Renal & Urinary

CKD: anemia, mineral bone disease, and complication management

Clinical Overview and When to Suspect CKD Complications

— Anemia (EPO deficiency, iron-restricted erythropoiesis) — usually emerges G3b–G4

— CKD–mineral and bone disorder (CKD-MBD): ↑phosphate, ↓1,25-vitamin D, ↑PTH, ↑FGF-23, vascular calcification, renal osteodystrophy

— Metabolic acidosis (non-anion gap initially, then mixed) — drives bone/muscle catabolism

— Hyperkalemia, volume overload/HTN, uremic symptoms, dyslipidemia, accelerated CV disease (leading cause of death in CKD)

— Fatigue, exertional dyspnea, pallor → check Hgb, iron studies

— Bone pain, fractures, pruritus, calciphylaxis lesions → CKD-MBD panel

— Muscle wasting, hyperventilation, Kussmaul → serum bicarbonate

— Worsening HTN, edema, weight gain → volume status reassessment

Step 3 management: At every CKD visit (every 3–6 months for G3, every 1–3 months for G4–G5), reflexively order CBC, BMP, phosphate, calcium, PTH, 25-OH vitamin D, bicarbonate, and UACR. Trending is more important than single values — the boards reward recognizing rate of decline and proactive workup before symptoms.

Board pearl: The #1 cause of death in CKD is cardiovascular, not uremia or dialysis complications — every management decision should be filtered through CV risk reduction.

Chronic kidney disease (CKD) is defined by ≥3 months of either GFR <60 mL/min/1.73 m² OR markers of kidney damage (albuminuria ≥30 mg/g, abnormal sediment, imaging, biopsy, electrolyte derangements from tubular disorders).

Staging combines G stage (G1 ≥90, G2 60–89, G3a 45–59, G3b 30–44, G4 15–29, G5 <15) with A stage (A1 <30, A2 30–300, A3 >300 mg/g albumin:creatinine). Risk of complications rises steeply at G3b and beyond.

Major complications cluster predictably and are the bread-and-butter of Step 3 longitudinal management:

When to suspect a complication is emerging:

Presentation Patterns and Key History

— Gradual fatigue, decreased exercise tolerance, dyspnea on exertion, restless legs, cold intolerance

— Worsening angina or CHF symptoms in patients with prior CV disease

— Typically normocytic, normochromic; microcytosis suggests concurrent iron deficiency or thalassemia

— Bone pain (often hips, low back), proximal myopathy, fragility fractures

— Pruritus (often nocturnal, generalized) — driven by hyperphosphatemia and uremic toxins

— Calciphylaxis: painful, violaceous, retiform skin lesions progressing to necrotic ulcers, classically on thighs/abdomen in dialysis patients

— Vascular/valvular calcification → accelerated atherosclerosis, aortic stenosis

— Etiology of CKD (diabetic nephropathy, hypertensive nephrosclerosis, glomerulonephritis, polycystic) — affects progression rate

— Nephrotoxin exposure: NSAIDs, PPIs (chronic), IV contrast, aminoglycosides, herbal supplements

— Prior transplant or dialysis access history

— Diet: protein load, phosphate sources (processed foods, colas), potassium-rich foods, sodium

— Adherence to phosphate binders, ESAs, antihypertensives

Board pearl: A CKD patient on NSAIDs for "arthritis" with worsening GFR and HTN — stop the NSAID first before adding antihypertensives. Boards love this stem.

Key distinction: Pruritus + violaceous skin lesions in a dialysis patient = calciphylaxis (calcific uremic arteriolopathy) — high mortality, urgent nephrology and wound care, sodium thiosulfate is the treatment.

CKD complications often present insidiously; Step 3 stems frequently embed clues in medication lists, comorbidities, and longitudinal labs rather than acute symptoms.

Anemia of CKD:

CKD-MBD / renal osteodystrophy:

Metabolic acidosis: nonspecific fatigue, anorexia, muscle wasting; may worsen hyperkalemia

Volume/HTN: peripheral edema, orthopnea, PND, resistant hypertension despite 3+ agents

Uremic syndrome (usually G5): nausea, anorexia, metallic taste, encephalopathy, pericarditis, platelet dysfunction with bleeding, asterixis

Key history elements:

Physical Exam Findings and Volume Assessment

— Hypervolemia: elevated JVP (>8 cm H₂O), bibasilar crackles, S3 gallop, hepatojugular reflux, pitting edema, ascites in advanced cases

— Euvolemia target for most CKD outpatients; dialysis patients target "dry weight"

— Orthostatic vitals: useful in dialysis patients with intradialytic hypotension or overaggressive ultrafiltration

— Bony tenderness, kyphosis from vertebral fractures, proximal muscle weakness

— Calciphylaxis lesions: painful, indurated, violaceous plaques with central necrosis on adipose-rich areas

— Uremic frost: rare, late finding — crystallized urea on skin

— Tertiary hyperparathyroidism → palpable parathyroid masses (uncommon)

— Asterixis, myoclonus, decreased mentation

— Pericardial friction rub → uremic pericarditis (urgent dialysis indication)

— Ecchymoses, mucosal bleeding from platelet dysfunction

— AVF/AVG: palpate thrill, auscultate bruit — loss of either suggests thrombosis (urgent vascular surgery)

— Inspect for aneurysm, infection, steal syndrome (cold/pale distal limb)

— Catheter sites for exit-site infection, tunnel tenderness

CCS pearl: In a CKD patient admitted with dyspnea, the first orders should include vitals, weight (compare to dry weight if dialysis), pulse oximetry, JVP assessment, chest exam, and an ECG/CXR — these guide whether you're treating volume overload (diuretics or urgent HD) vs. anemia-driven CHF vs. uremic pericarditis (effusion on echo, urgent HD).

