Introduction to Clinical Diagnosis Nephrology I. David Weiner, M.D. C. Craig and Audrae Tisher Chair in Nephrology Professor of Medicine and Physiology and Functional Genomics University of Florida College of Medicine 374-6102 David.Weiner@medicine.ufl.edu www.renallectures.com
How important are the kidneys? Regulate fluid and electrolyte balance Regulate blood pressure Sodium balance Renin Regulate hematocrit Erythropoietin Filter and excrete water-soluble impurities Prevent loss of blood proteins and cells Receive more blood flow per weight than any other organ
Why do I care how well the kidneys are working? Many kidney diseases are asymptomatic at early stages Kidney disease is, in general, most responsive to treatment at early stages If a person has kidney disease, Is it getting better or worse? Are my treatments working?
How should we measure kidney function? The vulcan mind-meld approach
A better approach Kidney function parallels glomerular filtration rate (GFR)
How to measure glomerular filtration rate? Find something present in blood Freely filtered by glomerulus Small Not bound to proteins Neither reabsorbed nor secreted by renal tubules More filtration lower blood level Less filtration higher blood level
What compounds can we use to measure GFR? Creatinine Produced by muscles Easy to assay (cheap!) Completely filtered Not reabsorbed Minimal tubular secretion In renal insufficiency, relative tubular secretion increases (may be 50% of creatinine excretion rate with severe renal insufficiency)
GFR (ml/min) Relationship between creatinine and GFR 120 100 80 60 40 120 60 Excretion 40 30 Generation GFR S Excretion 24 Cr GFR S Generation Cr GFR Generation S Cr 20 20 17 15 13 12 0 0 1 2 3 4 5 6 7 8 9 10 Serum Creatinine (mg/dl)
How to interpret a serum creatinine? Need to know creatinine generation rate Impacted by sex, age and race Best MDRD Formula egfr = 186 SCr -1.154 Age -0.203 0.742 if 1.21 if African-American Result is independent of weight or height Results presented as ml/min/1.73 m 2 Assumes no major physical deformities Paralysis Amputation Generation Excretion Excretion GFR S GFR Generation S Cr Cr No, you do not need to memorize this formula!
How to interpret a serum creatinine? Next best Cockcroft-Gault formula GFR = (140 age) / (72 x SCr) 0.85 if 1.2 if African-American Barely worth using Normal lab values (0.5 1.3 mg/dl) egfr if high normal creatinine (1.3), 80 yo, Caucasian and is 45, whereas normal is 100-120! Not worth using GFR = 100/SCr No, you do not need to memorize these formulas!
What else do we use to measure GFR? Urea (BUN, blood urea nitrogen) Produced by normal protein metabolism Problems with interpretation Production increased by intestinal bleeding, glucocorticoids, increased dietary protein intake Increased tubular reabsorption with intravascular volume depletion Excretion is less than glomerular filtration Blood level becomes higher than predicted from GFR Clinically used to suggest volume depletion
What else do we use to measure GFR? Urea (BUN, blood urea nitrogen) 4 common clinical factors, other than GFR, can alter BUN Increased urea production Intestinal bleeding Glucocorticoids High protein intake Decreased excretion Intravascular volume depletion Under normal conditions, Urea production ~10x greater than creatinine production BUN ~10-fold greater than creatinine
What else do we use to measure GFR? Inulin Gold standard Assay very difficult, not available for clinical use Iothalamate Radionuclide Used for best clinical research studies
When should you be wary of the serum creatinine? Serum creatinine is changing Creatinine lags 2-3 days behind actual GFR Abnormal production rate Less muscle mass Less creatinine production Lower creatinine than expected for any level of GFR Actual GFR less than egfr
When should you be wary of the serum creatinine? Serum creatinine is changing Creatinine lags 2-3 days behind actual GFR Abnormal production rate More muscle mass More creatinine production Higher serum creatinine Actual GFR more than egfr
Other ways to estimate GFR - 24 hour urine collection The amount filtered in a time period (Rate of plasma clearance) x (plasma concentration) Cl Cr P Cr Equals The amount in the urine U Cr V Collect all urine for a given time duration, typically 24 hours. Cl Cr = (U Cr V) P Cr Accuracy depends on accuracy of timed urine collection
What do the kidneys do? Separate out: What we might want to excrete Water soluble impurities From what we never want to lose in the urine Blood proteins and cells
Proteinuria/Albuminuria Indicator of glomerular disease Proteinuria present in UTI May contribute to progression of renal disease Measurement 24 hour urine collection Random urine protein:creatinine ratio Provides relative assessment tool Reproducible in a given individual Difficult to compare two individuals
Kidneys have many other functions: Dipstick measures of renal function Specific gravity urine concentration ph acid excretion Hemoglobinuria RBC Muscle breakdown (rhabdomyolysis) Proteinuria Only measures albumin Poorly quantitative Leukocyte esterase, nitrite WBC activation
Dipstick measures of renal function Glucose diabetes mellitus Ketones DKA Starvation Atkins Diet Bilirubin hepatic dysfunction
Urine microscopy Leukocytes Infection
Urine microscopy Leukocytes Bacteria
Other nucleated cells Renal tubular epithelial cells Never present in normal urine Cell death Acute tubular necrosis (ATN)
Other nucleated cells Squamous epithelial cells Source perineum Urinalysis is USELESS if present in more than trace numbers
Non-nucleated cells RBC (hematuria) Glomerulonephritis GU tract bleeding Cancer Infection Dysmorphic Erythrocytes
Non-nucleated cells RBC (hematuria) Glomerulonephritis GU tract bleeding Cancer Infection Red cell cast Essentially diagnostic of glomerulonephritis
Some renal disease are macroscopic Ultrasound Size Small bad Normal, 10-11 cm good Enlarged -? disease Echogenicity Increased fibrosis Decreased edema and inflammation Masses
Some renal disease are macroscopic CT scan Renal cancers generally do not enhance with radiocontrast material
Some diseases affect the renal artery Examples Fibromuscular dysplasia Atherosclerosis Vasculitis Manifestations Renovascular hypertension Renal ischemia (ischemic nephropathy)
When dealing with disease, Measure, don t guess Glomerular filtration rate Urinalysis Renal imaging Renal biopsy