Monday, 8 November 2010

MRCP revision battle 43.1: Post renal-transplant complications

I'll admit it: I've been avoiding renal revision.  It's complicated I never understand it and it leaves me internally angry.  However dear friends I'm afraid the time has come to face a fully renal day.  On the menu is...

MRCP revision battle 43.1: Post renal-transplant complications
MRCP revision battle 43.2: Polycystic kidney disease and renal cysts
MRCP revision battle 43.3: Renal tubular acidosis
MRCP revision battle 43.4: Haematuria
MRCP revision battle 43.5: Renal calculi
MRCP revision battle 43.6: Focal Segmental Glomerulonephritis
MRCP revision battle 43.7: Acute renal failure

MRCP revision battle 43.1: Post renal-transplant complications

A kidney transplant can give a renal patient their life back as it frees them from endless dialysis sessions.  However, with kidney transplants come the risk of rejection/failure, complications and the burden of immunosupression...


Acute rejection (less than 6 months post graft) presents as rising creatinine, possibly with fever and graft pain.  Biopsy would show immune cell infiltration.  Treatment is with high dose IV methylprednislone

Chronic rejection (greater than 6 months post graft) presents as gradually rising creatinine and proteinuria.  Biopsy would show fibrosis.  There is no effective treatment.

Overall graft survial is around 90% at 1 yr, 70% at 5 yrs and 50% at 10 yrs.

Non-renal complications

  • Non-Hogkins Lymphoma - 20-50x increased risk due to ciclosporin use
  • Skin cancer - 5-20x increased risk due to azothioprine
  • Widespread warts/fungi/herpes zoster due to T cell supression by immunosupressives
  • Cardiovascular disease - 10-20x increased risk
  • CMV - give oral ganciclovir
  • Pneumocystis carini pneumonia - give cotrimoxazole prophylaxis for first 6 months post transplant
  • if previous TB give isoniazid for first year
  • gout
  • Diabetes - develops in 3-5%, ?due to tacrolimus

The common immunosupressants

  • Ciclosporin
    • inhibits T cell phosphatase calcineurin
    • can cause tremor, hypertension, gum hypertrophy
  • Tacrolimus
    • decreases T cell activation
    • ?risk of diabeets
  • Azothioprine
    • contraindicated with allopurinol as risk of life-threatening bone marrow supression
    • is an anti-proliferation drug 
    • TPMT test can be used to look for patients prone to toxicity
    • side effects include bone marrow supression and pancreatitis.
  • Mycophenolate
    • anti-proliferative
    • causes diarrhoea
  • Sirolimus
    • blocks IL2 so inhibits T cell division
    • can provoke hyperlipidaemia

Now lets move on to polycystic kidney disease....

MRCP revision battle 43.2: Polycystic kidney disease and renal cysts

The classical cause of renal cysts is polycystic kidney disease.

Polycystic kidney disease affects around 1:1000.  

Type 1 is inherited on chromosome 16
Type 2 is inherited on chromosome 4

The US criteria for diagnosing polycystic kidney disease in a patient with a positive family history is:
  • 2 cysts if aged less than 30
  • 2 cysts in both kidneys if aged 30-59
  • 4 cysts in both kidneys if aged greater than 60

Signs/symptoms of polycystic kidney disease include:
  • renal enlargement
  • abdominal pain
  • hypertension
  • renal failure

Associated features include:
  • liver cysts
  • subarachnoid haemorrhage
  • mitral valve prolapse

Other causes of renal cysts include:
  • autosomal recessive polycystic kidney disease
    • chromosome 6
    • tend to develop end stage renal failure in childhood
    • fibrosis of liver
  • Von-Hippel-Lindau (see battle 15.2)
    • autosomal dominant on chromosome 3
    • pre-maligant
  • tuberous sclerosis
    • auto dom on chromosome 9 or 16
  • simple cysts
    • occur in less than 2% of under 50s but up to 20% of over 70s.

Now for some renal tubular acidosis...

MRCP revision battle 43.3: Renal tubular acidosis

Renal tubular acidosis is a condition caused by the kidneys failing to correctly acidify the urine.

