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Evaluation and Interpretation of Renal Function Dr. Shikha Rao University College of Medical Science & GTB Hospital, Delhi.

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Presentation on theme: "Evaluation and Interpretation of Renal Function Dr. Shikha Rao University College of Medical Science & GTB Hospital, Delhi."— Presentation transcript:

1 Evaluation and Interpretation of Renal Function Dr. Shikha Rao University College of Medical Science & GTB Hospital, Delhi

2 Functions of Kidney Regulation of fluid and electrolyte balance by –adjusting volume of water lost in urine –renin and angitensin system Regulate plasma ion concentrations: –sodium, potassium, and chloride ions (by controlling quantities lost in urine) –calcium ion levels (through synthesis of calcitriol) Regulation of acid-base balance –by controlling loss of hydrogen ions and bicarbonate ions in urine

3 Excretion of waste products of protein metabolism –urea, creatinine. Endocrine functions –renin, Erythropoeitin, –1,25 dihydroxycholecalciferol- conversion only in kidney

4 Why evaluating renal function is important To detect possible renal damage and assessment of its severity To diagnose renal disease To observe the progress of renal disease To monitor the safe and effective use of drugs which are excreted in the urine

5 Evaluation of renal function Clinical markers of renal function –urine output –BUN –S.Creatinine Assessment of GFR –S. Creatinine based nomograms –Renal clearance techniques

6 Tubular function tests –urinary concentrating ability –urine to plasma osmolar ratio –free water clearance –urine to plasma creatine ratio –sodium and urea conservation –indices of tubular injury Renal hemodynamics measurement –renal plasma flow and RBF

7 Urine output Perioperative oliguria <0.5 ml/kg/hr Prerenal response to intravascular hypovolemia or a physiologic response to surgical stress Complete / abrupt cessation – postrenal obstruction Unreliable marker of ARF –Vary from anuria to polyuria –Nonoligouric renal failure –MC manifestation of Acute kidney injury

8 Blood Urea Nitrogen Metabolism of NH3 in liver (Protein catabolism: Amino acid  Ammonia  (Liver)  Urea  (Kidney) Urea is readily filtered at glomerulus but 40-50% is reabsorbed Not a reliable indicator of renal function (GFR) Normal: 8-20 mg/dL

9 Decrease in: starvation, liver disease (protein def) Increase in : ↓GFR( renal disorders and urinary obstruction), ↑protein catabolism (trauma, sepsis, degradation of blood, high-protein diet)

10 Serum Creatinine Reflects the balance b/w Creatinine production (M: 20-25 mg/kg, F: 15-20 mg/kg): related to muscle mass, physical activity, protein intake and catabolism & Creatinine excretion by kidney Normal: M: 0.8 - 1.3 mg/dL, F: 0.6 - 1 mg/dL Reliable marker of stable renal function Inversely related to glomerular filtration rate (doubling of S.Creatinine implies a halving of GFR )

11 Relationship b/w S.creatinine and GFR

12 Increases: large meat meals, barbiturates,  acetoacetate (ketoacidosis), Cimetidine & trimethoprim- blocks creatinine secretion by tubule Decreases: N acetyl cysteine GFR declines with age (5% / decade), muscle mass also declines  creatinine relative normal despite decreased GFR

13 BUN / Creatinine Ratio BUN: CrLocationMechanism >20:1PrerenalBUN reabsoprtion is increased. BUN is disproportionately elevated relative to creatinine in serum 10-20:1 Normal or postrenal Normal range. Can also be postrenal disease. BUN reabsorption is within normal limits. <10:1IntrarenalRenal damage causes reduced reabsorption of BUN, therefore lowering the BUN: Cr ratio

14 Cystatin C Under Investigation Early detection of renal dysfunction – 2nd day Cysteine protease inhibitor Released into circulation by nucleated cells Completely filtered at glomerulus (not secreted) –Related to GFR & S. Creatinine –Disadv :Levels affected by immunosuppressive drugs, inflammation…

15 Measurement of GFR Glomerular filtration -index of overall excretory function Vol. of fluid filtered into Bowman’s capsule per unit time Methods clearance of inulin, creatinine, EDTA and DTPA S.Creatinine based nomograms

16 Assessment of GFR S.Creatinine based nomograms – based on population studies Avoid necessity of timed urine sample Eg- Cockcroft and Gault equation (GFR = Cr Cl) CrCl =(140-age) x weight (kg) x constant 72 x serum creatinine (mg/dl) For females, value is multiplied by 0.85

17 Body weight may alter GFR substantially (as in obese or edematous / cachectic patients) Modified by Robert & associates - whole body weight replaced by ideal body weight Limitation – rapidly changing renal function

