2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T79ab,

Summary Table

Feature	Details
Risk Factors	Diabetes mellitus (leading cause), hypertension (second leading cause), glomerulonephritis, polycystic kidney disease, prolonged NSAID use, older age, African American ethnicity, family history of kidney disease
Etiology	Progressive, irreversible loss of nephron function over months to years, most commonly from diabetic nephropathy or hypertensive nephrosclerosis
Patient Presentation	Often asymptomatic in early stages; fatigue, nocturia, foamy urine, peripheral edema, poor appetite, and pruritus in later stages
Classic Physical Exam	Hypertension, pallor (anemia), periorbital/peripheral edema, excoriations from uremic pruritus, pericardial friction rub (late/uremia), asterixis (uremic encephalopathy)
Key Diagnostic Results	Elevated serum creatinine, decreased GFR (< 60 mL/min/1.73 m² for ≥ 3 months), albuminuria (≥ 30 mg/g creatinine), renal ultrasound showing small echogenic kidneys bilaterally
Management	ACE inhibitors or ARBs for proteinuria and BP control, SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin), strict glycemic control in diabetics, dietary protein and sodium restriction, treat complications (anemia, hyperkalemia, metabolic acidosis, mineral bone disease), dialysis or transplant for ESKD
Keywords	"Bilateral small kidneys," "elevated creatinine over several months," "foamy urine," "normocytic anemia with elevated creatinine," "broad waxy casts," "renal osteodystrophy," "uremic frost"

1. Pathophysiology

CKD is defined as a sustained reduction in kidney function or evidence of kidney damage lasting three months or longer. The hallmark is progressive, irreversible nephron loss. Regardless of the initial insult, once a critical mass of nephrons is destroyed, the remaining nephrons undergo compensatory hyperfiltration. Each surviving nephron increases its single-nephron GFR to maintain overall clearance. While this is adaptive in the short term, the resulting intraglomerular hypertension accelerates further glomerular injury, creating a self-perpetuating cycle of damage. This is the central concept that explains why CKD progresses even after the original cause is controlled, and it is also the rationale for using ACE inhibitors and ARBs, which reduce intraglomerular pressure by dilating the efferent arteriole.

As GFR declines, the kidneys lose the ability to excrete waste products, regulate electrolytes, and maintain acid-base balance. Uremia refers to the clinical syndrome that emerges when toxic metabolites accumulate. Uremic toxins affect virtually every organ system: the pericardium (uremic pericarditis), the brain (encephalopathy, asterixis), the skin (pruritus, uremic frost), and the GI tract (nausea, anorexia). These manifestations typically become prominent when GFR falls below 15 mL/min/1.73 m².

The kidney also has critical endocrine functions. Loss of erythropoietin production leads to a normocytic, normochromic anemia that does not respond to iron supplementation alone. Decreased 1-alpha-hydroxylase activity impairs conversion of 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D (calcitriol), resulting in hypocalcemia. The hypocalcemia triggers secondary hyperparathyroidism, which drives bone resorption and contributes to renal osteodystrophy. Simultaneously, failing kidneys cannot excrete phosphate, so hyperphosphatemia worsens the hypocalcemia by forming calcium-phosphate complexes that deposit in soft tissues and further suppress calcitriol production.

Metabolic acidosis develops because the kidneys lose the ability to regenerate bicarbonate and excrete ammonium ($NH_4^+$). This is a non-anion gap metabolic acidosis in earlier stages (due to impaired ammonium excretion) that transitions to an anion gap metabolic acidosis in advanced CKD as unmeasured uremic anions accumulate.

