KDIGO DEFINITION

AKI = abrupt rise in creatinine ≥ 0.3 mg/dL within 48 hrs OR ≥ 1.5× baseline within 7 days OR UO < 0.5 mL/kg/hr > 6 hrs .

• KDIGO staging: Stage 1 = creatinine 1.5-1.9x baseline or UO < 0.5 mL/kg/h for 6-12 h; Stage 2 = 2-2.9x baseline or UO < 0.5 for >= 12 h; Stage 3 = >= 3x baseline or creatinine >= 4 mg/dL or RRT initiated or anuria >= 12 h.

• Clinical features: often silent early (detected on bloods); oliguria or anuria; features of uraemia (nausea, anorexia, confusion, asterixis, pericardial rub); fluid overload (raised JVP, peripheral oedema, pulmonary oedema); hyperkalaemia (palpitations, arrhythmia); metabolic acidosis (Kussmaul breathing). ATN classically evolves through oliguric -> diuretic -> recovery phases.
• Investigations: serial creatinine and urea; electrolytes (K+, bicarbonate, Ca/PO4); urinalysis with microscopy (muddy-brown granular casts = ATN, RBC casts = glomerulonephritis); urine sodium and FENa (pre-renal < 1%, intrinsic > 2%); renal ultrasound (size, obstruction, hydronephrosis); ABG (metabolic acidosis); ECG (hyperkalaemic changes); immunology (ANA, ANCA, anti-GBM, complement) if intrinsic GN is suspected.

Management:

• Treat cause; stop nephrotoxins; IV fluids for pre-renal; catheter/nephrostomy for post-renal
• Hyperkalaemia: Ca gluconate IV → insulin/dextrose → salbutamol → dialysis
• Fluid restrict in oliguric phase; diuretic phase: replace losses, monitor K⁺
• AEIOU indications for dialysis (Acidosis, Electrolytes, Intoxication, Overload, Uraemia)
• Complications: hyperkalaemia with cardiac arrhythmia/arrest, pulmonary oedema, severe metabolic acidosis, uraemic encephalopathy and pericarditis, increased infection and bleeding risk, and progression to chronic kidney disease.

DEFINITION

RTA = hyperchloraemic normal anion gap metabolic acidosis (NAGMA) with inappropriately alkaline or neutral urine, caused by defects in tubular H⁺ secretion or HCO₃⁻ reabsorption, with normal or near-normal GFR.

Diagnosis: Normal AG metabolic acidosis (AG = Na − (Cl + HCO₃) = 8–12 mEq/L); Urine anion gap = positive (UAG = urine Na + K − Cl) — positive UAG means kidneys cannot excrete NH₄⁺.

Management:

▶ Type 1: Sodium bicarbonate 1–2 mEq/kg/day + Potassium citrate (prevent nephrocalcinosis; alkalinises urine → ↓ calcium phosphate supersaturation)

▶ Type 2: High-dose bicarbonate (10–15 mEq/kg/day — because bicarb is continuously wasted); thiazide diuretics (induce mild volume depletion → ↑ PCT reabsorption)

▶ Type 4: Treat underlying disease; fludrocortisone 0.1 mg OD (if Addison's); dietary K⁺ restriction; stop offending drugs

• Complications: nephrocalcinosis and nephrolithiasis (calcium phosphate/oxalate stones) in Type 1 RTA due to hypercalciuria and alkaline urine; osteomalacia from chronic acidosis; hypokalaemic paralysis; growth retardation in children.
• Urine anion gap: UAG = urine (Na + K) - urine Cl; positive in RTA (impaired H+ secretion, low urine NH4+); negative in diarrhoea-related normal AG acidosis (high NH4+ excretion); a key tool to differentiate causes of normal anion gap metabolic acidosis.

