD patients die of CV disease, not ESRD

— Accelerated atherosclerosis, LVH, HF (HFpEF common), arrhythmias

— Sudden cardiac death is a leading cause in dialysis

— Manage aggressively: BP, statin, smoking cessation, antiplatelets per usual indications

— Calciphylaxis, fractures, secondary/tertiary hyperparathyroidism

— Adynamic bone disease (over-suppressed PTH)

— Uremic pericarditis (indication for urgent dialysis)

— Uremic encephalopathy

— Platelet dysfunction → bleeding (DDAVP can help acutely)

— Pruritus

— Restless legs

— Multifactorial: anorexia, acidosis, inflammation, dietary restrictions

— Marker of poor prognosis; albumin <3.5 associated with mortality

— Higher rates due to uremic immune dysfunction

— Vaccination and prompt treatment essential

— Tunneled catheters: bacteremia, endocarditis

— Drug-induced AKI superimposed on CKD

— Polypharmacy adverse effects

— Higher prevalence; screen with PHQ-9

— Depression worsens adherence and outcomes

— Requires renal replacement (hemodialysis, peritoneal dialysis, transplant) or conservative management

— Modality choice should be patient-centered

Key distinction: Indications for urgent dialysis (AEIOU): Acidosis (refractory), Electrolytes (refractory hyperkalemia), Ingestions (dialyzable toxins — methanol, ethylene glycol, lithium, salicylates), Overload (volume, refractory pulmonary edema), Uremia (pericarditis, encephalopathy, bleeding). Asymptomatic uremia alone does not mandate immediate dialysis.

Cardiovascular disease — the dominant complication:

Anemia: fatigue, reduced QoL, exacerbates LVH

CKD-MBD and vascular calcification:

Metabolic acidosis: muscle wasting, bone loss, accelerated CKD progression

Electrolyte derangements: hyperkalemia, hyperphosphatemia, hypocalcemia, hypermagnesemia (especially with Mg-containing laxatives/antacids)

Uremic complications (advanced):

Malnutrition / protein-energy wasting:

Infections:

Medication toxicities:

Cognitive impairment and depression:

Progression to ESRD:

When to Escalate Care — Urgent Referral and Inpatient Triage

— Hyperkalemia ≥6.5 or any K+ with ECG changes (peaked T waves, widened QRS, sine wave)

— Symptomatic uremia: pericarditis (friction rub, chest pain), encephalopathy, refractory nausea/vomiting

— Acute pulmonary edema in volume-overloaded CKD unresponsive to outpatient diuresis

— Hypertensive emergency (BP >180/120 with end-organ damage)

— Severe metabolic acidosis (bicarb <15 with symptoms)

— AKI on CKD with rapid creatinine rise, oliguria, or hemodynamic instability

— Active bleeding with uremic platelet dysfunction

— Sepsis in CKD patient (immunocompromised, lower threshold)

— Rapidly progressive GN (creatinine doubling over weeks)

— New nephrotic syndrome in adult

— Suspected vasculitis, anti-GBM disease, lupus nephritis flare

— Refractory hyperkalemia despite outpatient measures

— eGFR <15 not yet established with nephrology

— Hyperkalemia 5.5–6.4 without ECG changes

— New severe proteinuria

— Suspected medication-induced nephritis

— Hold ACEi/ARB/SGLT2i if hemodynamically unstable or AKI

— Avoid nephrotoxins: NSAIDs, aminoglycosides, IV contrast when possible

— Adjust drug doses for current eGFR

— Avoid PICC and subclavian lines in CKD G4–G5 (preserve vasculature)

— DVT prophylaxis with dose-adjusted heparin

— Reconcile medications carefully at discharge — restart renoprotective agents when safe

— Discharge summary must include: discharge weight, BP, K+, Cr trajectory, medication changes, and specific follow-up labs within 1–2 weeks

— Patient education on sick day rules

CCS pearl: On a CCS hospital case, after diuresing a CKD G4 patient for HF, order daily weights, daily BMP, hold ACEi until volume optimized, and schedule nephrology follow-up within 1 week of discharge — these are scored as appropriate management actions.

