Renal disease

27/28th November 2007

Case history

 A 78 year-old man was referred to an urologist because of the

following urinary symptoms. He complained of hesitancy, weak
stream (often intermittent) and straining to pass urine. He also
had urgency, frequency and nocturia.
 On rectal examination an enlarged, firm and nodular prostate
was palpated. Urodynamics confirmed obstruction to urine flow
and a significant degree of residual urine in the bladder following
micturition.
 The following tests were ordered – urine to be sent to the
microbiological laboratory; blood for a full blood count;
electrolytes; urea; creatinine; and prostate specific antigen
(PSA). All were reported as normal.
Question 1

 What is the likely  Benign prostatic

diagnosis? hyperplasia (BPH)
leading to urethral
compression and
urinary obstruction.
Question 2
 What is the rationale for ordering the  Urine – to exclude a urinary
tests listed above? infection to which patients with
obstructive uropathy are prone. The
residual urine in the bladder is liable
to become infected. E.coli is the
most common organism isolated.
 Blood – FBC as a routine, especially
if surgery is being contemplated.
Electrolytes, urea and creatinine to
assess renal function. Unrelieved
obstruction may result in hydroureter
and hydronephrosis and renal
impairment. Imaging would be used
to detect this if suspected.
 PSA – this can be raised particularly
in prostatic carcinoma but also in
other conditions such as prostatitis
or even simply following palpation of
the prostate. The upper limit of
normal is 4 ng/l.
Question 3

 What changes occur in  Hypertrophy of the

the bladder secondary muscle, increased
to long-standing trabeculation and
obstruction? diverticula. The latter
are prone to become
infected. Bladder
calculi may form if the
obstruction is not
relieved.
Question 4

 List some other causes of  Malignant causes –

bladder outlet obstruction prostatic adenocarcinoma,
strategically located bladder
carcinoma or invasion by
extra-vesical neoplasms.
 Benign strictures –
congenital or post-
inflammatory.
 Mechanical – calculus or
foreign body; cystocoele in
females.
 Neurogenic, e.g. in spinal
cord injury.
Question 5

 If bladder outlet  Renal calculi, acute

obstruction is not pyelonephritis (which
relieved and may be complicated by
hydronephrosis results, papillary necrosis),
what further septicaemia, renal
complications may failure.
ensue?
Question 6
 The histopathologist
reported the TURP
specimen as showing
benign prostate hyperplasia
but in addition, about 5% of
the sections showed the
presence of a well-
differentiated prostatic
adenocarcinoma.
 What is the significance of
this and what is the
subsequent management?
 This is a latent carcinoma
discovered incidentally in a
TURP specimen for BPH.
Follow-up only is required
and therapy is not instituted.
About 30% will progress
after 10 years, but there are
no tests to identify this
cohort.
Histological Gleason grade and anatomical stage

 The tumour is graded from 1 (well-differentiated) to 5 (poorly differentiated). Two grades

are combined to give a Gleason score, e.g. grade 3+4=7. Scores of 5 to 7 are
commonly reported in needle biopsies of the prostate. Scores of 8 to 10 indicate
advanced carcinoma, probably inoperable.
 Staging indicates the extent of spread of the tumour.

Diagnostic imaging is used to detect the spread and therefore stage of the tumour

 Direct spread – extracapsular to surrounding tissues, especially seminal vesicles.

 Lymphatic spread – to sacral, iliac and para-aortic lymph nodes.
 Blood spread – to bone (the vertebrae, the pelvis and femur), lung and liver.
 Bony metastases in prostatic carcinoma are more likely to be osteosclerotic than
osteolytic. Bone alkaline phosphatase is often raised in the peripheral blood indicating
increased bone formation. With widespread involvement of bone, a leukoerythroblastic
anaemia may develop.
 Prostate specific antigen is usually markedly raised in patients with prostatic carcinoma
but levels may be low (or rarely normal) and overlap with levels seen in benign
conditions. Its greatest use is in detecting recurrence of tumour following treatment.
Clinical findings in Renal disease
1. Acute nephritic syndrome – haematuria, proteinuria (but <3.5g
per day), hypertension, oedema, casts in urine
2. Nephrotic syndrome – proteinuria (>3.5g/day),
hypalbuminaemia, severe odema, hyperlipidaemia, lipiduria
3. Asymptomatic proteinuria
4. Painless haematuria
5. Acute renal failure – oliguria/anuria, rapid rise of urea and
creatinine
6. Chronic renal failure – uraemia (ie raised urea level combined
with nausea, vomiting, lethargy, drownsiness)
7. Renal tubular defects – polyuria, nocturia, electrolyte disorders
8. Urinary tract infections – pyuria, bacteriuria
9. Nephrolithiasis
 Congenital kidney disease
 Cystic disease of the kidney
 Disease of the glomerulus
 Disease of tubulointerstitial areas
 Vascular disease of the kidney
 Renal stones/Hydronephrosis
 Tumours of the kidney
Congenital disease of kidney

