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Renal Medicine - Clinical Learning Notes for Medical Students

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1. ACUTE KIDNEY INJURY (AKI)

Definition (KDIGO Criteria)

• Rise in serum creatinine ≥0.3 mg/dL within 48 hours
• Rise in serum creatinine to ≥1.5× baseline within 7 days
• Urine output <0.5 mL/kg/hr for ≥6 hours

Classification: Pre-renal / Intra-renal / Post-renal

Key formula: FENa (%) = (Urine Na × Plasma Cr) / (Plasma Na × Urine Cr) × 100 FENa <1% = pre-renal (kidney trying hard to retain sodium). In ATN, tubular damage = cannot reabsorb Na = FENa >2%. Exception: FENa may be <1% with contrast nephropathy, myoglobinuria, early obstruction, and with diuretic use (use FEUrea instead).

KDIGO Staging

Acute Tubular Necrosis (ATN)

1. Ischaemic ATN - prolonged hypoperfusion causes proximal tubular cell death
2. Nephrotoxic ATN - drugs (aminoglycosides, vancomycin, cisplatin, contrast agents), pigments (myoglobin, haemoglobin)

• Initiation phase → Oliguria/maintenance phase (1-2 weeks) → Polyuric recovery phase → Resolution

Novel Biomarkers of AKI

• NGAL (neutrophil gelatinase-associated lipocalin): rises within hours of injury
• KIM-1 (kidney injury molecule-1): proximal tubular marker
• Cystatin C: early GFR marker
• α1-microglobulin: predicts need for RRT (AUC ~0.86); useful in proximal tubular injury
• These are superior to creatinine for early detection because creatinine only rises once ~50% of nephrons are damaged

Clinical Features of AKI

• Oliguria (<400 mL/day) or anuria
• Fluid overload: peripheral oedema, pulmonary oedema, hypertension
• Uraemic features: nausea, vomiting, encephalopathy, pericarditis, asterixis
• Electrolyte disturbance: hyperkalaemia (most dangerous acutely), metabolic acidosis, hyperphosphataemia, hypocalcaemia

Indications for Emergency Dialysis (AEIOU)

• A - Acidosis (pH <7.1, unresponsive to bicarbonate)
• E - Electrolyte disorders (refractory hyperkalaemia >6.5 mmol/L)
• I - Intoxication (lithium, methanol, ethylene glycol, aspirin)
• O - Overload (pulmonary oedema unresponsive to diuretics)
• U - Uraemia (symptomatic: encephalopathy, pericarditis, bleeding)

Management

1. Treat underlying cause and remove nephrotoxins
2. Fluid optimisation - cautious resuscitation targeting MAP ≥65 mmHg
3. Treat hyperkalaemia: calcium gluconate (membrane stabilisation), insulin-dextrose, nebulised salbutamol, calcium resonium, dialysis
4. Adjust/withhold nephrotoxic drugs (NSAIDs, ACEi, ARBs, aminoglycosides, contrast media)
5. Nutritional support; avoid excessive protein restriction
6. Renal replacement therapy if indicated

Source: Fischer's Mastery of Surgery; Brenner and Rector's The Kidney

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2. PYELONEPHRITIS / URINARY TRACT INFECTION (UTI)

Definitions

• Bacteriuria: bacteria in urine >10⁵ CFU/mL (clean catch); >10⁴ CFU/mL (catheter specimen); any growth from suprapubic aspirate
• Cystitis: infection of the bladder (lower UTI)
• Pyelonephritis: infection reaching renal pelvis, tubules and interstitium (upper UTI)
• Complicated UTI: UTI in males, pregnancy, structural/functional abnormality, catheterisation, immunosuppression, recent instrumentation, diabetes, indwelling catheter

Microbiology

• E. coli - by far the most common (>85% of community UTIs)
• Proteus, Klebsiella, Enterobacter (especially hospital-acquired)
• Staphylococcus saprophyticus - young sexually active women (second most common community UTI)
• Enterococcus faecalis
• Immunocompromised: fungi (Candida), viruses (polyomavirus, CMV, adenovirus), Mycobacteria