Board pearl: A pericardial rub in a CKD patient is a dialysis indication, not a steroid/NSAID indication.

Physical exam in CKD complication assessment is hierarchical — volume status first, then organ-specific findings.

Volume assessment (drives diuretic vs. fluid decisions, dialysis prescription adjustments):

Anemia signs: conjunctival/palmar pallor, tachycardia, flow murmur, koilonychia if iron-deficient

CKD-MBD/bone exam:

Uremic findings (G5/late G4):

Vascular access exam (hemodialysis patients):

Diagnostic Workup — Initial Labs and Studies

— CBC with indices: confirm normocytic, normochromic

— Reticulocyte count: inappropriately low for degree of anemia

— Iron studies: ferritin, transferrin saturation (TSAT), serum iron, TIBC

— Vitamin B12, folate to exclude megaloblastic

— Peripheral smear: schistocytes (TMA), spherocytes, hypersegmented neutrophils

— Stool occult blood (rule out GI loss, common in uremic platelet dysfunction)

— Consider hemolysis labs (LDH, haptoglobin, indirect bili) if smear suspicious

— Absolute deficiency: ferritin <100 ng/mL (non-dialysis) or <200 (dialysis), TSAT <20%

— Functional: ferritin adequate but TSAT <20% — iron sequestered by hepcidin

— Serum calcium, phosphate, intact PTH, 25-OH vitamin D, alkaline phosphatase

— Bicarbonate (target ≥22 mEq/L)

— Renal ultrasound at initial CKD diagnosis: assess size (small/echogenic = chronic), exclude obstruction, evaluate for cysts/polycystic

— Bone imaging usually not needed unless fracture or atypical pain

— ECG, lipid panel, HbA1c if diabetic

— Echo at CKD G4 onset and before dialysis initiation — assess LV mass, EF, valvular calcification

Step 3 management: Don't transfuse a stable CKD patient just because Hgb is 9 — work up iron status first, replete iron, then consider ESA. Transfusions sensitize for future transplant (anti-HLA antibodies) and should be minimized in transplant candidates.

Board pearl: Target ferritin >100 and TSAT >20% before starting an ESA — giving EPO without adequate iron stores wastes drug and worsens hypertension.

Anemia of CKD workup (initiate when Hgb <10 g/dL in CKD, or symptomatic):

Iron-deficient vs. functional iron deficiency:

CKD-MBD panel (every 6–12 months in G3, every 3–6 months in G4, every 1–3 months in G5/dialysis):

Imaging:

Cardiovascular baseline:

Diagnostic Workup — Advanced and Confirmatory Studies

— If Hgb fails to respond to adequate iron + ESA, consider:

— Hyperparathyroidism (marrow fibrosis from severe secondary HPT) — check PTH

— Aluminum toxicity (historical, rare now)

— Inflammation/infection (CRP, occult abscess, vascular access infection)

— Hemolysis (smear, LDH, haptoglobin) — especially in dialysis with copper/chloramine contamination

— Pure red cell aplasia from anti-EPO antibodies (rare, with SC epoetin) — reticulocyte count near zero, bone marrow shows absent erythroid precursors

— Malignancy, MDS, hemoglobinopathy

— DEXA scan is now recommended in CKD G3–G5 if results would change management (KDIGO 2017 update)

— Bone biopsy with tetracycline labeling remains gold standard for distinguishing adynamic bone disease (low turnover, low PTH, often over-suppressed) from osteitis fibrosa cystica (high turnover, high PTH)

— Imaging for vascular calcification: lateral abdominal X-ray (aortic calcification), echo for valvular calcification

— Clinical diagnosis, but skin biopsy can confirm (small-vessel calcification, intimal hyperplasia, thrombosis) — biopsy carries risk of non-healing wound

Key distinction: Adynamic bone disease (over-suppressed PTH, often from excessive calcium-based binders or calcimimetics) presents with low PTH, low ALP, low turnover — fractures and vascular calcification — treatment is to reduce binders/calcimimetics and allow PTH to rise toward 2–9× upper limit of normal in dialysis patients.

Board pearl: PTH target in dialysis = 2–9× ULN (roughly 130–600 pg/mL) — not "normal range." Over-suppression causes adynamic bone disease.