DEFINITION & FEATURES

• Investigations: urinalysis and microscopy (dysmorphic RBCs + RBC casts = glomerular bleeding); urea and creatinine (often raised); serum complement (low C3 in PSGN, SLE, MPGN; normal in IgA nephropathy, anti-GBM, ANCA vasculitis); ASO titre and anti-DNase B (PSGN); ANA and anti-dsDNA (SLE); ANCA (vasculitis); anti-GBM antibody (Goodpasture); renal biopsy is definitive (light microscopy + immunofluorescence + electron microscopy).
• Complications: acute kidney injury, hypertensive emergency, fluid overload with pulmonary oedema, and progression to rapidly progressive (crescentic) glomerulonephritis.

Management: Treat underlying cause; salt/fluid restriction; antihypertensives (CCB, loop diuretic); steroids + cyclophosphamide for rapidly progressive forms; plasmapheresis for Goodpasture's.

DEFINITION & CLASSIFICATION

CAUSES OF PROTEINURIA

• Glomerular (most common): DM, HTN, GN (nephrotic/nephritic), SLE, amyloid
• Tubular: Fanconi syndrome, AIN, aminoglycosides — low-MW proteins (β2-microglobulin, lysozyme)
• Overflow: Myeloma — Bence-Jones proteins (light chains exceed tubular reabsorption capacity; detected by BJP in urine, NOT by dipstick )
• Functional/Physiological: Fever, exercise, orthostatic proteinuria (young adults; protein only when upright — disappears with recumbency; benign; no treatment needed)

Orthostatic proteinuria: Most common cause of persistent proteinuria in children/adolescents; benign; diagnose by split 24-hour urine (day upright vs night recumbent — protein only in day sample). No treatment needed; excellent prognosis.

Management:

• ACE-I/ARB — first-line for proteinuria reduction in DM, HTN, GN (reduces intraglomerular pressure + GBM permeability)
• SGLT2 inhibitors — reduce proteinuria and CKD progression independent of glycaemic effect
• BP < 130/80; low-salt diet (< 2 g Na/day); treat underlying cause
• Nephrotic-range proteinuria: > 3.5 g/day with hypoalbuminaemia, oedema, hyperlipidaemia, and lipiduria (oval fat bodies, fatty casts, maltese cross appearance on polarised light); complications include thrombosis (especially renal vein thrombosis), infection (loss of immunoglobulins), and malnutrition.
• Investigation of proteinuria: urine ACR on early morning sample (most practical); 24-h urine for quantification; urine protein electrophoresis (Bence Jones protein in myeloma); renal biopsy in adult-onset nephrotic syndrome to establish the histological diagnosis.

PRINCIPLES OF DIALYSIS

Dialysis removes uraemic toxins and excess fluid from the blood via two mechanisms: Diffusion (solute moves down concentration gradient across semi-permeable membrane) and Ultrafiltration (hydrostatic pressure drives fluid across membrane). Dialysis does NOT replace endocrine (EPO, vitamin D) or metabolic kidney functions.

Indications for RRT in CKD: GFR < 10 mL/min (GFR < 15 if diabetic) with symptoms of uraemia, hyperkalaemia, fluid overload, or malnutrition that cannot be managed conservatively.

OVERVIEW

CAPD = a form of peritoneal dialysis where the patient self-performs 4 manual exchanges per day (typically 2 L each exchange: at 08:00, 12:00, 18:00, 22:00). Each exchange dwells for 4–8 hours allowing diffusion/ultrafiltration. Done at home — patient is continuously ambulatory.

TECHNIQUE & SOLUTIONS

• Tenckhoff catheter — permanent silicone rubber catheter through abdominal wall into peritoneal cavity; tunnelled subcutaneously to prevent infection track
• Dialysate solutions: Lactate-buffered (converted to bicarbonate in vivo); Glucose concentrations: 1.5% (isotonic — minimal UF), 2.5% (moderate UF), 4.25% (hypertonic — maximum fluid removal; risk of hyperglycaemia)
• Exchange steps: Drain old dialysate → infuse 2 L fresh dialysate → dwell 4–8 hours → drain → repeat

ADVANTAGES OF CAPD

• Home-based — patient independent; better quality of life
• Continuous — gentler and more physiological than intermittent HD; better haemodynamic stability
• No anticoagulation needed; no vascular access complications; can preserve residual renal function longer
• Better preservation of residual renal function (important in early CKD G5)
• Preferred in: children, diabetics (no heparin), haemodynamically compromised patients, rural areas

