1. Dr David MAKANJUOLA Renal unit St. Helier hospital
Renal disease
Dr David MAKANJUOLA
Renal unit
St. Helier hospital

2. Case history 22 year old Afro-Caribbean male
Microscopic haematuria noted on registration with new GP.
No proteinuria
Normal creatinine (90µmol/l)
Blood pressure 120/70mmHg
No haematuria on dipstick testing at subsequent review in GP surgery.

3. Management should include
Haematuria
Management should include
Check serum creatinine in all patients
Check for proteinuria in all patients
(quantitate protein/creatinine ratio if positive)
Invisible (microscopic) haematuria without proteinuria, GFR>60ml/min/1.73m2
Microscopic haematuria with prot/creat ratio >50mg/mmol
Visible (macroscopic) haematuria

4. Major causes of haematuria by age and duration
From Up To Date
Schematic representation of the major causes of haematuria in relation to the age at which they usually occur (horizontal axis), transience or persistence (vertical axis), and frequency (blue implies more frequent).

5. Management should include Check serum creatinine in all patients
Haematuria
Management should include
Check serum creatinine in all patients
Check for proteinuria in all patients
(quantitate protein/creatinine ratio if positive)
Visible (macroscopic) haematuria
Invisible (microscopic) haematuria without proteinuria, GFR>60ml/min/1.73m2
Microscopic haematuria with prot/creat ratio >50mg/mmol
Usually fast track Urology referral for imaging and cystoscopy, unless strong pointers to acute renal disease
Refer to nephrology if urological investigations negative
Age >40, usually refer to Urology (recommended age may vary locally)
Age <40, or >40 with negative urological investigations, manage as Stage 1/2 CKD
Refer to nephrology
Lower levels of proteinuria, manage as Stage 1/2 CKD

6. Microscopic haematuria Refer to renal team.
Management should include
Check serum creatinine in all patients
Check for proteinuria in all patients
(quantitate protein/creatinine ratio if positive)
Microscopic haematuria
with GFR>60ml/min/1.73m2
(+/-prot/creat ratio >50mg/mmol)
Refer to renal team.
Visible (macroscopic) haematuria
Invisible (microscopic) haematuria without proteinuria, GFR>60ml/min/1.73m2
Microscopic haematuria with prot/creat ratio >50mg/mmol
Usually fast track Urology referral for imaging and cystoscopy, unless strong pointers to acute renal disease
Refer to nephrology if urological investigations negative
Age >40, usually refer to Urology (recommended age may vary locally)
Age <40, or >40 with negative urological investigations, manage as Stage 1/2 CKD
Refer to nephrology
Lower levels of proteinuria, manage as Stage 1/2 CKD

7. Case history Plan - manage as stage 1/2 CKD. Poor attender at surgery.
Develops flu-like illness with abdominal pain.
Gives history of intermittent flank pains, but no dysuria or history of renal stones.

8. Case history
Haematuria on dipstick testing on this occasion, but also, protein 1+, nitrites and leucocytes +ve.
BP 150/110mmHg
MSU sent. Form given for blood tests.
Commenced on Trimethoprim

9. Case history Blood tests while on antibiotics show the following:
Hb 15 Urea 6.5
WBC Creatinine 135
Platelets 225 Potassium 5.3
CRP 68
MSU – WCC > 100, RBC +
Coliforms, sens to Trimethoprim, Amoxycillin

10. A digression………
Trimethoprim inhibits the secretion of creatinine into the tubules and can reversibly increase the serum creatinine up to 10-15%.
CREATININE (~10-15%)
UREA (variable %)

11. Another digression………

12. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
ENaC
2 K+
Na+
Na+
Na+
Mineralocorticoid receptor

13. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+
Na+
Na+
Mineralocorticoid receptor

14. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+ K+
Na+ K+
Na+
Mineralocorticoid receptor

15. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+
Na+
Na+
Aldosterone
Mineralocorticoid receptor
Aldosterone

16. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+
ENaC
Na+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor

17. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+
ENaC
Na+ K+
Hypertension
Na+
Na+ K+
Na+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor K+ K+ K+
Hypokalaemia

18. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+
ENaC
Na+ K+
Na+
Na+ K+
Na+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor
Spironolactone K+ K+ K+

19. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
ENaC
Na+ K+
Na+ K+
Lower BP
Na+ K+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor
Spironolactone
Hyperkalaemia

20. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Na+
ENaC
2 K+
Na+
ENaC
Na+ K+
Hypertension
Na+
Na+ K+
Na+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor K+ K+ K+
Hypokalaemia

21. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Amiloride
ENaC
2 K+
Na+
ENaC K+
Na+ K+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor

22. Mineralocorticoid receptor
Tubular lumen
Tubular cell
Blood
3 Na+ Na K
ATPase
Na+
Amiloride
ENaC
2 K+
Na+
ENaC K+
Na+ K+
Na+
Aldosterone
Aldosterone
Mineralocorticoid receptor
Triamterene and Trimethoprim also work in a similar fashion

23. Case history
Blood tests repeated 1 week after the course of antibiotics show the following:
Hb 15 Urea 6.5
WBC Creatinine 150
Platelets 225 Potassium 5.3
CRP 5
Urine dipstick – blood 2+

24. Acute Kidney Injury (AKI)
Acute kidney injury is defined when one of the following
criteria is met:
Serum creatinine rises by ≥ 26µmol/L within 48 hours or