 Agenesis of kidney
 Hypoplasia
 Ectopic kidney
 Horseshoe kidney
Cystic disease of Kidney

 Hereditary/Developmental/
Acquired
1. Cystic renal dysplasia
2. Polycystic kidney disease
(Autosomal dominant or
autosomal recessive)
3. Medullary cystic disease
4. Acquired (dialysis
associated) cystic disease
5. Simple renal cysts
 Autosomal dominant polycystic
disease
•Occurs in adults, 1 in 400 to 1000
•Accounts for 10% of chronic renal
failure cases
•A systemic disease as cysts and
anomalies occur elsewhere
•PKD1 gene on Chromosome 16
•Gross: Bilateral cysts, enlarged
kidneys
•Micro: Cysts containing clear serous
fluid, some functioning nephrons
•Clinically: Asymptomatic, pain,
haematuria, proteinuria, polyuria,
hypertension
Glomerular diseases

1. Primary glomerulopathies
2. Systemic disease (DM, SLE, vasculitis,
amyloidosis)
3. Hereditary diseases

 Focal – only some glomeruli involved

 Diffuse – all glomeruli involved
 Segmental – only part of glomerulus involved
 Global – all of glomerulus involved (not always stated)
Glomerulopathies
1. Acute glomerulonephritis (acute nephritis, postinfectious/poststreptococcal,
immune complexes)
2. Rapidly progressive cresenteric glomerulonephritis (acute renal failure,
idiopathic, anti-GBM disease – eg Goodpasture’s syndrome, immune complex
disease eg SLE, Henoch Schonlein purpura, pauci-immune – eg Wegener
granulomatosis)
3. Membranous glomerulonephritis (nephrotic syndrome, immune complexes,
adults, idiopathic, secondary to systemic disease or other agents – drugs, SLE,
infection, metabolic disorders)
4. Minimal change disease (nephrotic syndrome, children, loss of foot processes of
epithelial cells, responds well to steroids, cause ?)
5. Focal segmental glomerulosclerosis (nephrotic syndrome, variant of MCD but
more severe, idiopathic, can occur in a number of settings)
6. Membranoproliferative glomerulonephritis (nephrotic syndrome, primary or
secondary causes, primary – type 1 [immune complex] and type 2 [complement
pathway], most complex GN)
7. IgA nephropathy (gross or microscopic haematuria, IgA deposits in mesangium,
common, children, young adults)
8. Chronic glomerulonephritis (end stage of many of the above, chronic renal
failure,
Glomerular diseases
Mechanism of disease:
 Antibody mediated injury
 In situ immune complex deposition

 Circulating immune complex deposition

 Cytotoxic antibodies

 Cell mediated injury

 Activation of alternative complement pathway

Histologic alterations:
 Hypercellularity

 Basement membrane thickening

 Hyalinisation

 Sclerosis
Diabetic nephropathy
•End stage kidney disease in 30% type 1 DM patients
•Histological changes: 1. capillary basement membrane thickening, 2.
diffuse diabetic golmerulosclerosis, 3. Nodular glomerulosclerosis
Diseases of tubulointerstitial areas

Acute tubular necrosis:

 A clinicopathologic entity characterised
morphologically by destruction of tubular epithelial
cells and clinically by acute suppression of renal
function
 Most common cause of acute renal failure.
 Causes:
 Toxins such as paracetamol, heavy metals, organic
solvents.
 Ischaemic causes such as shock, dehydration, hepatorenal
failure.
 Prognosis depends on clinicial setting.
Pyelonephritis

 Acute pyelonephritis:
 Acute suppurative inflammation of the kidney caused by
bacterial infection (often E.coli).
 Causes: urinary obstruction, instrumentation, reflux,
pregnancy, DM, immunosuppression, pre-existing renal
disease.
 Complications: septicaemia, acute renal failure (due to
papillary necrosis), abscess, pyonephrosis.
 Chronic pyelonephritis:
 Chronic tubulointerstitial disorder in which there is gross,
irregular scarring of the kidney.
 Important cause of end stage renal disease.
 An end result of many acute tubulointerstitial conditions.
Vascular diseases of kidney

 Renal infarcts – arterial obstruction usually

due to embolism
 Renal artery stenosis
 Benign and malignant nephrosclerosis
Tumours of the kidney

 Benign
 Renal papillary adenoma
 Renal fibroma
 Angiomyolipoma
 Oncocytoma
 Malignant
 Renal cell carcinoma
 Clear cell, Papillary, Chromophobe
 Urothelial carcinomas of the renal pelvis
 Wilm’s tumour (nephroblastoma)