Pathogenesis - Routes of Infection

1. Ascending infection (most common) - colonisation of distal urethra → bladder → ureter → kidney
   • Key virulence factor: P-fimbriae (pili) on E. coli bind uroepithelial receptors
   • Predisposed by: vesicoureteral reflux, obstruction, urinary stasis, catheterisation, female anatomy (short urethra)
2. Haematogenous spread - less common; Staphylococcus, fungi, Mycobacteria; seen with endocarditis, immunosuppression

Risk Factors

• Female sex (short urethra, proximity to anus, hormonal changes affecting mucosal adhesion)
• Sexual intercourse ("honeymoon cystitis")
• Pregnancy (urinary stasis from progesterone effect + ureteral compression → 40% risk of pyelonephritis if bacteriuria untreated)
• Urinary tract obstruction (BPH, stones, tumour)
• Vesicoureteral reflux (VUR) - present in ~30% of children with UTI
• Diabetes mellitus (neurogenic bladder, impaired immunity)
• Uncircumcised males (10× higher UTI risk in boys)
• Catheterisation (long-term catheter = nearly universal bacteriuria)

Clinical Features

Diagnosis

• Urinalysis: leucocyte esterase (+), nitrites (+), >5 WBCs/hpf (pyuria), WBC casts (suggest upper UTI)
• Urine culture: gold standard - >10⁵ CFU/mL (clean catch)
• Dipstick: high sensitivity in symptomatic patients but high false-negative rate in pregnancy - culture preferred
• Imaging in: recurrent/complicated UTI, males, children with febrile UTI, suspected obstruction
  • Renal USS: first-line, identifies obstruction, stones, abscess
  • CT KUB (non-contrast): best for stones
  • VCUG (voiding cystourethrogram): diagnoses VUR in children (demonstrates reflux during micturition)
  • DMSA scan: detects renal cortical scarring (most sensitive)

Morphology of Acute Pyelonephritis

• Patchy suppurative interstitial inflammation with intratubular neutrophil aggregates
• Neutrophilic tubulitis + tubular injury
• Glomeruli relatively spared early (characteristic)
• Three serious complications:
  1. Papillary necrosis: grey-white/yellow necrosis of papillae; seen in diabetics, sickle cell, obstruction
  2. Perinephric abscess: extension of infection through renal capsule
  3. Pyonephrosis: pus fills collecting system (needs urgent drainage)
• Chronic pyelonephritis → coarse, asymmetric cortical scarring; blunted calyces; reflux nephropathy

Treatment

Trimethoprim-sulpha and tetracyclines are contraindicated in early pregnancy (teratogenic). Pregnancy with pyelonephritis → hospitalise, IV antibiotics, hydration due to risk of septic shock, DIC, and ARF.

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3. GLOMERULONEPHRITIS (GN)

Overview

• Nephritic syndrome: haematuria, proteinuria (<3.5 g/day), hypertension, oliguria, RBC casts
• Nephrotic syndrome: proteinuria (>3.5 g/day), hypoalbuminaemia, oedema, hyperlipidaemia (covered separately)

Pathological Mechanisms of Glomerular Injury

1. Immune complex deposition - complement activation → inflammation (IgA nephropathy, post-streptococcal GN, lupus nephritis, membranoproliferative GN)
2. Anti-GBM antibodies - Goodpasture disease (anti-α3(IV) collagen antibody)
3. ANCA-mediated (pauci-immune) - granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic GPA (EGPA)
4. Direct cellular injury - T cell-mediated (minimal change disease)

Key Types of Glomerulonephritis

(A) Post-Streptococcal GN (PSGN)

