Chronic Kidney Disease

Chronic kidney disease (CKD) is a sustained (≥3 months) abnormality of kidney structure or function with implications for health. It is a perennial NEET PG favourite — staging, CKD-MBD, renal anaemia, and dialysis indications recur every year. Master the cut-offs and the mechanisms and you bank easy marks.

Definition & Classification

CKD is defined (KDIGO) by either of the following present for ≥3 months:

1. Markers of kidney damage (one or more): albuminuria (ACR ≥30 mg/g), urine sediment abnormalities, electrolyte/tubular disorders, histological abnormality, structural abnormality on imaging, or history of kidney transplant.
2. GFR <60 mL/min/1.73 m².

The KDIGO system uses two axes — G (GFR) and A (albuminuria) — the so-called "heat map" that predicts prognosis. Both must be quoted to stage correctly.

GFR categories (G stages)

Stage	GFR (mL/min/1.73 m²)	Description
G1	≥90	Normal/high (damage present)
G2	60–89	Mildly decreased
G3a	45–59	Mild–moderate
G3b	30–44	Moderate–severe
G4	15–29	Severely decreased
G5	<15	Kidney failure (ESRD if on dialysis)

High-yield: GFR 60–89 alone is NOT CKD unless a marker of damage (e.g. albuminuria) is also present — otherwise it may simply be ageing. A GFR <60 by itself qualifies regardless of damage markers.

Albuminuria categories (A stages)

Stage	ACR (mg/g)	ACR (mg/mmol)	Term
A1	<30	<3	Normal–mildly increased
A2	30–300	3–30	Moderately increased ("microalbuminuria")
A3	>300	>30	Severely increased ("macroalbuminuria")

A typical complete diagnosis reads "CKD G3b A2". The combination of low GFR and high albuminuria carries the worst prognosis (red zone of the heat map).

High-yield: Estimated GFR in adults is reported by the CKD-EPI 2021 equation (race-free, uses creatinine ± cystatin C). Cockcroft–Gault gives creatinine clearance and is still used for drug dosing.

Etiology

Globally and in India the leading causes:

1. Diabetic nephropathy → the single commonest cause of CKD and ESRD worldwide.
2. Hypertensive nephrosclerosis (second).
3. Chronic glomerulonephritis (IgA nephropathy is the commonest primary GN worldwide).
4. Chronic tubulointerstitial disease, obstructive uropathy, reflux nephropathy.
5. Polycystic kidney disease (commonest hereditary cause; ADPKD — PKD1 gene, chromosome 16).

High-yield: Diabetic nephropathy is the leading cause of CKD/ESRD. First detectable lab sign is microalbuminuria (A2); first histological change is glomerular basement membrane thickening; the classic nodular lesion is Kimmelstiel–Wilson nodules.

Pathophysiology

Whatever the initial insult, surviving nephrons hyperfilter to compensate. This glomerular hyperfiltration and intraglomerular hypertension is initially adaptive but ultimately maladaptive — it drives glomerulosclerosis, proteinuria, and progressive nephron loss (the "final common pathway"). Angiotensin II raises efferent arteriolar tone and intraglomerular pressure, which is why RAAS blockade (ACE inhibitor/ARB) slows progression independent of systemic BP control.

Consequences of declining GFR:

Nephron loss → ↓GFR → retention of solutes/fluid → uraemia, volume overload, electrolyte disturbance, metabolic acidosis, anaemia, mineral-bone disease → cardiovascular disease.

Key downstream derangements:

• Sodium/water: volume overload, hypertension (volume-dependent).
• Potassium: hyperkalaemia (especially with RAAS blockers, low GFR).
• Acid–base: high anion-gap metabolic acidosis (retention of sulphate, phosphate, organic acids).
• Haematology: normocytic normochromic anaemia (EPO deficiency).
• Bone-mineral: CKD-MBD (see below).
• Cardiovascular: accelerated atherosclerosis, LVH; CVD is the commonest cause of death in CKD.