All types of renal tubular acidosis are associated with:
  • hyperchloraemic metabolic acidosis
  • normal anion gap

The three main types of renal tubular acidosis are:

Type 1 renal tubular acidosis: Distal

This is due to the kidney not excreting hydrogen ions in the distal tubule

  • idiopathic
  • SLE/RA
  • hypercalcaemia
  • drugs: lithium, amphotericin
  • ricketts
  • growth failure
  • nephrocalcinosis
  • renal calculi - calcium phosphate stones
  • low potassium

Diagnosis is by oral acid load with ammonium chloride - the urine should acidify, but in type 1 renal tubular acidosis urine pH will remain >5.5

Treatment is with oral bicarbonate

Type 2 renal tubular acidosis: proximal

This is  due to the kidneys failing to reabsorb bicarbonate in the proximal tubule

Causes include:
  • Wilson's syndrome
  • Fanconi syndrome
  • cystinosis
  • myeloma
  • interstitial nephritis
  • drugs - lead, acetazolamide, old tetracycline

Complications include:
  • osteomalacia
  • low potassium

Diagnosis is by IV bicarbonate loading , which will result in a high fractional excretion of bicarb.

Treatment is with oral bicarbonate.

Type 4 renal tubular acidosis

This is caused by hypoaldosteronism, resulting in hyperkalaemia.

Treatment is to treat cause and control hyperkalaemia

The astute amongst you may have noted the lack of a type 3 - this is because those clever renal physicians decided that, upon reflection, what they had named type 3 was probably just a combination of types 1 and 2.

If you had to boil the above battle down to a set of key facts, I'd go with:
  • all cause hyperchloraemic metabolic acidosis with a normal anion gap
  • types 1 and 2 both cause hypokalaemia and are both treated with oral bicarb
  • type 3 causes a hyperkalaemia and is treated by treating the cause

Now on to a symptom-based battle...

MRCP revision battle 43.4: Haematuria

When considering haematuria you need to subdivide into microscopic and macroscopic.

Causes of transient, non-visible/microscopic haematuria include:
  • UTI/pyelonephritis
  • menstrual period
  • vigorous exercise
  • sex

Causes of persistent, non-visible/microscopic haematuria include:
  • renal stones
  • prostatitis
  • urethritis
  • stones
  • cancer
  • benign prostatic hypertrophy
  • IgA nephropathy
  • benign familial haematuria

Macroscopic haematuria can be caused by:
  • infection: UTI
  • renal disease: renal papillary necrosis, IgA nephropathy, glomerulonephritis
  • malignancy- although note just 4% of cases of bladder cancer will be asymptomatic except for haematuria
  • renal stones
  • prostatic hypertrophy

NICE guidelines demand urgent referral for:
  • patients of any age with painless macroscopic haematuria
  • patients aged 40+ with recurrent/persistent UTI and haematuria
  • patients aged 50+ with unexplained microhaematuria

And as always consider whether the result could be spurious;  false positive blood on dipstick can occur with:
  • beetroot
  • porphyria
  • alkaptonuria
  • rifampicin

Just a brief note at the end of this battle on benign familial haematuria.  This accounts for around 25% of patients referred to nephrologists with microscopic haematuria.  It is associated with the basement membrane being thinner than normal (<250nm compared with normal 450nm).   Patients generally have a normal BP and normal renal function.  They are however followed up as there is a small risk of renal failure.

Now on to a battle I fight daily in my current job... renal stones...

MRCP revision battle 43.5: Renal calculi

"Good god" exclaimed my medical student "that man looks like he's in labour!"  Indeed, glancing into cubicle 4 there was a man who resembled a woman trying to give birth - he was puffing away at the entonox the ambulance crew had given him, pacing as if he just couldn't get comfortable and every now and then was hit by a pain that caused him to yelp out.  "I think he's got renal stones" I said.  The medical student looked hugely impressed at my confident diagnosis from a distance; I'm sure however you aren't and the MRCP examiners wouldn't be either, giving a classical description of renal colic just to lull you into a false sense of security before asking you a random question on the minuitae, so lets dive into the small print...

