Dr David MAKANJUOLA Renal unit St. Helier hospital Renal disease Dr David MAKANJUOLA Renal 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.
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
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).
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
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
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
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 %)
Another digression………
Mineralocorticoid receptor Tubular lumen Tubular cell Blood 3 Na+ Na K ATPase Na+ ENaC 2 K+ Na+ Na+ Na+ Mineralocorticoid receptor
Mineralocorticoid receptor Tubular lumen Tubular cell Blood 3 Na+ Na K ATPase Na+ Na+ ENaC 2 K+ Na+ Na+ Na+ Mineralocorticoid receptor
Mineralocorticoid receptor Tubular lumen Tubular cell Blood 3 Na+ Na K ATPase Na+ Na+ ENaC 2 K+ Na+ K+ Na+ K+ Na+ Mineralocorticoid receptor
Mineralocorticoid receptor Tubular lumen Tubular cell Blood 3 Na+ Na K ATPase Na+ Na+ ENaC 2 K+ Na+ Na+ Na+ Aldosterone Mineralocorticoid receptor Aldosterone
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
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
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+
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
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
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
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
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 following criteria 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 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
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
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 - 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
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
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
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 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.
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 there are 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