COMPLICATIONS

• Peritonitis (#1 complication) — usually catheter-contamination during exchanges; *S. epidermidis* most common. Presents: cloudy effluent + abdominal pain ± fever. Diagnose: effluent WBC > 100/mm³ (> 50% neutrophils). Treat: intraperitoneal antibiotics (vancomycin + ceftazidime)
• Exit-site/tunnel infection — redness + discharge around catheter site; requires systemic antibiotics ± catheter removal
• Ultrafiltration failure — peritoneal membrane loses its osmotic gradient over years; high glucose absorption → less UF → fluid overload
• Hyperglycaemia — glucose absorbed from dialysate; especially problematic in diabetics
• Protein loss via dialysate (6–10 g/day); hypertriglyceridaemia; hernia (↑ intraabdominal pressure); leaks

DEFINITION

Microalbuminuria = urinary albumin excretion of 30–300 mg/day (or 20–200 μg/min; ACR 30–300 mg/g creatinine). It is NOT detectable by routine urine dipstick (dipstick detects > 300 mg/g only) — requires specific immunoassay (ACR test or 24-hour urine albumin).

CLINICAL SIGNIFICANCE

• Earliest marker of diabetic nephropathy — screening annually in Type 1 DM from 5 years after diagnosis and in Type 2 DM from diagnosis
• Independent cardiovascular risk marker — microalbuminuria = generalised endothelial dysfunction → predicts MI, stroke, and CV death in both diabetics and the general population
• Indicates early glomerular damage before GFR falls; up to 50% can be reversed with treatment

WHEN TO SCREEN

• Type 1 DM: from year 5 onwards, annually
• Type 2 DM: from diagnosis, annually (may have had DM years before diagnosis)
• Hypertension: annually
• Confirm microalbuminuria with 2 of 3 samples over 3–6 months (transient causes: exercise, UTI, fever, CCF, menstruation)

MANAGEMENT

▶ ACE inhibitor (ramipril 5–10 mg OD) or ARB (losartan 50–100 mg OD) — first-line even if normotensive; reduces ACR by 30–35%; slows progression to overt nephropathy

▶ SGLT2 inhibitor (dapagliflozin 10 mg OD) — reduces progression to macroalbuminuria and CKD progression (DAPA-CKD trial; EMPA-KIDNEY)

• Strict glycaemic control: HbA1c < 7%; strict BP control: < 130/80 mmHg
• Low-protein diet (0.6–0.8 g/kg/day); stop smoking; statin therapy (if dyslipidaemic)
• Pathophysiology: microalbuminuria reflects glomerular capillary wall damage with loss of charge-selective barrier; in diabetes, driven by hyperfiltration, advanced glycation end-products, and TGF-beta-mediated mesangial expansion; also a marker of systemic endothelial dysfunction.
• False positives: transient microalbuminuria can be caused by fever, UTI, vigorous exercise, menstruation, and acute illness; always confirm with two of three positive samples over 3-6 months.

DEFINITION & CLASSIFICATION

• Uncomplicated UTI: Structurally/functionally normal urinary tract; otherwise healthy non-pregnant woman; lower UTI (cystitis)
• Complicated UTI: Structural/functional abnormality, indwelling catheter, immunocompromised, pregnancy, males, upper UTI (pyelonephritis)
• Significant bacteriuria: ≥ 10⁵ CFU/mL on MSU culture (midstream urine); or ≥ 10³ CFU/mL with symptoms

RECURRENT UTI IN WOMEN

Defined as ≥ 2 episodes in 6 months OR ≥ 3 episodes in 1 year .