2. Classification and Clinical Manifestation

Clinical Manifestations of Chronic Kidney Disease

Organ System	Clinical Manifestation	Underlying Mechanism
Cardiovascular	Hypertension, left ventricular hypertrophy, accelerated atherosclerosis, uremic pericarditis (friction rub), heart failure	Sodium and water retention, RAAS activation, volume overload, uremic toxin-mediated inflammation, calcium-phosphate deposition in vessels
Hematologic	Normocytic normochromic anemia, platelet dysfunction (prolonged bleeding time with normal platelet count), impaired leukocyte function	Decreased erythropoietin production, uremic toxins inhibiting platelet aggregation and adhesion, impaired immune cell function
Neurologic	Uremic encephalopathy (confusion, asterixis, myoclonus, seizures), peripheral neuropathy (restless legs, stocking-glove sensory loss), sleep disturbances	Accumulation of uremic toxins crossing the blood-brain barrier, demyelination of peripheral nerves
Gastrointestinal	Anorexia, nausea, vomiting, metallic taste (dysgeusia), uremic fetor (ammonia-like breath), GI bleeding	Uremic toxins irritating the GI mucosa, urea conversion to ammonia by gut bacteria, platelet dysfunction contributing to mucosal hemorrhage
Musculoskeletal	Renal osteodystrophy (bone pain, fractures), osteomalacia, osteitis fibrosa cystica, growth retardation in children, muscle wasting	Secondary hyperparathyroidism driving osteoclastic bone resorption, calcitriol deficiency impairing bone mineralization, metabolic acidosis promoting protein catabolism
Dermatologic	Uremic pruritus, sallow yellow-brown skin discoloration, uremic frost (late finding), easy bruising, calciphylaxis (painful skin necrosis with calcified vessels)	Retained urochrome pigments, urea crystallizing on skin in advanced uremia, calcium-phosphate product deposition in dermal arterioles, platelet dysfunction
Endocrine / Metabolic	Secondary hyperparathyroidism, vitamin D deficiency, insulin resistance, dyslipidemia, sexual dysfunction (decreased libido, amenorrhea, erectile dysfunction), hypothermia	Loss of 1-alpha-hydroxylase activity, phosphate retention, uremic toxin interference with hormone signaling, impaired hepatic lipase activity
Electrolyte / Acid-Base	Hyperkalemia, hyperphosphatemia, hypocalcemia, hypermagnesemia, non-anion gap metabolic acidosis (early) transitioning to anion gap metabolic acidosis (late)	Decreased potassium and phosphate excretion, impaired calcitriol synthesis, reduced ammonium (NH4+NH_4^+ NH4+) excretion, accumulation of unmeasured organic anions
Pulmonary	Pulmonary edema ("butterfly" pattern on chest X-ray), pleuritis, Kussmaul breathing	Volume overload from sodium/water retention, uremic serositis, respiratory compensation for metabolic acidosis
Immunologic	Increased susceptibility to infections, impaired vaccine response, chronic inflammatory state	Uremia-induced immune suppression affecting both innate and adaptive immunity, malnutrition contributing to immunodeficiency

A key teaching point here is that CKD is never just a "kidney problem." The exam frequently tests your ability to connect a seemingly unrelated complaint (bone pain, bleeding, restless legs, pericardial friction rub) back to underlying renal failure. When a vignette presents any combination of anemia, bone disease, and electrolyte derangements in the same patient, your first instinct should be to look for an elevated creatinine or reduced GFR tying them all together.

GFR Staging

Stage	GFR (mL/min/1.73 m²)	Description	Clinical Features
G1	≥ 90	Normal or high GFR with evidence of kidney damage	Asymptomatic; detected by persistent albuminuria, hematuria, or structural abnormality
G2	60 - 89	Mildly decreased	Usually asymptomatic; mild concentrating defect may cause nocturia
G3a	45 - 59	Mild-to-moderate decrease	Anemia may begin; early mineral bone disease; hypertension worsens
G3b	30 - 44	Moderate-to-severe decrease	Fatigue, edema, hyperphosphatemia, secondary hyperparathyroidism becomes evident
G4	15 - 29	Severely decreased	Hyperkalemia, metabolic acidosis, volume overload, preparation for renal replacement therapy
G5	< 15	Kidney failure (ESKD)	Uremic symptoms: pericarditis, encephalopathy, bleeding, pruritus, nausea; requires dialysis or transplant

