USEFUL PHRASES AND STRATEGIES FOR PRESENTATIONS, Summaries of English Language

Download USEFUL PHRASES AND STRATEGIES FOR PRESENTATIONS and more Summaries English Language in PDF only on Docsity! Renal Function Gary L. Horowitz, MD Beth Israel Deaconess Medical Center Boston, MA Objectives  Define Chronic Kidney Disease  List the 4 variables in the MDRD Equation  List the limitations of dipstick protein testing  Define FE(Na) Definition of CKD (Chronic Kidney Disease)  Persistent GFR < 60 ml/min/1.73 m2 and/or  Urine albumin/creatinine ratio of > 30 mg/g (>3.4 mg/mmol) 6 Not Just for Diabetics  End Stage Renal Disease – affects 99,000 people in US – costs $20 billion per year, more than the entire NIH budget  Chronic Kidney Disease: – affects 20,000,000 people in US  8,000,000 with decreased GFR  12,000,000 with proteinuria A Pertinent Example www.nkdep.nih.gov  Consider a 50 year old white woman with hypertension and diabetes.  At what serum creatinine level would she be considered to have CKD?  77% of 600 primary care physicians said: >1.5 mg/dL (>133 umol/L)  The correct answer, though, is: >1.0 mg/dL ( >88 umol/L) Creatinine  produced in proportion to muscle mass  in muscle, CK catalyzes the conversion of creatine to phosphocreatine, a high energy compound  creatinine forms spontaneously and irreversibly from creatine, at a rate of roughly 1-2% per day of the total creatine  because it is freely filtered at the glomerulus, not re-absorbed or secreted by the tubules, its concentration is relatively constant over time unless there are changes in GFR  as GFR falls, [creatinine] rises, until its concentration is high enough that the new filtered amount equals the amount formed A Specific Example  Consider a 60 kg woman  Predicted daily creatinine production is 15 mg/kg/day, or 60*15=900 mg/day  Using the Clearance Equation (C = UV/P), let’s calculate her predicted serum creatinine at GFRs of 120 and 60 ml/min: 900 900 120 = ----------------- 60 = ----------------- Pcreat * 1440 Pcreat * 1440 Pcreat = 0.5 mg/dL Pcreat = 1.0 mg/dL (44 umol/L) (88 umol/L) So A True Clearance Should Work, Right?  Yes, but don’t underestimate the difficulties: – collecting a 24-hour urine is, at a minimum, a hassle – fraught with inaccuracies, too:  GFR = Ccreat = UV/P, where UV is total creatinine excreted  over-collection  GFR overestimated  under-collection  GFR underestimated – correct way  first morning X 1 (i.e., start, or end, with first morning urine)  gross estimate 15 mg/kg for women, 20 mg/kg for men  we don’t get weight, so we can’t know whether it’s complete Cockroft-Gault Equation (140 – Age) X (Lean Body Weight [kg]) GFR = ______________________________________ 72 X Pcreatinine (mg/dL) X (0.85 if female) • As age increases, GFR decreases at same creatinine • As body weight increases, at same creatinine, GFR increases • But if body weight increase is fat (not muscle), shouldn’t use equation • This is **not** normalized to a standardized BSA •  worst case, a large overweight person whose weight we get will be deemed to have good renal function ! ! ! ! MDRD Equation (for patients > 18) GFR = 175 X (Screat)-1.154 X (Age)-0.203 X 0.742 X 1.210 if female if African-American assumes mg/dL units (divide umol/L by 88.4) Comparison Creatinine Clearance (need 24-hr urine) Cockroft-Gault (need weight & BSA) MDRD Levey AS et al. Ann Intern Med 1999;130:461-470 Cystatin C  small molecular weight protein (122 amino acids)  produced by all nucleated cells  filtered at glomerulus, not reabsorbed or secreted  appears not to vary with age, sex, muscle mass  equations for calculating eGFR exist – with and without creatinine  a lot to recommend it 20  standardization has been a problem even when the same assay is used in different labs!  an advantage of creatinine, for screening, is that physicians are routinely ordering it already (no incremental cost) Ferguson MA et al. Established and emerging markers of kidney function. Clin Chem 2012;58:680-689. Definition of CKD (Chronic Kidney Disease)  Persistent GFR < 60 ml/min/1.73 m2 and/or  Urine albumin/creatinine ratio of > 30 mg/g (>3.4 mg/mmol) www.nkdep.nih.gov 22 Proteinuria Physiology  virtually all proteins are too large to be filtered through a healthy glomerulus  once proteins do leak, there is no mechanism to reabsorb them  urine protein concentration reflects amount leaked plus water content of urine , which varies with hydration  provides rationale for reporting urine protein not simply as concentration but as 24o collection 25 [protein]u is misleading  what can happen when you rely on [protein] alone  NB: conventional chemistry assay is no better !! sample dipstick protein (estimated) dipstick mg/dL Chemistry protein mg/dL creatinine mg/dL prot/ creat ratio 1 1+ 30 38 47 0.8 2 1+ 30 46 352 0.1 3 2+ 100 86 55 1.6 4 3+ 300 279 137 2.0 5 3+ 300 358 230 1.6 26 False Negative Type 1  Bence-Jones Protein (BJP) – monoclonal free light chains – by definition, very small (23 kD) – so small, filtered by normal glomerulus (even without albuminuria!!)  