![C) Creatinine Clearance (Cr CL)
- If the effect of secretion is ignored, then all of the
filtered Cr (equal to the product of the GFR and the
Serum creatinine concentration [SCr]) will be excreted
(equal to product of the urine creatinine concentration
[UCr] and the urine flow rate). Thus:
GFR x SCr = UCr x V
GFR = [UCr x V]
SCr
This formula is called the Cr Cl and tends to exceed the
true GFR by the 10 to >20% of urinary creatinine that is
derived from tubular secretion](https://image.slidesharecdn.com/lecture14assessmentofrenalfunction-paedsminiround-241111183722-a21b4afe/85/lecture-14-Assessment-of-Renal-Function-Paeds-mini-round-ppt-28-320.jpg)
lecture 14 Assessment of Renal Function - Paeds mini round.ppt
- 1. Dr. Awuonda B. B. Onyango Lecturer, Maseno University
- 2. Objectives Background Hx & PE Urine tests Tests for glomerular function Tests for tubular function Imaging Biopsy
- 3. Background Kidneys essential in maintaining internal mileu. Achieved by excretion of waste products of metabolism (eg urea, creatinine & uric acid) Regulate the excretion of water and solutes such as Na+, K+, and H+, largely by changes in tubular reabsorption or secretion.
- 4. Secrete hormones that:- - participate in the regulation of systemic and renal hemodynamics (renin, Ang II, PGs, NO, endothelin, and bradykinin) - red blood cell production (erythropoietin) - calcium, phosphorus, and bone metabolism (1,25-dihydroxyvitamin D3 or calcitriol). Perform miscellaneous functions as catabolism of peptide hormones and synthesis of glucose (gluconeogenesis) in fasting condition
- 5. Kidney function is assessed in clinical practice to:- - screen for kidney disease - to adapt dosage of medications for renal clearance - to follow the evolution of known kidney disease.
- 7. Main Fns of major nephron segments 1. Glomerulus -Forms an ultrafiltrate of plasma 2. Proximal tubule -Reabsorbs 60-65% of the filtered Na + and H2O -Reabsorbs 90% of the filtered HCO3- ; almost all of filtered glucose & amino acids, K+, PO4, Ca, Mg, urea, uric acid -Secretes organic anions (eg urate) and cations (eg creatine); Major site of ammonia production
- 8. 3. Loop of Henle - Reabsorbs 25-35% of filtered Na, Cl- - Countercurrent multiplier as NaCl reabsorbed in excess of water - Major site of active regulation of Mg excretion 4. Distal tubule - Reabsorbs about 5% of filtered NaCl but almost no water - Major site, with connecting segment, of active regulation of calcium excretion
- 9. 5. Connecting segment and cortical collecting tubule - Principal cells reabsorb Na+ & Cl- and secrete K+ under the influence of Aldosterone - Intercalated cells secrete H+, reabsorb K+, and, in metabolic alkalosis, secrete HCO3-. Reabsorb water in the presence of ADH 6. Medullary collecting tubule - Reabsorb NaCl; - reabsorb H2O and urea relative to the amount of ADH present, allowing a concentrated /dilute urine to be excreted - Secrete H+ and NH3; - reabsorption/secretion of K+
- 10. Evaluation of Pt with Renal Disease 1. Hx and P/E - Micturition disturb eg freq, hesistancy, dysuria, nocturia, polyuria, oliguria, haematuria - Pain-eg renal angle, suprapubic - Leg oedema/facial puffiness - Any systemic disease associated with renal dysfunction -Drug History (nephrotoxic) - Family Hx of renal dse; • consanguinity P/E should be thorough from head to toe
- 11. 2. Urine studies - The specimen should be examined within 30 -60 min of voiding; a midstream specimen. Note colour/turbidity - Centrifuge at 3000 rpm for 3-5 min, and the supernatant poured into a separate tube, small amount of sediment should be placed on a slide.