• Reinfection (> 80%) — new organism after previous cure; indicates risk factors (sexual activity, spermicides, post-menopausal oestrogen deficiency, incomplete bladder emptying)
• Relapse (< 20%) — same organism recurs within 2 weeks; indicates deep tissue infection, calculi, structural abnormality, or resistant organism

Management of recurrent UTI:

▶ Post-coital prophylaxis — single dose of nitrofurantoin or trimethoprim within 2 hrs of sexual intercourse (most effective in sexually-associated recurrences)

▶ Continuous low-dose prophylaxis — Nitrofurantoin 50–100 mg nocte OR Trimethoprim 100 mg nocte × 6 months; reduces recurrence by 95%

▶ Self-start therapy — patient-initiated treatment at first symptom (validated option for motivated patients)

• Topical oestrogen cream (post-menopausal women) — restores Lactobacillus flora; reduces recurrence
• Cranberry products, D-mannose (probiotics) — some evidence; generally well-tolerated adjuncts

Investigations in recurrent/complicated UTI:

• MSU culture and sensitivity — before antibiotics; identify organism + sensitivity
• Renal USS + Bladder scan (post-void residual) — exclude structural abnormality, calculi, incomplete emptying
• CT KUB / IVU — if recurrent pyelonephritis or calculi suspected; cystoscopy if haematuria

DEFINITION

AGN = acute inflammatory disease of the glomeruli characterised by the nephritic syndrome: haematuria + proteinuria + hypertension + oliguria , most commonly following an infection.

POST-STREPTOCOCCAL GN (PSGN) — THE CLASSIC

• Cause: Group A beta-haemolytic Streptococcus (GAS) — M types 1, 4, 12 (throat) and 49, 57 (skin). Latent period: 10–14 days post-pharyngitis or 3–6 weeks post-skin infection (impetigo/pyoderma)
• Pathogenesis: Immune complex (IgG + complement) deposition in glomeruli → inflammation. Type III hypersensitivity . Subepithelial humps (immune deposits between GBM and podocytes) on EM — pathognomonic
• C3 ↓ (with C4 normal) — alternate pathway activation; C3 normalises by 6–8 weeks (if persistent ↓C3 → think MPGN or lupus)
• ASO titre — elevated after throat infection; anti-DNase B — elevated after skin infection (anti-streptolysin not produced after skin infection)

CLINICAL FEATURES

• Haematuria — tea/cola/smoky-coloured urine; RBC casts on microscopy (pathognomonic of GN)
• Hypertension — often severe; risk of hypertensive encephalopathy (headache, seizures)
• Oedema — periorbital and facial oedema (worse in morning ); ankle/leg oedema
• Oliguria — reduced urine output; mild AKI may develop
• Preceded by history of sore throat or skin infection 1–3 weeks earlier

MANAGEMENT

• Antistreptococcal therapy: Penicillin V 250 mg QDS × 10 days (or benzathine penicillin 1.2 MU IM single dose) — eradicates residual GAS; does NOT change renal outcome (immune response already triggered)
• Salt and fluid restriction — Na < 2 g/day; fluid restrict if oliguria
• Antihypertensives: CCB (nifedipine/amlodipine) or loop diuretics (furosemide) — first-line; avoid ACE-I/ARB in acute phase (can worsen GFR)
• Furosemide 40–80 mg OD/BD — for oedema and hypertension management (natriuretic)
• Dialysis — if severe AKI (oliguric uraemia), life-threatening hyperkalaemia, or refractory pulmonary oedema
• Prognosis: Excellent in children (> 95% complete recovery); adults have worse prognosis (~30% develop CKD if underlying immune disease persists)

MANAGEMENT

▶ Penicillin V 250 mg QDS × 10 days — eradicate GAS (doesn't change renal outcome)

▶ Furosemide 40 mg OD/BD — oedema + hypertension; add nifedipine/amlodipine if BP not controlled

• Salt/fluid restriction; protein restriction if significant uraemia; dialysis if severe AKI
• Steroid NOT required in PSGN (unlike RPGN or lupus nephritis)
• Clinical features: oedema (periorbital in morning, pedal in evening), haematuria (cola/tea-coloured urine, RBC casts on microscopy), hypertension, oliguria, and mild proteinuria; children aged 5-12 years are most commonly affected and have the best prognosis.
• Investigations: low C3 with normal C4 (classical pathway consumption); elevated ASO titre and anti-DNase B; urinalysis showing RBC casts; throat/skin swab for GAS; renal biopsy only if atypical features or no recovery by 6-8 weeks.
• Prognosis and complications: complete recovery in > 95% of children; adults have a higher risk of persistent proteinuria, hypertension, and progressive CKD; acute complications include hypertensive encephalopathy, pulmonary oedema, and rapidly progressive GN.