Location of stone

Classical renal colic ("loin to groin pain") suggests the stone is in the ureter
Stones in the bladder/urethra may cause pain on passing water

Type of stone

Commonest stone = calcium oxalate = 75%
  • Calcium oxalate stones are spikey and radioopaque
  •  Foods associated with increased levels of oxalate include chocolate, tea, rhubarb and spinach
  • However, medical conditions which result in excessive colonic absorption of oxalate are more likely to predispose, for example:
    • Crohns disease
    • post ileal resection
    • chronic pancreatitis
    • short bowel syndrome
  •  Hypercalciuria/hypercalcaemia also predispose to calcium oxalate stones:
    • hyperparathyroidism
    • sarcoidosis
    • hyperthyroidism
    • vit D excess
    • drugs: lithium, loop diuretics
  • Prevention of calcium oxalate stones includes drinking more water and possibly thiazide diuretics  or pyridoxine

Next commonest stone = magnesium ammonium phosphate (=struvite, =triple phosphate) =10-20%
  • radiologically tend to be 'large' with a 'staghorn' appearence.  Radioopaque
  • tend to form in alkaline urine so UTIs with ureaplasma urealyticum or proteus predispose

Other radioopaque stones include calcium phosphate.

Cysteine stones (1% total) are semi-radio opaque and form when renal tubular defects are present.

Uric acid stones (5-10%) are radiolucent.  They form when there is excess uric acid.  Prevention includes allopurinol and urinary alkalinisation.

The other radiolucent stone is xanthine, but this accounts for <1% of all stones.

Blood on urine dipstick is often seen as a prerequisite for renal stones, however the reality is that 50% of those with loin to groin pain and a positive blood on dipstick won't have renal stones while 20% of those with loin to groin pain and real renal colic won't have any blood on their dipstick....

Lets now move on to continue our slow battle through the various forms of glomerulonephritis...

MRCP revision battle 43.6: Focal Segmental Glomerulonephritis

Focal segmental glomerulonephritis accounts for less than 10% of nephrotic syndrome in children but up to 20% in young adults.

The characteristic feature of focal segmental glomerulonephritis is IgM and C3 deposits in affected areas.

Focal segmental glomerulonephritis may be primary or secondary to:
  • reflux
  • IgA glomerulonephropathy
  • Alport's syndrome
  • heroin abuse
  • vasculitis

First line treatment is corticosteroids, which produce a response in around 30%.

25% of cases will progress to end stage renal failure, and if these are treated by renal transplant there is a 20-50% recurrence rate.

2% of patients suffer a rapid detioration

On that apt note lets move on to acute renal failure...

MRCP revision battle 43.7: Acute renal failure

Acute renal failure is one of those topics which is barely mentioned at medical school then suddenly becomes almost central to your day-to-day life as a medical houseofficer.  It also then pops up not infrequently in MRCP questions....

Acute renal failure is defined as a significant detioration in renal function occuring over hours to days.  

It is usually oliguric (<500mls/24 hrs)
However, it is non-oliguric in 10% of cases, including:
  • gentamycin/amphotericin toxicity
  • radio-contrast nephropathy
  • interstitial nephritis

When approaching renal failure everyone repeats the mantra 'is it pre-renal, renal or post-renal'.  A recap of a few of the causes follows:

Pre-renal causes:
  • sepsis
  • hypovolaemia
  • cardiac failure
  • liver failure
  • NSAIDS/ACE-i (interfere with renal blood flow)

Renal causes (generally acute tubular necrosis):
  • nephrotoxic drugs
    • gentamycin
    • amphotericin
    • tetracyclines
    • contrast agents
  • myeloma
  • myoglobin (rhabdomyolysis)
  • vasculitis
  • glomerulonephritis

Post renal:
  • any urinary tract obstruction

Important points to enable one to distinguish ATN from pre-renal uraemia are shown in the table below:

Essentially in pre-renal failure the kidneys are still working so are trying to concentrate the urine, whereas in ATN they aren't.

Going through the management of acute renal failure is a bit beyond the scope of this battle (and if you're taking MRCP you are probably already very familiar with it) so I'll finish by just briefly recapping indications for dialysis:

  • refractory pulmonary oedema
  • persistent hyperkalaemia (>7mmol/l)
  • severe metabolic acidosis (pH<7.2 or BE <10)
  • uraemic encephalopathy
  • uraemic pericarditis

Thats all the battles for today.  Tomorrow we're back for a mixed bag before embarking on another renal day....