Refractory or atypical anemia workup:

CKD-MBD advanced workup:

Calciphylaxis:

Acidosis workup: if anion gap elevated, evaluate for concurrent lactic acidosis, ketoacidosis, toxins

Hyperkalemia evaluation: ECG, repeat K+, review medications (ACEi/ARB, spironolactone, NSAIDs, trimethoprim, heparin)

Risk Stratification and Management Logic

— Refer to nephrology: GFR <30 (G4–G5), rapid GFR decline (>5 mL/min/yr), persistent UACR >300, refractory HTN/hyperkalemia, suspected hereditary kidney disease, age <18

— Step 1: Confirm anemia is from CKD (exclude blood loss, hemolysis, B12/folate, marrow disease)

— Step 2: Replete iron — oral iron (ferrous sulfate 325 mg) for non-dialysis CKD; IV iron (iron sucrose, ferric gluconate, ferric carboxymaltose) for dialysis or oral failure

— Step 3: Once iron adequate (ferritin >100 non-HD or >200 HD, TSAT >20%) and Hgb still <10, initiate ESA

— Target Hgb 10–11 g/dL — do NOT exceed 11.5 (TREAT, CHOIR, CREATE trials: higher targets → ↑stroke, thromboembolism, mortality)

— Step 1: Control phosphate first (dietary restriction + binders if needed)

— Step 2: Address vitamin D deficiency (25-OH <30) with cholecalciferol/ergocalciferol

— Step 3: If PTH persistently rising despite above, add active vitamin D analogs (calcitriol, paricalcitol) or calcimimetics (cinacalcet, etelcalcetide)

— Step 4: Parathyroidectomy for severe refractory tertiary HPT

Step 3 management: Phosphate target in dialysis is "toward normal" — strict <5.5 thresholds are no longer mandated, but persistent levels >5.5 warrant intensification. Calcium should be kept in normal range, avoiding hypercalcemia from binders or vitamin D analogs.

Board pearl: Hgb target in CKD = 10–11 g/dL. Going to 13 increases stroke and death — a classic Step 3 trap.

KDIGO heat map stratifies CKD risk by combining G and A stages into low, moderate, high, very high risk categories — drives nephrology referral and monitoring frequency.

Anemia management logic:

CKD-MBD management hierarchy (KDIGO):

Pharmacotherapy — First-Line Regimens

— Epoetin alfa (3×/week SC or IV) or darbepoetin alfa (weekly to monthly, longer half-life)

— Start when Hgb <10 with adequate iron; titrate to Hgb 10–11

— Black-box warning: ↑mortality, thromboembolism, stroke, tumor progression at higher Hgb targets

— Side effects: hypertension (most common — check BP before each dose), seizures, vascular access thrombosis

— Oral: ferrous sulfate, gluconate, fumarate — limited absorption in CKD (hepcidin); alternate-day dosing improves absorption

— IV: iron sucrose (200 mg doses), ferric gluconate, ferric carboxymaltose (large single dose, watch for hypophosphatemia), ferumoxytol (avoid in iron overload)

— Calcium-based: calcium acetate, calcium carbonate — risk of hypercalcemia, vascular calcification; limit to 1500 mg elemental Ca/day

— Non-calcium: sevelamer (also lowers LDL), lanthanum carbonate, ferric citrate (also provides iron), sucroferric oxyhydroxide

— Preferred non-calcium binders in patients with hypercalcemia, vascular calcification, adynamic bone disease

— Nutritional: cholecalciferol (D3), ergocalciferol (D2) — for 25-OH D <30

— Active analogs: calcitriol, paricalcitol, doxercalciferol — for elevated PTH despite repletion

Board pearl: Sevelamer is preferred when calcium load is a concern; ferric citrate doubles as a binder and iron source — useful in iron-deficient HD patients.

Erythropoiesis-stimulating agents (ESAs):

HIF prolyl-hydroxylase inhibitors (newer class): daprodustat — oral, stabilizes HIF, increases endogenous EPO and improves iron mobilization. FDA-approved for dialysis-dependent CKD anemia.

Iron:

Phosphate binders (taken with meals):

Vitamin D:

Calcimimetics: cinacalcet (oral), etelcalcetide (IV, HD only) — lower PTH by sensitizing CaSR; watch for hypocalcemia

Acidosis: sodium bicarbonate 650–1300 mg BID-TID to keep HCO₃ ≥22

Expanded Pharmacology — Advanced Therapies and Procedures

— IV sodium thiosulfate 25 g 3×/week post-HD — chelates calcium, antioxidant

— Stop warfarin (vitamin K antagonist worsens calcification) → switch to apixaban or other DOAC if anticoagulation needed

— Stop calcium-based binders and active vitamin D; switch to non-calcium binders

— Lower phosphate aggressively; consider cinacalcet

— Wound care, pain control, avoid debridement of stable lesions

— PTH persistently >800 pg/mL despite max medical therapy

— Symptomatic hypercalcemia, calciphylaxis, severe pruritus, fractures, or progressive vascular calcification

— Subtotal or total with autotransplant; watch for hungry bone syndrome post-op (severe hypocalcemia, hypophosphatemia, hypomagnesemia — replete aggressively)

— Acidosis refractory, Electrolytes (hyperkalemia refractory), Ingestion (dialyzable toxin), Overload refractory, Uremic symptoms (pericarditis, encephalopathy, bleeding)

— Chronic: typically initiate when GFR 5–10 with symptoms; don't initiate based solely on GFR number (IDEAL trial)

— SGLT2 inhibitors (empagliflozin, dapagliflozin) — for diabetic and non-diabetic CKD with albuminuria (DAPA-CKD, EMPA-KIDNEY)

— Finerenone — nonsteroidal MRA, reduces CV/renal events in diabetic CKD with albuminuria

— ACEi/ARB at max tolerated dose if UACR >300 (or >30 with diabetes)

CCS pearl: When you place an order in a CKD patient, always check the GFR-based dosing — metformin (avoid <30), gabapentin (reduce dose), enoxaparin (reduce or switch to UFH <30), gadolinium contrast (avoid <30 due to NSF risk).