DEFINITION

RPGN = clinical syndrome of rapidly declining renal function (loss of > 50% GFR within weeks to months) with cellular or fibrocellular crescents in > 50% of glomeruli on renal biopsy. Medical emergency — untreated → ESRD in weeks.

Hallmark histology: Crescents = proliferating parietal epithelial cells + fibrin + macrophages in Bowman's space → compress glomerular tuft → obliterate capillary lumen.

MANAGEMENT

▶ Pulse methylprednisolone (IV methylprednisolone 500 mg–1 g OD × 3 days) — immediately on diagnosis; then oral prednisolone 1 mg/kg/day

▶ Cyclophosphamide IV 15 mg/kg pulses monthly (or oral 2 mg/kg/day) × 3–6 months — induction therapy; watch: haemorrhagic cystitis, infections, gonadal toxicity

▶ Rituximab (anti-CD20) — alternative to cyclophosphamide in ANCA vasculitis; RAVE trial; fewer side effects

▶ Plasmapheresis — Type I (Anti-GBM disease); also Type III if pulmonary haemorrhage or dialysis-dependent; removes anti-GBM antibodies/ANCA rapidly

• Maintenance: Azathioprine 2 mg/kg/day × 18–24 months (less toxic than cyclophosphamide; CYCAZAREM trial)

DEFINITION

Acute pyelonephritis = acute bacterial infection of the kidney parenchyma and pelvis , usually from ascending UTI (via ureter from bladder) or, rarely, haematogenous spread.

CLINICAL FEATURES

• Classic triad: Fever (high-grade, > 38.5°C, with chills/rigors) + Loin/flank pain + Symptoms of lower UTI (dysuria, frequency, urgency)
• Costovertebral angle (CVA) tenderness — punch tenderness over the renal angle (just below 12th rib, paravertebral); highly characteristic sign
• Nausea, vomiting, malaise; rarely haematuria
• Complications: Perinephric abscess (fever not settling with antibiotics ); Emphysematous pyelonephritis (gas in renal parenchyma on CT — diabetics; emergency nephrectomy); septicaemia; CKD in recurrent episodes

INVESTIGATIONS

• Urine dipstick — positive nitrites (gram-negative bacteria) + leucocyte esterase; haematuria
• MSU culture + sensitivity — obtain BEFORE antibiotics; *E. coli* most common; ESBL-producing organisms increasingly common
• Blood cultures — mandatory in hospitalised patients (bacteraemia in 20–30%)
• Urine microscopy — WBC casts (indicates upper tract infection; pathognomonic), pyuria
• Renal USS — exclude obstruction, calculi, abscess; CT KUB if USS inconclusive or not improving
• CBC — leucocytosis with neutrophilia; ↑ CRP and procalcitonin; renal function (creatinine)

MANAGEMENT

▶ Outpatient (mild, oral): Ciprofloxacin 500 mg BD × 7 days OR Co-amoxiclav 625 mg TDS × 14 days (culture-guided; adjust if ESBL)

▶ Inpatient (severe, IV): Ceftriaxone 1–2 g IV OD × 10–14 days OR Piperacillin-tazobactam 4.5 g IV TDS (if complicated/Pseudomonas risk) OR Ertapenem 1 g IV OD (ESBL-proven)

• IV fluids + antipyretics; analgesia (NSAIDs only if no AKI); antiemetics
• Review at 48–72 hours: Clinical improvement expected; if NOT improving → USS/CT to exclude obstruction, abscess or resistant organism; culture-guide antibiotics
• Duration: 7 days for uncomplicated; 10–14 days for complicated/bacteraemic
• Women with recurrent pyelonephritis → investigate for structural abnormality (USS + cystoscopy)

STEROIDS IN NEPHROTIC SYNDROME

Steroid adverse effects (important for monitoring): Cushing's syndrome, hypertension, diabetes, osteoporosis (give calcium + vitamin D), GI ulcers (PPI cover), infections (Pneumocystis prophylaxis — co-trimoxazole), growth retardation (children), cataract, adrenal suppression.