not detected by dipstick method Adapted from Burtis, CA & Ashwood, ER. Tietz Fundamentals of Clinical Chemistry (4th Edition). Philadelphia: W.B Saunders, 1996, p.135. 27 Urine Protein Methods  dipstick: – method: protein error of pH indicators (c1909) – detects albumin > globulin > BJP  conventional chemistry assay: – method: denature protein, then detect resulting turbidity using spectrophometry – sensitive to all proteins, including BJP  If a sample is dipstick negative, chemistry positive, it’s probably BJP  (micro)albumin: – method: immunoassay – detects only albumin 30 Microalbumin Semantics  not a different kind of albumin – same 60 kD protein found in serum  rather, “micro” refers to small amounts – mg/L  serum protein is g/dL (10,000-fold greater)  urine protein is mg/dL (10-fold greater) 31 Microalbumin Physiology  at 60 kD, among the smallest proteins  leaks through glomerulus at earliest stage of disease, when larger proteins are not filtered  makes it an excellent early indicator of disease 32 Microalbumin: The Numbers  originally, 24o urine collections were advocated – disease threshold was 300 mg/24o  but, 24-hour urine collections are notoriously difficult and inaccurate  so, like urine protein, current recommendation is: – a random/spot urine for albumin/creatinine ratio Albumin Tina-quant @ Albumin Assay For optimal performance of the assay follow the directions given in this document for the analyzer concerned. Refer to the appropriate operator manual for analyzer-specific assay instructions. The performance of applications not validated by Roche is not warranted and must be defined by the user. Calibration Traceability: This method has been standardized against CRM 470. Roche/Hitachi 902 analyzers St 0.9% NaCl $2-6 Cas. PUC Calibration is performed with C.f.a.s. PUC via serial dilution (6-point calibration) Preparation of S1-6: NaCl solution (0.9%) Assigned value No. conversion factor Cfas. PUC 200 pL 0.0 20 pL 1440 iL 0.01370 860 pL 2 uC 0.02273 220 pL 20 uL 0.04545 110 ul 100 pL 0.47619 = 200 ul 4.00000 The calculated values for the dilution series are keyed into the analyzer. Roche/Hitachi 917/MODULAR analyzers 0.9% NaCl Cfas PUG Calibration is performed with C-f.a.s. PUC via serial dilution made Calculation ‘The analyzer automatically calculates the analyte concentration of each sample. Conversion factors: mg/L x 0.0152 = umol/L Limitations - interference’ Criterion: Recovery within + 10% of initial value. icterus: No significant interference up to an approximate conjugated bilirubin concentration of 66 mg/dL or 1128 umol/L. Hemolysis: No significant interference up ta an approximate hemoglobin concentration of 300 mg/dL or 186 pmol/L. No interference by acetone < 60 mmol/L, ascorbic acid < 5.68 mmol/L, creatinine < 44.2 mmol/L, glucose < 111 mmol/L, uric acid < 417 mmol/L. urea < 700 mmol/L and urobilinogen < 338 mmol/L. Seventeen frequently used pharmaceuticals were tested in vitro. Moai adh With the exception of the MODULAR P antigen excess check application, a high-dose hook effect may occur at albumin coneentrations above 2500_ mg/L (38.0 pmol/L). Fer diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination and other findings. Measuring range Roche/Hitachi 902 analyzers Measuring range:** 3-400 mg/L (0.046-6.08 umol/L) At higher concentrations manually dilute the sample with 0.9% NaCl (e.g 1 +1). Multiply the result by the appropriate dilution factor (e.g. 2). Roche/Hitachi 911/912/917/MODULAR analyzers Measuring range:** 3-400 mg/L (0.046-6.08 umol/L) Extended measuring range with rerun.*“* 3-3000 mall. (0.04645 6 umol/L) To eliminate the possibility of reporting falsely low results on specimens in excess of the Heidelberger limit (2500 mg/L), test these specimens with a urine dipstick and dilute appropriately before performing the assay. Multiply the result obtained by the appropriate dilution factor. 36 Microalbumin Summary  make sure you help clinicians order the right test: – for CKD screening (most sensitive), microalbumin & creatinine on random/spot urine  make sure you get the right answer: – check the package insert for your method – if appropriate (and it can’t hurt),  compare with urine total protein  run dilution on all samples, or  screen with dipstick protein Acute Kidney Injury (AKI)  Currently, we depend on increases in creatinine (or cystatin C) to detect AKI (acute kidney injury)  What if there was an AKI marker (akin to cardiac troponin) that increased before functional damage occurred? 37 Fractional Excretion Na (2)  in pre-renal AKI (low blood flow to kidneys), – FE(Na) < 1% – kidneys are reabsorbing maximal amounts of Na, to try to replete volume  in intrinsic AKI (e.g., Acute Tubular Necrosis), – FE(Na) > 2% – kidney tubules are damaged and cannot reabsorb Na  in patients taking diuretics, FE(Na) may not be reliable because diuretics increase Na excretion  FE(urea) can be helpful  FE(urea) < 35% suggests pre-renal AKI 40 41 Self-Assessment Question 1 Which of the following lab tests is used in making a diagnosis of CKD? A) serum cystatin C B) FE(Na) C) urine glucose D) urine albumin/creatinine