18 Clearance The “clearance” of a solute is the virtual volume of blood that would be totally cleared of the solute in a given time. Solutes come from blood entering the kidneys. Rate at which kidneys excrete solute into urine = rate at which solute disappears from blood plasma

19 Principles of clearance Some substances when filtered, enter the tubules are not reabsorbed and so 100% excreted= GFR (inulin= gold standard for GFR, creatinine (but this one partially reabsorbed, particularly in uremia, then clearance GFR Some substances are filtered, enter tubules, but are completely reabsorbed, so they do not reach the final urine

20 For solute X (using Ficks eqn) C x = U x x V PxPx Volume of urine formed in given time Conc. of X in systemic blood plasma Clearance Conc. of X in urine

21 Solutes used to measure GFR Required properties are: 1.Solute should be freely-filtered (conc. in Bowman’s space = conc in blood plasma) 2.Tubules do not absorb, secrete or metabolize X Thus, amount of X in urine per unit time = that which glomerulus filters per unit time INULIN is such a substance that satisfies all of these criteria and is commonly used to measure GFR

22 Inulin Clearance Inert polyfructose sugar Completely filtered by glomerulus Neither secreted nor reabsorbed by renal tubule Volume in ml of plasma cleared of inulin per minute represents GFR Measurement After IV loading dose 30-50 mg/kg Continuous infusion to establish steady state plasma concentration of 15-20 mg/dl Bladder is flushed with air to eliminate any pooled urine

23 Carefully timed plasma and urine samples are taken GFR: C in = U in x V P in Inulin clearance is “gold standard” for measurement of GFR laborious and requires meticulous attention to detail, time consuming- Seldom used clinically Normal inulin clearance –110-140 ml/min/1.73m 2 - males –95-125 ml/min/1.73m 2 - females

24 Creatinine clearance Endogenous end product of creatine phosphate metabolism simple inexpensive bedside estimate of GFR Usually measure over 24 hr period to get reliable results samples taken before breakfast C Cr = U Cr x V P Cr

25 Creatinine clearance can track changes in GFR as it alters creatinine excretion (UCr x V) Guide alteration in renal function & prognosis – nephrotoxic drugs ( aminoglcosides, calceneurin antagonists) When GFR very low- variability of CC is lost s/o deterirating renal function

26 Grouping of patients according to GFR Creatinine clearance (mL/min) Normal100-120 Decreased renal reserve60-100 Mild renal impairment40-60 Moderate renal insufficiency25-40 Renal failure<25 End-stage renal disease*<10 *This term applies to patients with chronic renal failure

27 Limitation Normally 20% creatinine is secreted by tubules, Creatinine clearance overestimates GFR (CC:IC = 1.2:1) In c/o decreasing GFR, tubular secretion of creatinine increases - CC:IC = 1.8:1

28 Plasma Clearance Measurement of rate of disappearance (plasma Clearance) of a substance that is completely eliminated by glomerular filtration Involves Bolus or infusion of a Marker followed by measurement of multiple plasma levels Markers used-Non Radio Active inulin and iothalamate, radio isotopes of EDTA & DTPA

29 Tubular function tests Measure urinary concentrating ability & sodium & urea handling Distinguish oliguria of dehydration (prerenal syndrome) from that due to tubular injury (ATN) Prerenal- reversed by restoration of intravascular volume (except severe sepsis & hepatorenal syndrome of liver failure)

30 Urinary Osmolality - measures concentrating ability Sensitive Marker Normal : 300-900mOsm/L Can reach maximum of 1200 mOsm/L Pre Renal States –urine osmolality markedly increased In ATN loss of concentrating ability l/t dilute urine with high sodium

31 Urine to Plasma osmolor Ratio (U: Pl osm ) Normal Serum osmolality = 280-300 mOsm/kg Pre Renal syndrome U : Pl osm > 1.5 Acute tubular necrosis U : Pl osm = 1.0 (isothenuria a/w oligouria) Isothenuria also seen in pre renal state when diuretics are administered

32 Free water clearance (C H2O ) –Measure of Renal Water regulation by tubular dilution or concentration of urine –C H2O vary from +18 l to -8 l /day –(Hypervolemia –positive C H2O, Hypovolemia-negative C H2O ) –Osmolor clearance of the solute is subtracted from urine flow rate to give free water clearance –With onset of ATN-Urine becomes isoosmolar and C H2O ~ 0 –C H2O – not provide much information

33 Urine to Plasma Creatinine Ratio Represents proportion of water filtered by the glomerulus that is abstracted by entire tubule Pre renal state increases 100 fold Acute Tubular necrosis < 20:1

