Disorders of Renal Function Flashcards
Describe renal clearance
-Rate at which a substance is removed from the blood stream (theoretical)
=a(urine)= c(urine) x v(urine)
=amount of ion cleared per minute= conc of urine x volume of urine
-Volume of plasma completely cleared of a substance per unit time
=V(plasma)= c(urine) . V(urine)/ c(plasma)
=clearance of ion from plasma= amount of ion cleared per min/ concentration of ion in plasma
What is GFR?
- Volume filtered by glomeruli, per unit time
- Clearance (for a substance that is completely lost from the plasma to the urine)
How do we calculate GFR?
-GFR= UO + V(vein)/min
=UO= V(ureter) per min
*Conc V(vein)= 0 as substance completely lost from plasma
-GFR= c(urine) . UO/ c(plasma) mL/min
What are the conditions for the substances measured to calculate GFR?
- Must not alter GFR
- Freely filtered at glomerulus
- Not reabsorbed/ actively secreted in nephron
- Not metabolised/ produced by kidney
Why do we measure GFR?
- Provides an assessment of global renal function
- Pathology causing loss/ damage to glomeruli affects kidney generally- GFR loss correlated with general loss of function
- Guides management in CKD
- Rate of decline predicts need for renal replacement therapy
- Used to guide dosing of potentially toxic (renally cleared) drugs
Examples of exogenous substances used in measuring GFR
*invasive and time-consuming so rarely used
-Inulin (fructose polymer, MW 5 kDa)
=Continuous IV infusion combined with timed urine collections
=Not generally used outside research
-Radioisotope tracers
=15Cr-EDTA, or 125I-iothalamate
=Single injection, followed by serial blood tests
=Again rarely used outside research
-Iohexol
=Non-radioactive contrast agent
=Single injection, followed by serial blood tests
=Sometimes used in paediatrics (unusually low muscle mass)
Examples of endogenous substances used in measuring GFR
-Creatinine
=Small molecule (113 Da)
=Produced at relatively constant rate (muscle metabolism)
=Some active tubular secretion
=Long-established role in GFR measurement
-Cystatin C
=Small protein (13kDa), inhibitor of proteases
=Produced by all nucleated cells
=No significant tubular secretion/ absorption
=10-20x more expensive to measure (than creatinine)
=Relatively new method of measuring GFR
Describe creatinine clearance
-Plasma creatinine measurement
-24hr urine collection
=Inconvenient for patient, inaccurate (not complete/ mis-timed), imprecise
-At very low GFR further inaccuracy
=less creatinine filtered, amount creatinine secreted proportionally larger
Can we measure plasma creatinine alone?
- Reciprocal relationship with GFR
- But very large inter-individual differences (muscle mass, age, gender, ethnicity)
What is the Cockcroft-Gault equation?
-Plasma creatinine
-Requires weight, age, sex
-Often used to adjust dosing for renally-excreted drugs with potential toxicity
-eGFR= (140-age)(weight)/ (Crx)
=x for men= 0.81, women= 0.85
What is the MDRD?
- Modified Diet in Renal Disease
- Equation only applicable to those with low GFR, shown to be inaccurate at “healthy” GFR (and very low GFR)
What is EPI?
-Updated eGFR equation by CKD Epidemiology Collaboration
-Generates more reliable eGFR at 60-90 ml/min/1.73m2
-May mean that progressive renal disease spotted earlier
Recommended by NICE
When do the equations lose applicability?
- Children, pregnancy, very elderly?
- Muscle mass extremes (frail, amputee, heavily built)
- Rapidly-changing renal function (overestimate in acute)
- Very low GFR
How does eGFR contribute to classification of CKD?
- CKD= progressive and irreversible loss of kidney function caused by irreversible damage to increasing numbers of nephrons
- Early treatment delays progression
- Classification also includes urinary albumin: creatinine ratio (ACR)
- Diagnosis usually requires eGFR consistently to be less than 60 mL/min/1.73m2
What can CKD be diagnosed above 60mL/min/1.73m2?
- Persistent proteinuria/ microalbuminuria
- Haematuria
- Renal anatomical/ genetic abnormality (biopsy-proven GN, or PKCD)
What is Acute Kidney Injury (AKI)?
An abrupt loss of renal function, commonly characterised by acute:
-Oliguria
-Increases in plasma urea and creatinine
Often accompanied by a loss of in ability to regulate water, electrolyte and acid-base balance
*Acute on chronic kidney injury refers to acute insult on background existing renal impairment
What is the clinical criteria for detecting AKI?
-Rely on creatinine and UO
-Increase in plasma creatinine of >/26 umol/L within 48 hours, >/50% in the last 7 days
=requires establishing creatinine baseline from previous results so early stage of AKI missed
-UO <0.5mL/kg/hr for >6hrs in adults (8 in children)
What are AKI e-alerts?
-Lab-computer based algorithm to:
=Determine creatinine baseline
=Calculate magnitude of creatinine rise
What are the functions of the renal tubules?
