Clinical Biochemistry and Renal Disease
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Clinical Biochemistry and Renal Disease. Dr Vivion Crowley Consultant Chemical Pathologist St James’s Hospital. What are the primary functions of the Kidney. Excretion of waste – urea, creatinine, urate Water and electrolyte balance Acid-base balance

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Clinical Biochemistry and Renal Disease

Dr Vivion Crowley

Consultant Chemical Pathologist

St James’s Hospital


What are the primary functions of the Kidney

  • Excretion of waste – urea, creatinine, urate

  • Water and electrolyte balance

  • Acid-base balance

  • Regulation of systemic circulation – Renin and Aldosterone

  • Production of hormones – Vit D, Erythropoietin

  • Participates in gluconeogenesis


What is the primary functional unit of the Kidney

  • Nephron

  • Proximal tubule – Na, K, H20, HCO3, PO4, aminoacids

  • Loop of Henle – Countercurrent multiplier system

  • Distal tubule – Na, K, Acid-base balance

  • Collecting duct – Osmoregulation


How do we assess Renal Function?

  • Glomerular filtration rate (GFR)

  • key measure of functioning renal mass

  • the sum of filtration rate of functioning nephrons

  • Normal GFR 120-130ml/min/1.73 m2 in young adults

  • -decreases with age

  • (consider GFR as approximately 100ml/min)


Are there plasma markers of GFR?

  • Plasma Urea

  • Breakdown product of protein metabolism

  • Produced in liver

  • Plasma Creatinine

  • Derived from creatine in muscle

  • Related to muscle mass




Caveats in the interpretation of PUrea and Creatinine

  • Increases in Urea and Creatinine above the upper

  • reference range are evident only when GFR is reduced

  • by 50% or normal

  • A normal urea and crea may not reflect a normal GFR

  • Consider other causes of elevations in Urea and Crea


Urinary clearance of filtration markers is

used to estimate GFR

  • Ideal filtration marker

  • Neither secreted nor absorbed by kidney tubule

  • Exogenous

  • Inulin

  • IV infusion

  • Difficult to assay

  • Other markers include Cr51-EDTA, I125-iothalamate


Endogenous filtration markers of GFR

  • Urinary urea as a filtration marker

  • easy to measure

  • Freely filtered at glomerulus

  • Reabsorbed in proximal and sistal tubule

  • Significantly Underestimates GFR

  • Urinary creatinine as a filtration marker

  • Most commonly used

  • Freely filtered at glomerulus

  • Secreted in renal tubule

  • Overestimates GFR by 10-20ml/min

  • Requires 24h urine collection

  • Problematic for patients

  • Over or under collection


Equations using serum creatinine can

be used to estimate GFR

  • Cockcroft–Gault equation

  • -Uses age, wt, gender, plasma creatinine

  • Really an estimation of creatinine clearance

  • MDRD equation for eGFR

  • Estimate of GFR rather than Creatinine clearance

  • 4 variable eqn.

  • Plasma crea, age, gender, ethnicity

  • Increasingly used to classify Chronic kidney Disease (CKD)


Equations used to estimate GFR

Cockcroft–Gault equation

MDRD equation for eGFR



Other potential markers of GFR

  • Plasma Cystatin C

  • Cysteine protease inhibitor

  • Freely filterd by gloerulus

  • Almost completelyReabsorbed and catbolised by tubules

  • Plasma levels correlate with GFR

  • Expensive test

  • Not routinely available


What is Renal Failure?

A deterioration in renal function leading to a

complex of symptoms and signs

Azotaemia

– increase in nitrogenous substances e.g. urea, crea

Uraemia

– symptoms of confusion etc. associated with azotaemia


How is Renal Failure classified?

  • Time of onset

  • Acute renal failure

  • An abrupt reduction in GFR

  • Usually over hours or days

  • Oliguria <400ml/day, anuria <100ml/day, polyuria>3L/day

  • Chronic Renal Failure



What are the causes of acute renal failure (ARF)

  • Prerenal

  • Volume depletion e.g. vomiting, diarrhoea, fistulae, renal Na wasting

  • Sepsis

  • Cirrhosis

  • Renal artery stenosis

  • Intrarenal

  • Vascular

  • Glomerular

  • Acute tubular necrosis (ATN)

  • Acute interstitial nephritis

  • Postrenal

  • Ureteral obstruction

  • Bladder obstruction


What is the biochemical profile associated

with pre-renal failure?

  • 53y old male

  • 3/7 hx of vomiting and diarrhoea



What is the biochemical profile associated

with established ARF e.g. ATN?


What are the causes of CRF?