Albuminuria Staging

Category	Albumin-to-Creatinine Ratio (mg/g)	Description
A1	< 30	Normal to mildly increased
A2	30 - 300	Moderately increased (formerly "microalbuminuria")
A3	> 300	Severely increased (formerly "macroalbuminuria")

Both GFR stage and albuminuria category together determine prognosis and treatment intensity. A patient at G3a-A1 has a very different risk profile from G3a-A3. The combination grid (often called the "heat map") is used to predict progression risk: higher albuminuria at any GFR stage signals faster decline and greater cardiovascular risk.

3. Diagnostic Workup

Test	Purpose	Key Findings
Serum creatinine and eGFR	Best initial test to assess kidney function	eGFR < 60 mL/min/1.73 m² on two or more occasions ≥ 3 months apart confirms chronicity
Urine albumin-to-creatinine ratio (UACR)	Quantify proteinuria and stage albuminuria	≥ 30 mg/g is abnormal; ≥ 300 mg/g indicates severe albuminuria
Urinalysis with microscopy	Evaluate for active sediment	Broad waxy casts suggest chronic disease; red cell casts suggest glomerulonephritis
Renal ultrasound	Best initial imaging	Bilateral small (< 9 cm), echogenic kidneys confirm chronicity and irreversibility
CBC	Evaluate anemia	Normocytic normochromic anemia from erythropoietin deficiency
BMP / CMP	Electrolyte and acid-base status	Hyperkalemia, hyperphosphatemia, hypocalcemia, elevated BUN, low bicarbonate
Intact PTH	Assess secondary hyperparathyroidism	Elevated PTH with low calcium and high phosphate
25-hydroxyvitamin D	Assess vitamin D stores	Often low; must be repleted before treating with active vitamin D analogues
Renal biopsy	Gold standard for determining etiology when unclear	Reserved for cases where the cause is uncertain or a treatable glomerulonephritis is suspected

The best initial test is serum creatinine with calculated eGFR combined with a urine albumin-to-creatinine ratio. These two values together establish both the presence and severity of CKD. The diagnosis of CKD requires that the abnormality (reduced GFR or albuminuria) be persistent for at least three months, which distinguishes it from acute kidney injury.

Renal ultrasound is the best initial imaging study. The classic finding of bilateral small, echogenic kidneys is highly suggestive of chronic, irreversible disease. This finding essentially rules out acute kidney injury, where kidneys are typically normal in size. There are notable exceptions: kidneys may remain normal-sized or even enlarged in CKD caused by diabetic nephropathy, HIV-associated nephropathy, amyloidosis, and polycystic kidney disease.

Urinalysis with microscopy provides clues about etiology. Broad waxy casts form in dilated, sluggish tubules of chronically damaged nephrons and are a hallmark of CKD. If an active urinary sediment (dysmorphic red cells, red cell casts) is present, suspect an underlying glomerulonephritis that may warrant biopsy.

Renal biopsy is not routinely performed. It is indicated when the etiology is unclear, when a potentially treatable glomerular disease is suspected, or when the clinical picture does not match the presumed diagnosis. In a patient with long-standing diabetes, retinopathy, and progressive proteinuria, the diagnosis of diabetic nephropathy is clinical and biopsy is not needed.