Send to ED / admit:

Urgent nephrology referral (within days–weeks):

Same-day phone consultation:

Hospital management priorities for CKD patient admitted for any reason:

Transitions of care:

Key Differentials — Other Causes of Reduced eGFR or Proteinuria

— Long DM duration, retinopathy, gradual proteinuria progression, bland sediment

— Most common cause of ESRD in US

— Atypical features (hematuria, rapid decline, no retinopathy) → biopsy for alternative diagnosis

— Long-standing HTN, mild proteinuria (<1 g), small kidneys, slow progression

— Disproportionately affects African Americans (APOL1 risk variants)

— IgA nephropathy: synpharyngitic hematuria, young adult, most common GN worldwide

— FSGS: nephrotic syndrome, African American, HIV, obesity-related; APOL1

— Membranous: adult nephrotic syndrome, anti-PLA2R, malignancy/HBV-associated

— Minimal change: children primarily; NSAIDs, lymphoma in adults

— MPGN: HCV with cryoglobulins, complement-mediated

— Post-infectious GN: weeks after strep, low C3

— Lupus nephritis: young woman, multisystem, low C3/C4

— ANCA vasculitis: RPGN, pulmonary-renal syndrome

— Chronic interstitial nephritis: NSAIDs, lithium, lead, aristolochic acid, sarcoidosis, Sjögren

— Reflux nephropathy: scarred kidneys from childhood VUR

— Obstructive uropathy: BPH, stones, retroperitoneal fibrosis, pelvic malignancy

— ADPKD: family history, large kidneys with cysts, hepatic cysts, berry aneurysms; tolvaptan slows progression

— Alport syndrome: hereditary nephritis, sensorineural hearing loss, lenticonus, X-linked dominant most common

— Fabry disease: alpha-galactosidase A deficiency, angiokeratomas, neuropathic pain

— Renal artery stenosis: atherosclerotic (elderly, vascular disease) or fibromuscular dysplasia (young women)

— Atheroembolic disease: after catheterization, livedo reticularis, eosinophilia

Board pearl: Bilateral enlarged kidneys with cysts in a 35-year-old with hypertension and a family history of stroke = ADPKD. Screen for intracranial aneurysms only if family history of SAH/aneurysm.

Same-category (intrinsic kidney) differentials:

Diabetic nephropathy:

Hypertensive nephrosclerosis:

Glomerulonephritides:

Tubulointerstitial disease:

Cystic and hereditary:

Vascular:

Key Differentials — Mimics and Other-Category Conditions

— AKI: rise in Cr ≥0.3 over 48 h or ≥1.5× baseline within 7 days; often reversible, normal-sized kidneys, may have specific cause

— CKD: sustained reduction ≥3 months, often small echogenic kidneys

— AKI-on-CKD: common — pre-renal from dehydration, NSAIDs, contrast, sepsis superimposed

— Baseline labs and ultrasound critical to differentiate

— Heart failure, cirrhosis, hypovolemia, NSAID effect

— Reversal with volume/HF optimization; fractional excretion of urea <35% suggests pre-renal in patients on diuretics

— BPH, pelvic mass, retroperitoneal fibrosis, neurogenic bladder

— Ultrasound: hydronephrosis

— Always check post-void residual in older men with new CKD — easy reversible cause

— Trimethoprim, cimetidine, cobicistat, dolutegravir — block tubular creatinine secretion

— High protein meal, intense exercise (rhabdo if severe)

— Body builders with high muscle mass

— Cirrhosis, sarcopenia, amputees, elderly with low muscle mass

— Use cystatin C-based eGFR for accuracy

— Orthostatic proteinuria (young adults, resolves with recumbent collection)

— Transient proteinuria from fever, exercise, CHF — recheck on 2 separate occasions

— Tamm-Horsfall protein elevation, dipstick limitations (alkaline urine false positive, primarily detects albumin)

— Glomerular: dysmorphic RBCs, RBC casts, proteinuria

— Non-glomerular: stones, malignancy (>40 with hematuria → cystoscopy + CT urogram), UTI, BPH, trauma

— Multiple myeloma (cast nephropathy, light chain deposition, amyloid)

— Amyloidosis (AL or AA)

— Sarcoidosis (granulomatous interstitial nephritis, hypercalciuria)

— Tuberculosis (sterile pyuria, papillary necrosis)

Key distinction: Trimethoprim raising creatinine by 0.3–0.5 is not AKI — it's blocked tubular secretion. True GFR is unchanged. Don't stop the antibiotic if otherwise appropriate; reassess after the course.

