Laboratory tests of renal function

Laboratory tests of renal function

1. Introduction

   • the
     • Tests require a clinical assessment of the patient to allow meaningful interpretation
     • Human kidney provides essential regulatory and excretory functions
     • Kidney provides a path of excretion
       • for
         • Blood-borne
         • Water-soluble
         • Low-molecular-weight compounds
     • Endocrine activity of the human kidney includes the secretion of the hormones erythropoietin and renin
       • and
         • The activation of vitamin D by hydroxylation to its 1,25-dihydroxycholecalciferol form
     • Body water content, plasma electrolyte composition and plasma pH
       • are
         • All under the regulatory control of the kidney

2. Assessment of renal function

   • the
     • Deviation from ‘normal’ levels of many blood and urinary constituents
       • can
         • Reflect renal insult or systemic disorder

3. Glomerular filtration rate (GFR)

   • the
     • GFR is measured in ml/minute and can be derived using the following formula: Cs = (Us x V)/Ps
       • where
         • Cs is the volume of plasma cleared of the substance per minute
         • Us is the urinary concentration of the substance
         • V is the volume of urine produced per minute
         • Ps is the plasma concentration of the substance
     • GFR is the rate at which substances are filtered from the blood
       • of the
         • Glomeruli into the Bowman’s capsules of the nephrons
     • Any substance freely filtered by the glomerulus and not subsequently secreted, reabsorbed or metabolized
       • by
         • The distal parts of the renal system has a clearance equivalent to the GFR
     • Renal clearance is the volume of plasma cleared of a specific substance per unit time
     • Exogenous markers
       • include
         • The carbohydrate compound inulin
         • 124I-iothalamate
         • Cr-EDTA

4. Creatinine clearance

   • the
     • Clearance value is then given and expressed in terms of milliliters per minute
       • thus
         • Giving an interpretable value for estimation of the GFR
     • Creatinine is the most commonly used endogenous marker for renal function
     • Creatinine is also secreted in small amounts in the proximal tubule
       • resulting
         • In a small overestimation of GFR
     • Measurement of the clearance of creatinine normally involves a 24-hour collection
       • of
         • Urine and a measurement of serum creatinine concentration
     • Limitations of this method include collection errors
       • and
         • Inconvenience for the patient

5. Creatinine-based equations for glomerular filtration rate

   • the
     • MDRD estimate is a poor measure of GFR in healthy individuals without renal pathology
     • Equations are therefore inappropriate in the assessment of acute kidney injury (AKI)
     • Predictions of GFR made from serum creatinine levels are more convenient
       • and
         • Are a mainstay of modern GFR assessment
     • Several mathematical models have been generated
       • the most commonly used are
         • The Cockroft-Gault (CG) and modification of diet in renal disease (MDRD) formulae
     • CG model estimates creatinine clearance (eCcr), and hence GFR
       • based on
         • Serum creatinine
         • Body mass
         • Age
         • Sex
     • Original formula: eCcr = ((140 - age) x weight (kg) x (0.85 if female))/72 x serum creatinine (mg/dl)
     • Formula is well supported as it provides a simple way to estimate GFR
       • but
         • Overestimates GFR in individuals who are obese or edematous and does not account for ethnicity
     • MDRD Study Group uses six measurements to estimate GFR (eGFR)
       • including
         • Blood urea nitrogen (BUN) and albumin levels
     • Initial diagnosis of chronic kidney disease, the CKD-EPI formula is recommended
       • by
         • NICE as the most appropriate method to estimate GFR
     • Equations are not validated in children
       • in whom an alternative
         • The Schwartz equation, should be used
     • Creatinine-based equations have many limitations
       • reflecting
         • The variability of creatinine production with many factors
     • Diuretics spironolactone and triamterene
       • as well as
         • Other drugs such as trimethoprim, cimetidine and probenecid
           • interfere with
             • Tubular secretion of creatinine, and thus can increase serum creatinine concentrations while not reflecting alterations in GFR

