Acute Renal Failure

1.6.07

• Broadly defined as rapid deterioration of renal function resulting in accumulation of waste products such as urea and creatinine.
• Pre-renal, renal, post-renal.

Pre-renal - causes of renal hypoperfusion
• Intravascular volume depletion e.g. through vomiting, diarrhoea.
• Trauma/burns/crash injury.
• Haemorrhage.
• Pancreatitis.
• Diabetic ketoacidosis.
• Addison's disease.

Pre-renal
• Decreased CO2.
• Changes in renal vascular resistance.
• Renovascular obstruction.
• Microvascular obstruction.
• Increased blood viscosity.
• Interference with renal autoregulation.

Intrinsic ARF
• Persistent pre-renal failure of any cause.
• Nephrotoxins.
• Haemoglobinuria/myoglobinuria e.g. from any crush injury.
• Radiological contrast material.
• Acute glomerulonephritis e.g. from Goodpasture's syndrome, Wegener's granulomatosis.
• Acute renal vasculitis.
• Obstetric causes e.g. ATN from severe hypovolaemia.

Obstructive uropathy
• Bilateral urinary tract calculi.
• Single urinary tract calculus.
• Retroperitoneal fibrosis.
• Crystal nephropathy.
• Cancer of bladder/cervix.
• Urethral stone.
• Following pelvic surgery.

Clinical features of urinary tract obstruction
• Anuria.
• Polyuria.
• Alternating anuria and polyuria.
• Pain.
• UTI.
• Uraemia of no apparent cause.

Golden clinical rules
• Assess volume status.
• Search to diagnose urinary tract obstruction:
-History.
-PR.
-Ultrasound.
• If pre-renal, fill up (with saline - isotonic to plasma).
• If renal, remove cause or treat condition.
• If obstructive, relieve obstruction.

Management
• Support renal failure.
-Fluids/CVP.
-Electrolytes e.g. high plasma K+.
-Insulin/dextrose.
-Ca2+ resonium.
-Haemodialysis for uraemia.
• Look for and fight infection.
• Don't forget nutrition - enteral/parenteral.
• Remember dangers of blood-borne agents e.g. HBV, HCV, HIV.
• Renal biopsy, if indicated.
• Treat any underlying treatable condition e.g. arteritis, myeloma, hypercalcaemia.

Acute or acute-on-chronic renal failure?
• Pre-existing renal disease suggested by:
-PMH of proteinuria, Nocturia, renal stones, DM or hypertension.
-Analgesic abuse.
-FH of polycystic kidneys, hereditary nephritis.
-Normochromic normocytic anaemia.
-Secondary hyperparathyroidism.
-Stunting of growth or failure of secondary sexual characteristics.
• Palpable or history of polycystic kidneys.
• Bilaterally small kidneys.

Complications
• Fluid/volume.
• Metabolic.
• Infection.
• Nutritional.
• Related to underlying problem.
• Stressful situation for patient and family.

Prognosis
• ~40% mortality.
• Worse if:
-Post-surgery.
-Infection.
-Catabolic.
-Increase in age and multiple diseases.
-Delay in referral and commencing dialysis.
-Complications.

Survivors
• If patient survives ARF, majority recover renal function to become dialysis independent.

Pathology Of Renal Failure

25.5.07

Renal function
• Blood supply 1250ml/min.
• GFR 150ml/min.
• Urine output 1ml/min.
• Filtration (glomerulus).
• Modification (PCT).
• Concentration (loop and DCT).
• Active processes.

Acute renal failure (ARF)
• Pre-renal - pump failure, volume loss, microvascular damage.
• Renal.
• Post-renal.

ARF: renal causes
• Ischaemia - worsened by crush injury.
• Toxins.
-Heavy metals.
-Solvents.
-Antibiotics.
-Venoms and mycotoxins.
-Bence Jones protein.

ARF: post-renal causes
• Obstruction from:
-Stones.
-Prostatic enlargement.
-Tumours.
-Ureteric stricture.
-[+Rarer causes.]

Features of ARF
• Anuria/Oliguria.
• Na+ <20mEq/L.
• High osmolality (ratio u/p >1.5).
• High urea and creatinine.
• May go on to acute tubular necrosis (ATN).

ATN
• Biochemical/laboratory features:
-Not anuric (may be polyuric).
-Urine Na+ >40mEq/L.
-Osmolality u/p <1.1:1.
-Numerous granular and cellular casts.