• Trigger: 2-3 weeks after Group A β-haemolytic Streptococcus (pharyngitis > impetigo)
• Mechanism: immune complex deposition (circulating complexes or planted antigens)
• Age: children 5-12 years typically
• Urine: haematuria ("cola/tea-coloured" urine), red cell casts, mild proteinuria
• Labs: ↓C3, ↓CH50, ↑ASO titre
• Biopsy: diffuse proliferative GN; "lumpy-bumpy" subepithelial immune deposits ("humps") on EM; granular IgG + C3 on IF
• Prognosis: mostly self-limiting in children (>95% recover); worse in adults

(B) IgA Nephropathy (Berger's Disease)

• Most common GN worldwide
• Mesangial IgA deposits; often after mucosal infection (upper respiratory, GI)
• Presents: episodic gross haematuria 1-3 days after infection (synpharyngitic haematuria) OR persistent microscopic haematuria ± mild proteinuria
• Biopsy: mesangial hypercellularity; IgA + C3 on IF; mesangial dense deposits on EM
• Treatment: RAAS blockade (ACEi/ARB) if proteinuria; immunosuppression in progressive disease; low-dose fish oils controversial

(C) Rapidly Progressive GN (RPGN)

• Medical emergency - renal function deteriorates over days to weeks
• Histology: >50% glomeruli with crescents (proliferation of parietal epithelial cells)
• Types:
  • Type I (Anti-GBM): Goodpasture disease - anti-α3(IV) collagen → linear IgG on IF; causes both GN + pulmonary haemorrhage (pulmonary-renal syndrome); triggers include smoking, hydrocarbon exposure, fluid overload
  • Type II (Immune complex): SLE, PSGN, IgA - granular IF
  • Type III (Pauci-immune/ANCA): GPA, MPA - negative IF; ANCA+ in blood
• Treatment: plasma exchange + high-dose steroids ± cyclophosphamide (especially anti-GBM)

(D) Membranous Nephropathy

• Most common cause of nephrotic syndrome in adults
• Primary: anti-PLA2R antibody (70-80%)
• Secondary: SLE, hepatitis B, malignancy, NSAIDs, gold, penicillamine
• Biopsy: subepithelial deposits creating "spike and dome" appearance on silver stain; granular IgG + C4d on IF
• Treatment: RAAS blockade; rituximab (anti-CD20) increasingly first-line; cyclophosphamide + steroids

(E) Membranoproliferative GN (MPGN)

• Mesangial proliferation + GBM thickening + duplication ("tram-track" appearance)
• Causes: hepatitis C (cryoglobulinaemia), chronic infections, complement dysregulation
• Low C3 persistently

(F) Lupus Nephritis

• ISN/RPS Classification I-VI (classes III and IV most severe)
• Class IV: diffuse proliferative LN - worst prognosis; "wire loop" lesions
• Labs: ↓C3/C4, ↑dsDNA antibodies; ANA+
• Treatment: mycophenolate mofetil + hydroxychloroquine; cyclophosphamide for severe disease

Nephritic Syndrome - Classic Features

• Haematuria (macroscopic = "smoky" or "cola" urine) + RBC casts (pathognomonic of GN)
• Hypertension (sodium/water retention)
• Oliguria
• Proteinuria (usually <3.5 g/day, sub-nephrotic)
• Periorbital oedema (especially morning, from fluid retention)
• ↑Creatinine (impaired GFR)

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4. TUBULO-INTERSTITIAL DISEASES

Definition

• No nephritic or nephrotic syndrome
• Tubular dysfunction: polyuria/nocturia (impaired concentration), salt wasting, metabolic acidosis (type IV RTA or Fanconi), ↓secretion/reabsorption of specific solutes

Classification

Causes of Tubulo-Interstitial Nephritis

Acute Drug-Induced Interstitial Nephritis

• Develops 2-40 days after drug exposure (immune-mediated, not dose-dependent)
• Classic triad: fever + rash + eosinophilia (only 10-30% have all three)
• NSAIDs: typically fever/rash absent; may co-present with nephrotic syndrome (minimal change)
• Checkpoint inhibitors (anti-PD-1, anti-CTLA-4): increasing cause; can resume treatment after recovery
• Urinalysis: pyuria, WBC casts, eosinophiluria (Hansel's stain), mild proteinuria, haematuria
• Activated T lymphocytes and eosinophils most characteristic cell types
• Renal biopsy: interstitial oedema, lymphocytic/eosinophilic infiltrate, tubulitis, ± granulomas (methicillin, thiazides, rifampicin)

