4 Anatomy 2 Glomerulus PCT Loop of Henle DCT Collecting system 130 to 180 liters is filtered across the glomerulus every day. 98 to 99 % of that filtrate is reabsorbed.
5 Estimations of Renal Function What do the kidneys do?How can we measure the function of the kidneys?What is the “ideal” substance to measure?What do we commonly use to measure renal function?Filter the bloodCompletely filteredNot secretedNot reabsorbed / transportedMeasure the glomeular filtration of a substance within the kidneysSerum Creatinine Concentration
6 CreatinineWater soluble breakdown product of creatine from skeletal muscle (and ingested meat, suplements).Creatinine is released into the circulation at a relatively constant rate.Creatinine is freely filtered in the glomerulus, and is not metabolized by the kidney.Approximately 15% of the urinary creatinine is secreted in the proximal tubule (in normally functioning kidney).Remember:Not all individuals will have the same amount of creatinine in their blood.Different drugs can affect the concentration of serum creatinine (without affecting a patient’s renal function).CimetidineTrimethoprimDecrease Creatinine Secretion Rise in serum level by up to 0.5 mg/dl
7 Effects on Serum Creatinine Decreased Creatinine SecretionCimetidine >> Ranitidine & FamotidineTrimethoprimInterfere with the AssayAcetoacetate (Diabetic Ketoacidosis)CefoxitinFlucytosineEnhanced Creatinine ProductionLarge meat mealCreatine containing supplementsRhabdomyolysis
8 Serum Creatinine and Renal Function Glomerular Filtration RateCockcroft-Gault MethodJelliffe MethodMDRD(140 – age) * weight (kg)72 * serum Creatinine(multiply by 0.85 for female)[98 – 0.8 * (age – 20)] * BSA1.73 * serum Creatinine(multiply by 0.9 for female)186 * sCr ^ (-1.154) * Age ^ (-0.203)Multiple by for femaleMultiply by 1.21 for African AmericanAssumes albumin = 4.0Assumes patient is ~ 1.73 m295 +/- 20 ml/min in women120 +/- 25 ml/min in men
9 Which formula should you use? Strengths & WeaknessesMDRDUnderestimates patients with normal renal functionOverestimates patients with severe renal impairment.Cockcroft-GaultUnderestimates patients at older agesOverestimates patients at younger agesAll of these formulas are best used in patient’s with stable renal function.It takes time for the serum creatinine level to accurately reflect renal function.We usually use the Modification of Diet in Renal Disease (MDRD) forumula.Levey et al. Ann Intern Med. Mar 1999.
10 What is Acute Renal Failure? Increase in sCr > 0.5 mg/dl (44 umol/l)Increase in sCr > 2-foldDecrease in GFR > 50%Decrease in GFR requiring dialysisDepends on who you talk to!
11 Classification of ARF Etiology Urine Output Pre-Renal Intrinsic Renal Post-RenalUrine OutputPolyuria > 3 liters / dayOligouria: 400 – 100 cc/dayAnuria: < 100 cc / day
12 Urinalysis Intrinsic Renal ARF usually has an abnormal urinalysis. Are there casts present?Is there proteinuria present?If hematuria is present, are the RBC’s dysmorphic?YOU SHOULD KNOW HOW TO SPIN A PATIENT’S URINE!
13 UrinalysisCollect 10 – 20 ml of freshly voided urine in a sterile specimen container.Take the sample to the laboratory.Centrifuge the specimen at 2,500 rpm for 5 minutes.Decant the supernatent.Place the specimen on a UA microscope slide.
16 Urinalysis Clinical Correlation Nephritis: “active” urinary sediment with casts, RBC’s, WBC’s.May be accompanied by HTN, proteinuria, ARF.Implies inflammation and glomerular damage.Nephrotic Syndrome: proteinuria without casts.Proteinuria (GBM defect)Edema (low albumin)HypoalbuminemiaLipid AbnormalitiesHypercoagguable State (AT III depletion)
17 Pre-Renal ARF Is the patient dry? Treatment? Etiology FENa < 1 %FEUrea < 35 %BUN / Cr ratioUrine Osm and SGUrine VolumeHeart Rate & BPPulse PressureSkin TurgorMucous MembranesThirstTreatment?EtiologyAcutely reduced renal perfusionAortic dissectionThromboembolic diseaseDrugs (NSAID, ACEI)Volume DepletionBleedingThird Spacing FluidDehydrationRelative HypotensionShockCardiac failure(Volume depletion)Urine Na * Plasma Cr * 100Plasma Na & Urine Cr
18 NSAID’s and ACE-I in the kidneys ACE-I inhibit arteriolar constrictionNSAIDInhibit PG-mediated dilatation
19 Post-Renal ARF Laboratory Evaluation Radiographic Evaluation FENa – variableUrine Osm – variableRadiographic EvaluationRenal US: hydonephrosis, hydroureter.Unilateral obstruction often does not cause rise in serum creatinine (unless patient only has a single functional kidney).Etiology of Obstruction?Foley malfunctionProstatic obstructionNeurogenic bladderPost-surgical complicationRetroperitoneal fibrosis / CABilateral Urolithiasis
20 Intrinsic Renal ARF “Active” Urine sediment implies renal involvement. Categorized based on location of injury:TubulesInterstitiumGlomerulusVesselsLess common systemic conditionsPre-eclampsiaTTP – HUSThadhani, R. et al. N Engl J Med 1996;334:
