Nephrology Flashcards
Renal function test
• Urea (2.5-10.7 mmol/L)
o Increase: dehydration, GI bleed/ catabolic state/ high-protein diet
o Decrease: intrinsic renal damage, liver disease, low-protein diet
• Urea-to-creatinine ratio:
o >100: pre-renal cause of AKI (urea reabsorption increased compared to creatinine)
o 40-100: normal or post-renal cause of AKI
o <40: intrinsic renal damage (urea fails to be reabsorbed à behave like Cr)
Hyponatraemia
HypoNa
1. R/o spurious hypoNa: drip arm
2. Serum osmolality
A. Normal (280-295) —> PseudohypoNa
—> Hyperlipideamia, high paraprotein —> Ix - lipid profile, LFT (A:G ratio)
B. Hyper-osmolar (>295)
- hyperglycaemia / high urea / Mannitol use
- Ix: glucose-adjusted Na = Na + 2.4 (glucose-5.5/5.5)
- Ix: RFT, Osmolar gap
- Volume status
- Hypervolemia —> Odema, weight gain, elevated JVP, SOB
- Hypovolemia: poor skin turgor, tachycardia, orthostatic hypotension, increased CR
A. Hypovolaemia
A.1 Renal loss (urine Na>20)
-> Diuretics, cerebral salt wasting, AKI, Adrenal insufficiency
A.2 Extra renal loss (Urina Na <20)
- GI loss, Skin loss
—> best determine by history and PE
—> replace Na deficit with NS
Na deficit = BWx0.6x(target Na-serum Na)
NS 500ml/h until BP normal
Then remaining with NS and Na supplement
B. Euvolemia
B.1 Urine Na > 40, Urine OsM >100
—> SIADH (R/o hypoT4 and Addison)
—> treat underlying cause, stop offending meds
Restrict fluid Intake <1L/day
Oral NaCl, increase dietary Na load +/- furosemide, correct hypoK
Refractory: consider Tolvaptan 15-30mg daily / demeclocycline
B.2 Urine Na <20
- primary poly dips is, beer potomania
C. Hypervolemia
- nephrotic syndrome, cirrhosis, CHF
- treat underlying cause, restrict fluid intake <1L/day, furosemide 40-80mg IV / 20-500mg PO daily
Clinical features
• Severity of symptoms related to degree of hypoNa (<125) + speed of development
o Severe symptoms: vomiting, coma, seizures
o Moderate symptoms: nausea, confusion, headache
Hints
• Rule out pseudohypoNa (normal OsM) and hyperosmolar hypoNa: check glucose, lipids, Ig
• Check history of prostatic / uterine surgery and review medication history (thiazide, anti-depressants)
• Investigations: LRFT, glucose, serum & urine OsM, spot urine Na & K, cortisol, TFT
Management
• Resuscitation if necessary: control airway, ventilation, seizures
• Acute symptomatic hypoNa (moderate / severe symptoms: refer to above)
o Consult ICU before cautious hypertonic saline replacement
o IV 3% saline 2ml/kg over 20min à Check [Na] à Repeat dose (if severe Sx), aim 1-2mmol/L/h x 3-4h
• Stable hypoNa: depend on volume status, refer to above diagram
• Rate of Na correction: ≤8-12mmol/24h – avoid central pontine myelinolysis (osmotic demyelination syndrome)
o S/S (delayed onset): fluctuating MS, seizure, loss of vision, quadriplegia
o Mx: withhold active treatment + IV D5 (free fluid) +/- IV DDAVP
Causes of SIADH
• CNS: encephalitis, stroke, SAH, head trauma
• Lung: pneumonia, TB
• Drugs: SSRI, carbamazepine, NSAID, Syntocinon;
thiazide (SIADH-like, but hypovolemic)
• Post-surgery
• Ectopic: SCLC, Ca prostate, Ca thymus
Hypernatraemia
Clinical features
• Headache, irritability, seizures, ICH/SAH (rare)
Hints
• Review medication history (lithium)
• Investigations: serum & urine OsM, serum glucose, Na, K, Ca
• Urine OsM <300 in hyperNa is highly suggestive of DI
Etiology
A. Hypervolemia
A.1 urine Na >20
- acute salt overload
—> NaHCO3 infusion, salt toxicity
A.2 urine Na <20
- Mineralcorticoid excess, e.g. primary hyperaldosternism, Cushing’s syndrome
B. isovolemia / hypocvolemia
B.1 urine Na>20 (renal free water loss)
- diuretics, diuretics: osmotic, post-obstructive, AKI polyuric phase, Diabetes insipidus
- DI —> UOsM < 300, water deprivation test
- Osmotic diuresis —> estimate daily solute excretion, UOsM approx. Equal sOsM
B.2 Extra renal free water loss: Urine Na <20, UOsM»_space;SOsM
- Dehydration
GI: GE, vomiting
Skin: sweating, burns
Reduced fluid intake
Mx:
Hypervolemia
• Treat underlying cause
• Start D5 infusion
• Add furosemide 40-80mg IV / PO
Q12-24h
Isovolemia / Hypovolemia
• Correct volume status by isotonic fluid (NS) especially if haemodynamically unstable
• Replace free water with hypotonic fluid (D5 or ½: ½) Q6-8h, closely monitor [Na] & glucose
• Free water deficit: BW(kg) x 0.6 x (measured[Na] – 140) / 140
Rate of correction: < 8-10mmol/24h to avoid cerebral oedema
Diabetes insipidus (DI)
1. Central DI
- Deficiency of ADH
- Causes:
• Idiopathic (MC)
• Infective: meningoencephalitis
• Neoplastic: craniopharyngioma,
metastatic tumors
• Head trauma
• Vascular (e.g. Sheehan’s syndrome)
• Iatrogenic: TSS
S/S:
- Polyuria, polydipsia, nocturia, euvolemic high-normal Na, hyperNa (if decreased intake)
Investigations
• Paired plasma & urine osmolarity & electrolytes: Hypernatraemia + dilute urine are diagnostic of DI; low Na & low Osm suggests primary polydipsia
• Water deprivation test only if high index of suspicion but normal [Na]
o Diagnostic if uOsM <300 during deprivation —> DDAVP: central vs nephrogenic (>50% rise in UOsM after DDAVP)
Management
- Low Na diet
- DDAVP (intranasal, SC, PO, IV)
- Chlorpropramide
Nephrogenic DI
- resistance to ADH
- Cause:
• Li toxicity
• Metabolic (hypoK, hyperCa)
• Hereditary (XR mutation in V2 receptor,
AD/AR mutation in AQP-2)
S/S:
- Polyuria, polydipsia, nocturia, euvolemic high-normal Na, hyperNa (if decreased intake)
Investigations
• Paired plasma & urine osmolarity & electrolytes: Hypernatraemia + dilute urine are diagnostic of DI; low Na & low Osm suggests primary polydipsia
• Water deprivation test only if high index of suspicion but normal [Na]
o Diagnostic if uOsM <300 during deprivation —> DDAVP: central vs nephrogenic (<50% rise in UOsM after DDAVP)
Management
- Low Na diet
- Thiazide (natriuresis) + amiloride (decrease K loss)
- NSAIDs (e.g. indomethacin)
Acute post-operative / traumatic DI:
• Triphasic pattern: transient DI (hours to days) —> antidiuresis (2-14 days) —> return of DI (may be permanent)
• Allow oral hydration if can drink + thirsty; IV fluids + DDAVP if unconscious
Hypokalemia
Clinical features
• Acute: weakness, ileus, respiratory failure
• Chronic: nephrogenic DI, rhabdomyolysis
Clinical pearls
• Check drug history esp. diuretics
• Resistant to K supplement —> consider Mg supplement
• Never give K replacement therapy in D5: stimulate insulin secretion and intracellular shift of K
• Never give bolus K!
Aetiology
A. Exclude pseudohypokalemia
B. Decrease in intake
C. Transcellular shift
- Drugs: insulin, beta-agonist, theophylline
- Thyrotoxic periodic paralysis
- Alkalosis
- B12
C. Increase in excretion
C.1 Urine <20 (non-renal loss)
- GI loss / skin loss
C.2 Renal loss urine >20
1. Normal acid/base
- hypomagnesium
2. Metabolic acidosis
- RTA type I and II
3. Metabolic alkalosis
3.1 Chloride responsive (urine Cl <10)
- vomiting / NG tube aspiration
3.2 Chloride resistant (urine Cl >10)
3.2.1 Normal BP —> Diuretics
3.2.2 Hypertension
- Hyperaldosteronism
- Cushing’s syndrome
- Hyperaldo mimics
Investigations
• ECG: prolonged PR, ST depression, flattened / inverted T wave, prominent U wave
• Bloods: RFT, Cl, Mg, TFT, cortisol
o VBG for HCO3 (usually a/w metabolic alkalosis)
- Acidosis: RTA, diarrhoea
• Urine: TTKG / spot urine K:Cr / 24h urine K
Management (SAQ!)
K > 2.5 + ECG changes absent:
• Oral KCl (e.g. 2-3g KCl syrup Q4h for 2-3 doses)
• IV KCl 10-20mmol/h in NS (not D5) if enteric route C/I
K < 2.5 and/or ECG changes present:
• Consult ICU + cardiac monitor
• IV KCl 40mmol/h in NS (use central line for high conc.)
• ± combine with oral syrup KCl 3-4g Q4h
• ± K-sparing diuretics if renal loss (e.g. amiloride)
Associated with metabolic acidosis: K citrate 15-30mL Q6h in juice after meals, start K replacement before HCO3
Hyperkalemia
Clinical features
• Neuro: tingling, paraesthesia, weakness, flaccid paralysis
• CVS: hypotension, bradycardia
Clinical pearls
• Exclude pseudohyperkalemia (esp. normal RFT): haemolysis, thrombocythaemia, EDTA, drip arm
• Important causes to bear in mind: renal failure (MC), DKA, adrenal insufficiency
• Check drug history: K supplement, NSAID, ACEI/ARB, MRA, digoxin
- Transcellular shift
- cell lysis
- acidosis
- hypertonic it’s
- DKA - Increase in intake
- Renal failure (creatinine >400)
- Drug use
- Problem with RAAS
- aldosterone deficiency
- Tubular disorders
- renin insufficiency
Investigations
• ECG:
o K > 5.5: diffuse tented T waves (A)
o K > 6.5: flattened P, prolonged PR (B)
o K > 7: widened QRS -> sine wave (C)
• Glucose: rule out DKA
• RFT and VBG: to differentiate renal impairment and acidosis from other causes
• Trans-tubular potassium gradient (TTKG)
o Aldosterone defect if TTKG < 7 (normal > 10)
- TTKG = (urine K / Serum K) x (serum osm / urine osm)
o Repeat TTKG after fludrocortisone to distinguish aldosterone deficiency vs resistance
Management (SAQ!)
Urgent cases: K > 6.5 and/or ECG changes
• Cardioprotection by Ca gluconate: omit if digoxin toxicity suspected
o Cardiac monitoring
o If hemodynamically unstable: IV Ca gluconate 10% 10ml over 2-5min —> Repeat if no effect in 5min
o If stable asymptomatic: IV Ca gluconate 10% 10ml in 100mL NS infusion over 1 hour
• Dextrose-insulin drip: 10 U Actrapid IV bolus + 250ml D10 / 50ml D50 over 30-60min, repeat Q4-6h if necessary
• IV NaHCO3 8.4% 100-150mL over 30-60min: if acidotic + not fluid overload (activation of Na/H antiport)
• Bowel: Resonium C/A 15-50g PO/ PR Q4-6h
o 1g Resonium binds 1mmol K (mechanism: ion exchange resin – use Na (A) / Ca (C) to exchange with K)
o Avoid long-term use (< 3 days): risk of bowel ischaemia & perforation
• Nebulized salbutamol 10-20mg (in 3mL NS)
• Diuretics: IV furosemide 40-80mg bolus
• Emergency hemodialysis
Chronic cases
Low K diet (<2g /day), diuretics (furosemide / thiazide), oral NaHCO3 (if acidotic), fludrocortisone (Type IV RTA)
Albumin corrected Ca level
Albumin-corrected Ca level = 0.02 x (40 – albumin (in g/L)) + serum Ca
Normal: 2.10-2.55 mmol/L
Hypercalcaemia
Aetiology
• PTH-mediated: primary hyperparathyroidism, familial hypocalciuric hypercalcaemia (mutation in CaSR gene)
• PTH-independent:
o Malignancy: HHM (PTHrP), local osteolysis from bone metastasis, calcitriol-
secreting lymphoma, ectopic PTH secretion, MM (esp. elderly)
o Granulomatous disease, e.g. TB, GPA, Crohn’s disease
o Drugs: Ca / vit D supplement, thiazide, vit A, lithium
Clinical features
• Painful bones: pathological fractures
• Renal stones: dehydration, nephrogenic DI
• Abdominal groans: n/v, constipation, peptic ulcer (gastrin secretion), pancreatitis
• Psychic moan: lethargy, anxiety, psychosis (severe)
Investigations
• ECG and cardiac monitoring
• CaPO4, PTH, vit D
• RFT (tertiary hyperparathyroidism), TFT, 24h urine Ca (FHH)
- suppressed PTH = malignancy, tuberculosis
- Inappropriately high PTH level —> 24 urine Ca level
—> Low = familial hypocalciuric Hypercalcaemia
—> normal or high —> RFT
—> normal = primary hyperparathyroidism
—> impaired = tertiary hyperparathyroidism
Management (SAQ!)
• Monitor I/O, electrolytes, RFT, cardiac monitoring
• Withhold Ca & vit D supplement, off thiazide diuretics
• Saline rehydration: IV NS infusion 200-500mL/h (4-6L per day), aim urine output ~100-150mL/h
• Loop diuretics: start IV furosemide 20-40mg after rehydration
• Bisphosphonates (ensure CrCl >30)
• Calcitonin SC/IM 4 units/kg Q12h
• Hydrocortisone
• Newer treatments: denosumab (HHM) / cinacalcet (2°/3° hyperPTH)
• Haemodialysis with low Ca dialysate
• Treat underlying cause
Hypocalcaemia
Aetiology
• high PO4 (PTH related): 2° hyperPTH (CKD), hypoPTH, hypoMg, PTH resistance (pseudohypoPTH)
• low PO4: vit D deficiency, sequestration (pancreatitis, rhabdomyolysis, tumor lysis syndrome), hungry bone Sx*
• Medication-induced (e.g. bisphosphonate, cinacalcet)
Clinical features
• Acute neuromuscular irritability: perioral numbness, finger paraesthesia,
carpopedal spasm, laryngeal spasm
• Chvostek’s sign: tapping of facial nerve below zygoma causes spasm of
angle of mouth (half-opened)
• Trosseau’s sign: inflate BP cuff around arm to induce ischaemia for
carpopedal spasm
Investigation
• Ionized Ca level, PO4, ALP, Mg, RFT, PTH, vit D, amylase, CK, ECG
Management
Acute management
• IV Ca gluconate 10% (2.2mmol/10ml) 10mL in 100mL NS/D5 over 10min
o Alternative: IV CaCl2 10% (9 mmol/10ml: more concentrated à more irritation)
• Then continue Ca infusion (e.g. 20-30mL Ca gluconate in 500mL NS/D5 Q4-6h)
• Correct hypoMg
Chronic management
• CaCO3 PO
• Vit D supplement: Rocaltrol (calcitriol) or alfacalcidiol
• Aim at lower limit of normal (~2.0-2.2): avoid hypercalciuria which may cause renal stones
Hungry bone syndrome
- usually after parathyroidectomy / thyroidectomy
• Chronic exposure to high PTH /
T4: bone turnover with
predominant osteoclastic activity
• Removal of hormone excess: shift
to osteoblastic activity —> Ca and
PO4 all move into bone
Hyper PO4
Causes:
• Chronic renal failure (MC)
• Cell lysis: tumor lysis syndrome,
rhabdomyolysis, hemolysis
• Iatrogenic: Phosphasoda bowel prep
(avoid in CKD —> use PEG)
Ix:
- RFT, CaPO4, ALP, PTH, vit D
Mx:
• Low PO4 diet
• Phosphate binders with meal:
calcium-containing (e.g. CaCO3),
non-calcium containing (e.g.
Sevelamer, Lanthanum),
aluminium hydroxide (only short-
term!)
• Treat hyperPTH
• Arrange dialysis if necessary
Hypo PO4
Causes:
• decreased intake: malabsorption, vitamin D deficiency
• Transcellular shift (refeeding
syndrome, resp alkalosis, hungry
bone syndrome)
• urinary loss: 1° PTH, FGF23, Fanconi syndrome
Ix:
- RFT, CaPO4, ALP, PTH, vit D
± FEPO4 (>5% = renal loss)
Mx:
Acute severe (PO4 < 0.3 w/ symptoms):
• IV 6mL potassium phosphates in
500mL NS/D5 Q6-12h
• Watch out for hypoCa
Chronic / Mild (PO4 < 0.5):
• Oral Sandoz-PO4 tablet QID
• Dipyridamole (decreased urinary PO4 loss)
Hyper Mg
Uncommon except renal failure / Mg
administration
Ix:
- RFT, K, Ca, ECG
Mx:
• Stop Mg supplement
• Saline diuresis (NS 500mL/h)
• 10% Ca gluconate 10mL
• Furosemide
• Urgent HD if necessary
Hypo Mg
Causes:
• Uncontrolled DM
• Chronic alcoholism
• Drug use: cyclosporin A, diuretics,
aminoglycoside, amphotericin B, PPI
Ix;
- RFT, K, Ca, ECG
± FEMg (>2% = renal loss)
Mx:
Emergency:
• IV 50% MgSO4 4mL over 15 mins
then infusion (10mL over 6h)
Chronic
• Mg supplement: Mylanta / Gelusil
• Amiloride (decreased urinary Mg loss
A-a gradient
Calculate A-a gradient by alveolar gas equation
• PAO2 (in kPa) = FiO2 x 94.5 – PaCO2 x 1.25
• ↑ if >2.7kPa: due to V/Q mismatch, diffusion abnormities
NAGMA
Aetiology
- GI HCO3 loss (hypoK): diarrhoea, pancreatic/ biliary drainage, urinary diversion
- Renal
• HypoK: type 1 RTA, type 2 RTA, CA inhibitors,
• HyperK: type 4 RTA, early uremic acidosis
Investigations
• Serum K: refer to fig. for DDx
• Urine pH: >5.5 diagnostic of Type I RTA
• Urine anion gap: should be -ve in
acidosis; +ve indicate low NH4 excretion
• Urine osmolar gap: normal >30,
abnormal indicates low NH4 excretion
Renal Tubular Acidosis
Type 1
- Failure of α intercalated cells to secrete H+ (defective H+ ATPase / distal H+ back-leak)
- Cause:
Autoimmune diseases (e.g.
Sjogren, SLE, RA)
Drugs (e.g. ampho B)
high Ca (e.g. hyperPTH)
- hypo K, pH >5.5
- positive urine AG
- Ix:
NH4 loading test (gold standard):
urine pH remains high & UAG inappropriately +ve
KUB for renal stones
Mx:
Oral NaHCO3 / K Citrate
Type 2 (proximal)
- ↓HCO3- reabsorption at
proximal tubules (self-limiting)
- Causes:
1. Fanconi syndrome* (generalised proximal tubular dysfunction —> aminoaciduria, phosphaturia, glucosuria, tubular proteinuria, etc.
• Causes: Wilson’s disease, MM, amyloidosis, drug-induced)
2. Monoclonal gammopathy
- Mild hypo K
- pH <5.5
- Positive / Negative Urine AG
- Ix:
Bicarbonate loading test:
FEHCO3 > 15%
Urine glucose, AA
- Mx:
Oral NaHCO3
K+ supplement@ e.g. K citrate
Type 4
- ↓ aldosterone secretion/ effect —> increase K —> ↓ NH4 excretion
- Causes:
Addison’s disease, CAH
DM nephropathy, CNI
(hyporenin hypoaldo)
Drugs (ACEI/ARB)
- hyper K
- pH <5.5
- positive < 5.5
- Ix:
TTKG < 7
Renin, aldo, cortisol
Mx:
Stop ACEI/ARB
Loop diuretics, low K diet ± NaHCO3
Fludrocortisone
Renal stones and nephrocalcinosis are common in Type 1 RTA:
• Acidosis-induced bone breakdown
• urine pH: ¯solubility of Ca and PO4
• ¯CaPO4 reabsorption in renal tubules
HAGMA
Etiology: MUDPILES + R
• Methanol
• Uremia (CKD)
• DKA / alcoholic
ketoacidosis / starvation
ketoacidosis
• Paraldehyde / propylene
glycol
• Iron, isoniazid, IEM
• Lactic acidosis
• Ethylene glycol
• Salicylate
• Rhabdomyolysis
Investigations (KOLT)
• RFT, glucose
• CK
• Plasma Ketones (BOHB)
• Osmolar gap (= toxic alcohol)
• Lactate: >4mmol/L is diagnostic
• Serum / urine Toxicology
• ± Corrected HCO3 / delta ratio: r/o concomitant NAGMA
Management
• IV 8.4% NaHCO3 infusion: consider if pH < 7.1
o NaHCO3 required (mmoL) = (ideal HCO3 – measured HCO3) x BW x 0.5
- 1mmol = 1mL if 8.4%
o Monitor ABG after infusion: risk of CO2 if poorly ventilated —> paradoxical resp. acidosis
o Complications:
- Volume overload —> acute pulmonary oedema
- HypoK
- HypoCa
- Cerebral acidosis: increased CO2 readily passes intracellularly
- Tissue hypoxia: shift of O2 dissociation curve
• Consider mechanical ventilation if APO to remove CO2
• Consider dialysis if volume overload / CKD / poisoning
• Treat underlying causes: refer to [Clin Pharm] for drug overdose
Alcoholic ketoacidosis
- Glucose infusion + thiamine
Lactic acidosis
- Correct haemodynamic disturbance
- HD if renal failure (PD has high lactate)
Metabolic alkalosis
U[Cl] < 20mmol/L
- Chloride (volume) depletion: vomiting, previous diuretics, post-hypercapnic alkalosis
U[Cl] > 20mmol/L
- Mineralocorticoid excess: Conn’s, Cushing’s, CAH, steroid, Batter/Gitelman
- Current diuretic use (loop / thiazide can increase urine Cl)
- Severe potassium depletion
Concept: initiation event (HCO3) followed by maintenance phase (e.g. hypovolemia, hypokalemia)
Chloride-responsive metabolic alkalosis (urine Cl < 20 mmol/L):
• NS ± KCl to correct ECF volume
• Acetazolamide 250mg QID
Chloride-resistant metabolic alkalosis (urine Cl >20 mmol/L):
• Treat underlying cause
• Mineralocorticoid blockade: spironolactone / amiloride
Acute kidney injury
Diagnostic criteria (KDIGO)
Any one of the followings:
• serum Cr > 26.5 umol/L in 48h
• serum Cr to 1.5x baseline in 7 days
• Oliguria <0.5ml/kg/h for 6h (or < 400ml/day)
Anuria: <50mL/day
- Complete urinary tract obstruction
- Bilateral renal artery occlusion
- Acute cortical necrosis
- Rapidly progressive GN
Limitation of serum Cr as marker:
- Insensitive for early AKI: GFR
already decrease 50% when Cr increase
- Not useful if on dialysis: Cr is
removed by dialysis
Aetiology
- Small vessels (glomerulonephritis, vasculitis)
- Tubules (toxic ATN, ischemic ATN)
- Large vessels (renal artery embolus, dissection, vasculitis, renal vein thrombosis)
- Intratubular
- Interstitium (allergic, infection, infiltration, inflammation)
Ix to differentiate prerenal failure and ATN
Prerenal failure
- Increased reabsorption due to hypovolaemia
- FENa <1%
- Urine Na <20
- UOsm >500: dehydration
- Plasma Urea/Cr >100
- Urine/plasma Cr >40
- Urine/plasma urea >20
ATN
- Failed tubular reabsorption and secretion
- FENa >2%
- Urine Na >40
- UOsm <350: impaired concentrating ability
- Plasma Urea/Cr <40
- Urine/plasma Cr <20
- Urine/plasma urea <10
• Most cases of AKI are due to prerenal cause (MC) or ATN
• Renal biopsy: consider if prerenal cause or ATN unlikely, or persistent oliguria > 6 weeks
- Prerenal: volume depletion / hypoperfusion
- Renal hypoperfusion:
• Absolute: hemorrhage, GI loss, skin loss
• Effective: CHF, cirrhosis, sepsis (vasodilation)
- Renal vasoconstriction:
• NSAID: decreased PG & bradykinin —> AA vasoconstriction
• ACEI/ARB: Ang II constricts EA > AA
• Cyclosporin
Ix: Fluid challenge
(500-1000mL over 1-2h)
- Renal: destroyed Tubular function —> loss of urine concentrating ability
- Glomerular: glomerulonephritis (GN) (5%)
- Tubular: acute tubular necrosis (ATN)
• Ischemia (50%): progression of pre-renal failure
• Nephrotoxin (35%):
o Extrinsic: paracetamol, aminoglycosides, amphotericin B,
cisplatin, contrast
o Intrinsic: myoglobin, uric acid (TLS), myeloma cast
- Interstitial (10%): acute interstitial nephritis (AIN)
• Drug-induced: penicillin, NSAID
• Infection: bacterial pyelonephritis
• Inflammation: SLE, Sjogren’s syndrome
Vascular:
• Large vessel disease: renal vein thrombosis
• Medium vessel disease: polyarteritis nodosa
• Small vessel disease: TTP/HUS, malignant hypertension
Ix:
- Urine biochemistry (Na, OsM, urea, Cr, FENa), microscopy, C/ST, uPCR
- GN: C3/4, ANA, anti- dsDNA, HBsAg, anti-
HCV, ASOT
- AIN: CBC d/c (eosinophilia)
- Vascular: Doppler USG (renal vein thrombosis)
- Post renal
- Luminal: stones, clots
- Mural: malignancy (ureteric, bladder, prostate), BPH
- Extramural: pelvic malignancy, retroperitoneal fibrosis
Ix: Bladder scan: urine retention
USG renal system: hydronephrosis
Management
• Resuscitation: correct fluid status
o Chart BP, I/O, daily BW (<1kg increase per day)
- Fluid intake allowed = 500 mL + volume of urine output
o Optimize pre-load for hypovolemia: IV NS 500-1000mL over 1-2h
o If fluid overloaded + adequately resuscitated: IV frusemide 80mg bolus +/- metolazone 5mg daily
• Correct electrolyte disturbance: hyperK / hypoCa / hyperPO4 / metabolic acidosis
o Low salt diet (<100mmol/day), low K diet (<20mmol/day), low phosphorous diet (<800mg/day)
o Metabolic acidosis: low protein diet (0.6-0.8/kg/day), IV NaHCO3 (beware of volume overload and worsening of hypoCa)
• Watch out for uremic complications: platelet dysfunction, pericarditis, neuropathy, encephalopathy
• Dialysis: Indications of urgent dialysis (AEIOU):
• Refractory metabolic acidosis (C/I to NaHCO3)
• Electrolyte disturbance (e.g. refractory hyperK)
• Intoxication
• Refractory pulmonary oedema
• Uraemic pericarditis/ encephalopathy
o Modalities: intermittent haemodialysis (IHD), continuous hemofiltration, acute PD
• Specific management
o Prerenal: withhold ACEI/ NSAID
o Renal: withhold nephrotoxin (e.g. aminoglycoside)
o Postrenal: Foley catheter, nephrostomy
Specific cause of AKI
Rhabdomyolysis
- Risk factors: Trauma: crush, seizure, Non-traumatic statin, hypothyroid/hyperthyroid
- S/S: Dark brown urine
Urine microscopy: myoglobin, pigmented granular casts, no RBC
- high CK, high K, low Ca, high PO4, high urate, DIC, AKI
- May later become high Ca
- Ix: urine microscopy, CK, RFT, CaPO4, urate
- Fluid resuscitation: NS 1.5L/h until stable
IV NS alternating with D5, target urine output 300ml/h, continue until CK decrease to <5000 IU/L
- Add NaHCO3 to D5 to keep urine pH > 6.5 (monitor ABG & Ca: stop if blood pH > 7.5 or symptomatic hypo Ca
- Add mannitol (keep plasma osmolar gap < 55)
- Allopurinol if uric acid >476
- Hemodialysis if fail above
- Look out for compartment syndrome
Contrast nephropathy
- Risk factors: dehydration, large dose, contrast, age
- S/S: serum creatinine increase >25% from baseline / increase 44 umol/L 48-72h after contrast exposure
- GFR < 30: contraindicated for contrast
GFR 30-60:
• Adequate hydration (IV NS)
• N-acetylcysteine PO 600mg BD 1 day before & after procedure
• Avoid ACEI/ARB, diuretics, NSAID
Chronic kidney disease
Definition
Structural or functional abnormality in
kidney that persists more than 3 months
• Structural: albuminuria
• Functional: decreased GFR
Aetiology
• Diabetic nephropathy 35%
• Glomerulonephritis (IgAN is most common 25%)
• HT (hypertensive nephrosclerosis)
• Polycystic kidney disease 5%
• Others: autoimmune (e.g. SLE, vasculitis), renovascular disease, congenital (e.g. Alport disease)
• “Unknown” (20%): may be due to genetic mutation
Investigations
• Bloods: CBC, LFT, RFT (+ eGFR), bone profile
• Urine: dipstick, microscopy, quantify proteinuria (24h urine protein / spot uACR)
• Tests for etiology: HbA1c, lipids, autoimmune, HBV/HCV
• Imaging: USG kidney, KUB ± renal biopsy
Clinical features of uraemia
• General: anorexia, nausea (most specific), malaise, pruritus
• Uremic fetor, café-au-lait complexion
• Uremic pericarditis
• Uremic encephalopathy
• Uremia-induced platelet dysfunction & EPO deficiency
• Urinary symptoms: dysuria, LUTS, oliguria (seldom anuria c.f. AKI)
Features suggesting CKD but not AKI:
• low Ca, high PO4, high ALP
• Anemia of chronic disease
• USG: Small atrophic kidneys, decrease corticomedullary differentiation
ESRD (GFR < 15): eGFR and 24h CrCl
are not accurate in estimating renal
function —> Take average of both
Causes of death
• Vascular (50%)
• Infection (30%)
• Termination of dialysis (7%)
GFR estimation
- CKD-EPI
- MDRD (underestimate GFR when >60)
- age, gender, race, Cr - Cockcroft-Gault equation
- drug dosing
- depends on body weight
Mx of CKD
General management: to slow disease progression (SAQ!)
• Fluid: fluid restriction, chart I/O, daily BW (limit < 1kg/day increase)
• Dietary restriction (“renal diet”):
o Calorie 30-35kcal/kg/day (note 500-700kcal from CAPD dialysis fluid already)
o Protein: low protein diet, balance risk of proteinuria vs malnutrition
o Low salt diet (for HT & volume overload): Na <100mmol/day
o Low K diet (for hyperK): < 1mmol/kg/day
o Low PO4 diet (for 2o hyperPTH): < 800mg/day
o ± vit C, folic acid supplements
• BP control and renoprotective medications
o Target 130/80 (but consider comorbidity and life expectancy)
o RAAS blockade: ACEI/ ARB ([RENAAL]: Role of losartan in DM nephropathy)
- Caution: check Cr & K at baseline & 2 weeks after initiation/ changing dose
- high Cr
• RAAS blockade: efferent arteriole dilation; stop if increase Cr > 30%
• AKI: NSAID (afferent arteriole constriction), intravascular volume depletion
• Renal artery stenosis
- high K
Review other drugs, consider diuretics / NaHCO3 / resonium, change to CCB
o SGLT2 inhibitors: beneficial for all diabetic CKD and
o Finerenone (non-steroidal MRA): beneficial if T2DM CKD + persistent albuminuria despite ACEI/ARB &
SGLT2i
• CV risk reduction: exercise, weight loss, aspirin, statin, DM control (early switch to insulin)
• Vaccination (due to impaired immunity): influenza, pneumococcus, HBV
• RRT: Refer nephrologist at stages 4/5 or uremic symptoms, even if RRT is anticipated to be inappropriate
Management of complications
- Anemia
• Iron-deficiency anaemia: TSAT <20% + ferritin < 100 (if non-dialysis / PD) or <200 (if HD)
o Ix: TSAT & ferritin (ferritin alone NOT useful: affected by CKD and inflammation)
o Mx: IV iron (Monofer) (avoid oral due to ↑hepcidin)
o S/E: constipation
• EPO stimulating agent (ESA), e.g. darbepoietin SC Q4week, mircera SC
o Benefits: decrease need of blood transfusion (Hb fluctuation, availability, alloantigenic Ab)
o Start if Hb < 10 and r/o Fe def, target Hb 10-11.5 (no need normal)
o S/E: HT, malignancy risk, risk of AV access thrombosis
o ESA resistance due to: uraemic inhibitors (hyperPTH, hepcidin), ongoing blood loss,
reduced RBC half-life, iron/ B12/ folate deficiency
• Transfusion: start if Hb < 7, target Hb 10-11.5
o If on HD: transfuse pack cells during dialysis
o If on PD: transfuse pack cell with extra PD fluid cover
• New agent: HIF stabiliser (roxadustat) - Hyperkalemia
- Avoid K-sparing drugs, e.g. ACEI, aldosterone antagonist
- Resonium C, oral furosemide / thiazide - Met. acidosis
- NaHCO3 to replenish HCO3 store, but may induce HT & oedema
Proven benefit if HCO3 < 22: can slow down GFR decline and reduce sarcopenia - Volume overload
- Loop diuretics (e.g. furosemide) - CKD-MBD (CKD-related mineral and
bone diseases) ~ renal osteodystrophy
- Patho: ↑PO4, ↓Ca/ calcitriol (↓1α-hydroxylase activity) —> 2o hyperPTH
Types:
• Osteitis fibrosa cystica (OFC): ↑ bone turnover due to 2o hyperPTH —> bone pain
• Adynamic bone disease: ↓bone turnover due to excessive parathyroid suppression
• Osteomalacia: aluminium deposition in bone (use of Al-containing antacid)
• Mixed uraemic osteodystrophy: abnormal bone turnover and bone mineralisation
S/S: bone pain, fracture, tendon rupture, muscle weakness
Ix: XR (subperiosteal erosion, brown tumour, rugger jersey spine, pepper pot skull)
Mx:
• Low phosphate diet
• Phosphate binders: CaCO3 (NOT as Ca supplement: given with meal to decrease excess Ca absorption), aluminium hydroxide (more effective, but risk of
neurotoxicity & osteomalacia —> only short-term), non-Ca (e.g. sevelamer, lanthanum)
• Vit D analogue: alfacalcidol, calcitriol
• Calcimimetic: cinacalcet, IV Etelcalcetide, PO evocalcet (act on CaSR —> decrease PTH secretion)
• Parathyroidectomy: subtotal or total; complications: adynamic bone disease - Uraemia bleeding
- Patho: platelet dysfunction
- Mx: DDAVP (to reverse platelet dysfunction), cryo/FFP, Premarin (estrogen), dialysis - Uraemia pruritis
- Mx: emollients, gabapentin, difelikefalin
pruritis - Neurological
- Generalised myopathy: poor nutrition, 2o hyperPTH, electrolyte disturbance
- Neuropathy: advanced disease
- Dialysis
DDx of bone pain in CKD patients
• Renal osteodystrophy: osteitis fibrosa, osteomalacia
• Treatment-related: dialysis-related amyloidosis, osteomyelitis due to infected vascular access, nerve compression
from AV fistula
Perioperative management
• Consult renal team for peri-operative dialysis
o HD: 1 day before operation
o CAPD: continue CAPD, cap off Tenckhoff catheter and drain PD fluid before abdominal operation
o APD: adjust regimen to CAPD, then follow above
• Transplant recipient: continue immunosuppressants + steroid cover
• Treat bleeding tendency: transfuse, DDAVP, cryo/FFP, dialysis if necessary
Indications of RRT
AKI
• Refractory metabolic acidosis (C/I to NaHCO3)
• Electrolyte disturbance (e.g. refractory hyperK)
• Intoxication
• Refractory pulmonary oedema
• Uraemic pericarditis/ encephalopathy
CKD
• eGFR < 5 mL/min (regardless of S/S)
• eGFR 5-15 mL/min + uremic complications
(pericarditis, pleuritis, encephalopathy)
• Other indications: poor nutrition, refractory volume overload / acidosis / hyperK / hyperPO4
PE for RRT
Mode of RRT (PD: sacs and Tenckhoff catheter, HD: tunnelled CVC, AV fistula/graft, Renal transplant
Adequacy of RRT
- hydration status
- Signs of uraemia: confusion, asterixis, scratch mark, tachypnea, pericardial rub
Complications of Renal failure
- Anemia
- Collar scar: parathyroidectomy
Complication of immunosuppressants:
• Steroids: BP, H’stix marks, proximal myopathy, abdominal striae
immunosuppressants
• CNI: gum hypertrophy, hirsutism, coarse tremor
Underlying cause of renal failure
• PCKD: ballotable kidneys
• Stigmata of rheumatological diseases
RRT complication
• Malnutrition
• Accelerated atherosclerosis
• Dialysis-related amyloidosis
• Acquired cystic disease ± malignant transformation
• Dialysis-related dementia (cerebral aluminium toxicity)
Peritoneal dialysis
Mechanism
• Advantages of peritoneal membrane: thin & semi-permeable, large surface area, highly vascularized
• Solutes are removed via
o Diffusion: movement across concentration gradient, effective for molecules NOT present in dialysate
o Ultrafiltration: movement across osmotic pressure gradient ( by adding dextrose / icodextrin to dialysate)
Contraindications
• Abdominal adhesions (decrease peritoneal membrane surface area): multiple abdominal surgery, peritonitis, pelvic irritation, diverticulitis
• VP shunt placement
• Pleuroperitoneal leak
• Poor self-care: frequent PD peritonitis
Types
• Manual:
o Continuous ambulatory PD (CAPD): 3 exchanges during day + overnight dwell
o Intermittent PD: used post-Tenckhoff insertion, to allow wound healing & CAPD training
• Automated (APD)
o Nocturnal intermittent PD (NIPD): cycling at night without daytime dwell
o Continuous cycling PD (CCPD): cycling at night + daytime dwell
Setup and components
1. Catheter
Tenckhoff catheter: silicon
• Tip of catheter: face downwards
inside peritoneal cavity
• Dacron cuffs x2:
o Inserted ≥2 weeks before PD for
local inflammation & fibrosis
o Prevent fluid leak and
bacterial migration along
catheter
• Entrance site (catheter enters
peritoneum): paramedian
incision
• Exit site (catheter exits skin)
o Face downwards to prevent accumulation of bacteria
o Visible by patient
o Usually left side: reserve right side for transplant
- System
“Y-set” (fig.): “flush before fill” to reduce risk of peritonitis - Osmotic agent
• Low MW agents: e.g. dextrose (MC)
o Different concentrations available: 1.5%, 2.5%, 4.25%
(higher conc. for DM patients)
o Problems: metabolic complications, glucose degradation products (GDP) affect peritoneal host
defence mechanism
• High MW agents: e.g. icodextrin (glucose polymer), amino-acid based solutions
o Less absorption: increase duration of ultrafiltration, suitable for uncontrolled DM patients - Electrolytes and buffers
• Lactate buffer: control metabolic acidosis
• No K: patients usually hyperK
Other additives to dialysate:
• Heparin: prevent obstruction of catheter lumen by fibrin, added if blood-stained
dialysis effluent (likely subcutaneous bleed)
• Insulin: DM patients, better than OHA in ESRD
Prescription
Example: “1.5% 2 litre dwell, 3 bags per day”
• Volume: 2L (1L if just after Tenchkoff insertion)
• Concentration: 1.5% or 2.3% usually
• Adequacy: Kt/V ratio ≥ 1.7 (K = dialysate flow rate, t = time, V = body water volume)
Complications
Monitor exit site condition and dressing daily
• Early
o Insertion: bleeding (inf. epigastric a.), infection, perforation
o Catheter: kinked catheter, thrombosis, omental wrapping (Mx: Tenckhoff revision
+ omentectomy)
o Pleuro-peritoneal fistula
• Late
o CAPD peritonitis
o Exit site infection
o Metabolic complications: hyperglycaemia, hyperlipidemia
o Dialysis-related amyloidosis: accumulation of large β2-microglobulin
o Encapsulating peritoneal sclerosis (intermittent IO, fatal)
Blood-stained dialysate
• Causes:
o Old blood (dark red without clots): residual blood in peritoneum after laparotomy
o New blood (bright red with clots): arterial puncture during laparotomy
• Management: IP heparin to prevent clot formation
Outflow failure
• Sites of obstruction
o Inside catheter: blood / fibrin clot
o Outside catheter, inside patient: faecal
loading, kinking of catheter, omental wrap
o Outside catheter, outside patient: kinking of catheter, clamped catheter
• Management:
o Check all knobs and tubing
o Assess whether it is inflow or outflow
problem
- inflow problem, —> spike off, inform renal team
- outflow problem: fibrin—>IP heparin, Turbid—>treat CAPD peritonitis, clear but slow effluent —> change to lateral/standing positive, fleet enema, KUB, spike off, surgical removal and insertion of new catheter
Pleuro-peritoneal fistula
• Suspect when pleural effusion with high glucose level (“sweet hydrothorax”)
• Diagnosis: CT peritoneogram (inject dye via Tenckhoff), peritoneal scintigraphy (Tc-99m albumin), IP methylene blue
• Management:
o Supportive treatment: stop PD and change to HD for 4-8 weeks
o Definitive treatment if large hole: VATS-guided pleurodesis (Talc on fistula)
CAPD peritonitis
• Pathogens: G+ (50%, S aureus), G- (25%), no growth (15%), mixed (workup for intra-abdominal pathology!)
• Diagnostic criteria: at least two of
o Clinical S/S (abdominal pain, vomiting, diarrhoea, fever) and/or cloudy PD effluent
o PD effluent cell count: WBC > 100 and >50% polymorphs
o PD effluent culture +ve
• Management (important!)
o PD effluent Ix: cell count d/c, Gram stain and culture
o Analgesia e.g. Panadol ± tramadol
o Rapid flush 3 bags of PD fluid with IP heparin 500units/L to prevent catheter block (decrease fibrin clot)
o Step up to 4 exchanges per day to improve ultrafiltration
o Empirical antibiotics to cover both G+ and G-: IP cefazolin 1g (G+) + ceftazidime 1g (G-)
- Dwelling time: at least 6h (loading dose + maintenance dose in last bag every day)
- Use IV if features of sepsis
- Duration: at least 21 days
o Consider PO nystatin to prevent secondary fungal peritonitis
o Adjust antibiotics according to C/ST:
- G-: give 2 different antibiotics acting in different ways (e.g. IP amikacin + IP ceftazidime)
- Fungal: IV amphotericin B, until 2 weeks after catheter removal
o Repeat PD effluent Ix at Day 4 & after completion of antibiotics
o Refractory peritonitis:
- Remove Tenckhoff catheter —> temporary HD
- Continue antimicrobials for 2 weeks after catheter removal
- Work-up for fungal & mycobacterium causes
- Re-insert catheter after completion of treatment
CAPD exit site infection (ESI)
• Purulent discharge ± erythema of skin around exit site
• Management:
o Equivocal ESI: chlorhexidine dressing tds + local Tx (e.g. mupirocin cream) tds
o Definitive ESI:
- Exit site swab for microscopy, Gram stain, C/ST
- Oral antibiotics x 14 days: cloxacillin/cephalexin (if suspect G+), levofloxacin (if suspect G-)
- Adjust antibiotics: add rifampicin if unresolving S. aureus,
- Consider removal of catheter / shaving of external cuff
• Prevention: personal hygiene, avoid excessive traction on catheter, screen for MRSA carriage
Haemodialysis
Usually if C/I to PD (e.g. abdominal adhesions) or failed PD (fibrosis of peritoneal membrane)
Mechanism
• Counter-current: blood is always meeting a less concentrated dialysate
• Solutes are removed via
o Diffusion: movement across concentration gradient, for small solutes (e.g. urea)
o Ultrafiltration: for larger solutes and water
Types of vascular access
AV fistula / AV graft: for long-term HD
AV fistula
- preferred if large vein (>2mm) available
- Adv: Better long-term patency, Lower risk of thrombosis & infection
- Technicality: Maturation of AV fistula: rule of 6 (evaluated 4-6 weeks after creation, ≥6mm diameter, ≤6mm deep, flow ≥600mL/min)
End-to-side anastomosis preferred, usually
between cephalic vein & radial artery
AV graft
- options if small vein
- Adv: Shorter time to first cannulation
Easier cannulation
Less likely 1° failure
- Material: Teflon (PTFE)
Types: looped / straight
Examination of AV fistula
• Inspection:
o Erythema / swelling (infection)
o Distal extremities: ischemia (vascular steal), edema (venous hypertension)
o Collapse during elevation of arm
• Palpation
o Tenderness
o Pulse
o Thrills (soft thrill is normal)
o Direction of flow
• Auscultation for bruits
Double-lumen (or triple-lumen) central venous catheter:
• Types: non-tunnelled (emergency HD), tunnelled (long-term HD but poor
candidate or bridging for AV access)
• Access sites: jugular, subclavian, femoral
• Lumens: red port (proximal), blue port (distal), ± extra port for blood taking
• Insertion: USG-guided, Seldinger technique (guidewire), Trendelenburg
position (decrease risk of air embolism), fluoroscopy to confirm position
Prescription
• 2-3 sessions/ week (4-6h each)
• Blood flow rate 150-250mL/min
• Dialysate flow rate 500mL/min (fixed)
• Anticoagulation: UFH or LMWH
• Adequacy: Kt/V ratio ≥ 1.2 (K = dialysate flow rate, t = time, V
= body water volume)
• Avoid blood taking / BP measurement from AV fistula arm
• Monitor AV fistula daily
Complications
• First-use syndrome: anaphylactoid reaction with chills, urticaria, loin pain
• Dialysis washout: hypotension, fatigue, chest pain, leg cramp, headache
• Dialysis dysequilibrium syndrome:
o Cerebral oedema due to rapid reduction of plasma urea and change in extracellular osmolarity
o S/S: n/v, confusion, seizure
o Diagnosis by exclusion: after ruling out hypoglycaemia, uraemic encephalopathy, haemorrhagic stroke (due to heparin), sepsis
o Management: slow down/ stop ultrafiltration, infuse isotonic (hypertonic saline if severe)
o Prevention: short (1-2h), slow dialysis for the first session
• Vascular access-related:
o Related to insertion: pneumothorax, bleeding, arrhythmia, air embolism (Mx: left lateral + 100% O2)
o Infection: Any febrile HD patient with a catheter has catheter-related infection until proven otherwise
• Pathogens: CoNS, S aureus
• Investigations: blood culture through catheter
• Management: remove catheter + vancomycin after each HD for 2-3 weeks
o Thrombosis:
• Catheter: Mx urokinase
• Native AV fistula: usually stenosis at AV anastomosis, Mx balloon angioplasty or embolectomy
• Teflon AV graft: alert if sudden loss of thrill; similar Mx as thrombosis in native AV fistula
o Vascular steal syndrome: upper limb ischemia
• Ix: Allen’s test (occlude radial artery and ask patient clench fist)
• Dialysis-related amyloidosis: due to accumulation of β2-microglobulin
Renal transplant
Types of allograft
• Living: (genetically) related or unrelated
• Cadaveric: heart-beating (brainstem death) or non-heart-beating
(cardiac death)
Procedure
• Donor nephrectomy: open (cadaveric), laparoscopy (living)
• Transplanted kidney placed in iliac fossa (usually right-sided: vessels more superficial) extraperitoneally (∵more rapid return of bowel function, easier to observe haemorrhage / urine leak)
• Vessel anastomosis: usually to external iliac artery & vein (∵IIA many branches & risk of pelvic organ ischemia)
• Ureteroneocystostomy
Criteria for living donor
• Donor factor: first-degree relative,
married couple > 2y
• Disease factor: no significant
comorbidities (long-standing HT/DM)
• Organ factor: HLA-A, B and DR
matched (ABO-incompatible transplant
permitted)
C/I for living donor: uncontrolled infections, Hx of malignancy (with exceptions)
Pre-transplant work-up
1. Donor
- HLA typing, ABO typing
- Bloods: CBC, RFT (GFR ≥80), LFT, OGTT (to rule out DM kidney), HBV/ HCV/ HIV
Urinalysis: proteinuria / hematuria
- Imaging: CXR, ECG
Renal arteriogram (to confirm vascular supply, notify surgeon if renal accessory artery +ve)
- Recipient
- HLA typing, ABO typing, X-match (antibodies against foreign
HLA)
- Bloods: HBV/HCV/HIV/TB/CMV, G6PD (Septrin prophylaxis)
• Give prophylactic antivirals before immunosuppressants
• Match hepatitis status of donors and recipients (usually possible for HBV, +/- for HCV)
Nephrectomy
Native diseased kidney is usually not removed unless
• Huge polycystic kidney
• RCC
• Resistant infection, e.g. abscess, tuberculoma
Post-transplant management
Monitoring
• Urine output, serum Cr, GFR
• Proteinuria at 3, 6, 12mo and every 12mo afterwards
• Screen for infections: CMV, polyomavirus (BK, JC virus), bacterial UTI
Immunosuppressant therapy
• Triple therapy: steroid + CNI (cyclosporin/ tacrolimus) + antimetabolite (azathioprine/ MMF / sirolimus)
o Usual regimen: prednisolone + cyclosporin A + MMF
• Add antibodies for induction (first 2 weeks) if at high risk of rejection
o Polyclonal: anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG)
- S/E: cytokine release syndrome (fever, chills, hypotension), serum sickness (Type 3 HSR)
o Monoclonal: anti-CD3 (OKT3), anti-IL2 / anti-CD25 (basiliximab, daclizumab)
• Switch CNI to mTOR inhibitors (e.g. sirolimus, everolimus) if CNI toxicity / new cancer after renal transplant
Additional medications
• Prophylaxis for infections: cotrimoxazole (PJP) + acyclovir (CMV) for 6 months
• Anti-hypertensive: diltiazem is preferred (DDI: can reduce dosage of CyA needed)
• Statins
Complications
• Transplant rejection: immunosuppressants
- Hyperacute
—> Minutes
—> Preformed IgG
—> No effective treatment
Prevention: cross-match
- Acute
—> Days - weeks
—> T cell mediated rejection (TCMR): anti-
foreign HLA T cells
Antibody-mediated rejection (ABMR)
—> Mx:
TCMR: pulse steroid + Ab
ABMR: plasma exchange + Ab
- Chronic
—> Months – years
—> Immune + non-immune (e.g. HT, DM,
cyclosporin-related toxicity)
—> Untreatable once initiated
Control BP, lipid, DM
Change cyclosporin to MMF or
sirolimus
• Metabolic: HT, DM, lipid, Cushing’s, obesity, IHD
o Disease-related
o Drug-related, e.g. steroid, CNI, mTORi
• Infection:
o Types of infection
- First month: line/ wound infection, pre-existing infection (e.g. HSV, TB)
- 1-6 months: opportunistic infections (CMV, PJP)
- After 6 months: chronic viral infection
o Management
- Mild (e.g. uncomplicated cystitis): PO Augmentin (outpatient), no need stop immunosuppressants
- Severe (e.g. graft pyelonephritis): admit and stop MMF ± decrease CNI + increase stress-dose steroids + IV broad-
spectrum antimicrobials (e.g. 3rd generation cephalosporin)
- Avoid giving macrolides: may increase CyA levels
• Bone (persistent hyperPTH): AVN, osteopenia
• Malignancy: related to immunosuppression - HCC (HBV), post-transplant lymphoproliferative disease (EBV), Kaposi’s sarcoma (HHV8)
• Recurrence of original disease: MPGN > IgAN
Emergency in renal transplant patients
1. Fever
• Infection: opportunistic infections if <6 months post-transplant, usual infections if ≥6 months
• Graft rejection: increase serum Cr >20% after excluding other causes
2. AKI
• Pre-renal: dehydration, transplant artery
stenosis / vein thrombosis
• Renal: transplant rejection, calcineurin inhibitor toxicity, recurrence of renal disease, acute
tubular necrosis
• Post-renal: ureteric anastomotic stenosis, urinary leakage
Workup:
• Bloods: CBC, LRFT, CaPO4, INR
immunosuppressant trough level
• Septic work-up
• ± CMV pp65 antigen / CMV DNA,
• ± urine BK virus / JC virus, decoy cells*
• Urine: MSU C/ST, 24h urine protein & Cr
• ± Drain urea & Cr (if suspect urine leakage)
• Urgent USG graft kidney + Doppler study
• ± Stand-by MAG-3 / DTPA scan
• Early graft renal biopsy for acute rejection
Note: Acute GE, macrolide antibiotics and fluconazole may increase CyA / tacrolimus levels
*Decoy cells: pathognomonic for BK nephropathy à Mx: reduce immunosuppressants
Proteinuria
Protein
- <150mg/day*
- Proteinuria: >150mg/day
- Nephrotic range proteinuria: >3.5g/day
Albumin
- <30mg/day
- Microalbuminuria: 30- 300mg/day; not detectable by urine dipstick
- Macroalbuminuria: >300mg/day
Methods to quantify proteinuria
1. Urine dipstick
- Easy to use, low cost, Specific but not
sensitive to albumin
- Cannot detect microalbuminuria / others (e.g. BJ, IgG)
2. 24h urine collection
- Gold standard, Best for monitoring
proteinuria
- common for incomplete collection
3. Spot uPCR
- only 1 spot sample
- Inaccurate if proteinuria >1g/day
Influenced by daily Cr production
4. Spot uACR
- Only 1 spot sample
Only for screening DM
microalbuminuria
- Inaccurate if proteinuria >1g/day
Influenced by daily Cr production
• Unit conversion: spot urine (mg/g) —> 24h urine (mg/day)
Algorithm:
• Screening for proteinuria: routine urine albustix ≥1+ (non-DM); high-sensitivity urine dipstick +ve / uACR (DM)
• Screening test +ve x 2 but asymptomatic:
o Early morning uPCR for quantification of proteinuria & exclude orthostatic proteinuria
o Urine microscopy for casts / white cells / red cells, blood for RFT (GN)
o Urine for C/ST (UTI)
Classification of proteinuria
1. Physiological
- Orthostatic
- Transient (exercise, CHF, fever)
2. Pathological
A. Tubulointerstitial (impaired resorption)
- <2g/d
- Faconi’s syndrome
B. Glomerular
Primary:
- Minimal change GN
- Membranous GN
- FSGS
- Membranoproliferative GN
- Post-streptococcal GN
- IgA nephropathy
Secondary
- Systemic disease: SLE, DM, vasculitis
- Infectious: HIV, HBV, HCV, bacterial endocarditis
- Hereditary: Alport’s
- Medications: NSAIDS
- Cancer: lymphoma, solid tumour
- Others: cryoglobulinemia, hypertensive nephrosclerosis
C. Overflow (overproduction of low molecular weight proteins)
- multiple myeloma, amyloidosis, Waldenstrom’a macroglobulinemia
Workup for suspected GN
Indicated if: Proteinuria > 1g/day or proteinuria > 0.5g/day with microscopic haematuria
• Refer nephrology, start ACEI/ARB if not C/I
• Urine: microscopy, C/ST, UPCR
• Bloods: BP, CBC, CRP/ ESR, clotting, RFT, LFT (decrease albumin), CaPO4, HbA1c
• Imaging: CXR (pleural effusion), abdominal USG (ascites, kidney size, obstruction, renal vein thrombosis)
• Etiology:
o C3/C4, ANA, anti-dsDNA, ANCA, anti-GBM
o HBsAg, anti-HCV, ASOT
o Immunoglobulin:
- Age < 50y: simple Ig pattern for IgA
- Age > 50y: SPE + urine for BJ protein/ serum FLC (amyloidosis)
o Optional (with clinical suspicion): anti-HIV, VDRL, cryoglobulin
o Malignancy screening (e.g. FOBT, colonoscopy, CXR, AFP) if age >50y
• Renal biopsy (refer to prev section for indications and C/I)
Reduced C3/ C4:
• Lupus nephritis
• HCV-related MPGN
• Post-strep GN
• Cryoglobulinemia
Haematuria
Definitions
• Gross haematuria: red-coloured urine visible to naked eye
• Microscopic haematuria: ≥3 RBC/HPF in 2/3 properly collected urine (freshly voided, clean-catch, mid-stream
urine processed by centrifugation)
Aetiology
1. -ve dipstick, no RBCs
- pseudohematuria by food, medication
2. +ve dipstick, +ve RBCs
A. Haematological
- Coagulopathy, sickle cell
B. Renal
- Primary:
- Membranoproliferative GN
- Post-streptococcal GN
- Rapidly=progresion
- Interstitial nephritis GN
- Papillar necrosis
- IgA nephropathy
Secondary
- Connective tissue disease: Granulomatosis with polyangiitis, Goodpasture’s, SLE, Churg-Strauss, HSP
- Infectious: pyelonephritis
- Hereditary: Alport’s, PCKD
C. Urologic:
- Nephrolithiasis, trauma, tumour, prostatitis, urethritis
- Dysuria or flank pain common
- Isomorphic RMCs, no casts
- Blood at beginning (urethritis) or end (prostate, bladder) of stream
History taking - highlights
• Timing relative to urine stream: beginning (lower urinary tract), throughout (above bladder), terminal (prostate)
• Any blood clots = urologic causes (urokinase in glomerular filtrate prevents formation of blood clots)
• Gross painless haematuria: malignant until proven otherwise —> urological examination
• Associated symptoms:
o Concomitant frothy urine (GN)
o Urologic:
- Dysuria, frequency, urgency (UTI)
- Obstructive symptoms, hematospermia (prostate)
- Loin pain: colicky (stone), constant (inflammation, infection)
o Autoimmune:
- Rash: purpuric rash (HSP, vasculitides), malar rash (SLE)
- Arthralgia, myalgia (SLE)
o Respiratory:
- Recent URTI (concurrent = IgA nephropathy; 7-10d ago = post-strep GN)
- Epistaxis, rhinorrhoea (GPA)
- Pleuritic chest pain, SOB (SLE)
- Haemoptysis (pulmonary-renal syndrome)
o Systemic: fever, weight loss, TOCC (TB)
• Drug history: cyclophosphamide/ifosfamide (haemorrhagic cystitis), RT (radiation cystitis)
• Family history: PCKD, hereditary nephritis (e.g. Alport’s, TBMD)
Investigations
Urine dipstick +Ve
—> repeat several days later
—> if +ve again
—> urine microscopy and culture
—>treat UTI if positive
-Isomorphic RBC
—> urologic disease
—> cystoscopy and TU
- dysmorphic RBC or RBC casts
—> glomerular disease
—> if concomitant proteinuria or renal insufficiency
—> refer nephrology
—> check BP, RFT, uPCR
—> if isolated microscopic haematuria
—> periodic FU
Pearls
• All Hb-positive dipstick should be accompanied by urine microscopy to differentiate haematuria vs pigmenturia
• Antiplatelet/ anticoagulant use is not a satisfactory explanation for haematuria, except in warfarin OD
• Evaluation for
o Haemoglobinuria: centrifuged urine for supernatant haem, LDH, bili, haptoglobin
o Myoglobinuria: centrifuged urine for supernatant haem, CK
• If urological cancer is ruled out, treat as CKD, i.e. monitor RFT & urinalysis yearly
Glomerulonephritis and glomerulonephritis with predominant nephrotic features
Histological terms of glomerular changes
Types of changes
• Membranous changes: thickened GBM (2: membranous nephropathy)
• Proliferations:
o Hyperplasia +/- inflammation in VEC (3: MCD)
o Mesangial cells (4: IgA nephropathy)
o Parietal epithelial cell (5: crescentic GN)
Extent of changes
• % of glomeruli affected: diffuse (>50%), focal (<50%)
• Affected part of involved glomeruli: global, segmental (only part of glomerulus abnormal)
Spectrum of clinical presentations
Glomerulopathies can present as more than one syndrome at different times
• Asymptomatic haematuria/ proteinuria
• Nephrotic syndrome: nephrotic range proteinuria, hypoalbuminaemia, generalised oedema, hypercholesterolaemia
• Acute nephritis: haematuria + proteinuria, HT, impaired RFT (oliguria, oedema)
• ESRD
GN with predominant nephrotic features
Definition of nephrotic syndrome
• Heavy proteinuria >3.5 g/day (>40mg/h/m2 in children)
• Generalized edema
• Hypoalbuminemia (<30g/L)
• Hyperlipidemia —> Lipiduria
Pathophysiology
1. Bland sediment (no cellular element)
- Primary
Minimal change disease
Focal segmental glomerulosclerosis (FSGS)
Membranous nephropathy
- Seconadry
Diabetic nephropathy
Amyloidosis
2. Active sediment (RBC/WBC/cast)
- Primary
Membranoproliferative GN
MCD variants (e.g. IgM nephropathy, C1q
nephropathy)
- Secondary
Lupus nephritis
Cryoglobulinemia
General management
• Monitor: I/O, vitals, BW daily (aim 1kg/day loss), urine dipstick
• Anti-edema: Low sodium diet + fluid restriction + diuretics
o High dose frusemide +/- thiazide/ spironolactone
• Anti-proteinuric drugs (ACEI/ARB): for all glomerulopathies - decrease glomerular pressure, decrease rate of GFR decline
• Statins: if hyperlipidemia persists after Tx
• DVT prophylaxis: compressive stockings ± anticoagulation if high risk
• Investigations: refer to above for details
o Children: steroid trial (90% MCD); renal biopsy if atypical features or failed response to steroid
o Adults: immunological screen, renal biopsy (unless diagnosis obvious e.g. DM nephropathy, PLA2R+)
• Management of complications
- Resistant oedema/ anasarca
- Causes:
Poor drug/ diet compliance
Frusemide malabsorption due to gut wall
oedema
- Mx:
Change to IV frusemide
Add thiazide/ potassium-sparing diuretics
IV albumin - AKI
- Hypovolaemia due to over-diuresis
ATN
Crescentic transformation (RPGN)
- Lower dose/ withhold diuretics
Rehydration - Renal vein thrombosis
- Hypercoagulability by compensatory
production of clotting factors by liver
- Doppler USG, CT angiography
If AKI: thrombolysis ± embolectomy
If non-AKI: LMWH/UFH —> warfarin for
minimum 6-12 months while still nephrotic - SBP (only in child)
- Loss of Ig
- Antibiotics - CV disease
- Long-term complications
- CV risk modifications
Clinical course
• Steroid dependent: 2 consecutive relapses during tapering of steroids / within 14 days of cessation
• Steroid resistant (10%): persistent proteinuria despite full-dose prednisolone x 4 weeks
Specific diseases
1. Minimal change disease (MCD)
- MC cause in children
- Causes:
Idiopathic (MC)
Haematological neoplasms (e.g. HL, NHL)
Drugs: NSAID, COX2
- Presentation: Nephrotic
- Lab finding:
LM normal
EM podocyte effacement
IF -ve
- Mx
1st line: high dose prenisolone (1mg/kg) x 4-8 weeks
2nd line: cyclophosphamide, cyclosporine
Resistant: repeat renal Bx
- Membranous nephropathy
- MC cause in adult
- Causes:
1°: a/w anti-PLA2R
2°: - SLE, RA
- Infections: HBV/HCV, syphilis
- Malignancy: adenoCA (lung, prostate, GIT)
- Drugs: captopril, gold, penicillamine
- Presentations: Nephrotic
Prognosis: 1/3 remit, 1/3 remain nephrotic, 1/3 progress to ESRD
- Lab findings:
Anti-PLA2R
LM: diffuse GBM thickening
EM: subepithelial electron-dense deposits (spike and dome)
IF: granular staining - IgG/C3
- Mx:
Primary: Observation (low risk), immunosuppressant (high risk)
- poor RFT: High dose steroid +CyP (+Mesna to prevent haemorrhaging cystitis+ PCP prophylaxis)
- Good RFT: rituximab
Secondary: treat underlying cause - Focal segmental glomerulosclerosis
- Causes:
1°
2°: Analgesic nephropathy, heroin, HIV, HBV
- Presentations:
1°: nephrotic —> progress to ESRD
2°: non-nephrotic
- Lab findings
LM: segmental sclerosis
EM: podocyte effacement
Mx:
1°: steroids (poor response) —> cyclosporine
2°: steroids not helpful, treat underlying cause - Membranoproliferative GN
- Causes:
Viral: HBV, HCV
Autoimmune: SLE, RA,
scleroderma
- Presentations:
70% Nephrotic
30% Nephritic
Mixed nephrotic/nephritic
- Lab findings:
LM: GBM mesangial thickening
- Mx:
Treat underlying cause
Idiopathic MPGN: Steroid +/- Cyclophosphamide (if dRFT) - Amyloidosis
- Causes:
MM, malignancy
Inflammatory: TB, RA
- Presentations:
Nephrotic, POEMS syndrome
- Mx: treat underlying cause
GN with predominant nephritic features
Definition of nephritic syndrome / acute glomerulonephritis
Acute onset of glomerular inflammation
• Glomerular haematuria
• Variable proteinuria (usually non-nephrotic)
• Variable renal impairment: azotemia (urea, Cr), fluid retention (HT, APO), oliguria
- IgA nephropathy
- S/S: IgAN (variable)
• Recurrent synpharyngitic haematuria (gross haematuria within 1-2 days of URTI)
• Microscopic hematuria
• Nephrotic syndrome
• RPGN
- Lab findings:
Blood: increase IgA (50%)
Renal biopsy: MEST criteria (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy)
- Mx:
Tight BP control & proteinuria: diet,
ACEI/ARB, monitor Q6-12m
Immunosuppressants only if
• Proteinuria >1g/day despite ACEI
• Crescentic GN (as below)
Regimen: steroids ±
cyclophosphamide/azathioprine - Henoch-Schonlein purpura
- S/S:
Systemic vasculitis
“FA GASP”: Fever, arthralgia, GN, colicky abdominal pain, skin rash, periarticular edema
-Mx:
Self-limiting, analgesia with NSAIDS
GI bleed / intussusception: steroids - Post-strep GN
- S/S:
7-10 days after strep throat / impetigo
Variable: asymptomatic haematuria to full blown nephritic Sx / RPGN
- Lab findings:
Decrease C3 (normalise by 4 weeks; persist —> consider lupus nephritic / MPGN)
- Mx:
Ix: ASOT, throat swab
Self resolved
Penicillin V if active strep throat
No need prophylactic Abx - Anti-GBM disease (Good-pasture’s syndrome if lung involved)
- S/S:
RPGN +/- Pulmonary haemorrhage (SOB, cough, haemoptysis)
- Lab findings:
Anti-GBM +ve
CXR
DLCO
IF: linear
- Mx:
IV pulse MP x 3 days + oral prednisone +/- cyclophosphamide / IV rituximab +/- plasma exchange
Crescentic / Rapidly progressive glomerulonephritis (RPGN)
• Clinical syndrome but NOT a specific etiology of GN – can be caused by all types of GN (except MCD)
o Haematuria, proteinuria and decrease RFT that leads to ESRD within 2 weeks of onset if untreated
• Histology: >50% glomeruli with crescent
• Classified based on IF staining pattern (refer to above figure)
o Type I (linear IF): anti-GBM
o Type II (granular IF): immune complex-mediated
o Type III (negative IF): pauci-immune, usually ANCA +ve
• Management: usually require IV pulse steroids ± other immunosuppressants (e.g. cyclophosphamide, rituximab)
o Plasma exchange for fulminant MPA / GPA or Goodpasture’s syndrome
Hereditary nephritis
• Alport syndrome: XR mutation in COL4A5 (Type IV collagen), present as asymptomatic hematuria and bilateral
SNHL (Ix: pure tone audiogram)
• Thin basement membrane disease: heterozygous AD mutation in COL4A3/4
Tubulointerstitial nephritis (TIN)
Definition
• Inflammatory infiltrates affecting primarily the renal interstitium and tubular cells
- Acute tubular necrosis
- Decline in RFT in mins
- Aetiology:
Ischaemic: progression of prerenal failure
Nephrotoxins: paracetamol, AG, contrast - Acute interstitial nephritis (AIN)
- Decline in RFT in days
- Classical triad: fever + eosinophilia +
rash
- Aetiology:
Drugs: antibiotics (esp. penicillin), NSAID
Infection: bacterial pyelonephritis
Inflammation: SLE, Sjogren’s syndrome - Chronic interstitial nephritis (CIN)
- Decline in RFT in weeks
- Aetiology:
Drugs: analgesics (NSAID, paracetamol), cisplatin
Urinary tract obstruction: reflux nephropathy
Radiation
Inflammation: TB, GPA, sarcoidosis
Renal artery stenosis
Aetiology
• Atherosclerosis
• Takayasu’s arteritis (common in Asia)
• Fibromuscular dysplasia
Possible presentations
• Secondary/ resistant hypertension with hypokalemia (hyperreninaemia)
• Multiple episodes of flash pulmonary oedema
• AKI (esp. after ACEI)
Investigations
• Screening: duplex doppler USG
• Confirmatory: angiogram (renal/ CTA/ MRA)
Management
• Medical: antihypertensive (avoid ACEI), CV risk reduction (aspirin)
• Radiological: angioplasty +/- stenting
• Surgical: grafting
Polycystic kidney disease
• Incidence: 1/400 to 1/1000
• Genetics: Autosomal dominant, 100% penetrance, variable expressivity
- PKD1 gene (Chr 16): polycystin 1 (85%)
-> More severe: more renal cysts, poorer prognosis
- PKD2 gene (Chr 4): polycystin 2 (15%)
Less severe: later onset of cysts / ESRD
• Pathogenesis: Ciliopathy —> Progressive formation of epithelial-lined cysts in kidney
• Differential diagnoses: multiple renal cysts, acquired cystic disease (long-term dialysis), TSC, VHL
Clinical features
Renal S/S
• Bilateral ballotable kidneys
• Flank pain: cyst complications / stones
• Haematuria: cyst haemorrhage
• UTI: cyst infections
• Frequency / urgency / nocturia: loss of urinary concentrating ability
• RCC: NOT more common, but more likely bilateral and more difficult to diagnose
Extra-renal cysts
• Polycystic liver disease (MC): esp. women with multiple pregnancies
• Pancreatic cysts (5%)
• Seminal vesicles
Cardiac S/S
• Mitral valve prolapse (30%)
• Aortic regurgitation: aortic root dilation
• Young-onset hypertension
Vascular S/S
• Berry aneurysm: may cause SAH
• Aortic dissection
Other S/S
• Respiratory: bronchiectasis
• GI: diverticular diseases, ventral hernia
Investigations
• Bloods: CBC D/C, LFT, RFT
• Urine: dipstick (haematuria, seldom proteinuria), osmolarity (aim <280), PCr
• Imaging:
o USG if asymptomatic
o CT/MRI if palpable kidneys / decrease eGFR: more sensitive than USG, MRI preferred if eGFR < 60
- Allow measure of height-adjusted total kidney volume (htTKV)
• ± Genetic testing (if imaging equivocal)
• ± Detection of complications
o Echocardiogram
o MRI angiography for aneurysm screening (indicated if symptomatic, PMHx/FHX of stroke, high-risk OT, high-risk occupations)
Diagnostic criteria
• Positive family history + imaging-based criteria (age-dependent: frequency of simple renal cyst with age)
o Example: Ravine USG criteria for PKD1
- Age 15-29 ≥ 2 renal cysts (totally)
- Age 30-59 ≥ 2 renal cysts in each kidney
- Age ≥ 60 ≥ 4 renal cysts in each kidney
• No family history: no established imaging-based criteria
o ≥ 10 cysts, each ≥5mm, in each kidney: support Dx of ADPKD
o Genetic testing should be performed
Prognostic tools
• Mayo’s classification:
o Typical (bilateral diffuse cysts) vs
Atypical (unilateral / asymmetric /
parenchymal artrophy)
o Further divide into Class 1A-1E based
on age, eGFR, rate of htTKV
• Pro-PKD score: estimate median age of
ESRD onset
Management
• Screening in family members ≥20y
• Na restriction (<2g/day)
• Encourage fluid intake (unless ESRD): suppress ADH —> inhibit cyst growth
o Maintain UOsM ≤ 280
• Analgesics for flank pain
• BP control by ACEI/ARB
o Target: 110/75 (if 18-50yo & eGFR > 60), otherwise 130/80
• Treat CKD: renal diet, treat hyperPO4, low threshold for statins
• Treat complications
o Cyst infection: lipid-soluble antibiotics (e.g. quinolones, vancomycin) for cyst penetration
o Cyst haemorrhage: bed rest, analgesics, segmental arterial embolization if severe
• Disease-modifying agent: tolvaptan (V2 receptor antagonist) [TEMPO, REPRISE]
o Rationale: vasopression bind to V2R à—> stimulate cAMP —> stimulate cyst growth via fluid secretion & cyst cell proliferation
o Indications: Mayo Class 1C-1E + eGFR ≥ 25
o C/I: liver impairment, concurrent use of CYP3A4 inhibitors (e.g. azoles)