- 12. i) Dipstick for proteinuria -trace (10-20mg/dl) - 3+ (300mg/dl) -1+ (30mg/dl) - 4+ (1000-2000mg/dl) -2+ (100mg/dl) ii) 24 hr urine protein- cumbersome, open to manipulation. UL= 150mg/24 hr (4mg/m²) Normal 4-40 mg/m²; Nephrotic range >40mg/m² (>3.5g/24hr) iii) Spot urine protein/creatinine ratio (UPr/Ucr)- Ratio>3:1 is nephrotic (>200mg/mmol)
- 13. iv) Haematuria- detection of atleast 5 rbc/hpf Significant if >50 rbc/µL v) Pyuria- may be present without a UTI and vice versa. On culture > 10⁵cfu significant for UTI vi) Nitrites and leukocyte esterases- +ve in UTI vii) Others:- pH - glucose - ketones - bilirubin/urobilinogen - osmolality and SG
- 15. A. Red cell cast B. White cell cast
- 16. A. Epithelial Cast B. Dysmorphic RBCs
- 17. A. Granular cast B. Sediment in ATN
- 18. Hypovol. (Pre- renal) ATN AIN GN OBSTRUCT N Sediment Bland Active Brownish, granular casts WBCs, eosinophils, cellular casts RBCs RBC casts Bland/ Haematuria Protein None/min None/min Maybe ↑ with NSAIDs ↑ >100mg/dl min Urine Na+ meq/L < 20 > 30 > 30 < 20 < 20 Urine osmol mosm/kg > 400 < 350 < 350 > 400 < 350 FeNa % UNa xPCr PNa x UCr <1 >1 Varies <1 <1 acute >1 few dys
- 19. Tests for glomerular function 1. Blood Urea Nitrogen (BUN) - Made by the liver as a means of disposing of ammonia from protein metabolism. - Clinical chemists used to measure only the nitrogen in urea, hence the "urea nitrogen" measurement on lab reports. The real conc. of urea is BUN x (60/28), or BUN x 2.14. - Normal BUN is 8-25 mg/dL (2.9-8.9 mmol/L). Factor is 0.357 - Urea is filtered by the glomerulus and is readily reabsorbed
- 20. Sensitive indicators of renal disease, ↑ when renal function ↓s by 25-50% ↑↑ BUN is, azotemia. It is due either to incrd protein catabolism or impaired kidney fn. The rate of urea prodn ↑s with a high protein diet and with enhanced tissue breakdown due to hemorrhage, trauma, or corticosteroids; MI; high fever A ↓ protein diet or liver disease can ↓the BUN without change in GFR. Thus, liver disease may be associated with near normal values for both the BUN (due to ↓ urea productn) despite a relatively large ↓ in GFR
- 21. 2. Glomerular Filtration Rate (GFR) GFR is the best quantification of kidney function. but because it cannot be measured directly, it is estimated from serum concentration or urinary clearance of a filtration marker. Properties of an ideal marker:- - produced at a constant rate - No protein binding, freely filterable - No tubular reabsn/secretion - No extra-renal degradation/elimination - Safe, convenient, inexpensive, accurate, reproducible
- 22. a) Serum creatinine Breakdown product of creatine-P released from skeletal muscle at a steady rate. (small amt. from meat in the diet.) primarily excreted by glom. filtration; 10-15% actively secreted May not ↑ until late stages of disease (>50% loss of kidney function) Normal SCr is 0.6-1.5 mg/dL (53-133 µmol/L) Factor 88.4. Varies with age, gender, lean body mass, inactivity (paraplegia), and increases with maturation from infancy, approaching adult mean values at approx 2 yrs of age
- 23. Normal GFR in children and adolescents Age Mean GFR+/- SD (ml/min/1.73 m²) 1 wk (male/female) 41+/- 15 2-8 wk (male/female) 66+/- 25 > 8 wk (male/female) 96+/- 22 2-12 yr (male/female) 133+/- 27 13-21 yr (male) 140+/- 30 13-21 yr (female) 126+/- 22 National Kidney Foundation (2002) Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification.K/DOQI clinical practice guidelines. Am J Kidney Dis 39:S1–S266
- 24. SCr at birth is equal to the mother’s (usu < 88µmol). It ↓ to 27-44µmol in 1/52 in stable term, and in 2-3/52 in prematures. In the very prem, SCr may paradoxically ↑ due to tubular reabsptn. Renal embryogenesis complete by 35/40, 0.6-1.2 million nephrons/kidney Transition renal physiology:- after birth ↓renal vascularity, ↑ renal blood flow; ↓ tubular concentrating ability etc Consider renal insufficiency in neonates when SCr > 133 µmol/L