Chronic renal failure (CRF)
• Leakage of proteins (damage to filter).
• Na+ and water retained.
-Oedema and hypertension.
• Haematuria.
• Decrease in GFR.
-<20% abnormal (<5% = ESRF).
• Raised urea, creatinine, K+.
• Decreased Ca2+.

CRF: syndromes
• Nephritic:
-Decreased urine output.
-Modest proteinuria.
-Hypertension.
-Retention of Na+ and water.
-Haematuria.
• Nephrotic:
-Protein loss>3.5g/day.
-Hypoalbuminaemia.
-Oedema.
• Rapidly progressive renal failure.
-Generally with crescentic glomerulonephritis.

Membranous glomerulonephritis
• Nephrotic syndrome.
• Drugs, tumours, infections, SLE, DM.
• Thickened glomerular basement membrane diffusely and universally.
• Spikes (complexes) on silver stain.

Immune complex glomerulonephritis
• Circulating complexes trapped in glomeruli.
• Injury mainly due to complement binding.
• Tend to cause Membranoproliferative pattern of injury.
• See in e.g.
-SLE.
-HBV.
-HCV.
-HIV.
-Endocarditis.
-Chronic infections.
-Parasitic invasions.

Amyloidosis
• Abnormal amount of polymerised protein (β-pleated sheet).
• Plasma cell and inflammatory types.
• Trapped in glomeruli in filtration.
• Result in nephrotic syndrome.
• Stains brick red with Congo red dye.
• Apple green birefringence with Congo red.

Interstitial nephritis
• Pyelonephritis.
• Drug induced.
-NSAIDs.

Renal papillary necrosis
• Osmotic stress.
• DM.
• NSAIDs.
-Australia.
-Vultures.

Systemic hypertension
• Benign hypertension tends to have minimal effects on GFR.
• Risk increased in black people in USA.

Summary
• ARF.
• CRF.
-Polycystic.
-Systemic.
§DM, SLE, hypertension.
-Glomerular.
-Interstitial.
-Obstruction.

Glomerulonephritis

21.5.07

Definition
• Disease affecting kidneys - classified according to changes seen in glomerulus on light, immunofluorescence and electron microscopy.

Clinical presentation
• Persistent microscopic haemuturia.
• Persistent proteinuria.
• Nephrotic syndrome.
• Recurrent macroscopic haemuturia.
• Acute nephritic syndrome.
• Acute/subacute renal failure.
• Chronic renal failure.

Proteinuria
• Normal range <0.2g/24 hours.
• Nephrotic syndrome.
• Definition: proteinuria >5g/24 hours.
• Oedema.
• Hypoalbuminaemia.
• Hypercholesterolaemia.
• Persistent proteinuria: above normal range, but not nephritic and usually asymptomatic.

Types of glomerulonephritis
• Based on histology.
• Although patients may share same histological type, clinical presentation may be variable.
• Some clinical presentations more characteristic of certain types.

Minimal change glomerulonephritis
• Usually presents as nephritic syndrome.
• Commonest cause of nephritic syndrome in children.
• Usually responds to oral steroids, if not cyclophosphamide/cyclosporin may be used.

Focal segmental glomerulonephritis
• Usually presents as nephritic syndrome.
• Responds less well to immunosuppression than minimal change glomerulonephritis.
• May be found in association with AIDS and with IVDU.
• ~50% will progress to ESRF.
• Focal segmental changes may be found late in course of patients whose initial biopsy showed minimal change glomerulonephritis.

Membranous glomerulonephritis
• Accounts for 20-30% adult nephritic syndrome and up to 5% children.
• May also present as asymptomatic proteinuria/chronic renal failure.
• In 20-30% cases, secondary to another cause.
• Up to 30% may develop ESRF.
• Up to 30% will resolve spontaneously.
• Immunosuppression reserved for those with intractable nephritic syndrome/progressive renal failure.
• Regimes include:
-Prednisolone.
-Cyclophosphamide.
-Azathioprine.
-Chlorambucil.
-Cyclosporin A.
-Mycophenolate.

Causes of secondary membranous glomerulonephritis
• Cancer: bronchus, breast, GI tract, prostate.
• Infection: hep B, syphilis, leprosy, filiriasis.
• Drugs: gold, penicillamine, captopril.
• Multisystem: SLE, sarcoidosis, RA.

IgA nephropathy
Presentation
• Often with recurrent episodes of macrohaematuria occurring within 12-24 hours of onset of URTI.
• Frequently accompanied by muscle and loin pain and fever out of proportion to severity of URTI.
• Commonest form of idiopathic GN worldwide.
• Typically affects young males M:F = 3:1.

