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Clinical Biochemistry and Renal Disease

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

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  1. Clinical Biochemistry and Renal Disease Dr Vivion Crowley Consultant Chemical Pathologist St James’s Hospital

  2. 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

  3. 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

  4. 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)

  5. 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

  6. Causes of abnormal plasma urea

  7. Causes of abnormal plasma creatinine

  8. 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

  9. 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

  10. 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

  11. 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)

  12. Equations used to estimate GFR Cockcroft–Gault equation MDRD equation for eGFR

  13. Use of MDRD to classify CKD

  14. 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

  15. 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

  16. 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

  17. How else can renal failure be classified?

  18. 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

  19. What is the biochemical profile associated with pre-renal failure? • 53y old male • 3/7 hx of vomiting and diarrhoea

  20. How do you distinguish between Pre-renal failure and ATN?

  21. What is the biochemical profile associated with established ARF e.g. ATN?

  22. What are the causes of CRF? • Diabetic nephropathy • Glomerulonephritis • Hypertensive nephropathy • Tubulointerstitial disease • Polycystic kidney disease • Reflux nephropathy • In many instances cause is unknown

  23. 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

  24. How is progression of CRF monitored?

  25. What is the biochemical profile associated with ESRD 65y old male C/O malaise, tiredness, nocturia O/E BP 182/110, pale

  26. What effect does dialysis have on ESRD biochemical profile?

  27. 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)

  28. How does Tubulointerstitial disease manifest?

  29. 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

  30. 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

  31. How do you investigate proteinuria?

  32. 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

  33. 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

  34. 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%

  35. 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

  36. 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

  37. 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

  38. Remember Read Your Clinical Biochemistry Books!

  39. 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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