1. Renal disease 27/28 th November 2007

2. 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.

3. Question 1 What is the likely diagnosis? Benign prostatic hyperplasia (BPH) leading to urethral compression and urinary obstruction.

4. Question 2 What is the rationale for ordering the tests listed above? Urine – to exclude a urinary 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.

7. Question 3 What changes occur in the bladder secondary to long-standing obstruction? Hypertrophy of the muscle, increased trabeculation and diverticula. The latter are prone to become infected. Bladder calculi may form if the obstruction is not relieved.

9. Question 4 List some other causes of bladder outlet obstruction Malignant causes – 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.

10. Question 5 If bladder outlet obstruction is not relieved and hydronephrosis results, what further complications may ensue? Renal calculi, acute pyelonephritis (which may be complicated by papillary necrosis), septicaemia, renal failure.

11. 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.

14. 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.

15. 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

16. 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

18. Congenital disease of kidney Agenesis of kidney Hypoplasia Ectopic kidney Horseshoe kidney

19. 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

20. 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

22. 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)

23. 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,

24. 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

25. 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

28. 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.

30. 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.

33. Vascular diseases of kidney Renal infarcts – arterial obstruction usually due to embolism Renal artery stenosis Benign and malignant nephrosclerosis

34. 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)