- 25. Estimation of GFR Many formulae exist but The Kidney Disease Outcome Quality Initiative of the National Kidney Foundation (NKF-K/DOQI) recommends the following 3 formulae for estimation of GFR:- i) Cockroft and Gault equation ii)Modification of Diet in Renal Disease (MDRD) study equation iii) Schwartz formula National Kidney Foundation (2002) Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. K/DOQI clinical practice guidelines. Am J Kidney Dis 39:S1–S266
- 26. Schwartz formula GFR in mls/min/m²= (Ht (cm) x coefficient) serum Cr(µmol/L) Coefficient 29 in Preterms 40 in term babies 48 in children >2yrs 62 in adolescents
- 27. Req a steady state SCr- not useful in AKI Cimetidine, TMP-SMX, interfere with SCr secretion; bilirubin intereferes with SCr assay In critically ill children, there is muscle loss and a relative malnutrition; in these cases, SCr could also indicate GFR values ↑er than the actual levels Collection of a 24-hr urine sample for measurement of CrCL, or measurement of clearance of an exogenous filtration marker, provide better estimates of GFR than prediction equations.
- 28. C) Creatinine Clearance (Cr CL) - If the effect of secretion is ignored, then all of the filtered Cr (equal to the product of the GFR and the Serum creatinine concentration [SCr]) will be excreted (equal to product of the urine creatinine concentration [UCr] and the urine flow rate). Thus: GFR x SCr = UCr x V GFR = [UCr x V] SCr This formula is called the Cr Cl and tends to exceed the true GFR by the 10 to >20% of urinary creatinine that is derived from tubular secretion
- 29. d) Serum cystatin-C Cystatin C, a LMW protein, is filtered at the glom. not reabsorbed. Is produced by all nucleated cells; its rate of production is thought to be constant, and not affected by changes in diet (unproven). Thought to be unaffected by gender, age or muscle mass. It is affected by hyper- and hypothyroidism, and has been correlated with markers of inflammation Testing is only available in a ltd. number of labs. The ser cystatin C may correlate more closely with the GFR than the SCr. Cystatin C could detect renal dysfn 1-2 days before Cr Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children Critical Care 2007, 11:R59 (doi:10.1186/cc5923)
- 30. e) β-2 microglobulin β2M is a LMW protein, short chain of HLA class I proteins. Freely filtered by the glom. and reabsorbed and catabolized by proximal tubular cells. It is not influenced by age, gender, or muscle mass. However, unlike production of cystatin C, that of β2M increases in infectious or inflammatory process, proliferative syndromes, and hepatic and autoimmune illnesses β2M also increases before Cr; some studies found β2M to be less adequate than cystatin C as a GFR marker Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children Critical Care 2007, 11:R59 (doi:10.1186/cc5923)
- 31. f)Urine Neutrophil Gelatinase- associated lipocalin (N-GAL) SCr – the main AKI biomarker used in the clinical setting – is a late marker of reduced GFR. NGAL, a ubiquitous 25 kDa protein, gen. expressed in low conc, but greatly ↑s in the presence of epithel. injury & inflammation Zapitelli et al found that uNGAL concentrations in AKI patients exhibited a 6fold ↑ in concentration that persisted frm 48 hrs before to 48 hrs after dvpt of AKI. Children with sepsis have ↑er uNGAL conc. than do those without sepsis, but the relatnshp btwn uNGAL and AKI is maintained. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study Critical Care 2007, 11:R84 (doi:10.1186/cc6089)