POLYURIA — Definition & Causes

Polyuria = urine output > 3 L/day (or > 2 mL/kg/hr) in adults.

ACE INHIBITORS IN RENAL DISEASE

• Mechanism: Block conversion of AngI → AngII → ↓ efferent arteriolar vasoconstriction → ↓ intraglomerular pressure → ↓ proteinuria + renoprotective effect (independent of systemic BP lowering)
• Indications in renal disease: Diabetic nephropathy (macro/microalbuminuria); CKD with proteinuria > 300 mg/day; Non-diabetic proteinuric CKD; Hypertension in CKD
• Renoprotective effect: Reduces progression to ESRD by 30–40% in diabetic nephropathy (MICRO-HOPE, ADVANCE trials)
• Key side effects: Dry cough (ACE-I-specific; bradykinin — switch to ARB if troublesome); hyperkalaemia; ↑ creatinine (acceptable up to 30% from baseline — reflects ↓ intraglomerular pressure, NOT true deterioration); angioedema; hypotension
• AVOID in: Bilateral renal artery stenosis (or unilateral in single functioning kidney) — precipitates acute renal failure; pregnancy (teratogenic — Trimester 2+3); hyperkalaemia > 5.5 mEq/L; serum creatinine > 3.5 mg/dL (use with caution)

DEFINITION & CAUSES

RAS = narrowing of renal artery → ischaemia to kidney → RAAS activation → renovascular hypertension + progressive renal failure (ischaemic nephropathy).

• Atherosclerotic RAS (~90%) — older patients (> 55); male; bilateral in 30–40%; ostial (at origin of renal artery); associated CV risk factors (DM, HTN, smoking)
• Fibromuscular Dysplasia (FMD) (~10%) — young women; mid/distal artery; 'string of beads' appearance on angiography; hyperplasia of vessel wall media

CLINICAL FEATURES — SUSPECT RAS

• Resistant hypertension — BP refractory to ≥ 3 drugs (including diuretic); or sudden-onset severe HTN in young woman (FMD) or elderly man (atherosclerotic)
• Renal impairment with ACE-I/ARB — rise in creatinine > 30% after starting ACE-I = hallmark of bilateral RAS or RAS in single kidney
• Unexplained flash pulmonary oedema (Pickering syndrome) — sudden pulmonary oedema with bilateral RAS and normal/preserved LV function; RAAS-driven Na retention + ↑ afterload
• Abdominal bruit — epigastric/flank bruit (systolic ± diastolic); lateralises to affected side; present in ~50%
• Asymmetric kidneys on USS (> 1.5 cm difference); hypokalaemia (secondary hyperaldosteronism)

INVESTIGATIONS

• Doppler USS (first-line) — screening test; elevated peak systolic velocity (PSV > 180–200 cm/s) + ↑ renal resistive index; affected kidney may be smaller
• CT angiography (CTA) (best non-invasive) — gold standard for anatomical assessment; shows degree and extent of stenosis; avoids radiation risk of conventional angio in most
• MR angiography (MRA) — no contrast; good for screening; may overestimate stenosis
• Selective renal angiography (DSA) — GOLD STANDARD; combined diagnostic + interventional (angioplasty at same time); invasive
• Captopril renogram — split renal function; affected kidney shows delayed Tc-MAG3 excretion; captopril exaggerates this (unmasks RAAS dependency); now less commonly used

MANAGEMENT

• Medical (ALL patients ): Intensive cardiovascular risk factor management; statin; antiplatelet (aspirin); tight BP control; avoid ACE-I/ARBs in bilateral RAS

▶ Calcium channel blockers (amlodipine) — safest antihypertensive in RAS; do NOT reduce renal blood flow