4. Management and Treatment

Intervention	Details	When to Initiate
ACE inhibitor or ARB	First-line for slowing progression; reduces intraglomerular pressure and proteinuria	All CKD patients with albuminuria (UACR ≥ 30 mg/g), titrate to max tolerated dose
SGLT2 inhibitor	Dapagliflozin 10 mg daily or empagliflozin 10 mg daily; provides additional nephroprotection independent of diabetes status	eGFR ≥ 20 mL/min with UACR ≥ 200 mg/g (can initiate even without diabetes)
Finerenone	Nonsteroidal mineralocorticoid receptor antagonist, 10-20 mg daily	Diabetic CKD with albuminuria despite ACEi/ARB; check potassium before starting
Blood pressure target	< 130/80 mmHg (or < 120 systolic per SPRINT if tolerated)	All CKD patients
Glycemic control	HbA1c target around 7% in diabetic CKD; avoid overly aggressive targets in advanced CKD due to hypoglycemia risk	Diabetic patients; reduce metformin dose when eGFR < 30, stop when < 20
Sodium bicarbonate	650 mg two to three times daily (target serum bicarb ≥ 22 mEq/L)	Metabolic acidosis with serum bicarbonate < 22 mEq/L
Phosphate binders	Sevelamer or calcium acetate, taken with meals	Hyperphosphatemia (serum phosphate > 4.5 mg/dL in CKD G3-G5)
Active vitamin D	Calcitriol or paricalcitol	Secondary hyperparathyroidism not responding to phosphate control and vitamin D repletion
Erythropoiesis-stimulating agents	Epoetin alfa or darbepoetin; target hemoglobin 10-11.5 g/dL (do not exceed 13)	Symptomatic anemia with Hb < 10 g/dL after excluding iron deficiency
Iron supplementation	IV iron preferred in advanced CKD/dialysis; target ferritin > 100, TSAT > 20%	Iron deficiency confirmed before or alongside ESA therapy
Dietary modification	Sodium < 2 g/day, potassium restriction in hyperkalemia, protein 0.8 g/kg/day in non-dialysis CKD	All stages, intensify as CKD progresses
Dialysis	Hemodialysis or peritoneal dialysis	GFR < 10-15 mL/min or when uremic symptoms, refractory hyperkalemia, volume overload, or pericarditis develop
Kidney transplant	Preferred long-term renal replacement therapy	ESKD; can be preemptive (before dialysis initiation) if a donor is available

ACE inhibitors or ARBs are the cornerstone of CKD management. They reduce proteinuria and slow progression by lowering efferent arteriolar tone, which decreases intraglomerular pressure. Expect a 10-30% rise in creatinine after initiation; this is hemodynamic and acceptable. Discontinue only if creatinine rises by more than 30% or hyperkalemia becomes refractory. Never combine an ACEi with an ARB, as dual blockade increases the risk of hyperkalemia and acute kidney injury without additional benefit.

SGLT2 inhibitors have become a pillar of CKD therapy following landmark trials (DAPA-CKD, EMPA-KIDNEY). They reduce intraglomerular pressure through tubuloglomerular feedback by increasing sodium delivery to the macula densa, which triggers afferent arteriolar constriction. The nephroprotective benefit is independent of glycemic status. An initial dip in eGFR of up to 5 mL/min is expected and is not a reason to discontinue.

For anemia of CKD, always check and replete iron stores before starting erythropoiesis-stimulating agents (ESAs). The target hemoglobin is 10 to 11.5 g/dL. Targeting hemoglobin above 13 g/dL with ESAs is associated with increased cardiovascular events, stroke, and mortality.

Metabolic acidosis should be corrected with oral sodium bicarbonate when serum bicarbonate falls below 22 mEq/L. Correction of acidosis slows CKD progression and reduces protein catabolism.

CKD-Mineral Bone Disease is managed in a stepwise fashion: first restrict dietary phosphate, then add phosphate binders, replete 25-hydroxyvitamin D, and finally add active vitamin D analogues (calcitriol) if PTH remains elevated. Avoid calcium-based binders in patients with vascular calcification or adynamic bone disease.

Emergent indications for dialysis can be remembered by the mnemonic AEIOU: Acidosis (refractory), Electrolyte abnormalities (refractory hyperkalemia), Ingestion of dialyzable toxins, Overload (volume, refractory to diuretics), and Uremic symptoms (pericarditis, encephalopathy, bleeding).