AKI vs CKD vs AKI-on-CKD:

Pre-renal mimics of CKD progression:

Post-renal (obstructive uropathy):

Falsely low eGFR (creatinine elevation without true GFR drop):

Falsely normal eGFR despite low GFR:

Proteinuria mimics:

Hematuria differential:

Systemic conditions causing CKD:

Secondary Prevention and Long-Term Plan

— Goal <120/80 SBP (KDIGO) with proper technique, or <130/80 pragmatically

— Home BP monitoring essential; teach proper cuff use

— ACEi/ARB titrated to max tolerated dose

— A1c 6.5–8.0% individualized; tighter for low CV risk young patients, looser for elderly/frail

— SGLT2i first for renal/CV protection; GLP-1 RA for additional benefit

— Avoid hypoglycemia (insulin clearance prolonged)

— Goal >30% reduction from baseline with ACEi/ARB + SGLT2i ± finerenone

— Persistent UACR >300 → intensify therapy

— Dietary sodium <2 g/day

— Protein 0.6–0.8 g/kg/day in non-dialysis CKD (controversial; balance with malnutrition risk)

— Plant-based diet improves outcomes; lower acid load, lower phosphate bioavailability

— Avoid salt substitutes (KCl) at G3b and beyond

— Smoking cessation — accelerates CKD and CV disease

— Weight loss if BMI >30; bariatric surgery may slow progression

— Moderate exercise; aerobic + resistance training

— Avoid chronic NSAIDs absolutely

— Limit PPIs to indicated duration

— Annual medication reconciliation

— Avoid IV contrast when possible; use lowest effective dose with hydration

— Statin for age ≥50 CKD

— Aspirin for established CVD (not primary prevention routinely)

— Smoking cessation, BP, glucose, lipids

— Standard age-appropriate (colon, breast, cervical, lung if eligible)

— Hematuria workup in adults >40

— Discuss at G4 — modality preferences, conservative care, code status, healthcare proxy

— Especially important for elderly/frail patients where dialysis may not extend or improve life

Step 3 management: A 68-year-old with T2DM, eGFR 38, UACR 450 on lisinopril, atorvastatin — add empagliflozin, consider finerenone (if K+ ≤4.8), counsel on sodium <2 g/day, refer to dietitian, schedule labs in 3 months.

Slowing progression — the core mission:

Blood pressure:

Glycemic control (diabetic CKD):

Albuminuria reduction:

Lifestyle:

Medication stewardship:

Cardiovascular prevention:

Cancer screening:

Advance care planning:

Follow-Up, Monitoring, and Counseling

— Low risk: eGFR + UACR annually

— Moderate risk: every 6 months

— High risk: every 3–6 months

— Very high risk (G4–G5): every 1–3 months with nephrology

— Weight, BP (with home BP log review)

— BMP (eGFR, K+, bicarb), UACR

— Medication review — confirm renoprotective agents at max tolerated dose

— Symptom review — fatigue, edema, dyspnea, restless legs, pruritus, GI

— Adherence and lifestyle reinforcement

— CBC, ferritin, TSAT (anemia)

— Calcium, phosphate, PTH, 25-OH vitamin D (G3b+)

— Lipid panel

— A1c (diabetics)

— Hepatitis B surface antibody titer (vaccinate if <10)

— BMP at 1–2 weeks to assess K+ and Cr

— Adjust as needed

— Sick day rules: hold ACEi/ARB, diuretics, SGLT2i, metformin, NSAIDs if acutely ill with vomiting/diarrhea/poor PO; resume when well

— Recognize signs of volume overload (weight gain >3 lb in 2 days, swelling, dyspnea)

— Recognize hyperkalemia symptoms (weakness, palpitations) — go to ED

— Hydration without overload — generally adequate water intake; no need to "flush kidneys"

— Medication list to carry to all providers

— Modality education sessions

— Vascular access referral when eGFR 15–20 if HD chosen

— Transplant referral at eGFR <20

— Hepatitis B vaccination series (higher dose)

— Psychosocial support, social work

— Encouraged for CKD with CVD; structured programs improve QoL

— Screen for depression annually with PHQ-9; CKD-related depression is common and treatable

Board pearl: A patient with CKD G3b who reports starting OTC ibuprofen for "arthritis" warrants immediate counseling, switch to topical NSAID/acetaminophen/duloxetine, and BMP in 1 week to assess for AKI.

Monitoring frequency by KDIGO risk:

Each CKD visit should include:

Annually (or more often as indicated):

After medication changes (ACEi/ARB/diuretic/SGLT2i/MRA):

Patient counseling pillars:

Dialysis/transplant preparation (G4 onward):

Cardiac rehab/exercise:

Mental health:

Ethical, Legal, and Patient Safety Considerations

— Dialysis is not always the right answer, especially in frail elderly with multiple comorbidities

— Conservative kidney management (CKM) is a legitimate path — focuses on symptom control, QoL, advance care planning, without dialysis

— Studies show octogenarians with high comorbidity may not gain survival advantage from dialysis and may lose functional independence

— Provide balanced information about dialysis (burden, complications, survival, QoL) vs CKM; document the conversation