6. Creatinine and acute kidney injury

   • Serum urea
     • the
       • Serum urea has long been used as a marker of renal dysfunction
       • Serum urea levels can be raised by increased production
         • as seen
           • After a nitrogenous dietary load, or decreased excretion, as seen in renal dysfunction
   • the
     • Serum creatinine concentration is limited in reflecting the extent of renal damage
       • in
         • AKI and is a late diagnostic aid
     • Serum creatinine levels are a longstanding and convenient method of assessing AKI
     • Serum creatinine levels underestimate the extent of renal function deterioration
     • Small increase in serum creatinine within its normal range reflects a large decrease
       • in
         • GFR hence early rises in creatinine over short periods of time require scrutiny
     • Serum creatinine levels lag the acute injury process
       • with
         • Levels only rising a day or so after the initial renal insult

7. Novel measures of renal function

   • Serum cystatin C
     • the
       • Urinary cystatin C is not a useful clinical marker of GFR
         • as it
           • Is reabsorbed and metabolized by the proximal tubule
       • Alkaline non-glycosylated protein is produced at a constant rate
         • by
           • Almost all nucleated cells and is freely filtered at the glomerulus
       • Initially it was thought that serum levels of cystatin C were independent
         • of
           • Age
           • Sex
           • Body morphology and composition
       • GFR declines, serum levels of cystatin C rise, which can precede a rise
         • in
           • Serum creatinine levels by 1 to 2 days
       • Cystatin C is recommended by NICE for diagnosis or exclusion of CKD but only in patients
         • with a
           • Sustained creatinine-based eGFR of 45 - 59 ml/minute/1.73 m2 and no proteinuria
       • Levels may be falsely raised in conjunction with immunosuppressive agents
         • therefore
           • Are not validated for use in renal transplant recipients
   • Novel biomarkers of renal injury
     • the
       • Biomarkers such as TIMP-2 and IGFBP7
       • Several biomarkers are being researched and evaluated for diagnosis of AKI/CKD
         • and
           • Prediction of outcomes such as renal replacement therapy (RRT) or mortality
       • Arguably the most well supported in this role at present
         • is
           • Neutrophil gelatinase-associated lipocalcin (NGAL)

8. Neutrophil gelatinase-associated lipocalcin

   • the
     • NGAL may be less useful in those with pre-existing renal disease
       • or
         • Multiple comorbidities than incident AKI in healthy individuals
     • NGAL is a protein of the lipocalcin family that is expressed
       • by
         • Neutrophils and epithelial cells including the proximal tubule
     • NGAL was a useful predictor of AKI with prognostic value; uses included predicting need for RRT
     • NGAL has been assessed in both the ED and ICU for AKI diagnosis
   • Kidney injury molecule (KIM-1)
     • the
       • Advantages of urinary KIM-1 are that it is highly specific to kidney injury
       • KIM-1 is a transmembrane glycoprotein that is not detectable in normal kidney tissue or urine
         • but
           • Is up-regulated in the proximal tubule in AKI
       • KIM-1 can be detected in the urine of patients within 6-12 hours
         • of
           • Acute tubular necrosis thus allowing early diagnosis
   • Liver-type fatty acid-binding protein (L-FABP)
     • the
       • L-FABP may be of use in assessing the severity of sepsis associated with AKI and response to treatment
       • Nine reported types of FABP; L-FABP was first recognized in the liver
         • but
           • Is expressed in renal proximal tubules
       • Urinary L-FABP has been shown to be significantly raised in hospitalized patients with AKI

9. Free water clearance

   • the
     • Benefits in the assessment of hypernatremia in resolving acute renal failure
     • Separating urine into two components: one consisting of isosmotic urine
       • containing
         • All solutes and the other containing only free water
     • Diagnosis of acute renal failure this measurement yields no advantage
       • over
         • Creatinine clearance, and it is subject to limitations by factors that affect urine osmolality