Calciphylaxis treatment (high mortality, multidisciplinary):

Parathyroidectomy indications in tertiary HPT:

Dialysis initiation indications (AEIOU mnemonic for acute, plus chronic):

Transplant referral: GFR <20, preferably pre-emptive (before dialysis) — best outcomes

Vascular access planning: refer for AVF creation when GFR ~15–20 to allow maturation (6+ weeks); avoid PICC lines and subclavian catheters in CKD (preserve veins)

Newer agents reducing CKD progression:

Special Populations — Elderly and Multimorbid CKD

— Creatinine-based eGFR (CKD-EPI) less accurate at extremes of muscle mass — sarcopenic elderly may have "normal" creatinine with truly low GFR

— Consider cystatin C or measured GFR (iothalamate, iohexol) when decisions hinge on GFR (chemotherapy dosing, transplant eligibility)

— 2021 CKD-EPI equation removed race coefficient — slightly lower eGFR in Black patients vs. prior equation

— Review all meds at every visit; renal-dose anything cleared by kidney

— Avoid: NSAIDs, nephrotoxic abx without indication, gadolinium <30, metformin <30

— Cautions: digoxin (reduce dose, narrow window), opioids (morphine and codeine accumulate — use hydromorphone or fentanyl), gabapentin/pregabalin (sedation, falls)

— Higher risk of thromboembolism from ESAs — keep Hgb target on lower end (10)

— Screen for occult GI losses; iron-deficiency anemia in elderly always warrants colonoscopy/EGD evaluation independent of CKD

— Elderly have overlap of osteoporosis + renal osteodystrophy — bisphosphonates are contraindicated when GFR <30 (or use cautiously); denosumab can be used but watch for severe hypocalcemia in CKD

— DEXA may underestimate fracture risk in CKD due to abnormal mineralization

— Conservative (non-dialytic) management is a legitimate option for frail elderly with limited life expectancy — symptom-focused, ESA, diuretics, dietary management

— Studies suggest dialysis may not extend life or improve QoL in frail >80 with multiple comorbidities

Step 3 management: When considering dialysis initiation in elderly, have an explicit goals-of-care conversation documenting prognosis, expected functional trajectory, and option of medical management without dialysis — this is highly testable.

Board pearl: Bisphosphonates contraindicated when GFR <30–35; use denosumab with caution and replete vitamin D/calcium first to avoid severe hypocalcemia.

Elderly CKD is the modal Step 3 patient — most CKD in the US is in age >65.

GFR estimation caveats:

Polypharmacy and drug dosing:

Anemia in elderly CKD:

Bone disease:

Frailty and goals of care:

Special Populations — Pregnancy, Pediatrics, Transplant

— CKD increases risk of preeclampsia, IUGR, preterm delivery, and accelerated maternal CKD progression

— Pre-pregnancy counseling: GFR <60 or UACR >300 warrants high-risk maternal-fetal medicine co-management

— Discontinue ACEi/ARB and renin inhibitors — teratogenic (oligohydramnios, renal dysgenesis, skull hypoplasia); switch to labetalol, nifedipine, methyldopa, or hydralazine

— Stop SGLT2 inhibitors, finerenone, statins, mycophenolate in pregnancy

— ESAs are safe in pregnancy; iron supplementation continues; vitamin D supplementation continues

— Hgb target may be slightly higher (~11) given physiologic plasma expansion

— Major causes: congenital anomalies of kidney/urinary tract (CAKUT), hereditary disease (Alport, ARPKD)

— Growth failure is a key complication — recombinant growth hormone indicated for growth failure in CKD

— Anemia and CKD-MBD targets adjusted for age; nutrition critical

— Anemia post-transplant: often from immunosuppressants (MMF, azathioprine, sirolimus), CMV, parvovirus B19, ACEi/ARB

— Post-transplant erythrocytosis (Hgb >17) — treat with ACEi or phlebotomy

— Bone disease post-transplant: persistent HPT, steroid-induced osteoporosis, low turnover bone — DEXA monitoring, bisphosphonates if GFR allows

— New-onset diabetes after transplant (NODAT) — from tacrolimus, steroids

Key distinction: ACEi/ARB are renoprotective in CKD but teratogenic in pregnancy — the boards love this switch. In a woman of reproductive age with CKD, document contraception or switch antihypertensives proactively when pregnancy is planned.

Board pearl: Parvovirus B19 causes pure red cell aplasia in transplant recipients — treat with IVIG and reduce immunosuppression.