• Percutaneous transluminal angioplasty (PTA) — first-line revascularisation for FMD (excellent response; curative in > 70%); stenting NOT usually needed
• Renal artery stenting — for atherosclerotic RAS + stent required after PTA to prevent resection; flash pulmonary oedema episodes; preserving renal function in ischaemic nephropathy
• Surgical revascularisation — aorto-renal bypass; reserved for complex anatomy or failed stenting

• Urinalysis (dipstick + microscopy): detects proteinuria, haematuria and casts (RBC casts = glomerular, WBC casts = pyelonephritis, granular casts = ATN); quantify proteinuria with urine ACR or PCR on an early-morning sample.
• GFR estimation: eGFR (CKD-EPI from creatinine +/- cystatin C) is used for CKD staging; 24-h creatinine clearance overestimates GFR (tubular secretion of creatinine); measured GFR (inulin/iohexol clearance) is most accurate but research-only.
• Imaging: renal ultrasound assesses size, cortical thickness, obstruction and cysts (small kidneys = chronic disease; large = PKD/infiltration); CT/MR angiography for renal artery stenosis; isotope scans (DTPA/MAG3) for split function and obstruction.
• Renal biopsy: indicated in unexplained AKI, glomerulonephritis, adult nephrotic syndrome, or systemic disease with renal involvement; gives the histological diagnosis (light microscopy + immunofluorescence + electron microscopy).

DEFINITION & GENETICS

ADPKD = most common inherited cause of CKD (1:400–1:1000); autosomal dominant with near complete penetrance. Two genes: PKD1 (chromosome 16; 85%; polycystin-1) — more severe; PKD2 (chromosome 4; 15%; polycystin-2) — milder, later onset. Cysts gradually enlarge → destroy renal parenchyma → ESRD by age 50–70 in PKD1.

CLINICAL FEATURES

• Hypertension — earliest manifestation (50% by age 30); from cyst expansion → RAAS activation → renal ischaemia
• Flank/loin pain — from cyst expansion, haemorrhage into cyst, or stone passage
• Haematuria — gross haematuria from cyst rupture into collecting system; also haemorrhage into cyst (acute loin pain + haematuria)
• Palpable bilateral enlarged kidneys — bosselated (irregular surface); can be massive; distinctive on examination
• Recurrent UTI — especially pyelonephritis and infected cysts (tricky to treat); gram-negative bacteria
• Renal stones (uric acid + calcium oxalate) — in 20% of patients

EXTRA-RENAL MANIFESTATIONS

• Intracranial aneurysms (Berry aneurysms) — 8–12% of patients; risk of subarachnoid haemorrhage (most serious extrarenal complication); screen if family history of SAH or ruptured aneurysm (MR angiography)
• Hepatic cysts (most common extra-renal manifestation; ~80%); liver function usually preserved; may cause massive hepatomegaly
• Pancreatic cysts; Mitral valve prolapse (25–26%); Aortic/cardiac valve abnormalities; Inguinal hernia

INVESTIGATIONS & MANAGEMENT

• Renal USS — diagnostic; multiple bilateral cysts (Ravine criteria: age-adjusted number of cysts); CECT for equivocal cases; MRI (most sensitive)
• Genetic testing — if USS equivocal or family counselling required; PKD1/PKD2 mutation analysis

▶ Tolvaptan (V2 receptor antagonist / vasopressin antagonist) — slows rate of cyst growth; approved for rapidly progressing ADPKD (TEMPO 3:4, REPRISE trials); side effects: thirst, polyuria, hepatotoxicity

▶ ACE inhibitor/ARB — for hypertension (which is universal); target BP < 130/80 mmHg; also may slow cyst growth

• Treat UTI promptly (fluoroquinolones penetrate cysts — preferred for infected cysts over beta-lactams)
• Renal replacement therapy (dialysis/transplant) when ESRD reached (typically 50–60 years in PKD1)
• Genetic counselling — 50% chance of inheritance in offspring; pre-implantation genetic diagnosis available