Clinical Features

Early CKD is largely asymptomatic — detected on screening. As GFR falls, uraemic features appear (usually GFR <15–20):

• General: fatigue, anorexia, nausea/vomiting, weight loss, metallic taste, uraemic fetor.
• Neurological: encephalopathy, asterixis, peripheral neuropathy, restless legs.
• Skin: pruritus, sallow/uraemic frost, easy bruising.
• Cardiovascular: hypertension, uraemic pericarditis (a dialysis indication), accelerated atherosclerosis.
• Haematological: anaemia (pallor, dyspnoea), platelet dysfunction → bleeding.
• Skeletal: bone pain, proximal myopathy, fractures.

High-yield: Uraemic pericarditis and uraemic encephalopathy are absolute, urgent indications for dialysis irrespective of the numeric GFR.

Diagnosis & Investigation of Choice

Confirm chronicity — distinguishing CKD from AKI is examinable:

Feature	CKD	AKI
Kidney size (USG)	Small, shrunken (<9 cm)	Normal/enlarged
Duration	>3 months	Days–weeks
Anaemia	Usually present	Often absent early
Renal osteodystrophy	Present	Absent
Cortical thickness/echogenicity	Thin cortex, ↑echogenicity	Normal
Reversibility	Largely irreversible	Often reversible

Exceptions — CKD with NORMAL or LARGE kidneys: diabetic nephropathy (early), amyloidosis, ADPKD, HIV-associated nephropathy, obstructive uropathy, infiltrative disease. A classic MCQ.

Investigations:

• Serum creatinine + eGFR (CKD-EPI) — staging.
• Urine ACR / spot protein-creatinine ratio — albuminuria axis; preferred over 24-h collection.
• Ultrasound abdomen — investigation of choice for chronicity (size, echogenicity, obstruction, cysts).
• Urinalysis + microscopy (casts, dysmorphic RBCs, sediment).
• Electrolytes, calcium, phosphate, PTH, 25-OH vitamin D, ABG/bicarbonate.
• Haemogram + iron studies (ferritin, transferrin saturation).
• Renal biopsy if cause unclear and kidneys are not small/shrunken.

CKD–Mineral and Bone Disorder (CKD-MBD)

A perennially tested area. The cascade:

↓GFR → phosphate retention (hyperphosphataemia) + ↓1-α-hydroxylase → ↓calcitriol (active vit D) → hypocalcaemia → ↑PTH (secondary hyperparathyroidism). Phosphate also directly ↑FGF-23, which further suppresses calcitriol.

High-yield: FGF-23 (from osteocytes) is the EARLIEST biochemical abnormality in CKD-MBD, rising before phosphate or PTH. It promotes phosphaturia and suppresses calcitriol.

Types of renal osteodystrophy

Type	Bone turnover	PTH	Mechanism
Osteitis fibrosa cystica	High	High	Secondary hyperparathyroidism (commonest)
Adynamic bone disease	Low	Low/suppressed	Over-suppression of PTH, ↑Ca, oversedation with vit D/calcium
Osteomalacia	Low	Variable	Vitamin D deficiency, historically aluminium toxicity
Mixed uraemic osteodystrophy	Mixed	High	Combination

High-yield: Osteitis fibrosa cystica (high-turnover, due to 2° hyperparathyroidism) is the commonest renal osteodystrophy. Adynamic bone disease is now increasingly seen because of aggressive PTH suppression — beware over-treatment.

Tertiary hyperparathyroidism = autonomous parathyroid hyperplasia with hypercalcaemia developing after long-standing secondary hyperparathyroidism; treated by parathyroidectomy.

Management of CKD-MBD

1. Dietary phosphate restriction (first step).
2. Phosphate binders with meals:
   • Calcium-based (calcium acetate/carbonate) — risk of hypercalcaemia, vascular calcification.
   • Non-calcium (sevelamer, lanthanum) — preferred when calcium high or vascular calcification present.
   • Avoid aluminium-based binders (aluminium toxicity → encephalopathy, osteomalacia).
3. Active vitamin D / calcitriol to suppress PTH (monitor calcium × phosphate product).
4. Calcimimetic — cinacalcet lowers PTH by increasing calcium-sensing receptor sensitivity (lowers Ca, useful when calcium high).
5. Parathyroidectomy for refractory/tertiary hyperparathyroidism.