Pregnancy and CKD:

Pediatric CKD:

Kidney transplant recipients:

Dialysis pregnancy: intensified HD (>36 hr/wk) improves outcomes; pregnancy is possible but high-risk

Complications and Adverse Outcomes

— Worsening LVH (already prevalent in CKD), CHF exacerbation, increased mortality

— Fatigue, cognitive impairment, reduced quality of life

— Increased need for transfusion → HLA sensitization → transplant candidacy compromised

— Stroke, MI, VTE, vascular access thrombosis, hypertensive crisis, increased mortality (TREAT, CHOIR)

— Tumor progression in cancer patients

— Vascular and valvular calcification → accelerated CAD, aortic stenosis, peripheral arterial disease

— Calciphylaxis: mortality >50% at 1 year

— Renal osteodystrophy: fractures, deformity, bone pain, proximal myopathy

— Tertiary HPT: autonomous PTH secretion, hypercalcemia

— Pruritus: severely impaired QoL

— Severe hypocalcemia, hypophosphatemia, hypomagnesemia — bone rapidly remineralizes

— Tetany, seizures, QT prolongation, arrhythmia

— Treat with IV calcium gluconate infusion, oral calcium, calcitriol; replete Mg and phosphate

Key distinction: Uremic pericarditis (pre-dialysis or under-dialyzed) → ECG often without diffuse ST elevation seen in viral pericarditis (uremia doesn't inflame the epicardium). Treatment is intensified dialysis, NOT NSAIDs/steroids.

Board pearl: DDAVP (0.3 mcg/kg IV) acutely improves uremic bleeding (e.g., before procedure) by releasing vWF; also consider cryoprecipitate and conjugated estrogens for longer-term effect.

Untreated anemia:

Over-treated anemia (Hgb >12–13):

Hyperphosphatemia/CKD-MBD complications:

Adynamic bone disease: low turnover, fractures, vascular calcification — paradoxically from over-treatment (excess calcium binders, calcitriol, calcimimetics over-suppressing PTH)

Hungry bone syndrome post-parathyroidectomy:

Iron overload from chronic IV iron: hepatic, cardiac iron deposition (rare but watch ferritin >500–800)

ESA hypertension: 20–30% of patients; up-titrate antihypertensives or reduce ESA dose

Uremic complications: pericarditis (effusion, tamponade), encephalopathy, platelet dysfunction with bleeding, peripheral neuropathy, malnutrition (protein-energy wasting)

When to Escalate Care — Consults, Hospitalization, ICU

— GFR <30 (G4–G5)

— Rapid progression (>5 mL/min/year)

— Persistent UACR >300 mg/g, refractory hyperkalemia or acidosis, refractory HTN

— Unclear etiology, suspected glomerular disease, hereditary kidney disease

— Anemia, CKD-MBD not responding to first-line management

— AEIOU: severe acidosis (pH <7.1), refractory hyperkalemia (>6.5 with ECG changes), ingestion/toxin, fluid overload with pulmonary edema not responding to diuresis, uremic emergencies (pericarditis, encephalopathy, bleeding)

— Calciphylaxis with new lesions or systemic illness

— Hemodynamic instability requiring CRRT

— Hyperkalemia with arrhythmia

— Pulmonary edema requiring BiPAP/intubation

— Massive GI bleed in uremic patient

— Severe hypocalcemia with tetany/seizure (e.g., hungry bone syndrome post-parathyroidectomy)

— Parathyroidectomy for refractory tertiary HPT

— Vascular surgery for AVF/AVG creation, access thrombosis or aneurysm, calciphylaxis wound care

— Transplant surgery for evaluation

CCS pearl: A CKD G5 patient with hyperkalemia (K+ 7.2) and peaked T waves — immediate orders: IV calcium gluconate (cardiac membrane stabilization), insulin + D50, albuterol nebulizer (intracellular shift), loop diuretic if making urine, patiromer or sodium zirconium for sustained removal, call nephrology for urgent HD. Sodium polystyrene (Kayexalate) is falling out of favor due to colonic necrosis risk and slow onset.

Board pearl: Don't forget IV calcium first in hyperkalemia with ECG changes — it doesn't lower K+ but prevents arrhythmic death while you set up shifting and removal.

Nephrology referral (outpatient, urgent):

Urgent dialysis evaluation / hospitalization:

ICU triage:

Surgical consults:

Cardiology: any new heart failure, ACS workup (troponin baseline often elevated in CKD — trend it), pre-transplant CV clearance

Palliative care: frail elderly weighing conservative management, intractable symptoms, ESKD with limited prognosis

Key Differentials — Other Renal Causes of Anemia and Bone Disease

— Iron deficiency anemia alone: microcytic, ferritin <30, TSAT <20 — work up GI losses

— Anemia of chronic inflammation/disease: elevated ferritin (acute-phase), low TSAT, low TIBC; common in CKD with concurrent inflammation (RA, IBD, infection)

— Thalassemia trait: microcytic with normal/elevated RBC count, target cells, elevated HbA2 (β-thal) or family history (α-thal)

— Megaloblastic anemia: macrocytic, hypersegmented PMNs, low B12 or folate

— Hemolytic anemia: elevated retic, LDH, indirect bili, low haptoglobin, smear findings (schistocytes in TMA — also consider in CKD from HUS, TTP, scleroderma renal crisis)

— MDS in elderly with refractory cytopenias and dysplastic features

— Multiple myeloma: rouleaux, elevated globulin gap, bone pain, hypercalcemia, renal failure (cast nephropathy) — SPEP/UPEP and free light chains