Diagnosis
• Serum polyclonal IgA sometimes increases, but not of prognostic significance.
• On renal biopsy, mesangial deposits of IgA and C3.

Outcome
• Up to 50% adults: slowly progressive renal failure of 15-20 years of often asymptomatic progression.

Treatment
• Depends on presentation and progression.
• Immunosuppression often tried in severe nephritic syndrome/rapid progression of renal failure.

Membranoproliferative glomerulonephritis
• Usually presents as persistent proteinuria/nephritic syndrome/chronic renal failure.
• 3 histological types.
• May be secondary to systemic disease.
• Immunological abnormalities.
• Low serum, C3 complement found in 60-100% type I and 30-40% type II.
• Complement abnormalities indicate activation of alternative pathway.
• Treatment:
-If secondary to another disease, treat underlying disease.
-In idiopathic forms, no specific treatment of consistently proven benefit.

Rapidly progressive glomerulonephritis
• Form of glomerulonephritis causing renal damage - may progress from onset to ESRF within weeks/months.
• Characteristic lesion: focal necrotising glomerulonephritis with crescent formation.
• 3 main causes:
1. Antiglomerular basement membrane disease.
2. Vasculitis.
3. SLE.
• However, many other causes, including systemic disease, drugs, infections, neoplasia.
• Clinical presentation:
-Often dependent on presence/absence of systemic disease.
-If absent, patients may present with non-specific features of renal failure:
§Oliguria.
§Oedema.
§Dyspnoea/uraemic symptoms.
-Macroscopic haemuturia and loin pain sometimes reported.

Antiglomerular basement membrane disease
• Rare: affects M>F.
• May be associated with pulmonary haemorrhage.
• Characterised by presence of circulating antiglomerular basement membrane antibodies and deposition of IgG in basement membrane.

Vasculitis
• Rapidly progressive renal lesion may be seen in variety of systemic diseases, notably polyarteritis nodosa and Wegener's granulomatosis.
• Often associated with circulating anti-neutrophil cytoplasmic antibodies.

Post-streptococcal glomerulonephritis
• Occurs usually between 7 and 21 days after group A streptococcus infection.
• During epidemic, clinically detectable glomerulonephritis occurs in 5-10% after pharyngitis and ~25% after skin infections.
• Young children at highest risk.
• Presentation can vary from microhaematuria to full-blown nephritic syndrome.
• Investigations:
-Throat/skin swab.
-ASO titre.
-C3 and C4 complement may be decreased.

Alport's syndrome
• Inherited as x-linked trait.
• In males, usually progressive form of renal disease causing ESRF commonly between 16-35 years.
• Associated with sensorineural deafness and anterior lenticomus.

Renal Transplantation

21.5.07

History
• In 01/02, Emerich Ullmann reported first case of renal autotransplantation performed in neck of dog.
• In same year, presented first xenotransplantation of kidney (goat with dog's).

First successful human kidney transplantation: Boston (1954) - identical twins.

Treatment options for ESRF
DIALYSIS
(long term)

Peritoneal Haemodialysis

TRANSPLANTATION

Cadaveric Live donor

What life is like on dialysis
• Poor quality of life.
• Usually unable to work.
• Little/no holidays.
• Feel ill most of time.

Transplantation optimum renal replacement therapy for most patients.

Cadaveric donor operation - donor selection criteria
• 2-75 years.
• No infection.
• No DM.
• No cancer except primary brain tumours.
• No HIV.

Donor selection - UK code
• Brainstem death.
• Preconditions: irreversible coma.
• Exclusions.

Imaging renal anatomy: angiogram.

Matching of kidney
• ABO.
• HLA.
• Lymphocytotoxic crossmatch.

Surgical complications
• Renal artery thrombosis.
• Renal vein thrombosis.
• Urine leak and ureteric stenosis.
• Lymphocele.

Long-term complications
• Infection.
• Cancer.
• Drug side-effects.
• Rejection.
• Graft loss.

Side-effects of immunosuppression
• Drug-specific.
• Total burden of immunosuppression.
• Additional chronic renal failure.
• Progression of primary disease.

Predictors of long-term graft function
• Factors impacting on graft survival (HLA match, donor type etc).
• Factor impacting on patient survival.

Module 2.14

The Tax Inspector's Appointment.
21.5.07 - 1.6.07.