High-yield mnemonic — phosphate binders: "Sevelamer Saves vessels" (non-calcium, no hypercalcaemia/calcification). Cinacalcet lowers calcium; calcitriol raises calcium.

Renal Anaemia

• Mechanism: deficient erythropoietin (EPO) production by peritubular interstitial fibroblasts; compounded by iron deficiency, uraemic inhibition of erythropoiesis, shortened RBC lifespan, and hepcidin excess.
• Type: normocytic, normochromic (becomes microcytic if iron-deficient).

Management flow:

Correct iron stores first → start ESA → monitor Hb target.

1. Replete iron before/with ESA — target ferritin >100 ng/mL (often >200 in dialysis) and transferrin saturation >20%. IV iron preferred in haemodialysis.
2. Erythropoiesis-stimulating agents (ESAs) — epoetin alfa, darbepoetin.
3. Newer: HIF-PH inhibitors (e.g. roxadustat) — oral, raise endogenous EPO.

High-yield: Target haemoglobin 10–11.5 g/dL — do NOT normalise to ≥13 g/dL. Over-correction with ESAs increases stroke, thrombosis, hypertension, and mortality (TREAT/CHOIR/CREATE trials).

General Management of CKD

The goals: slow progression, treat complications, prepare for renal replacement therapy.

Slowing progression:

• BP control, target generally <120 mmHg systolic (KDIGO, standardised measurement) or <130/80.
• RAAS blockade (ACEi or ARB) — drug of choice when albuminuria present (A2/A3) or diabetic; reduces intraglomerular pressure and proteinuria. Do not combine ACEi + ARB.
• SGLT2 inhibitors (dapagliflozin/empagliflozin) — now cornerstone; reduce CKD progression and CV events in diabetic and non-diabetic CKD (DAPA-CKD, EMPA-KIDNEY).
• Finerenone (non-steroidal MRA) in diabetic CKD with albuminuria.
• Glycaemic control (HbA1c ~7%), smoking cessation, statin for CV risk.

Treating complications:

• Acidosis → oral sodium bicarbonate (target HCO₃⁻ ≥22).
• Hyperkalaemia → dietary K restriction, potassium binders (patiromer, SZC), loop diuretics.
• Volume/HTN → salt restriction, loop diuretics (thiazides ineffective at low GFR).
• CKD-MBD and anaemia as above.

High-yield: A small, reversible rise in creatinine (up to ~30%) after starting ACEi/ARB is acceptable and expected — only stop if rise exceeds 30% or hyperkalaemia is significant. A >30% jump suggests bilateral renal artery stenosis.

Renal Replacement Therapy (RRT) & Dialysis Indications

Indications for urgent dialysis — mnemonic "AEIOU":

• A — Acidosis (severe metabolic, refractory)
• E — Electrolytes (refractory hyperkalaemia)
• I — Intoxications (dialysable: methanol, ethylene glycol, lithium, salicylates, theophylline)
• O — Overload (refractory pulmonary oedema/fluid)
• U — Uraemia (pericarditis, encephalopathy, intractable nausea/bleeding)

High-yield: Uraemic pericarditis is an absolute indication for dialysis; heparin-free dialysis is preferred to avoid haemorrhagic transformation/tamponade.

Haemodialysis vs Peritoneal dialysis

Feature	Haemodialysis (HD)	Peritoneal dialysis (PD)
Site	Blood through dialyser	Peritoneum as membrane
Schedule	3–4 h, thrice weekly (centre)	Daily/continuous (home)
Access	AV fistula (best), graft, catheter	Tenckhoff catheter
Clearance	Diffusion across membrane	Diffusion + osmosis (glucose dialysate)
Main complication	Hypotension, disequilibrium, access infection	Peritonitis (commonest cause of PD failure)
Haemodynamics	Less stable	More stable; preserves residual function
Suitability	Most patients	Self-care, children, poor vascular access, CV instability

High-yield: AV fistula (Brescia–Cimino, radiocephalic at wrist) is the preferred long-term HD access — lowest infection/thrombosis; needs ~6 weeks to mature. PD peritonitis is most commonly due to coagulase-negative Staphylococcus/S. aureus; effluent WBC >100/µL with >50% neutrophils is diagnostic.