Pathogenesis

Management of Drug-Induced AIN

1. Stop offending drug - essential; recovery may take weeks-months
2. Prednisolone (0.5-1 mg/kg/day for 4-8 weeks) - may accelerate recovery if used early
3. Support renal function; dialysis if severely impaired
4. Monitor for progression to CKD if delayed diagnosis

Chronic TIN / Analgesic Nephropathy

• Long-term use of analgesic combinations (historically phenacetin; now paracetamol + NSAIDs)
• Papillary necrosis → shrunken, scarred kidneys
• Also seen in: diabetes, sickle cell disease, obstruction, TB (focal)
• Clinical: slowly progressive CKD, tubular dysfunction, sterile pyuria
• Urate nephropathy (gout): urate crystal deposition → tubular obstruction → interstitial fibrosis; treat with allopurinol/febuxostat

TINU Syndrome

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5. CYSTIC KIDNEY DISEASES

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• Most common inherited kidney disease (1:400-1000 live births)
• Mutations: PKD1 (chromosome 16; 85%) or PKD2 (chromosome 4; 15%); encode polycystin-1 and -2
• PKD2 mutations = milder phenotype; ESRD ~10 years later than PKD1

• Cysts detectable on USS from late teens
• Pain (cyst haemorrhage, infection, stones)
• Hypertension (early; due to intrarenal RAAS activation by cysts compressing vessels)
• Haematuria (cyst haemorrhage)
• Urinary tract infections (cyst infection - may need IV antibiotics, fluoroquinolones penetrate cysts best)
• Renal calculi (20-30%)
• Bilateral renal enlargement (may be massive)
• ESRD: median age ~55 years for PKD1

• Hepatic cysts (most common; usually asymptomatic)
• Intracranial aneurysms (5-8%; berry aneurysms, mainly circle of Willis; screen if family history of rupture)
• Cardiac valve abnormalities (MVP most common)
• Pancreatic cysts, seminal vesicle cysts, colonic diverticula

• Renal USS: required cyst number increases with age (Ravine criteria)
• MRI: most accurate for total kidney volume (prognostic)
• Genetic testing if equivocal imaging

• BP control: ACEi/ARB (target <130/80 mmHg) - HALT-PKD trial
• Tolvaptan (V2 receptor antagonist) - slows cyst growth and GFR decline in rapid progressors; requires monitoring for hepatotoxicity
• Avoid NSAIDs, nephrotoxins
• Cyst infection: fluoroquinolones (penetrate cysts) ± drainage
• ESRD → dialysis or transplantation

Autosomal Recessive PKD (ARPKD)

• Less common; PKD1 gene (PKHD1, encodes fibrocystin/polyductin)
• Presents in neonates/infants (severe) or children/adolescents (milder)
• "Potter sequence" in severe cases (oligohydramnios → pulmonary hypoplasia, facies, limb deformities)
• Invariably associated with congenital hepatic fibrosis (portal hypertension)
• Kidneys: greatly enlarged, echogenic, with radial cyst pattern

Other Cystic Diseases

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6. NEPHROTIC SYNDROME

Definition

• Proteinuria >3.5 g/day (>40 mg/m²/hr in children) - "nephrotic range"
• Hypoalbuminaemia (<25 g/L)
• Oedema (pitting; periorbital in AM, dependent in PM)
• Hyperlipidaemia (↑LDL, ↑cholesterol, ↑triglycerides)
• Lipiduria (fatty casts, oval fat bodies - Maltese cross pattern under polarised light)