10. Other serum biochemistry in GFR reduction

    • the
      • Acute reduction in GFR is often accompanied by an elevation
        • of
          • Reduction in serum bicarbonate and calcium levels
          • Serum potassium
          • Urate and phosphate
      • Serum electrolyte levels are non-specific markers of renal dysfunction
        • and
          • Offer little in the way of quantitative analysis

11. Tests for tubular dysfunction

    • the
      • Recovery of concentrating ability, which is indicated by an increase
        • in the
          • Urine osmolality of greater than 50% after administration of desmopressin
      • Proximal tubular failure causes acidosis accompanied by a fall
        • in
          • Serum potassium
          • Phosphate
          • Urate and bicarbonate levels
          • Reflecting a failure of reabsorption
      • Acidification of the urine by oral ammonium chloride
        • is occasionally
          • Carried out to indicate the presence of renal tubular acidosis
      • Exclusions to this test include alkaline urine in the presence of metabolic acidosis and hepatic impairment
        • and
          • Difficulties in interpretation occur when urinary infection, low potassium or elevated calcium is present
      • Ability of the distal tubules to reabsorb water may be assessed by the water deprivation test
      • Measurement of urine osmolality provides information on the ability
        • of
          • The kidneys to concentrate urine in response to water balance

12. Urinalysis

    • the
      • Presence of macroalbuminuria (>200 mg/minute or >300 mg/day) suggests diabetic nephropathy
      • Physicochemical properties of urine as well as the presence and concentration of substances
        • can be used as
          • Non-specific markers of renal disease but are also assessors of renal function
      • Urine specific gravity reflects the concentration of the urine
        • providing
          • An indication of tubular function
      • Presence of dysmorphic RBCs and RBC casts suggests glomerulonephritis
        • or
          • Significant tubule damage with RBC leakage
      • WBC casts may indicate intrarenal disease such as pyelonephritis or glomerulonephritis
        • because
          • These casts are formed in the kidney not in the distal urinary tract
      • Microalbuminuria, as defined by an albumin excretion of more than 20 mg/minute
        • or
          • 30-300 mg/day, suggests hypertensive disease in patients with diabetes

13. Endocrine tests in renal disease

    • the
      • Elevated parathyroid hormone levels can indicate secondary or tertiary hyperparathyroidism
      • Presence of anemia with coexisting chronic kidney disease suggests impaired erythropoietin production
      • Hormones such as PTH can be conducted
        • as part of the
          • Overall assessment of a patient with chronic renal failure

14. Urine tests for differentiation between pre-renal and intrarenal failure

    • the
      • Pre-renal failure is characterized by concentrated urine with low sodium excretion (<20 mEq/liter)
        • and
          • A fractional excretion of sodium (FENa) of less than 1%
      • Use of urinary components to distinguish between pre-renal compromise and acute tubular necrosis
        • relies on the
          • Normal response of the kidney to conserve sodium and water in the presence of reduced renal perfusion.
      • Inadequate management of pre-renal failure can result in the development of intrarenal damage
      • Intrarenal failure typically has a FENa of greater than 2%
        • and
          • A urinary sodium concentration over 20 mEq/liter

15. Made by: David Leonardo López Sánchez

16. ·

    • Took from: Chadwick, L., & Macnab, R. (2015 ). Laboratory tests of renal function. ANAESTHESIA AND INTENSIVE CARE MEDICINE, 257 - 261.

17. ·

    • Took from: Chadwick, L., & Macnab, R. (2015 ). Laboratory tests of renal function. ANAESTHESIA AND INTENSIVE CARE MEDICINE, 257 - 261.

18. ·

    • Took from: Chadwick, L., & Macnab, R. (2015 ). Laboratory tests of renal function. ANAESTHESIA AND INTENSIVE CARE MEDICINE, 257 - 261.

19. ·

    • Took from: Mayo Clinic. (s.f.). MAYO CLINIC. Obtenido de MAYO CLINIC: https://www.mayoclinic.org/es-es/diseases-conditions/chronic-kidney-disease/symptoms-causes/syc-20354521

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