STEPTRACKERRENAL | PATHOLOGY + PHYSIOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Chronic Kidney Disease

Lost nephrons mean lost functions — what the kidney stops excreting, stops making and stops regulating.

FOCUS ON
CKD = GFR < 60 or kidney damage for ≥ 3 months; top causes diabetes and hypertension. The kidney fails at: making EPO (anemia), activating vitamin D and excreting phosphate (secondary hyperparathyroidism, renal osteodystrophy), excreting K⁺, acid and water, and clearing toxins (uremia). Cardiovascular disease is the main cause of death.
CONSEQUENCE
MECHANISM
FINDINGS
MANAGEMENT · CLUE
Causes & staging
Diabetic nephropathy, hypertensive nephrosclerosis, glomerulonephritis, ADPKD, obstruction
Staged by GFR and albuminuria; small, scarred kidneys (except DM, ADPKD, amyloid, HIV)
ACEi/ARB, SGLT2i slow progression
Anemia
↓ erythropoietin from peritubular interstitial cells
Normocytic normochromic anemia, low reticulocytes
Iron + ESA (epoetin) · ESA → hypertension, thrombosis
Mineral-bone disorder
↓ phosphate excretion + ↓ 1α-hydroxylase (↓ calcitriol) → ↓ Ca²⁺, ↑ PO₄³⁻, ↑ FGF23 → secondary hyperparathyroidism
Renal osteodystrophy: osteitis fibrosa cystica, osteomalacia, adynamic bone; vascular calcification
Phosphate binders (sevelamer), calcitriol, cinacalcet
Tertiary hyperparathyroidism
Long-standing stimulation → autonomous parathyroid hyperplasia
↑↑ PTH with high calcium
Parathyroidectomy
Metabolic acidosis
↓ ammoniagenesis and H⁺ excretion; later retained anions
Normal anion gap early → high anion gap late
Oral bicarbonate · acidosis worsens bone loss
Hyperkalemia
↓ K⁺ excretion; worsened by ACEi, ARB, spironolactone, NSAIDs
Peaked T waves, weakness, arrhythmia
Calcium gluconate, insulin + glucose, binders, dialysis
Volume & blood pressure
Na⁺ and water retention, ↑ renin
Hypertension, edema, heart failure, LVH
Loop diuretics, salt restriction
Uremic syndrome
Retained nitrogenous toxins
Nausea, anorexia, pruritus, pericarditis, encephalopathy, asterixis, neuropathy, uremic frost
Indication for dialysis
Uremic bleeding
Uremic toxins impair platelet function (vWF–GpIb interaction)
↑ bleeding time with normal platelet count, PT and PTT
Desmopressin, dialysis
Cardiovascular disease
Accelerated atherosclerosis, vascular calcification, LVH
MI, stroke, sudden death — leading cause of death in CKD
Statins, BP control
Drug dosing
↓ renal clearance
Adjust: aminoglycosides, vancomycin, digoxin, lithium, LMWH, gabapentin
Metformin → lactic acidosis at low GFR
Dialysis-related
β₂-microglobulin not cleared; long-term dialysis
Dialysis amyloid (carpal tunnel, arthropathy), acquired cysts (→ RCC), calciphylaxis (painful necrotic skin)
Transplant → see rejection (2.09)

Mechanism — CKD mineral-bone disorder

↓ Nephrons
→
↑ PhosphateBinds Ca²⁺, ↑ FGF23
↓ 1α-hydroxylase↓ Calcitriol
→
↓ Calcium
→
↑ PTHSecondary HPT
→
Bone resorptionOsteitis fibrosa cystica

Phosphate is the driver: control it with diet and binders before giving calcitriol.

Hyperparathyroidism compared

TYPE
PTH
Ca²⁺
PO₄³⁻
Primary (adenoma)
↑
↑
↓
Secondary (CKD)
↑
↓ / normal
↑
Secondary (vit D deficiency)
↑
↓ / normal
↓
Tertiary (long CKD)
↑↑
↑
↑

How it's tested

COMMON CONFUSIONPhosphate is high in CKD-related secondary hyperparathyroidism but low in primary hyperparathyroidism and vitamin D deficiency, where the kidney still responds to PTH.
THE TRAPA bleeding uremic patient with normal platelet count and normal PT/PTT has platelet dysfunction. Desmopressin (releases vWF) is the quick fix.
YOUR APPROACHFor each kidney job — excrete, regulate, produce — name what goes wrong in CKD, the lab that shows it, and the treatment.

If you see… think…

CKD with normocytic anemia, low reticulocytes → ↓ EPO — give ESA (after iron)
CKD with ↑ PTH, low Ca²⁺, high PO₄³⁻ → secondary hyperparathyroidism
Years of dialysis, now ↑ PTH with high calcium → tertiary hyperparathyroidism
Subperiosteal bone resorption, brown tumors → osteitis fibrosa cystica
Pericardial friction rub in uremia → uremic pericarditis — dialysis
Bleeding with normal platelets, PT and PTT in CKD → uremic platelet dysfunction
Dialysis patient with carpal tunnel syndrome → β₂-microglobulin amyloid
Painful violaceous necrotic skin plaques in ESRD → calciphylaxis
Phosphate binder that isn't calcium-based → sevelamer
Drug that lowers PTH by sensitizing the Ca²⁺-sensing receptor → cinacalcet