— Vascular access placement, transplant evaluation, kidney biopsy all require informed consent including bleeding/infection/failure risks

— Living donor consent: must be free of coercion; psychosocial evaluation; donor advocate independent of recipient's team

— Discuss code status, healthcare proxy, preferences at G4

— POLST/MOLST forms portable across care settings; particularly important for dialysis patients with high mortality

— "Time-limited trial" of dialysis is ethically appropriate — agree on goals, reassess at defined intervals

— End-stage renal disease registry — providers must report to CMS via CMS-2728 form at dialysis initiation

— Living donor outcomes reported nationally

— Suspected elder abuse in dialysis patients (missed sessions, malnutrition, fearful demeanor) — mandatory reporting

— Hospital discharge: medication reconciliation errors common (restarting nephrotoxins, wrong doses)

— CKD patients have high 30-day readmission rates — schedule follow-up within 7–14 days

— Pediatric-to-adult transition: structured programs reduce graft loss and adherence failure

— Snowbird/seasonal patients on dialysis need coordinated transient HD scheduling

— 2021 race-free eGFR equation removed Black race coefficient — improves equity in transplant listing and drug dosing

— Living donor outcomes equitable counseling required

— Insurance coverage for ESRD via Medicare regardless of age after 90 days of dialysis or with transplant

— Medication errors (heparin dosing), access complications, water quality, dialyzer reuse standards

Step 3 management: An 88-year-old with CKD G5, dementia, and limited functional status — convene family meeting with palliative care, present CKM as a valid option, document goals of care, and avoid coercive framing toward dialysis.

Shared decision-making for dialysis initiation:

Informed consent edge cases:

Advance directives:

Mandatory reporting and public health:

Transitions of care — high-risk handoffs:

Health equity considerations:

Patient safety in dialysis:

High-Yield Associations and Rapid-Fire Facts

— 2021 CKD-EPI is the standard eGFR equation (race-free)

— eGFR <60 for ≥3 months = CKD

— UACR ≥30 mg/g = albuminuria

— KFRE 2-yr ≥10% = prepare for RRT

— 30% Cr rise after ACEi is acceptable

— Hb target 10–11.5 on ESAs

— Bicarb goal ≥22

— BP <120/80 (KDIGO) or <130/80 pragmatic

— Protein 0.6–0.8 g/kg/day non-dialysis

— Sodium <2 g/day

— Diabetic nephropathy + retinopathy — almost universal in T1DM

— Nephrotic syndrome adult + anti-PLA2R = membranous (often primary)

— Hematuria + sensorineural hearing loss = Alport

— Flank pain + hematuria + family history of SAH = ADPKD

— Recurrent sinusitis + hemoptysis + RPGN = GPA (PR3-ANCA)

— HCV + MPGN + cryoglobulins = classic triad

— Bone pain + anemia + AKI + hypercalcemia = multiple myeloma

— Livedo + eosinophilia + AKI post-cath = atheroembolic

— Flash pulmonary edema + asymmetric kidneys = bilateral RAS

— AKI after ACEi = bilateral RAS or volume depletion

— SGLT2i works down to eGFR 20; continue on transplant

— Finerenone distinct from spironolactone — less hyperkalemia, indicated specifically in DKD

— Tolvaptan for ADPKD progression

— Patiromer/SZC preserve RAAS therapy in hyperkalemia

— Apixaban preferred DOAC in CKD

— Avoid gadolinium at eGFR <30 (older agents)

— Refer at eGFR <20

— Pre-emptive living donor = best outcomes

— Avoid live vaccines post-transplant

— TMP-SMX for PJP prophylaxis

Board pearl: A landmark "buzzword to diagnosis" map plus knowing the modern pillars of therapy (ACEi/ARB + SGLT2i + finerenone + GLP-1 RA + statin) will answer most Step 3 CKD questions.

Equations and numbers:

Disease-defining associations:

Drug pearls:

CKD-MBD ladder: phosphate restriction → binders → vitamin D analog → calcimimetic → parathyroidectomy (refractory)

AEIOU for urgent dialysis: Acidosis, Electrolytes, Ingestions, Overload, Uremia

Transplant rules:

Board Question Stem Patterns

— "A 58-year-old with HTN has Cr 1.4, eGFR 52 on routine labs..." → Repeat in 3 months with UACR before labeling CKD. Don't anchor on a single value.

— Diabetic patient on lisinopril and metformin with eGFR 45, UACR 300 → Add SGLT2 inhibitor (and consider finerenone). High-yield trial-driven answer.