- 32. g) Inulin An inert polymer of fructose, doesn’t bind to plasma proteins, freely-filtered at the glom, neither reabsorbed or secreted by tubules, therefore comes closest to the “ideal” exogenous marker for GFR. Drawbacks- req. constant bladder catheterisation, constant water intake, continuous IV infusion-cumbersome, problem of residual urine/incomplete bladder emptying. Therefore currently use is ltd. to research
- 33. f) Non-radiolabelled contrast media Principle- Stable iodine-containing contrast media introduced with analysis of iodine by fluorescent activation i)Iodothalamate ii)Iohexal g) Radionuclides Radio-labelled therefore more precise, smaller amounts necessary i) Cr 51 edetic acid ii)Tc 99 Diethylenetriamine penta acteic acid (DTPA)
- 34. CKD - Stages 1 Kidney Damage with Normal or Increase GFR > 90 2 Kidney Damage with Mild Decrease GFR 60-89 3 Moderate Decrease GFR (Irrespective of kidney abn) 30-59 4 Severe Decease GFR 15-29 5 ESRD< 15 or dialysis Am J Kidney Disease 2002;39 (Suppl 1):S46-S75
- 35. Tests of Tubular Function i) N-acetyl-beta-D-glucosaminidase (NAG)- is a lysos. Enz. found in serum and urine. Urinary NAG is a proposed marker for tubular disease, especially subtle industrial poisoning, acute PN, early ATN, and early transplant rejection. ii)Long ammonium chloride test checks for RTA type I - Ammonium chloride is administered orally and a person with "RTA I" supposedly will not be able to acidify the urine as low as pH 5.4. iii) Adenosine Deaminase Binding Protein- is an enzyme from the brush borders of the proximal tubule. Like NAG, its presence in urine indicates tubular disease. iv) Urinary ALP in urine comes from the proximal tubular brush border
- 36. v)Urine β2 microglob- It appears if levels in the ser. and glom. filtrate exceed what the prox. tubule can reabsorb or if there is renal tubular disease. It is very sensitive as an indicator of the latter. vi) Urinary amino acids and maximum concentrating ability are sensitive screens for tubular damage. vii) Urine specific gravity provides very important information about tubular function and hydration. viii) FeNa- values <1% indicate prerenal azotemia; values > 2% indicate acute tubular necrosis Review: Kid. Int. 32: 635, 1987.
- 37. Radiological studies i) Renal U/S:- All patients presenting with acute or chronic kidney disease of unknown etiology should undergo ultrasonography, the modality of choice to assess possible obstructive disease. Assesses kidney size, hydronephrosis, renal cysts. ii) IV urography- in voiding disorders; renal calculi; non-glom haematuria iii) Micturating cystourethrogram (MCU)- suspected distal obstructive uropathy eg PUVs
- 38. iv) Radionuclide scanning- uses Tc 99-labelled isotopes to define renal filtration and tubular secretion. In suspected renal blood flow disruption (DMSA and DTPA) iv) CT scan- can demonstrate calculi, renal parenchymal disease v) MRI and MRA- to evaluate renal masses, detecting main renal A stenoses; Dx renal vein thrombosis
- 39. DTPA
- 42. Renal biopsy Indications i)Unexplained AKI/CKD ii)Acute nephritic syndrome iii)Unexplained proteinuria/haematuria iv)Prognostication/to plan for Mx eg in Lupus nephritis, Wegener’s, Good pasture’s v)Suspected allograft rejection
- 43. Relative Contraindications i) Solitary/ectopic kidney (except graft) ii)Horse shoe kidney iii)Uncorrected bleeding disorders iv)Severe uncontrolled hypertension v)UnRxd renal infection vi)Renal neoplasm vii)Hydronephrosis viii)ESRD ix)Congen anomalies eg ADPKD x)Mulitple cysts xi)Unco-operative patient
- 44. Questions?
- 45. Summary Renal function Hx & PE Urine tests Tests for glomerular function Tests for tubular function Imaging Biopsy
- 46. THANK YOU FOR YOUR ATTENTION