34 Sodium and Urea Conservation Urine Sodium Pre Renal state –Oliguria with very low urine sodium(U Na )<20 mEq/l Acute Renal Failure –Urine sodium exceeds 60-80 mEq/l

35 Fractional Excretion of Sodium –Additional means to evaluate tubular function in hyper and hypo volumia –F ENa expresses sodium clearance as a percentage of creatinine clearance –In Hypovolemia, Sodium clearance and F ENa is less than 1% of creatinine clearance –Tubular dysfunction increases to more than 3%

36 Indices of Tubular function  2 microglobulin Protein component of MHC Normally filtered by glomerulus & undergoes partial tubular reabsorption Distinguish glomerular & tubular injury

37 Glomerular injury – serum levels of  2 microglobulin increase whereas urinary levels decrease used as early sign of rejection in renal transplantation Primary tubular injury-impaired reabsorption leads to vice- versa

38 Urinary N Acetyl B- D-glucosaminidase (NAG) Tubular enzyme raised in subclinical tubular injury Uses –early detection of rejection in transplant pts –follow course of CRF therapy

39 Renal Plasma Flow & Renal Blood Flow-using p- Aminihippurate clearance There are certain substances which the kidneys completely clear from plasma during a SINGLE PASSAGE through them. –Glomerular filtration –Proximal tubular secretion p-aminohippurate (PAH) is such a special solute.

40 Renal clearance of PAH = arterial renal plasma flow Thus, PAH clearance is a good estimate of renal plasma flow Laborious technique Effective RPF = 660 ml/min/1.73m 2 Limitation –renal failure –surgical stress

41 Renal handling of PAH PAH is an organic acid that is not usually present in the body, so given by IV infusion Note that there is none left in the renal vein - all cleared in first pass

42 Filtration fraction Fraction of RPF that is filtered at glomerulus FF = GFR RPF Normal = 0.2 Represents changes in periglomerular arteriolar tone

43 Total renal blood flow Flow probes – doppler technique Thermodilution estimation of renal vein effluent Contrast ultrasonography

44 Drugs with active or toxic metabolites excreted renally MorphineM-3-Glucuronide M-6-Glucuronide Antanalgesic Analgesic x 40 MeperidineNormeperidineConvulsions DiazepamOxazepamSedative Midazolam1-OH-midazolamSedative SNPThiocyanateNeurotoxic EnfluraneFlourideNephrotoxic VecuroniumDesacetyl vec.Relaxant Pancuronium3-OHpancuroniumrelaxant

45 References Miller’s Anaesthesia, 7th ed. Functional anatomy and renal physiology. Wylie and Churchill Davidson’s. Functional anatomy and renal physiology, 6th ed. Barash Clinical Anaesthesia, Functional anatomy and renal physiology, 5th ed. Ganong WF. Review of Medical Physiology, 20th ed.

46 Urinanalysis - Appearance Blood (haematuria) –Check with Dipstix (blood, sugar, protein). –Simple, cheap, routine, easy to re-check and unlikely to make mistakes. But not quantifiable, just checks for presence. Very concentrated – dark/smoky colour. Very clear urine with high frequency of urination indicates it’s less likely to be a bacterial problem. Discoloration may also be due to:(normal-pale yellow or amber) –Jaundice, haemoglobinuria. –Drugs (e.g. antibiotics). –Food (e.g. beetroot). –Disease (e.g. porphyria – Madness of King George where his urine was purple)

47 Drawbacks of Clearance Methods Measuring clearance means, overall nephron function (~2 million nephrons in both kidneys) This gives the sum of all transport processes occurring along nephrons So, no information about precise sites and mechanisms of transport Must therefore use studies on individual nephrons, tubule cells or cell membranes to obtain this data

48 Urinalysis Routinely done for evaluating renal function Routine urinalysis: pH, specific gravity, glucose, protein, bilirubin, urinary sediment Specific gravity > 1.018 after overnight fast  adequate renal concentrating ability

49 Measurement of Normal valueInterpretation pH (4.6-8.0) average 6.0pH helps indicate acid-based balance. Urine that stands for several hours becomes alkaline, an acid pH helps protect against bacterial growth Protein (none or upto 8 mg/100 ml) Normally absent. Seen with damage to glomeruli or tubules Glucose (none) Ketone (none) Blood (upto 2 RBCs)Damage to glomeruli or tubule, trauma, disease, surgery of lower urinary tract. In women may be contaminated with menstrual flow Specific gravity (1.010-1.025)Measure concentration of particles in urine. High specific gravity – concentration urine, low specific gravity – diluted urine Microscopic examination WBCs (0-4 / low power field)Greater – indicate urinary tract infection Bacteria (none) Casts (none)Presence always as abnormal finding

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