21 Acute Tubular Necrosis UrinalysisIso-osmolar (300 – 400 mOsms)Urine Na > 20FENa > 1 %“Muddy brown casts” are nonspecific, but sensitive.Urine OutputOligouria: more tubular damage, longer recovery.Non-oligouria: less tubular damage, shorter recovery time.Still carries a high mortality.For those who improve90% will do so within 3 weeks99% will do so within 6 weeksMost common cause of ARF due to intra-renal causes (~ 75%)Many causes of ATNTransient ischemic episodeToxic injury to the kidneysMyoglobinuria (Rhabdomyolysis)Heavy metalsContrast exposure
23 Tubular Necrosis: Ischemia EtiologySystemic HypotensionCardiogenic ShockDistributive Shock (sepsis)Hypovolemia (burns, trauma, blood loss).Post-Surgical AnesthesiaDistributive HypoperfusionThyroid StormHeart Failure? Hepato-Renal SyndromeTubular cells have a high metabolism (i.e. are sensitive to states of low blood flow, hypoxia, or hypotension).Continuum with pre-renal azotemia
24 Tubular Necrosis: Nephrotoxins Common Drugs:Amphotericin B toxicity is dependent on the total dose (>3 gram); can also cause an RTA.Aminoglycosides cause proximal tubule damage resulting in non-oligouric ATN.Cisplatin is directly toxic to the tubules; also causes a magnesuria and hypomagnesemia.MethotrexateRadiocontrastIVIGThadhani, R. et al. N Engl J Med 1996;334:
25 Contrast Induced Nephropathy Pathogenesis is not fully understoodRenal vasoconstriction?Direct toxic effect of contrast?Tubular injury from oxygen radicals?Patient’s at highest riskDiabetes with renal insufficiencyBaseline CKD (sCr > 1.5 mg/dl)High total dose of contrast (> 70 cc)Multiple MyelomaHypovolemia (or distributive state)Concurrent Nephrotoxic DrugsRadiocontrast agentsOsmolalityFirst generation contrast agents had very high osmolality (1500 – 1800 mosm/kg)Second generation contrast agents have lower osmolality (600 – 800 msom/kg): iohexolThird generation agents have even lower osmolality (~290 mosm/kg): iodixanolIonic versus non-ionicFirst generation were ionic compounds, newer products are non-ionic.
26 Contrast Induced Nephropathy Prevention & Treatment Don’t use contrast (MRI?)Use smallest amounts possible of non-ionic, low-osmolar contrast media.Avoid volume depletionAvoid NSAID’sSodium BicarbonateD5W + 3 amps NaHCO3/liter (~130 MEQ)Run at 3.5 cc/kg*hour (ideal body weight) for 1 hour prior to study, and 1.2 cc/kg*hour for 6 hours after exposureN-acetylcysteine (Mucomyst)600 mg PO BIDAdminister 2 doses prior to study, and 2 doses after study.
27 In Reality…ATN is commonly multifactorial – nephrotoxic drugs exposed to kidneys with decreased perfusionThadhani, R. et al. N Engl J Med 1996;334:
28 Interstitial Nephritis Antibiotic AINClassic Triad = fever, rash, eosinophilia.Presentation is acuteCommon AgentsBeta-Lactams (esp Methicillin)TMP/SMXCephalosporinsRifampinFQNSAID AINClassic triad often absentPresentation subacute, or after months of use of NSAID.Acute Interstitial NephritisSlight proteinuria+/- Renal tubular acidosis+/- Urine Eosinophils+/- RBC, WBC, and WBC CastsCaused by allergic reaction to medication / exposureChronic Interstitial NephritisChronic analgesic abuseHeavy Meatals (lead, cadmium)Sjogren’s DiseaseChronic Renal Outlet ObstructionSickle Cell AnemiaMultiple Myeloma
29 GlomerulonephritisLow ComplementRenal PresentationPIGNMPGNSystemic PresentationSLESBECryoglobulinemiaNormal ComplementANCA + RPGNIgA NephropathyAlport’s SyndromeGoodpasture’s SyndromeTTP – HUSVasculitisFirst determine patient has glomerulonephritis (not just nephrotic syndrome).If active sedimentWhat are the serum complement levels?Does the patient have systemic symptoms?Wegener’sPANIdiopathic ANCAAny of the nephritic syndromes can be considered an RPGN, if it becomes rapidly progressive!
30 Consultation…If the patient has glomerulonephritis, you should be talking to nephrology!
32 Acute Indications for Hemodialysis AEIOU:Acidosis: Which is not responsive to medical therapyElectrolytes: HyperkalemiaToxic Ingestion: Lithium, TCA, Ethylene Glycol, Methanol, Salicylates, (many others)Fluid Overload: Especially in heart failure patientsSymptomatic Uremia: Bleeding, encephalopathy, pericarditis.
33 What do you need to do as the Intern? Learn about the patient’s historyPMHx (CKD, CHF, Cirrhosis).Hospital CourseRecent Surgery?Contrast exposures?Hypoxic episode?Hypotensive episode?New drugs?LabsRepeat the P2Check a UA with micro (look at the microscope slide yourself!)Estimate proteinuria (spot protein/creatinine ratio)Is the patient making urine?Post-obstruction (foley, BPH, atonic bladder, etc)Hypovolemia or Pre-renalExamine the PatientVital signsFluid status (S3, JVD, edema)Mental Status (uremia?)Bleeding (uremia? hypovolemia?)GU Exam +/- RectalBladder scan and/or renal USWhat is the patient’s volume status?
34 Intern Evaluation, cont… What category of renal failure is present?Pre-renalIntrinsic renalPost-renalIs there an indication for acute hemodialysis?AEIOUWhat can you do to support the patient?Fluid challenge if oligouric / anuricRemove potential nephrotoxinsDose medications for patient’s GFREnsure adequate renal perfusion (BP)Electrolyte managementFluid management (especially if h/o CHF, and/or if patient is anuric!)Remember that ARF is usually not a disease in itself, but rather the final common pathway of a variety of disease states.