  • Diabetic nephropathy

  • Glomerulonephritis

  • Hypertensive nephropathy

  • Tubulointerstitial disease

  • Polycystic kidney disease

  • Reflux nephropathy

  • In many instances cause is unknown


What are the metabolic consequences of CRF

  • Na handling

  • - reduced Na excretory capacity – oedema, HT

  • H2O handling

  • Urine becomes isosmotic – inability to dilute or conc urine

  • Hyperkalaemia

  • Acidosis – RTA and high anion gap

  • Bone disease

  • Hypocalcaemia

  • Hyperphosphataemia

  • Secondary hyperparathyroidism

  • Acidosis

  • Anaemia – reduced erythropoietin

  • Dyslipidaemia

  • Endocrine – hyperprolactinaemia, hypogonadism



What is the biochemical profile associated with ESRD

65y old male

C/O malaise, tiredness, nocturia

O/E BP 182/110, pale



Causes of Tubulointerstitial Disease

  • Immunologic – SLE, Amyloidosis, Sjoogren’s syndrome, MM

  • Drugs – NSAIDs, Chemotherapy

  • Heavy metals- lead, cadmium, mercury

  • Sickle cell disease

  • Lymphoma

  • Pyelonephritis

  • Sarcoidosis

  • Hyepruricaemia (Gout)



How do you check for proteinuria?

  • Urine dipstick

  • Protein – detects albumin >200-300mg/L

  • Does not detect Bence-Jones protein (Ig light chains)

  • pH, Glucose, Hb, Bilirubin, Urobilinogen

  • Nitrite, Leukocyte esterase

  • Timed urine collection

  • 24h urine

  • First morning voided urine – Albumin:creatinine ratio

  • used in detecting microalbuminuria in DM


How is proteinuria classified?

  • Time:

  • Transient – exercise-related, acute illness

  • Persistent – requires further investigation

  • Cause:

  • UTI

  • Overflow proteinuria

  • - Bence-Jones, Amylase, Hb, Myoglobin, lysozyme

  • Orthostatic proteinuria

  • No proteinuria in first morning urine

  • Proteinuria detectable when patient ambulant

  • Glomerular

  • - Leaky glomerulus – glomerulonephritis

  • Tubular

  • - Tubulointerstitial disease



What is nephrotic syndrome?

  • Nephrotic range proteinuria >3.5g/24h

  • Hypoalbuminaemia

  • Oedema – periorbital, dependent

  • Hyperlipidaemia – marked hypercholesterolaemia

  • Causes

  • Primary renal disease – glomerulonephritis

  • Systemic disease – DM, amyloidosis, SLE

  • Multiple Myeloma

  • Infection – HepB, HIV, TB

  • Malignancy

  • Drugs – Gold, Penicillamine

  • Pre-eclampsia


Biochmeical investigation of Proteinuria should include:

  • Urine dipstick

  • Urine protein/creatinine ratio ( random urine sample)

    >40mg/mmol suggests underlying proteinuria

    24 hour urine collection for protein

    > 300mg/24hr suggests proteinuria


What are the most common kidney stones?

  • Calcium Oxalate and Phosphate – 40%

  • Calcium Oxalate – 30%

  • Calcium Phosphate – 10%

  • Struvite (MgNH4PO4)– 10%

  • Urate – 7%

  • Cystine – 2%

  • Miscellaneous – Xanthine etc.- 1%


What factors predispose to nephrolithiasis?

  • Idiopathic Hypercalciuria

  • Primary hyperparathyrodism

  • Hyperoxaluria

  • 1o Autsomal recessive

  • 2o Small bowel resection, bypass or inflammation

  • Hyperuricosuria – associated with gout

  • Renal tubular acidosis

  • Cystinuria – cystinosis

  • UTI

  • Hypocitraturia

  • Idiopathic nephrolithiasis

  • Most likely a genetic predisposition


What is idipopathic hypercalciuria (IH)?

  • Hypercalciuria - Urine Ca > 10mmol/24h

  • IH

  • - affects 10% of population

  • 40% of renal stone formers

  • Absoprtive hypercalciuria

  • Intestinal calcium hyperabsorption

  • ? Increased sensivity to VitD

  • Renal phosphate leak

  • Renal hypercalciuria


How would you investigate a patient with Nephrolithiasis?

Plasma

Na, K, Urea, Creatinine, HCO3, Ca, PO4, Urate, PTH, VITD

Urine

- Dipstick for pH, protein

- 24 h urine collection

Ca, PO4, Mg, Urate

Occasionally – Oxalate, Citrate, Cystine, Xanthine

Direct stone analysis

Nonbiochemical investigation

- microbiology, radiology


Remember

Read Your Clinical Biochemistry Books!


Recommended Reading

Lecture Notes in Clinical Biochmesitry 7th Edition

G Beckett, S Walker, P Rae, P Ashby (Blackwell publishing)

Clinical Chemistry 5th Edition

W J Marshall, S K Bangert (Pubslished by Mosby)

An illustrated Colour text - Clinical Biochmeistry 3rd edition

Alan Gaw et al (Churchill Livingston)

Handbook of Clinical biochmeistry 1st Edition

R Swaminathan (Oxford University Press)

Clinical Chemistry in diagnosis and treatment

Philip Mayne (Edward Arnold)

A Guide to Diagnostic Clinical Chemistry 3rd Edition

Walmsely & White (Blackwell)


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