Pathophysiology of Oedema

1. Underfill theory: proteinuria → ↓albumin → ↓oncotic pressure → fluid moves to interstitium → ↓plasma volume → ↑RAAS + ↑ADH → salt/water retention
2. Overfill theory: primary renal NaCl retention (independent of volume) → plasma expansion → oedema

• Minimal change disease: usually underfill (contracted plasma volume, activated RAAS)
• Other causes: usually overfill (expanded plasma volume, suppressed RAAS)
• Consequence: furosemide resistance in nephrotic syndrome (albumin binding reduces free furosemide; filtered albumin binds drug in tubule)

Complications of Nephrotic Syndrome

1. Thromboembolism - especially renal vein thrombosis, DVT, PE (loss of antithrombin III, protein C/S in urine; ↑platelet aggregation; hyperviscosity)
2. Infection - loss of immunoglobulins + complement in urine → ↑susceptibility (pneumococcal infection, gram-negative peritonitis in children)
3. Hyperlipidaemia - atherosclerosis risk; ↑VLDL synthesis, ↓LPL activity
4. AKI - from hypovolaemia, sepsis, renal vein thrombosis
5. Protein malnutrition - loss of transferrin (anaemia), thyroid-binding globulin (↓T4), vitamin D-binding protein (↓25-OH vit D → ↑PTH)

Primary Causes by Age

Key Primary Causes

Minimal Change Disease (MCD)

• Normal light microscopy; "foot process effacement" on EM (podocyte injury)
• Negative IF (no immune deposits)
• Pathogenesis: T-cell dysfunction → circulating permeability factor damages podocytes
• Highly steroid-responsive (>90% adults/children achieve remission with prednisolone)
• Relapses common; cyclophosphamide or cyclosporin for frequent relapsers
• Associated: Hodgkin's lymphoma, NSAIDs, mercury

Focal Segmental Glomerulosclerosis (FSGS)

• Focal (<50% of glomeruli) and segmental (<entire glomerulus) sclerosis
• Most common cause of idiopathic nephrotic syndrome in Black adults
• Causes: primary (permeability factor), HIV-associated nephropathy (HIVAN - collapsing variant), heroin, pamidronate, obesity, reflux (secondary)
• LM: focal segmental sclerosis ± hyaline deposits; IF: IgM and C3 in sclerotic areas (non-specific)
• Steroid-resistant more often than MCD; treat with calcineurin inhibitors (tacrolimus, cyclosporin)

Membranous Nephropathy

• Subepithelial immune deposits → "spike and dome" appearance
• Anti-PLA2R antibodies (primary); useful for diagnosis and monitoring response
• Secondary causes: HBV, HCV, SLE, malignancy, drugs (gold, penicillamine)

Secondary Causes of Nephrotic Syndrome

Management

1. Treat underlying cause
2. Proteinuria reduction: ACEi or ARB (reduce intraglomerular pressure; anti-fibrotic)
3. Oedema: loop diuretics ± aldosterone antagonist; avoid rapid diuresis (↑thrombosis risk)
4. Hyperlipidaemia: statin therapy
5. Anticoagulation: heparin → warfarin if serum albumin <20 g/L (high thrombosis risk) or proven thrombosis
6. Infection prophylaxis: pneumococcal vaccine; penicillin prophylaxis in children
7. Corticosteroids ± immunosuppression per diagnosis

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7. RENAL REPLACEMENT THERAPY (RRT)

Indications for RRT

Modalities Overview

Haemodialysis (HD)

• Blood flows along one side of a semipermeable membrane; dialysate flows in opposite direction (counter-current)
• Diffusion: small solutes (urea, creatinine, K⁺) move down concentration gradient
• Ultrafiltration: hydrostatic pressure removes fluid
• Blood flow rates: 200-350 mL/min (higher = more efficient)

• Rapid, efficient solute removal (ideal for hyperkalaemia, toxin ingestion)
• 3x/week schedule allows "off" time
• Less anticoagulation needed vs. CRRT (due to high flow rates)