— Osteoporosis (postmenopausal, senile, glucocorticoid-induced) — can coexist with renal osteodystrophy

— Osteomalacia: vitamin D deficiency, low calcium, low phosphate, high ALP — overlap with CKD-MBD

— Adynamic bone disease: low PTH, low ALP — usually iatrogenic over-suppression

— Osteitis fibrosa cystica: severe secondary/tertiary HPT, high PTH, high ALP, brown tumors

— Multiple myeloma: lytic lesions, hypercalcemia, anemia, renal failure — order SPEP

— Bisphosphonate-related atypical femur fracture or ONJ (history of long-term use)

Key distinction: A CKD patient with bone pain + hypercalcemia + anemia + renal failure — think multiple myeloma, not just CKD-MBD. Order SPEP, UPEP, serum free light chains, skeletal survey, and refer to hematology.

Board pearl: High ALP in CKD-MBD reflects bone turnover — high in osteitis fibrosa, low in adynamic bone disease.

Anemia differentials within renal/hematologic axis:

Bone disease differentials in CKD patient:

Key Differentials — Non-Renal Mimics

— Heart failure (HFrEF or HFpEF) — overlapping volume overload; check BNP/NT-proBNP (note BNP is renally cleared, elevated baseline in CKD — trend rather than absolute), echo

— Pulmonary hypertension (common in CKD/dialysis from volume, AV fistula, LV dysfunction)

— Sleep apnea (common in CKD, worsens HTN, fatigue) — polysomnography

— Depression (high prevalence in CKD/dialysis)

— Hypothyroidism (common in elderly CKD)

— Uremic pruritus (CKD-MBD related, phosphate, opioid system dysregulation) — treat: gabapentin, difelikefalin (kappa-opioid agonist, FDA-approved for HD pruritus), phototherapy, optimize phosphate

— Cholestatic pruritus (PBC, drug-induced) — elevated ALP, GGT, bilirubin

— Polycythemia vera (aquagenic pruritus) — elevated Hgb, JAK2 mutation

— Scabies, contact dermatitis, xerosis

— Vertebral compression fracture (osteoporosis, malignancy)

— Avascular necrosis (steroids, SLE) — MRI

— Septic arthritis or osteomyelitis — especially in dialysis with S. aureus bacteremia from access

— Renovascular disease (atherosclerotic or fibromuscular) — flash pulmonary edema, refractory HTN, asymmetric kidneys on US

— Primary aldosteronism — hypokalemia, suppressed renin

— OSA, pheochromocytoma, Cushing

Step 3 management: Refractory HTN in CKD on 3+ agents including a diuretic → screen for secondary causes (Doppler renal arteries, plasma aldo/renin ratio, sleep study, urinary metanephrines).

Board pearl: BNP is elevated at baseline in CKD — use trends and clinical context. A normal BNP makes acute heart failure unlikely even in CKD.

Fatigue and dyspnea in CKD patient — don't anchor on anemia:

Pruritus in CKD — differentials:

Bone pain in CKD:

Hypertension in CKD — secondary causes:

Secondary Prevention and Long-Term Plan

— ACEi or ARB at max tolerated dose if UACR >300 (or >30 with diabetes); monitor K+ and creatinine 1–2 weeks after initiation/titration (acceptable creatinine rise up to 30%)

— SGLT2 inhibitor (dapagliflozin, empagliflozin) in CKD with eGFR ≥20 and UACR ≥200 — even without diabetes

— Finerenone in diabetic CKD with albuminuria, normal K+

— GLP-1 RA (semaglutide) in T2DM with CKD — emerging renoprotective and CV benefit (FLOW trial)

— Strict glycemic control (HbA1c target 7%, individualized)

— BP target <120/80 (per KDIGO 2021, using standardized BP measurement); <130/80 by ACC/AHA

— Dietary sodium <2 g/day, protein 0.6–0.8 g/kg/day in advanced CKD

— Avoid nephrotoxins

— Statin therapy for all CKD patients age ≥50, regardless of LDL (SHARP trial — simvastatin + ezetimibe reduces CV events)

— Aspirin only for established ASCVD (not primary prevention in most CKD)

— Smoking cessation

— Continue iron repletion (oral or IV), monitor ferritin/TSAT every 3 months

— Continue ESA titrated to Hgb 10–11; check Hgb every 2–4 weeks during titration, then monthly

— Continue phosphate binders with meals, monitor Ca/Phos/PTH per stage

— Cinacalcet or vitamin D analog as indicated

— Annual influenza, pneumococcal (PCV20 or PCV15 + PPSV23), Hepatitis B (higher dose 40 mcg series — Recombivax HD or Engerix-B double-dose; check anti-HBs titers), COVID-19, RSV in older adults, shingles

Board pearl: Hep B vaccination is essential in pre-dialysis CKD — use the high-dose regimen and check titers; revaccinate if anti-HBs <10.