- Essential for electrolyte, water and acid-base homeostasis
- Reabsorption of water that occurs in distal tubules allows urine to be variably concentrated or diluted, according to need
- Distal tubules also perform “fine-tuning” of electrolyte homeostasis
Describe acid-base homeostasis
- Kidneys play important role in maintaining plasma H+ concentration within tight limits
- Responsible for excreting H+, re-absorbing and regenerating bicarbonate
(plasma. ECF bicarbonate buffer) - Urine usually significantly more acidic than plasma (5.5 vs 7.35-7.45)
- Any significant damage to tubules can impair urine acidification
- However overt rise in urine pH is relatively rare
What is Renal Tubular Acidosis (RTA) Type 1?
- Can lead to pH (urine)>5.5
- Distal tubular cells unable to secrete H+ (abnormally permeable to H+)
- Many possible causes: autoimmune, paraproteinemia, nephrocalcinosis
What is the Ammonium chloride loading test?
- Used to confirm suspected RTA type 1
- NH4Cl administration leads to metabolic acidosis (so rarely used)
- Of pH urine >5.5 persists them RTA type 1 confirmed
Describe electrolyte homeostasis
-Imbalances of plasma electrolytes may be renal in origin
-Renal causes may be identified/ excluded by investigation of plasma and urine
=Hypokalaemia- causes: renal loss, GI loss (vomiting/diarrhoea), shifts into cells
=Spot urine K+ <20mmol/L usually excludes renal loss
How can spot urine tests be more efficient?
- 24hr urine collection
- Measure creatinine (or osmolarity) to correct for variability in urine conc. and blood concentration (fractional excretion)
Describe sodium and fluid balance in the tubules
-Plasma sodium more an indicator of fluid balance than total body sodium
=hypernatremia reflects water deficit rather than sodium overload
-135-145 range
-Urine Na+ <30mmol/L= tubules appropriately re-absorbing Na and water (pre-renal failure caused by hypotension)
-Urine Na+ >30mmol/L inappropriate loss- tubular dysfunction/damage/inadequate aldosterone action (intrinsic/ established renal failure caused by untreated pre-renal failure)
Describe the urine concentrating ability
- Assessed by measuring urine osmolality (and plasma osmolality for comparison)
- Loss of urine concentration ability may be accompanied by polyuria
How can the relative values of osmolality help diagnosis?
- Chronic renal failure- osmolality urine=plasma= end stage: oliguria
- Acute tubular necrosis (following pre-renal failure)- urine=plasma- initially oliguric, recovery phase often polyuria
- Diabetes mellitus- urine=/>plasma= osmotic diuresis, polyuria, high glucose overwhelms urine concentration ability
- Diabetes insipidus- urine
How can the water deprivation test by used in suspected diabetes insipidus
- Involves with-holding fluids over several hours
- Potentially dangerous, must be monitored very closely (true DI= hypernatremia)
- DI involves failure of action of vasopressin (or ADH)
- May be cranial (hypothalamic/pituitary pathology), nephrogenic (tubular problem)
- Normal response: plasma osmolality static, urine osmolality rises (kidney conc urine)
- DI: plasma osmolality will rise= urine remains dilute
- Cranial DI should be responsive to DDAVP (synthetic vasopressin)
What is a “Point of Care” test?
- Rapid, simple, convenient, cheap
- Number of tests varies by manufacturer
- Readout: coloured strip, or printed report
What are the types of Point of Care tests?
- Glucose (diabetes?)
- Ketones (ketoacidosis?)
- Protein (albumin)- not as sensitive as lab measurement
- Blood (detects Hb: calculi, bladder ca., glomerulonephritis)
- Leukocytes (UTI)
- Nitrites (produced by nitrate-reducing UTI bacteria)
- Bilirubin (jaundice)
- Urobilinogen (absent in cholestatic jaundice)
- pH, specific gravity (related to osmolality)
Describe physiological vs. pathological urine protein levels
-Glomeruli prevent passage of most large plasma proteins
-Tubules actively re-absorb/ catabolise low MW proteins
=Increased glomerular permeability- increasing urinary albumin, detectable levels of large MW proteins not normally found in urine
=Decreased tubular protein reabsorption= increased conc. of low MW proteins
How is proteinuria detected?
-Dipstick testing (not as sensitive as lab testing)
-Lab-based albumin/ protein measurement, sometimes 24hr collection but usually a spot urine using creatinine to adjust for urinary concentration
=Protein: creatinine ratio (PCR)
=albumin: creatinine ratio (ACR)- used to classify CKD
What is Microalbuminuria?
- Refers to abnormal level of albumin, usually too low for detection by urine dipstick
- ACR>3.5,g/mmol in men >2.5mg/mmol in women
- Important for prevention of significant diabetic nephropathy
- Can occur transiently (post-trauma, surgery, pyrexia, vigorous physical exercise)