• Haemodynamic instability (rapid fluid shifts → hypotension)
• Risk of disequilibrium syndrome (rapid urea fall → cerebral oedema)
• Requires vascular access (AV fistula preferred; tunnelled catheter; graft)

Continuous RRT (CRRT)

1. SCUF (slow continuous ultrafiltration) - volume removal only
2. CVVH (continuous venovenous haemofiltration) - convection; filtration of plasma water
3. CVVHD (continuous venovenous haemodialysis) - diffusion; dialysate used
4. CVVHDF (continuous venovenous haemodiafiltration) - both convection + diffusion

• Haemodynamically well tolerated (slow, continuous fluid removal)
• Allows high volumes of IV medications/nutrition
• Avoids abrupt concentration changes Disadvantages:
• Requires anticoagulation (citrate preferred in ICU; heparin alternative)
• Continuous monitoring required (ICU setting)
• No clear superiority over iHD in outcomes

Peritoneal Dialysis (PD)

• Hypertonic glucose solution infused into peritoneal cavity
• Peritoneum acts as natural semipermeable membrane
• Water removal driven by osmotic gradient (glucose concentration)
• Two forms: CAPD (continuous ambulatory PD - 4 exchanges/day) and APD (automated PD - overnight machine)
• Advantages: home-based, steady-state solute control, preserves residual renal function longer than HD
• Complications: peritonitis (most serious; Staphylococcus epidermidis most common), exit site infection, hernias, hydrothorax, encapsulating peritoneal sclerosis

Kidney Transplantation

• Best form of RRT for eligible patients - superior survival, quality of life, and cost compared to dialysis
• Donor sources: living (related/unrelated) or deceased (DBD/DCD)
• Immunosuppression: induction (basiliximab or ATG) + maintenance (tacrolimus + mycophenolate + prednisolone)
• Complications: rejection (hyperacute, acute, chronic), infection (CMV, EBV/PTLD, PCP), malignancy, nephrotoxicity from calcineurin inhibitors
• Contraindications: active malignancy, active infection, non-compliance, severe cardiovascular disease (relative)

Vascular Access for HD

1. AV Fistula (gold standard) - native artery-vein anastomosis; lowest infection/thrombosis risk; needs 4-6 weeks to mature
2. AV Graft - prosthetic material (PTFE); faster usable; higher complications than fistula
3. Tunnelled Central Venous Catheter (Permcath) - immediate access; highest infection/thrombosis risk; temporary bridge or permanent if no other access possible

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8. CHRONIC KIDNEY DISEASE (CKD)

Definition

• Structural abnormalities (imaging, biopsy) OR
• eGFR <60 mL/min/1.73m²
• Markers of damage: albuminuria, abnormal urinary sediment, electrolyte disorders

Staging (KDIGO 2012)

Common Causes

1. Diabetes mellitus - ~50% of ESRD cases; diabetic nephropathy = nodular glomerulosclerosis (Kimmelstiel-Wilson nodules); microalbuminuria (A2) is earliest sign
2. Hypertension - hypertensive nephrosclerosis; ischaemic nephropathy (especially in elderly with large vessel disease)
3. IgA nephropathy
4. ADPKD
5. Lupus nephritis
6. Recurrent pyelonephritis / reflux nephropathy
7. Obstructive uropathy
8. Hereditary (Alport syndrome - X-linked COL4A5 mutation; α3 chain type IV collagen; sensorineural deafness + ocular abnormalities + haematuria)

Estimating GFR

• CKD-EPI equation (most accurate, preferred): uses creatinine ± cystatin C
• MDRD: GFR = 1.86 × (SCr)^-1.154 × (Age)^-0.203 × (0.742 if female) × (1.21 if Black)
• Cockcroft-Gault: CrCl = (140 - Age) × Weight / (72 × SCr) [× 0.85 if female]

Clinical Features: Uraemic Syndrome

CKD-Mineral and Bone Disorder (CKD-MBD)