• Dialysis disequilibrium syndrome: cerebral oedema from rapid urea removal in first sessions → headache, seizures; prevent by slow, gradual clearance.
• Transplantation is the treatment of choice for ESRD — best survival and quality of life; living-donor pre-emptive transplant is ideal.

Complications (summary)

• Cardiovascular disease — leading cause of death.
• Anaemia, bleeding tendency (platelet dysfunction — corrected acutely by desmopressin/DDAVP, cryoprecipitate).
• CKD-MBD, vascular calcification, calciphylaxis.
• Hyperkalaemia, metabolic acidosis.
• Malnutrition, growth failure (children).
• Increased infection susceptibility.
• Uraemic pericarditis, encephalopathy, neuropathy.

Key Differentials

• AKI vs CKD (kidney size, anaemia, osteodystrophy, chronicity) — see table above.
• Acute-on-chronic kidney disease — superimposed reversible insult (sepsis, nephrotoxin, volume depletion, contrast) on baseline CKD; look for an acute jump in creatinine over chronic baseline.
• Causes of bilateral small kidneys vs the "normal/large kidney CKD" list (diabetes, amyloid, ADPKD, HIVAN, obstruction).

Recently asked / exam angle

• KDIGO G and A staging — assigning a stage from given eGFR + ACR (e.g. eGFR 38, ACR 80 → G3b A2).
• Earliest abnormality in CKD-MBD = FGF-23; commonest renal osteodystrophy = osteitis fibrosa cystica.
• Sevelamer as the non-calcium phosphate binder of choice; cinacalcet mechanism (calcium-sensing receptor agonist).
• Target Hb in renal anaemia 10–11.5 g/dL; dangers of over-correction.
• AEIOU indications for emergency dialysis; uraemic pericarditis as absolute indication.
• Diabetic nephropathy = commonest cause of ESRD; Kimmelstiel–Wilson nodules.
• SGLT2 inhibitors now reduce CKD progression even in non-diabetics (EMPA-KIDNEY/DAPA-CKD).
• AV fistula as best HD access; PD peritonitis effluent criteria (>100 WBC/µL, >50% neutrophils).
• Causes of CKD with normal-sized kidneys.
• Drug dosing: which drugs to avoid/adjust (metformin contraindicated at low GFR, avoid NSAIDs, gadolinium → nephrogenic systemic fibrosis at GFR <30).

Rapid revision

1. CKD = kidney damage marker or GFR <60 for ≥3 months; stage by G + A (KDIGO heat map).
2. Diabetic nephropathy is the commonest cause of CKD/ESRD worldwide and in India.
3. eGFR by CKD-EPI 2021 (race-free); ultrasound is the investigation of choice for chronicity — small, echogenic kidneys.
4. CKD with normal/large kidneys: Diabetes (early), Amyloid, ADPKD, HIVAN, Obstruction.
5. Renal anaemia = EPO deficiency; correct iron first; target Hb 10–11.5 g/dL — never normalise.
6. FGF-23 is the earliest CKD-MBD abnormality; osteitis fibrosa cystica is the commonest osteodystrophy.
7. Phosphate handling: restrict diet → non-calcium binder (sevelamer) if calcium high; cinacalcet lowers Ca/PTH; calcitriol raises Ca.
8. ACEi/ARB + SGLT2 inhibitor slow progression; a ≤30% creatinine rise after ACEi is acceptable.
9. Dialysis indications = AEIOU; uraemic pericarditis/encephalopathy are absolute.
10. AV fistula = best HD access; PD peritonitis = effluent WBC >100/µL with >50% neutrophils.
11. Dialysis disequilibrium = cerebral oedema from rapid urea removal — dialyse slowly initially.
12. Renal transplant = treatment of choice for ESRD; CVD is the leading cause of death in CKD.