5. Differential Diagnosis and Distractors

Differential	Why It Looks Similar	Key Discriminator
Acute Kidney Injury (AKI)	Elevated creatinine, may have oliguria, hyperkalemia, and acidosis	AKI develops over hours to days with a prior normal baseline; kidneys are normal-sized on ultrasound; no anemia or bone disease; creatinine trend is acute, not months-long
AKI on CKD	Patient with known CKD has an acute creatinine spike	Look for a new precipitant (nephrotoxin, hypotension, obstruction) causing creatinine to rise above a known elevated baseline; features of both chronicity (anemia, small kidneys) and acute injury
Prerenal azotemia	Elevated BUN and creatinine, oliguria	BUN-to-creatinine ratio > 20:1, fractional excretion of sodium < 1%, responds to volume resuscitation; kidney size is normal
Nephrotic syndrome	Proteinuria, edema, hypoalbuminemia	Presents acutely with heavy proteinuria (> 3.5 g/day), hyperlipidemia, and lipiduria; eGFR may be normal initially; kidneys are normal-sized
Primary hyperparathyroidism	Elevated PTH and calcium	In primary hyperparathyroidism, both calcium and PTH are elevated; in CKD-related secondary hyperparathyroidism, calcium is low and phosphate is high with elevated PTH
Iron deficiency anemia	Normocytic (early) or microcytic anemia, fatigue	Low ferritin and low TSAT distinguish iron deficiency; CKD anemia has normal or elevated ferritin with low erythropoietin levels and an elevated creatinine
Chronic glomerulonephritis	Progressive renal failure, proteinuria, hypertension	This is actually a cause of CKD, not a separate entity; biopsy may show the underlying pattern; presence of active sediment (RBC casts) points toward glomerulonephritis as the etiology

6. Traps and High-Yield Pearls

The most common way students lose points on CKD questions is by confusing AKI with CKD. The vignette will often present an elevated creatinine and expect you to determine chronicity. The key discriminators are bilateral small echogenic kidneys on ultrasound, the presence of normocytic anemia, and evidence of mineral bone disease (elevated PTH, hyperphosphatemia, hypocalcemia). If any of these are present, the process is chronic, not acute.

A second common trap involves the ACEi/ARB creatinine rise. After starting an ACEi, a mild creatinine increase (up to 30%) is expected and reflects reduced intraglomerular pressure, which is the therapeutic goal. Students who see a rising creatinine after ACEi initiation may incorrectly choose to stop the drug. You discontinue only if the rise exceeds 30% or if hyperkalemia is unmanageable. However, if a vignette describes creatinine doubling after ACEi in a patient with hypertension and a renal bruit, suspect bilateral renal artery stenosis, where the kidneys are entirely dependent on angiotensin II to maintain GFR via efferent arteriolar tone.

Another frequently tested concept is the anemia target. ESAs should raise hemoglobin to 10-11.5 g/dL, never above 13 g/dL. A question may present a CKD patient on epoetin with hemoglobin of 12.5 and ask the next step. The answer is to reduce or hold the ESA dose, not increase it.

Finally, do not forget the exceptions to the small kidney rule. When a vignette describes CKD with normal-sized or enlarged kidneys, think diabetic nephropathy, HIV-associated nephropathy, amyloidosis, or polycystic kidney disease. This detail alone can point you toward the correct etiology.

The core competency being tested across CKD questions is your ability to recognize chronicity from acute disease, sequence the diagnostic workup correctly, and apply nephroprotective strategies in the right clinical context.

1e:["$","$L2d",null,{"article":{"id":"ba0eb5aa-ccc9-4ffb-a781-a732910a379c","title":"Gagal Ginjal Kronik (CKD)","content":"$2e","category":"Uronefrologi","created_at":"2026-05-11T03:55:19.087427+00:00","status":"published","subcategory":null},"questionCount":2,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]