Slow CKD progression (renoprotection package):

Cardiovascular risk reduction:

Anemia maintenance:

CKD-MBD maintenance:

Vaccinations (immunosuppressed by uremia):

Transplant referral at GFR <20 for preemptive transplant evaluation

Follow-Up, Monitoring, and Counseling

— G1–G2 with A1: annually

— G3a: every 6–12 months

— G3b: every 3–6 months

— G4: every 3 months

— G5/dialysis: monthly to weekly (dialysis units monitor labs monthly)

— BP, weight, edema assessment, medication reconciliation

— BMP (Cr/eGFR, K, HCO3), CBC, UACR

— Annual: lipid, HbA1c if diabetic, vitamin D

— CKD-MBD panel per stage frequency

— Hgb every 2–4 weeks during ESA titration, then monthly when stable

— Iron studies every 3 months in dialysis, every 6 months non-dialysis

— Hold ESA if Hgb >11; resume at 25% lower dose when Hgb <10

— Diet: low sodium, controlled protein, phosphate-aware (avoid colas, processed cheese, additives — read labels for "phos"), potassium-aware in G4–G5

— Medication safety: avoid OTC NSAIDs (acetaminophen for pain), avoid contrast unless necessary, alert all providers about CKD

— Vascular access protection: no BP cuffs, IVs, or blood draws on the access arm; preserve veins

— Smoking cessation, weight management, exercise

— Advance care planning: dialysis vs. conservative management, transplant interest, surrogate decision-maker

— Vascular access creation (AVF preferred)

— Modality education (in-center HD, home HD, peritoneal dialysis, transplant)

— Transplant referral

Step 3 management: A CKD patient discharging from the hospital after an AKI superimposed on CKD needs nephrology follow-up within 1–2 weeks, BMP within 1 week, medication reconciliation (often hold ACEi/ARB/diuretics transiently), and clear documentation of the next steps. Transitions of care are a high-yield Step 3 testing point.

Board pearl: Phosphate is hidden in processed foods as additives — counsel patients to read labels for "phos-" prefixes.

Visit cadence by stage:

At each visit:

Anemia monitoring:

Counseling pillars:

Dialysis preparation (start at GFR ~20):

Ethical, Legal, and Patient Safety Considerations

— Step 3 expects shared decision-making: discuss prognosis, expected QoL, modality options, and option of conservative (non-dialysis) management

— Disclose that dialysis may not extend life or improve function in frail elderly with multiple comorbidities

— Document goals of care and surrogate decision-maker

— Ethically and legally permissible at the patient's request (or surrogate if patient lacks capacity)

— Median survival after withdrawal ~7–10 days; engage palliative care for symptom management

— No requirement to continue dialysis the patient does not want — this is withholding/withdrawing, not euthanasia

— Deceased donor allocation per UNOS rules; living donor evaluation must protect donor autonomy (independent donor advocate)

— Patients cannot pay donors (NOTA — National Organ Transplant Act prohibits valuable consideration)

— Disclose risks of immunosuppression long-term

— Medication reconciliation at every transition — common errors: failing to restart held ACEi/ARB or diuretic, continuing nephrotoxin started in hospital, dosing errors for renally cleared drugs

— Contrast safety: weigh benefit vs. risk; gadolinium <30 GFR → nephrogenic systemic fibrosis (use group II agents if essential); iodinated contrast → AKI risk (hydration, lowest osmolar contrast)

— Fall risk: elderly CKD with anemia, hypotension from over-diuresis, polypharmacy — assess at every visit

Step 3 management: A dialysis patient with progressive dementia whose family wants to stop dialysis — confirm the patient's prior expressed wishes (advance directive), verify surrogate decision-making per state law, engage palliative care, document the conversation thoroughly. The Step 3 answer is respect the patient's previously expressed values via surrogate, not unilateral continuation.

Board pearl: Gadolinium and NSF: avoid group I agents at GFR <30; use group II (gadobutrol, gadoteridol) only if essential.

Informed consent for dialysis initiation:

Withdrawal from dialysis:

Transplant ethics:

Patient safety / transitions of care:

Mandatory reporting: dialysis vascular access infections may be reportable per CMS quality measures (NHSN dialysis event reporting)

Disability and financial protections: ESRD qualifies for Medicare regardless of age after 90 days of dialysis (or immediately with transplant) — counsel patients and connect with social work

High-Yield Associations and Rapid-Fire Facts

Board pearl: When a CKD vignette mentions "declining Hgb on stable ESA dose," think about new iron deficiency, blood loss (occult GI), inflammation, hyperparathyroidism, or anti-EPO antibodies (pure red cell aplasia) — work it up before just raising the ESA.

Hgb target in CKD: 10–11 g/dL (do not exceed 11.5)

Ferritin and TSAT thresholds before ESA: ferritin >100 (non-HD) or >200 (HD), TSAT >20%

PTH target on dialysis: 2–9× ULN (~130–600 pg/mL)

Phosphate binders with meals; calcium-based limited to 1500 mg elemental Ca/day

Sevelamer also lowers LDL; ferric citrate doubles as iron source

Cinacalcet → hypocalcemia (most common adverse effect)

Sodium thiosulfate → calciphylaxis treatment

Hungry bone syndrome → post-parathyroidectomy hypocalcemia, hypophosphatemia, hypomagnesemia

Bisphosphonates contraindicated at GFR <30

Metformin avoid at GFR <30; reduce dose at 30–45

Gabapentin/pregabalin reduce dose in CKD (sedation, falls)

SGLT2 inhibitors: dapagliflozin, empagliflozin — start down to GFR 20, continue if started; CV and renal benefit