— Cr rises from 1.1 to 1.4 (27%) two weeks after starting lisinopril → Continue lisinopril, recheck in 2 weeks. Rises >30% or K+ >5.5 → reassess.

— K+ 5.4 on ACEi/SGLT2i → Dietary counseling, loop diuretic, correct acidosis, ± patiromer to maintain therapy. Don't immediately stop ACEi.

— Hematuria + RBC casts + proteinuria + AKI → Urgent nephrology + serologic workup (ANA, ANCA, anti-GBM, complements, hepatitis) + biopsy. Not "watchful waiting."

— On ACEi at 8 weeks → Stop ACEi today, start labetalol/nifedipine, ASA 81 mg at 12 weeks, MFM referral.

— CKD G4 on gabapentin for neuropathy with new altered mental status → Reduce or stop gabapentin (renally cleared, accumulates).

— Flash pulmonary edema, AKI after ACEi, asymmetric kidneys → Renal artery duplex/MRA, consider revascularization in select cases (CORAL was negative for routine stenting).

— Cr rises 0.4 on TMP-SMX, otherwise stable → Pseudo-AKI from blocked tubular secretion; complete course.

— Frail 87-year-old G5 → Discuss conservative management, don't reflexively dialyze.

— G4 patient with eGFR 18 → AVF referral now (matures over months).

— Order eGFR, UACR, BMP, CBC, urinalysis, US, A1c, lipids, PTH/vit D/phos at G3b → start ACEi + SGLT2i + statin → recheck in 2 weeks then 3 months → refer nephrology at eGFR <30.

Key distinction: Step 3 vignettes reward the next best step in outpatient management — usually adding a guideline-directed drug, scheduling appropriate follow-up labs, or referring at the right threshold — not invasive heroics.

Pattern 1 — The Incidental Finding:

Pattern 2 — The "Add Renoprotection" Stem:

Pattern 3 — The ACEi Reaction:

Pattern 4 — The Hyperkalemia + ACEi Dilemma:

Pattern 5 — The Active Sediment:

Pattern 6 — The Pregnant CKD Patient:

Pattern 7 — The Elderly with Confusion:

Pattern 8 — The Bilateral RAS:

Pattern 9 — The Trimethoprim Mimic:

Pattern 10 — The Dialysis Decision:

Pattern 11 — The Access Question:

Pattern 12 — The CCS Outpatient Case:

One-Line Recap

CKD is defined by eGFR <60 or albuminuria persisting >3 months, staged by G (1–5) and A (1–3) categories, and managed in the outpatient setting with aggressive BP control, RAAS inhibition, SGLT2 inhibitors, finerenone in diabetic kidney disease, lifestyle modification, complication surveillance (anemia, CKD-MBD, acidosis, hyperkalemia), and timely nephrology/transplant/access referral as patients approach kidney failure.

— Confirm chronicity over ≥3 months; use 2021 race-free CKD-EPI; combine eGFR with UACR for KDIGO risk staging

— Renal ultrasound on every new CKD; urinalysis with microscopy distinguishes glomerular from non-glomerular

— Cystatin C eGFR resolves ambiguity at G3a A1 and in patients with abnormal muscle mass

— ACEi or ARB titrated to max tolerated dose

— SGLT2 inhibitor (down to eGFR 20) for proteinuric CKD with or without diabetes

— Finerenone for diabetic CKD with K+ ≤4.8

— GLP-1 RA for T2DM + CKD (FLOW trial)

— Statin for CKD age ≥50 not on dialysis

— Anemia: iron first, ESA to Hb 10–11.5

— CKD-MBD: phosphate → binders → vitamin D → calcimimetic ladder

— Acidosis: bicarb to ≥22 with oral NaHCO3

— Hyperkalemia: diet, diuretic, patiromer/SZC before stopping ACEi

— Vaccinate (flu, pneumococcal, hep B high-dose, COVID, shingles)

— Nephrology at eGFR <30, rapid decline, UACR >300, or refractory complications

— Transplant evaluation at eGFR <20 (pre-emptive living donor best)

— AV access referral at eGFR 15–20 if HD planned

— Conservative kidney management is a legitimate, patient-centered option for frail elderly — present without coercion

Board pearl: Master the 2021 race-free equation, KDIGO heat map, the four-pillar regimen, expected ACEi creatinine bump (≤30%), urgent dialysis indications (AEIOU), and the shared decision-making framework for dialysis vs CKM — these themes account for the vast majority of Step 3 CKD questions.

Diagnostic essentials:

Therapeutic pillars (the modern quartet plus a statin):

Complication management:

Referral and transitions: