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🥠 Nephrology
It is essential to understand the anatomy of the kidney to understand where each disease effects.
- Interstitium: Intertubular, extraglomerular, extravascular space of the kidney.
- Tubules: Proximal convoluted tubule, loop of Henle, and distal convoluted tubule, emptying into the collecting duct.
Key anatomy to remember:
- Afferent arteriole: Afferent = artery.
- Arteries are always before capillaries (basically what the glomerulus is)
- NSAIDs constrict the afferent arteriole
- Efferent arteriole: Efferent = exit.
- ACEi and ARBs dilate the efferent arteriole → Lower pressure within the glomerulus → Less damage to the glomerular membrane
Abnormalities of kidney structure or function, present for ≥3 months, with implications for health.
What problem is caused when the following mechanisms of the kidney are no longer functioning:
- Uraemia: Pericarditis, encephalopathy
- Hypertension
- Peripheral/pulmonary oedema
- Metabolic acidosis (↑ anion gap)
- Anaemia
- Hypocalcaemia
What is the pathophysiological issue based on the following presentations:
- ↓ EPO production due to eGFR < 35
- Interstitial fibroblasts of the kidney
- Iron replacement (depending on the iron studies)
- Darbepoietin (EPO) supplementation
- ↓ 1-ɑ-hydroxylation → ↓ Ca²⁺ → Secondary hyperparathyroidism → Osteoporosis & osteomalacia
- Low calcium → ↑ PTH → Breakdown of hydroxyapatite → High phosphate
- CKD → Low clearance of phosphate from kidneys
- Alfacalcidol (calcitriol) → Already been hydroxylated so doesn’t require 1-ɑ-hydroxylase
- Calcium containing (e.g. calcium carbonate) → If calcium is low and phosphate is high.
- Non-calcium containing (e.g. sevelamer) → If calcium normal and phosphate high.
Two reasons:
Calcium:
Phosphate binders:
Bedside:
- Urinalysis: Haematuria and/or proteinuria
Bloods:
- U&E: Cr, eGFR, electrolytes
- FBC: Anaemia
- Iron studies: Investigating anaemia further
- Bone profile: Calcium, phosphate
Imaging/other:
- Renal ultrasound: Small kidneys; obstruction/hydronephrosis; kidney stones
- AXR: Show calcium-containing stones
- Renal biopsy: Looking for underlying cause of CKD, e.g. IgA nephropathy
- Albumin : Creatinine Ratio (ACR): Picks up microalbuminuria
eGFR
- Creatinine
- Age
- Gender
- Ethnicity
- Pregnancy
- Muscle mass: Anorexia/muscular
- Eating red meat within the last 24h
- GFR: Times on a clock from G3a–G5.
- Albumin: All the 3s (3, 30, 300).
- Stage 3a
- A1
- Stage 4
- A3
- Stage 1 (GFR > 90 w/ evidence of kidney damage)
- A2
- Stage 2 (GFR < 90 with signs of kidney damage)
Management:
- ACE inhibitor / ARB (e.g. ramipril): Shown to reduce intra-glomerular pressure independently of blood pressure (through vasodilation of the efferent arteriole)
- SGLT-2 inhibitor (e.g. dapagliflozin): Shown to have renoprotective effects independent of diabetes status
- Statin
- Anaemia → EPO-stimulating agent (e.g. darbepoetin)
- Hyperphosphataemia → Phosphate binders
- Sevelamer (non-calcium containing)
- Calcium acetate (calcium containing)
- Hypercalcaemia → Cinacalcet
- Signals the body to produce less parathyroid hormone (PTH)
AEIOU
- Acidosis: pH < 7.2
- Electrolytes: Persistent refractory K⁺ > 7
- Intoxication: Severe drug damage
- Overload: Refractory pulmonary oedema
- Uraemia: Encephalopathy / pericarditis
Types:
- Access:
- Arteriovenous fistula (AVF)
- Line: Usually a jugular line with two lumens to pull blood to the machine & push blood back
- Machine:
- Dialysate: The dialysate is the fluid that the blood is run against that creates osmotic gradients to remove potassium, calcium, etc.
- Dialyser: The dialyser is the ‘kidney’ that acts as the membrane between the dialysate and blood
- Ultrafiltration: This is the amount of fluid removed on dialysis
- Duration: The usual regimen is 3 sessions a week, having 3-5 hours per session
- Risks:
- Endocarditis from line / fistula
- Haemodynamic instability from fluid shifts
- Continuous peritoneal dialysis: Dialysate sits in the abdomen for 6-8 hours while the exchanges occur.
- Automated peritoneal dialysis: Dialysis at night over 8 hours using an automated machine.
- Spontaneous bacterial peritonitis (SBP)
- S. epidermis is most common cause
- Tacrolimus
- Mycophenolate
- Prednisolone
- Immunosuppression → Risk of SCC due to sun exposure → Sun cream and avoidance
- Steroids → Osteoporosis
- CMV infection
- Lymphoma
Acute decline in kidney function, leading to a rise in serum creatinine and/or a fall in urine output.
Injury due to impaired kidney perfusion
- Older age (above 65 years)
- Diabetes
- Heart failure
- Nephrotoxic medications: NSAIDS, ACE inhibitors
- Chronic kidney disease
- Contrast
- Hypovolaemia (e.g. in D&V)
- Urea : creatinine ratio.
- If this is high then likely due to dehydration (Urea is more concentrated)
- Urea will be high because the low intravascular volume means it appears more concentrated within the blood
- Haemorrhage
- Sepsis
- Third-spacing of fluid (e.g. in pancreatitis)
- Renal artery stenosis
- Activation of the RAAS system: Angiotensin II → Aldosterone release → Sodium & water resorption at the collecting duct
- Vasoconstriction of the glomerular efferent arteriole and dilation of the afferent arteriole, is intended to maintain glomerular filtration
- Hypothalamus → ADH release → Increased tubular water re-absorption
Direct injury to the kidney parenchyma
- Acute tubular necrosis (e.g. from toxins)
- Glomerulonephritis
- Interstitial nephritis
- Haemolytic uraemic syndrome
- Thrombosis
What is the diagnosis based on the following presentations:
- Rhabdomyolysis (covered in 🚇 Tubule / Interstitium)
- Acute tubular necrosis (covered in 🚇 Tubule / Interstitium)
- Myoglobin in rhabdomyolysis
- Lead
- Radiocontrast
- Aminoglycosides, e.g. gentamicin
- Haemolytic uraemic syndrome: E. coli 0157 infection
- Acute interstitial nephritis (covered in 🚇 Tubule / Interstitium)
- Acute pyelonephritis (covered in 🚇 Tubule / Interstitium)
Injury due to urinary outflow obstruction
- Kidney stones
- Prostatic hypertrophy / cancer
- External ureteric compression
- Abdominal malignancy
- Obstruction → Increased intratubular pressure → Tubular ischaemia & atrophy
- Relieve the obstruction: Insert a catheter, remove the kidney stone, etc.
Investigations & Management:
- A rise in creatinine of ≥ 26 mmol in 48 hours
- A rise in creatinine by 1.5X in 7 days
- Urine output < 0.5 ml/kg/hr
Increase in creatinine by the following times of baseline:
- 1.5-1.9 X
- 2-2.9 X
- ≥ 3 X
Urine production:
- < 0.5 ml/kg/hr for 6 hours
- < 0.5 ml/kg/hr for 12 hours
- < 0.3 ml/kg/hr for 24 hours
- Urinalysis
- Renal ultrasound
- Micturating cystography
- Acute tubular necrosis
- Urine Na⁺ > 30 mmol/L
- Pre-renal AKI
- Urine Na⁺ < 20 mmol/L
- Conservatively: Often with IV fluids or with encouraging oral intake.
- Metformin
- ACEi/ARB
- NSAIDs
- Diuretics
- Aminoglycosides
- Membrane stabilisation: IV calcium gluconate
- Pushing potassium intracellularly: Insulin/dextrose (& nebulised salbutamol)
- Permanent lowering: Calcium resonium (PO/PR)/diuretics/dialysis
If you believe there is a disease of the glomerulus, you must differentiate between nephrotic and nephritic syndrome.
- Nephrotic: Proteinuria (> 3-3.5g/day) → Hypoalbuminaemia → Oedema
- Albumin : creatinine ratio (ACR)
- Nephritic: Haematuria, hypertension & proteinuria
Bedside:
- Urinalysis: Looking for haematuria and proteinuria
- Urine microscopy: Looking for red cells and red cell casts
- 24-hour urine collection: Protein excretion rate ≥3.5 g per 24 hours indicates nephrotic-range proteinuria
- Urine PCR ≥ 300 mg/mmol → Nephrotic-range
Bloods:
- FBC: Hb → Anaemia
- U&E: eGFR, creatinine (? AKI), electrolytes
- ESR → Inflammation
- CRP → Inflammation
- Immunology
- Immune complex disease
- Eosinophilic granulomatosis with polyangiitis
- Microscopic polyangiitis (MPA)
- Granulomatosis with polyangiitis
- Goodpasture’s
- Post-streptococcal
- Rheumatoid arthritis
- Post-streptococcal
- Systemic lupus erythematosus (SLE)
- Systemic lupus erythematosus (SLE)
What differential do these tests point to if positive:
Imaging / Other:
- Renal ultrasound: Small kidneys (thinning of cortex) or normal
- Renal biopsy (gold standard): Tells us the underlying cause through looking at histology.
- Treat the underlying cause:
- Immunosuppression: Reduce the inflammation from inflammatory diseases
- Corticosteroid (e.g., prednisolone)
- Corticosteroid-sparing agent (e.g., cyclophosphamide, rituximab, mycophenolate)
- Stop causative drugs
- Treat infection with antibiotics / antivirals
- Blood pressure management: Block the renin-angiotensin system to manage hypertension
Name causes of the following:
Breakdown of glomerular membrane.
Accounts for ~ 90% of cases in children under the age of 10 years.
- Children presenting to A&E with:
- periorbital oedema
- peripheral oedema
- shortness of breath (pleural effusions and/or pulmonary oedema)
- Primary: Majority are idiopathic
- Secondary:
- Medications, e.g. NSAIDs
- Malignancy, e.g. lymphoproliferative disorders
- Infections, e.g. syphilis
- High-dose prednisolone
Sclerosis in parts of at least one glomerulus.
- Diabetes mellitus
- Buerger's disease
- Sickle cell
- HIV
- Steroids or cylophosphamide/ciclosporin
Glomerular basement membrane thickening without significant cellular proliferation on histology.
- Primary: Autoimmune reaction against important antigens (PLA2R) in the filtration barrier
- Secondary:
- Cancer: Breast, lung, colon
- Systemic disease: SLE, thyroid
- Infection: HepB
- Drugs: Gold, penicillamine
- "Spike & dome" pattern
- Thickening of the basement membrane
- Build up of amyloid proteins around tissues → Organ dysfunction
- In the kidney: Amyloid proteins are deposited in the mesangium & capillary loops → Disruption of the glomerular basement membrane
- Unexplained weight loss
- Fatigue
- Oedema resistant to diuretic therapy
- Congo red staining → Apple-green birefringence
Glucose deposits on the basement membrane causing damage (see Endocrine for more diabetes detail)
Why are they predisposed to:
- ↑ loss of proteins into urine → ↑ loss of antithrombin III, protein C & protein S → Hypercoagulability
- Commonly in the renal veins as it clots as soon as it leaves the kidney, but they can also have a VTE due to this.
- Loss of immunoglobulins in the urine
- ↓ oncotic pressure → ↑ rate of lipoprotein synthesis in the liver → ↑ cholesterol
Inflammation of the glomerular membrane: SHARP AIM
Consider this as a differential — See Rheumatology notes for SLE presentation, investigations & management.
This is an IgA vasculitis. It leads to IgA nephropathy, but is also referred to as HSP nephritis.
- Purpura
- Joint pain
- Abdominal pain
- Renal involvement: Glomerulonephritis (HSPN) occurs in 30-50% of HSP patients, consider as a differential in those with a clinical presentation of HSP.
- X-linked (most common), but can be autosomal dominant or autosomal recessive
- Ears: Bilateral sensorineural hearing loss
- Eyes: Anterior lenticonus / retinitis pigmentosa
- Kidneys: Microscopic haematuria
All causes of nephritic syndrome can also be rapidly progressive but usually aren't.
- ✚ cANCA.
- Triad:
- Haemoptysis
- Systemic vasculitis
- RPGN
- ✚ pANCA (anti-MPO)
- Triad:
- Allergic asthma
- Eosinophilia
- RPGN
- ✚ pANCA (anti-MPO)
- Triad:
- Pulmonary infiltrates
- CNS/MSK abnormalities
- RPGN
- Crescentic glomerulonephritis
- 10-14 days following an URTI
- Anti-Streptolysin O (ASO) titre
- Anti-DNase antibody
- Antibiotics & conservative management
Anti-GBM antibodies attack type 4 collagen in the basement membrane of the lungs & kidneys.
- Lungs → Haemoptysis
- Kidneys → Haematuria
- Granulomatosis with polyangiitis
- Antibodies: cANCA & anti-GBM
- Plasmapheresis: Remove the circulating antibodies
- High dose IV steroids / cyclophosphamide
- 2 days following an URTI with:
- macroscopic haematuria or;
- asymptomatically with microscopic haematuria and proteinuria.
- Time from infection to presentation:
- Days from infection → IgA nephropathy
- Weeks from infection → Post-streptococcal
- IgA deposits
- Glomerular mesangial proliferation
Deposits in the basement membrane causing thickening, with the membrane being rebuilt around them causing ‘team-tracking’.
Bimodal:
- 20 year olds
- 60 year olds
- Deposits of IgG and complement on the basement membrane
- Primary: Majority are idiopathic
- Secondary:
- Haemolytic uraemic syndrome
- Autoimmune diseases: SLE, scleroderma, Sjögrens
- Cancer: Leukaemia, lymphoma
- Infections: Hepatitis B/C
Epithelial death of the renal tubules due to ischaemia or toxins.
- The cells can regenerate in 1-3 weeks therefore it is reversible.
- Ischaemia:
- Sepsis
- Shock (e.g. hypovolaemic)
- Dehydration
- Toxins:
- NSAIDs
- Radiology contrast dye
- Gentamicin
- Muddy brown casts
- Supportive management, e.g. adequate hydration with IV fluids
- Stop nephrotoxic medications
- Hyperchloraemic metabolic acidosis (normal anion gap)
- Type 4
- Type 2
- Type 1
- Type 1: ↓
- Type 2: ↓
- Type 4: ↑
Common relationships:
- Type 2
- Type 1
- Type 1
A genetic disorder causing cysts develop from cells in the tubular portion of the nephron and collecting ducts.
- PKD 1 — Accounts for more cases and has a more severe phenotype
- PKD 2 — Accounts for around 15% of ADPKD and is less severe
- Dilatation and out-pouching of tubule wall → Glomerulus filters fluid into the newly formed cyst → Cysts separate from nephron, isolating them → Impaired renal function.
Symptoms:
- Abdominal pain
- Renal colic
- Haematuria
- Polyuria, polydipsia, nocturia: Unresponsive to ADH → Unconcentrated urine
- Dysuria
Signs:
- Abdominal mass
- Hypertension
- Hepatomegaly
- Liver: Hepatic ducts express the same proteins
- Pancreas: Pancreatic ducts express the same proteins
- Brain: Cerebral aneurysms
- Heart: Valvular disease
Bedside:
- Urinalysis
Bloods:
- FBC: looking for anaemia if PKD causing CKD
- U&E: assessing renal function
- Bone profile: calcium/phosphate regulation given 1-ɑ-hydroxylase produced in the kidney
- LFT: looking for hepatic impairment
- CRP: looking for cyst infection
Imaging:
- Ultrasound abdomen
- CT KUB: if presenting with renal colic and querying a stone
- Renal MRI/CT
- Cerebral imaging
- Manage hypertension (< 130/80 mmHg)
- Vasopressin (V2) receptor antagonists may be used in patients high-risk of progression
- Treat UTIs and infected cysts
ARPKD is a rarer and often more severe form of cystic disease, involving the kidneys and biliary tract.
- In utero or in the neonatal period with bilaterally enlarged echogenic kidneys and can be life-threatening.
- In older children it manifests as portal hypertension or cholangitis.
- PKHD1 gene on chromosome 6 → Codes for fibrocystin/polyductin protein complex (FPC) → Creation of tubules and maintaines healthy renal, hepatic and pancreatic epithelial tissue.
Rhabdomyolysis: Injury to skeletal muscle cells → Release of intracellular ions, myoglobin, creatine kinase (CK) & urates → Obstruction & direct toxicity to renal tubules.
- Recent crush injury: Traumatic injury
- Prolonged immobilisation: Long lie
- Muscular pain, swelling or weakness
- Dark urine
- Other risk factors: Alcohol, cocaine, amphetamine, phencyclidine, narcotics, diuretics
Bedside:
- Urinalysis: + Blood
Bloods:
- Serum CK > 5 times normal or > 1000 IU/L
- U&E: ↑ potassium, magnesium, and phosphate; ↓ calcium
- FBC: ↓ haemoglobin & platelets (looking for DIC)
- Hydration: IV fluids (400 mL/hour with a range of 200 mL/hour to 1000 mL/hour is considered reasonable as goal-directed therapy)
- Correct electrolytes: Correct hyperkalaemia if present
High concentration of ions and molecules passing through tubules → Precipitation & deposition of crystals → Tubular obstruction → AKI +/- CKD.
- Methotrexate
- Aciclovir
- Ciprofloxacin
- Amoxicillin
Monoclonal gammopathy (e.g. multiple myeloma) → Light-chain deposition in tubules → Light-chain cast nephropathy → Renal insufficiency.
- Consider this as a differential but it’s rare and unlikely to come up in exams.
- ~ 20% of patients with multiple myeloma have renal failure at the time of diagnosis.
- Nephrotic syndrome: Oedema, effusions
- Hepatomegaly
- Heart failure features if overloaded
- Serum protein electrophoresis with immunofixation
- 24-hour urine for urine protein electrophoresis and immunofixation
- Renal biopsy
Acute inflammation of the renal tubulo-interstitium usually triggered by medications.
- Inflammation of the renal interstitium secondary to a hypersensitivity reaction
- Triggering medication causing hypersensitivity symptoms:
- Rash
- Fever
- Arthralgia
- Signs & symptoms of renal dysfunction:
- Antibiotics (e.g. penicillins, sulfa drugs, cephalosporins & quinolones)
- NSAIDs
- Diuretics
- Rifampicin
- Allopurinol
- Vasculitis
- Systemic lupus erythematosus
- Sjogren syndrome
- Sarcoidosis
Bedside:
- Urinalysis: Sterile pyuria; low-grade proteinuria; WBC casts
Bloods:
- FBC: May show eosinophilia
- U&E: Renal dysfunction
- Antibodies: ANCA, ANA, anti-ds DNA, complement
- Stop potentially triggering medications: AKI may resolve following this.
- Supportive care: Fluid and electrolyte balance.
- Diuretics: Use if retaining fluid, e.g. 40-100 mg IV furosemide.
- Steroids: If inflammatory cause, steroids are suggested to improve the rate and extent of renal recovery.
Severe infectious inflammatory disease of the renal parenchyma, calices, and pelvis that can be acute, recurrent, or chronic.
- Enteric bacteria (e.g. E. coli) that either:
- ascend from the lower urinary tract or;
- spread haematogenously to the kidney
- Flank pain
- Costo-vertebral angle tenderness
- Fever
- New or different myalgia, or flu-like symptoms
- Presence of risk factors: UTI, diabetes mellitus, stress incontinence, catheter, renal calculus
Bedside:
- Urinalysis: Leukocytes, nitries, WBC casts
- Urine culture: Presence of bacteria
Bloods:
- FBC: Leukocytosis, elevated infection markers.
- CRP: Elevated
- U&E: Renal dysfunction
Imaging:
- Renal ultrasound: Looking for stones & structural abnormalities
- CT KUB (with contrast): Identify renal stones, consider if kidneys can tolerate contrast
- Antibiotics: Follow local guidance.
- When considering antibiotics, we need to note whether they’re pregnant, relation to menopause, urological abnormalities or co-morbidities.
- Antibiotics may include: Cefalexin, amoxicillin, trimethoprim or ciprofloxacin (avoid if pregnant).
- Supportive care: Fluids & analgesia.
- Underlying medical problems (e.g. diabetes mellitus, HIV)
- Genitourinary anatomical abnormalities
- Obstruction (e.g. benign prostatic hypertrophy, calculi)
- Multi-drug-resistant pathogens, more likely in some patient groups (e.g. pregnant women & men)
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