Finerenone: nonsteroidal MRA, diabetic CKD, monitor K+

ACEi/ARB: acceptable Cr rise up to 30%; hold if >30% or K+ >5.5

Uremic pericarditis → urgent HD, not NSAIDs/steroids

DDAVP for uremic bleeding (acute, peri-procedure)

Hep B vaccine: high-dose (40 mcg) series in pre-dialysis; check anti-HBs titers

AVF preferred over AVG over catheter for HD access (fistula first)

Preserve veins: no PICC, no subclavian, protect non-dominant arm

Difelikefalin: kappa-opioid agonist for HD-related pruritus

Daprodustat / HIF stabilizers: oral alternative to ESAs

SHARP trial: simvastatin + ezetimibe → ↓CV events in CKD

TREAT/CHOIR/CREATE: high Hgb targets → harm

DAPA-CKD / EMPA-KIDNEY: SGLT2i benefit in CKD even without diabetes

CKD-EPI 2021: race-free creatinine-based equation

BP target KDIGO 2021: <120/80 (standardized measurement)

Board Question Stem Patterns

Board pearl: When in doubt on a CKD anemia question, the answer is usually "check/replete iron" or "don't push Hgb above 11."

Pattern 1: CKD G4 patient with Hgb 9.2, ferritin 80, TSAT 15% → answer: iron repletion first, not ESA. If already iron-repleted, then start ESA targeting Hgb 10–11.

Pattern 2: HD patient with Hgb 12.5 on darbepoetin → answer: hold or reduce ESA dose by 25%; do not continue same dose.

Pattern 3: HD patient with PTH 900, calcium 10.8, phosphate 6.5 on calcium acetate → answer: switch to non-calcium binder (sevelamer) and add cinacalcet (lowers both PTH and calcium).

Pattern 4: HD patient with painful violaceous plaques on thighs → answer: calciphylaxis; treatment is sodium thiosulfate, stop warfarin and calcium-based binders.

Pattern 5: Post-parathyroidectomy patient with perioral tingling, Chvostek sign, QT prolongation → answer: hungry bone syndrome; IV calcium gluconate infusion, replete Mg and phosphate.

Pattern 6: CKD G4 woman planning pregnancy on lisinopril and atorvastatin → answer: stop both before conception; switch to labetalol or nifedipine for BP.

Pattern 7: Dialysis patient with pericardial rub, ECG without diffuse ST changes → answer: uremic pericarditis → intensify dialysis, not NSAIDs.

Pattern 8: CKD patient with K+ 6.8 and peaked T waves → answer: IV calcium gluconate first, then insulin + D50, then nebulized albuterol, then patiromer/sodium zirconium and urgent HD.

Pattern 9: CKD patient with refractory pruritus, normal LFTs, optimal phosphate → answer: gabapentin or difelikefalin.

Pattern 10: Frail 86-year-old with CKD G5, dementia, declining function → answer: goals-of-care conversation including conservative management, not automatic dialysis initiation.

Pattern 11: Diabetic CKD patient with UACR 600, eGFR 45 on max ACEi → answer: add SGLT2 inhibitor (and consider finerenone if K+ allows).

Pattern 12: Stable HD patient with new low Hgb despite ESA, near-zero retic count → answer: anti-EPO antibody-mediated pure red cell aplasia (rare); discontinue ESA, hematology consult.

One-Line Recap

In CKD, anticipate and proactively manage the predictable complication cluster — anemia (iron then ESA, target Hgb 10–11), CKD-MBD (phosphate binders → vitamin D → calcimimetics, PTH 2–9× ULN), acidosis, hyperkalemia, volume overload, and cardiovascular risk — while protecting future options (transplant candidacy, vascular access, vaccinations) and engaging shared decision-making about dialysis vs. conservative care.

Board pearl: The Step 3 CKD question is almost never about diagnosing CKD — it is about what to do next in a longitudinal management timeline. Memorize the target numbers (Hgb 10–11, PTH 2–9× ULN, ferritin >100/200, TSAT >20%, BP <120/80, GFR <20 for transplant referral, GFR <30 for bisphosphonate/gadolinium/metformin contraindication) and the trial-driven medication additions (SGLT2i, finerenone, statin/ezetimibe).

Anemia: Replete iron first (ferritin >100/200, TSAT >20%), then ESA to Hgb 10–11; never push >11.5 (stroke, VTE, mortality). Consider HIF stabilizers (daprodustat) as oral alternative.

CKD-MBD: Phosphate first (binders with meals, non-calcium preferred if hypercalcemia/calcification), then 25-OH D repletion, then active vitamin D analogs or calcimimetics; PTH target 2–9× ULN in dialysis; sodium thiosulfate for calciphylaxis; watch for adynamic bone disease from over-treatment.

Renoprotection: Max ACEi/ARB + SGLT2 inhibitor + finerenone (diabetic) + statin (age ≥50) + BP <120/80 + Hep B vaccine + nephrotoxin avoidance + transplant referral at GFR <20.

Transitions and safety: Renally dose every medication, avoid NSAIDs and gadolinium <30 GFR, preserve veins for future access, document goals of care, engage palliative care for frail patients, nephrology follow-up within 1–2 weeks after AKI-on-CKD hospitalization.