SLIME

Week 4: Renal Medicine

Nephritic and nephrotic syndrome.

Proteinuria:

Normal protein loss: <150mg/day

Microalbuminuria: 30-300mg/day (early sign of diabetic nephropathy)

Proteinuria: 300mg – 4.5g/day ( if >2g/day + microscopic haematuria +/- renal impairment  renal biopsy)

Protein loss <2g/day could be glomerular or tubular or overflow proteinuria

Protein loss >2g/day is usually glomerular.

Causes of proteinuria:

  • Myeloma (Bence-Jones protein- immunological light chains)
  • Diabetic nephropathy (initially microalbuminuria)
  • Glomerulonephritis
  • Amyloidosis
  • Drugs (NSAIDs, DMARDs)
  • SLE (lupus nephritis)

Nephrotic syndrome

  • Proteinuria (protein: creatinine ratio (PCR) greater than 200 mg/mmol)
  • Oedema (children usually present with facial swelling, adults with peripheral oedema)
  • Hypoalbuminaemia (serum albumin <25g/L)
  • Hyperlipidaemia (total cholesterol >10 mol/L)

Causes:

Primary renal causes:

  • Glomerulonephritis:
  • Minimal change disease,
  • Membranous nephropathy,
  • Focal segmental glomerulonephritis

Secondary renal causes:

  • Diabetes mellitus
  • Renal amyloid
  • Drugs (NSAIDs, DMARDs)
  • SLE
  • Post-infective e.g. HIV, TB

Complications:

  • Hypercoagulability  DVT / renal vein thrombosis and dramatic worsening of Renal function.
  • Infection: as hypogammaglobulinaemia and impaired immune system.

Treatment:

  • Salt and fluid restrict (refer to dietician)
  • Diuretics to reduce oedema (care not to cause hypovolaemia which will worsen renal function)
  • ACEi to reduce protein loss and any hypertension
  • Statins
  • Warfarin (evidence base: only warfarinise post-VTE, however, some warfarinise if alb <20)
  • Minimal change disease responds to steroids.
  • Other glomerulonephritides respond to immunosuppressants e.g. cyclophosphamide.

Nephritic Syndrome

  • Haematuria
  • (Mild proteinuria (not enough to cause hypoalbuminaemia))
  • Oedema (unable to excrete water) occasional oliguria
  • Hypertension
  • Uraemia (varies according to GFR)

↓GFR  oliguria  Na retention  HTN

Causes:

Primary renal causes:

  • Glomerulonephritis:
  • Rapidly progressive glomerulonephritis

Secondary renal causes:

  • Post-streptococcal GN (2-3 weeks post B-haemolytic strep throat infection)
  • Multisystem systemic diseases - eg systemic lupus erythematosus, vasculitis, Henoch-Schönlein purpura, Goodpasture syndrome, Wegener granulomatosis

Treatment:

  • Diuretics
  • ACEi
  • Dialysis may be needed for uraemia.
  • Treatment dependent on underlying cause

Glomerulonephritis

A range of immune-mediated inflammatory disorders that cause inflammation within the glomerulus and other compartments of the kidney.

Features raising suspicion of GN:

  • Proteinuria + Haematuria (especially red cell casts)
  • +/- Renal impairment

Primary GN: affects only both kidneys symmetrically.

Secondary GN: systemic illness, also causing GN e.g. Wegner’s granulomatosis, SLE, Diabetes.

•Primary glomerulonephritis classified according to:

–Clinical syndrome e.g. rapidly progressive GN

–Histopathological appearance e.g. minimal change GN

–Underlying aetiology. E.g. lupus nephritis

•Glomerulonephritides may be:

–Minimal change.

–Diffuse: affecting all glomeruli.

–Focal: affecting only some of the glomeruli.

–Segmental: only affecting parts of an affected glomerulus.

Acute GN

  • Rapidly progressive GN
  • Nephritic syndrome.
  • Crescentic-shaped proliferation of cells in the Bowman’s capsule
  • Commonly seen in vasculitidies
  • Wegner’s
  • Goodpasture’s syndrome (ARF and pulm haemorrhage caused by anti GBM)
  • Post-infectious GN after strep infection.
  • Develops to renal failure within days
  • Needs aggressive Tx early.
  • Membraneous GN
  • Nephrotic syndrome
  • Electron microscope: Thickened glomerular basement membrane due to immune deposition
  • Causes:
  • SLE
  • Drugs
  • Infection
  • Malignancies
  • Minimal change GN
  • Nephrotic syndrome
  • Light microscope: fused podocyte foot processes
  • Commonest in children.

Chronic GN

Small shrunken kidneys  CRF with GN on biopsy

Often don’t biopsy as won’t change management and poses risk to kidneys.

Ix:

  • Renal function (serum creatinine, GFR)
  • Dipstick urine (protein, blood)
  • Microscopy for casts
  • 24h urine protein excretion
  • Renal US for size

Significant proteinuria >1g/day suggests GN

Is this primary or secondary?

  • pANCA, (WG)
  • anti-GBM (Goodpasture’s)
  • anti dsDNA (SLE)
  • ANA , Scl-70 (scleroderma)
  • Biopsy unless kidneys are small.

Clinical Scenario

A 24 year old man presents to clinic because he has been feeling more tired recently. He has no systemic symptoms on questioning. The only thing he has noticed is that his urine is more frothy than normal, but he has no urinary symptoms and has not noticed any blood. He is normally fit and well and on no regular medication. He does not smoke and drinks alcohol socially. Examination is unremarkable. A urine dip shows +++ protein

What are your main differential diagnoses for this gentleman? (make sure these include all important differentials that must be ruled out)

How would you investigate this gentleman?

What would your management plan be for this gentleman?

What are the features of nephrotic syndrome and nephritic syndrome?

What are the complications of nephrotic syndrome?