25. Acute Kidney Injury (AKI)
Acute kidney injury is defined when one of the following
criteria is met:
Serum creatinine rises by ≥ 26µmol/L within 48 hours or
Serum creatinine rises ≥ 1.5 fold from the known reference value*, or
The rise in serum creatinine of ≥ 1.5 is presumed to have occurred within one week or

26. Acute Kidney Injury (AKI)
Acute kidney injury is defined when one of the following
criteria is met:
Serum creatinine rises by ≥ 26µmol/L within 48 hours or
Serum creatinine rises ≥ 1.5 fold from the reference value, which is known or
The rise in serum creatinine of ≥ 1.5 is presumed to have occurred within one week or
Urine output is < 0.5ml/kg/hr for >6 consecutive hours

27. Acute Kidney Injury (AKI)
The reference serum creatinine should be the lowest creatinine value recorded within 3 months of the event.
If a reference serum creatinine value is not available within 3 months and AKI is suspected,
repeat the serum creatinine within 24 hours.
A reference serum creatinine value can be estimated from the nadir serum creatinine value if the patient recovers from AKI.

28. AKI - classification Stage Serum creatinine (SCr) criteria
Urine output criteria 1
increase of ≥ 26 μmol/L within 48h or
increase of ≥1.5 to 1.9 X reference SCr
<0.5 mL/kg/hr for > 6 consecutive hrs

29. AKI - classification Stage Serum creatinine (SCr) criteria
Urine output criteria 1
increase of ≥ 26 μmol/L within 48h or
increase of ≥1.5 to 1.9 X reference SCr
<0.5 mL/kg/hr for > 6 consecutive hrs 2
increase of ≥ 2 to 2.9 X reference SCr
<0.5 mL/kg/ hr for > 12 h

30. AKI - classification Stage Serum creatinine (SCr) criteria
Urine output criteria 1
increase ≥ 26 μmol/L within 48h or
increase ≥1.5 to 1.9 X reference SCr
<0.5 mL/kg/hr for > 6 consecutive hrs 2
increase of ≥ 2 to 2.9 X reference SCr
<0.5 mL/kg/ hr for > 12 h 3
increase of ≥3 X reference SCr
or increase of ≥354 μmol/L
or commenced on renal replacement therapy (RRT) irrespective of stage
<0.3 mL/kg/ hr for > 24 h
anuria for 12 hrs

31. Possible outcomes from AKI
Cerda, J. et al. Clin J Am Soc Nephrol 2008;3:

32. Case history Auto-immune screen –ve Hb electrophoresis normal
Vasculitis screen –ve
Abdominal ultrasound scan shows multiple cysts in both kidneys, as well as some cysts in the liver.
Family history – no known FH of CKD, but his father died in his 40s of a stroke.

33. Polycystic kidneys

34. Polycystic kidneys Epidemiology Genetics Clinical features Diagnosis
Treatment

35. Polycystic kidneys - Epidemiology
Common – occurs in 1 in every 400-1,000 live births.
Family history - can be negative in up to 25% of cases:
New mutation
Adopted individual
Affected parent died without PKD being noted

36. Polycystic kidneys - Genetics
Autosomal recessive PKD
Predominantly a disease of childhood.
Much less common than autosomal dominant PKD.

37. Polycystic kidneys - Genetics
Autosomal dominant (adult) PKD
PKD 1 – abnormality on chromosome 16
PKD 2 – abnormality on chromosome 4
In PKD 2, development of cysts and also, of ESRD tends to occur later in life and has a less severe phenotype than PKD1.

38. Polycystic kidneys - Clinical features (Renal)
Haematuria – macro and microscopic.
Proteinuria – usually <1g/day (PCR 100mg/mmol)
Hypertension
Renal stones in up to 20% (50%urate stones)
Flank and abdominal pains
Renal cancers –
often bilateral, and frequently present with a fever.
diagnosis difficult.

39. Polycystic kidneys - Clinical features (Extra-renal)
Cerebral aneurysms
Routine screening is recommended only for high-risk patients, such as those with:
a previous rupture
a positive family history of an intra-cerebral bleed or intracranial aneurysm
warning symptoms
a high-risk occupation in which loss of consciousness would place the patient or others at extreme risk
and
prior to surgery that is likely to be associated with hemodynamic instability with hypertension

40. Polycystic kidneys - Clinical features (Extra-renal)
Hepatic cysts
Pancreatic cysts
Diverticular disease
Epididymal cysts
Herniae
Cardiac disease –
Mitral valve prolapse
Aortic regurgitation

41. Polycystic kidneys - Diagnosis
Ultrasonography
Best not to do it in people under the age of 18:
Possibility of false negative scan especially with PKD2
Adverse consequences – emotional, career, insurance, etc. outweigh benefits of early diagnosis, especially as there is no curative treatment.

42. Polycystic kidneys - Diagnosis
Ultrasonographic criteria: Positive family History of PKD
Age
Criteria
15-39
At least 3 unilateral or bilateral cysts
40-59
At least 2 cysts in each kidney
>60
At least 4 cysts in each kidney

43. Polycystic kidneys - Diagnosis
Ultrasonographic criteria:
Negative family Hx of PKD – difficult.
Suspect it if there are > 10 cysts in each kidney,
especially if the kidneys are large, and/or there
are also liver cysts.

44. Polycystic kidneys - Treatment
Hypertension
Statins
Vasopressin receptor antagonists
mTOR inhibitors e.g Sirolimus, Everolimus
Caffeine restriction
Dialysis and Transplantation

45. REFERENCES
UpToDate