Renal disease

Dr David MAKANJUOLARenal unit

St. Helier hospital

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.

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

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).

Major causes of haematuria by age and duration

From Up To Date

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

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

Microscopic haematuria

with GFR>60ml/min/1.73m2

(+/-prot/creat ratio >50mg/mmol)

Refer to renal team.

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.

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

Case history

• Blood tests while on antibiotics show the following:

• Hb 15 Urea 6.5• WBC 13.5 Creatinine 135• Platelets 225 Potassium 5.3• CRP 68

• MSU – WCC > 100, RBC +• Coliforms, sens to Trimethoprim, Amoxycillin

UREA (variable %)

CREATININE (~10-15%)

A digression……… Trimethoprim inhibits the secretion of creatinine into the tubules and can reversibly increase the serum creatinine up to 10-15%.

Another digression………

Tubular cellTubular lumen Blood

ENaCNa+

3 Na+

2 K+

Na+

Na+

Na+

Mineralocorticoid receptor

Tubular cellTubular lumen Blood

ENaCNa+ Na+3 Na+

2 K+

Na+

Na+

Na+

Mineralocorticoid receptor

Tubular cellTubular lumen Blood

ENaCNa+ Na+3 Na+

2 K+

K+

K+

Na+

Na+

Na+

Mineralocorticoid receptor

Tubular cellTubular lumen Blood

Aldosterone

ENaCNa+

Na+

Na+

Na+

3 Na+

2 K+Na+

Mineralocorticoid receptor

Aldosterone

Tubular cellTubular lumen Blood

Aldosterone

ENaC

ENaC

ENaC

ENaC

Na+

Na+

Na+

Na+

3 Na+

2 K+Na+

Mineralocorticoid receptor

Aldosterone

Tubular cellTubular lumen Blood

Aldosterone

ENaC

ENaC

ENaC

ENaC

Na+

Na+

Na+

Na+K+

K+

Na+

Na+

Na+

3 Na+

2 K+Na+

K+

K+K+

Aldosterone

Mineralocorticoid receptor

Hypertension

Hypokalaemia

Tubular cellTubular lumen

Blood

Aldosterone

ENaC

ENaC

ENaC

ENaC

Na+

Na+

Na+

Na+K+

K+

Na+

Na+

Na+

3 Na+2 K+Na+

K+

K+K+

Aldosterone

Mineralocorticoid receptor

Tubular cellTubular lumen

Blood

Aldosterone

ENaCNa+

K+

K+

Na+

Na+

Na+

3 Na+2 K+Na+

ENaC

ENaC

ENaC Na+

Na+

Na+

K+

K+K+

Aldosterone

Mineralocorticoid receptor

Lower BP

Hyperkalaemia

Tubular cellTubular lumen Blood

Aldosterone

ENaC

ENaC

ENaC

ENaC

Na+

Na+

Na+

Na+K+

K+

Na+

Na+

Na+

3 Na+

2 K+Na+

K+

K+K+

Aldosterone

Mineralocorticoid receptor

Hypertension

Hypokalaemia

Tubular cellTubular lumen Blood

Aldosterone

ENaC

ENaC

ENaC

ENaC

Amiloride

Amiloride

Amiloride

Amiloride

Na+

K+

K+

Na+

Na+

Na+

3 Na+

2 K+

Mineralocorticoid receptor

Aldosterone

Tubular cellTubular lumen Blood

Aldosterone

ENaC

ENaC

ENaC

ENaC

Amiloride

Amiloride

Amiloride

Amiloride

Na+

K+

K+

Na+

Na+

Na+

3 Na+

2 K+

Mineralocorticoid receptor

Aldosterone

Triamterene and Trimethoprim also work in a similar fashion

Case history

• Blood tests repeated 1 week after the course of antibiotics show the following:

• Hb 15 Urea 6.5• WBC 6.5 Creatinine 150• Platelets 225 Potassium 5.3• CRP 5

• Urine dipstick – blood 2+

Acute Kidney Injury (AKI)Acute kidney injury is defined when one of the followingcriteria is met:

• Serum creatinine rises by ≥ 26µmol/L within 48 hours or

Acute Kidney Injury (AKI)Acute kidney injury is defined when one of the followingcriteria 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

Acute Kidney Injury (AKI)Acute kidney injury is defined when one of the followingcriteria 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

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.

AKI - classificationStage 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

AKI - classificationStage 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

AKI - classificationStage 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 hor anuria for 12 hrs

Possible outcomes from AKI

Cerda, J. et al. Clin J Am Soc Nephrol 2008;3:881-886

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.

Polycystic kidneys

Polycystic kidneys

• Epidemiology• Genetics• Clinical features• Diagnosis• Treatment

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

Polycystic kidneys - Genetics

• Autosomal recessive PKD

• Predominantly a disease of childhood.

• Much less common than autosomal dominant PKD.

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.

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.

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

Polycystic kidneys - Clinical features (Extra-renal)

• Hepatic cysts• Pancreatic cysts• Diverticular disease• Epididymal cysts• Herniae• Cardiac disease – – Mitral valve prolapse– Aortic regurgitation

Polycystic kidneys - Diagnosis

UltrasonographyBest 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.

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

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 thereare also liver cysts.

Polycystic kidneys - Treatment

• Hypertension• Statins• Vasopressin receptor antagonists• mTOR inhibitors e.g Sirolimus, Everolimus• Caffeine restriction

• Dialysis and Transplantation

REFERENCES• http://www.renal.org/Clinical/GuidelinesSection/

• UpToDate