MODALITIES OF RRT

INDICATIONS FOR STARTING RRT IN CKD

• eGFR < 10 mL/min (or < 15 if diabetic) with symptomatic uraemia — anorexia, nausea, weight loss, encephalopathy
• Uraemic complications: Pericarditis (refractory to treatment); uraemic encephalopathy; uraemic bleeding (platelet dysfunction)
• Refractory hyperkalaemia (K⁺ > 6 mEq/L despite medical management)
• Refractory fluid overload (pulmonary oedema not responding to diuretics)
• Severe metabolic acidosis (pH < 7.1 refractory to bicarbonate)
• Malnutrition — inability to maintain adequate nutrition due to uraemia + dietary restrictions
• Haemodialysis access: arteriovenous fistula (AVF) is the preferred access (Cimino-Brescia fistula, typically radiocephalic); needs 4-6 weeks to mature before use; tunnelled central venous catheter used as a bridge or when AVF is not possible.
• Peritoneal dialysis: CAPD (continuous ambulatory peritoneal dialysis) uses the peritoneum as a natural membrane; 4 exchanges per day; main complication is peritonitis (S. aureus, S. epidermidis most common); contraindicated after abdominal surgery or with severe abdominal adhesions.
• Renal transplantation: gold standard RRT; best quality of life and survival; living donor preferred; immunosuppression with tacrolimus + mycophenolate + prednisolone; monitor for rejection (acute - rising creatinine, tender graft; treat with IV methylprednisolone) and opportunistic infections.

DEFINITION

CKD = kidney structural/functional abnormality persisting > 3 months , with health implications. Defined by eGFR < 60 mL/min/1.73m² AND/OR kidney damage markers (proteinuria > 30 mg/g, abnormal renal imaging).

STAGING (KDIGO 2024)

• G1 (eGFR ≥ 90) — Normal/high GFR; diagnosis by damage markers only
• G2 (60–89) — Mildly decreased; usually asymptomatic
• G3a/b (30–59) — Mild to moderately decreased; complications begin (anaemia, bone disease)
• G4 (15–29) — Severely decreased; prepare for RRT; refer nephrologist
• G5 (< 15) — Kidney failure; RRT required

KEY COMPLICATIONS

• Cardiovascular disease (#1 cause of death in CKD) — hypertension, LVH, accelerated atherosclerosis
• Anaemia — ↓ EPO → normocytic normochromic; treat with IV iron → ESA (target Hb 10–12 g/dL )
• Renal osteodystrophy — 2° HPT; treat with phosphate binders + calcitriol + cinacalcet
• Hyperkalaemia — life-threatening; diet restriction + patiromer/SZC + dialysis
• Metabolic acidosis — oral bicarbonate; target HCO₃ ≥ 22 mEq/L

MANAGEMENT PYRAMID

• Treat underlying cause (DM glycaemic control; HTN management)
• Slow progression: ACE-I/ARB + SGLT2 inhibitor + BP < 130/80 mmHg
• Manage complications: Anaemia, bone disease, hyperkalaemia, acidosis
• Prepare for RRT: Dietitian referral; vascular access creation; transplant evaluation; hepatitis B vaccination
• Renal replacement therapy: Dialysis (HD/PD) or transplantation at G5

• Causes: diabetic nephropathy (#1 worldwide), hypertensive nephrosclerosis (#2), chronic glomerulonephritis, ADPKD, obstructive uropathy, reflux nephropathy, interstitial nephritis; identify and treat the underlying cause to slow progression.
• CKD-mineral bone disorder (CKD-MBD): as eGFR falls, phosphate rises, FGF-23 rises (inhibits 1-alpha-hydroxylase), calcitriol falls, calcium falls, PTH rises (secondary hyperparathyroidism); treat with dietary phosphate restriction, calcium-based or non-calcium binders (sevelamer), and active vitamin D analogues (alfacalcidol or calcitriol).
• Cardiovascular risk: CKD is an independent cardiovascular risk factor; all-cause mortality is largely driven by cardiovascular events; manage BP aggressively (ACE-i/ARB + SGLT2 inhibitor), control lipids (statin), and treat anaemia.