• Dietary phosphate restriction
• Phosphate binders: calcium carbonate (avoid in hypercalcaemia), sevelamer, lanthanum carbonate
• Active vitamin D analogues: alfacalcidol, calcitriol
• Cinacalcet (calcimimetic): activates calcium-sensing receptor → ↓PTH (tertiary HPT)

Management of CKD

Differentiating AKI from CKD

Note: In DM and ADPKD, kidneys may be large even in ESRD - size alone insufficient

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9. HIV AND THE KIDNEYS

Overview

1. Direct viral infection of renal cells (podocytes, tubular cells)
2. Immune complex deposition (HIV antigens)
3. Antiretroviral drug toxicity (tenofovir, indinavir)
4. Opportunistic infection-related nephropathy
5. Comorbid disease (hypertension, diabetes, HCV co-infection)

HIV-Associated Nephropathy (HIVAN)

• Most important and distinctive HIV-related kidney disease
• Predominantly affects Black patients (APOL1 high-risk genotypes G1/G2 strongly associated)
• Characterised by collapsing FSGS - the defining lesion
• Pathological features:
  • Glomeruli: collapsing sclerosis (global capillary collapse + overlying podocyte hyperplasia)
  • Tubules: microcystic dilatation, tubular injury
  • Interstitium: inflammatory infiltrate
  • "Tubuloreticular inclusions" on EM in endothelial cells (interferon signature)
• Clinical features: nephrotic-range proteinuria, rapidly progressive renal failure, echogenic enlarged kidneys on USS (unusual - most other glomerulonephritis does not cause this)
• CD4 count: typically low; occurs at any CD4 level but more common in advanced disease

Immune Complex Kidney Disease in HIV

• HIV immune complex kidney disease (HIVICK): deposits of IgA, IgG, IgM; mesangial/subendothelial; resembles lupus nephritis on biopsy ("lupus-like nephritis")
• More common in non-Black patients with HIV
• Also: MPGN, IgA nephropathy in the context of HIV
• Hepatitis C co-infection: cryoglobulinaemic MPGN

Thrombotic Microangiopathy (TMA)

• HIV can cause TMA (similar to TTP/HUS) via endothelial injury
• Features: haemolytic anaemia (microangiopathic), thrombocytopenia, AKI
• ADAMTS13 deficiency in some patients

Antiretroviral Drug Nephrotoxicity

Fanconi Syndrome (from TDF)

• Glycosuria (with normal blood glucose)
• Phosphaturia → hypophosphataemia → osteomalacia/pathological fractures
• Aminoaciduria, uricosuria
• Type II (proximal) RTA → metabolic acidosis
• ↓K⁺ absorption
• Screen with: urine glucose (in normoglycaemia), phosphate TmP/GFR, urine protein on dipstick

Comorbid Risk Factors Increasing Renal Risk in HIV

• APOL1 risk variants: G1 and G2 alleles dramatically increase HIVAN risk in African-ancestry patients
• Hypertension (very common in HIV; accelerates CKD)
• Diabetes (metabolic complications of ART)
• HCV co-infection: MPGN, cryoglobulinaemia, membranous nephropathy
• CMV (in severe immunosuppression): interstitial nephritis
• Tuberculosis: granulomatous interstitial nephritis

Management of HIV-Related Kidney Disease

1. Start/optimise ART - most important intervention for HIVAN; ART alone can induce remission
2. ACEi/ARB: anti-proteinuric benefit in HIVAN (reduce intraglomerular pressure)
3. Switch from TDF to TAF (tenofovir alafenamide) if tubular toxicity
4. Treat underlying infection/malignancy contributing to kidney disease
5. Standard CKD care (BP, anaemia, bone disease management)
6. ESRD: dialysis; transplantation feasible in virologically suppressed, CD4 >200 cells/µL (HIV+ to HIV+ donor transplants now possible)
7. Screen: urine protein/creatinine ratio + eGFR at ART initiation and annually

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Summary Table: Key Distinguishing Features

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