Introduction to Renal Failure Introduction to Renal Failure and Acute Renal Failureand Acute Renal Failure

Jeffrey T. Reisert, DO

University of New England

Physician Assistant Program

20-27 JAN 20010

Contact InformationContact Information

Jeffrey T. Reisert, DO

Jeffrey.T.Reisert@Hitchcock.org

103 Boulder Point Rd., Suite 3

Plymouth, NH 03264

603-536-6355

603-536-6356 (fax)

Genitourinary Section-Part 1Genitourinary Section-Part 1

Male urogenital disorders/Impotence Nephrolithiasis Urinary Tract Infections

Genitourinary Section-Part 2Genitourinary Section-Part 2

Introduction to Renal Failure Acute Renal Failure Chronic Renal Failure Glomerulopathies (builds on prior topics) Tubular disorders (builds on prior topics) Hematuria Proteinuria

Introduction Introduction

Two syndromes of renal failure– Acute– Chronic

Diagnosis-2 Patterns– Clinical suspect with signs and symptoms– Found incidentally on lab screen (serum or

urine)

AgendaAgenda

General evaluation of renal failure

– Definitions Acute Renal Failure (ARF)

– Etiology

– Diagnosis/Evaluation

– Treatment Chronic Renal Failure (CRF)

– Pathogenesis

– Complications

– Treatment of the complications

Definition-Renal failureDefinition-Renal failure

Spectrum of disease with declining kidney function

Decreased glomerular filtration rate Resultant increase in nitrogenous waste

products in the blood (azotemia) Alteration in fluid an electrolytes

Definitions-Part IIDefinitions-Part II

Oliguria=Urine output (UOP) of less than 400 or 500 cc/24 hours

Anuria=No UOP Uremia

– Decreased renal function– Azotemia– Symptoms

Definitions-Part IIIDefinitions-Part III Polyuria

– Excessive or frequent urination– Excessive water intake– Medical conditions?

Diabetes insipidus (Inability to concentrate urine)

– Renal disease Hematuria-blood in urine Proteinuria-protein in urine

AssessmentAssessment

Labs– Urine– Serum

Radiographic

Assessment-Labs IAssessment-Labs I

Blood urea nitrogen-BUN Creatinine BUN/Creatinine ratio

– >40 in prerenal azotemia– <20 in intrinsic renal failure

Electrolytes– Potassium especially!

CreatinineCreatinine

Goes up quickly in ARF due to ischemia and radio contrast (complication of x-ray dye studies such as IVP, CT scans)– Peaks 3-5d after contrast– Peaks 7-10d after ischemia

Not correlative with symptoms

ElectrolytesElectrolytes

Sodium reflects volume status Potassium, phosphate, and uric acid

increase

Assessment-Labs IIAssessment-Labs II

Urine output (UOP)-Monitor I’s and O’s Urine sodium (reflects concentrating ability

of kidneys) Body weight Toxin levels (i.e.: CPK-MM fraction in

rhabdomyolysis)

Glomerular filtration rateGlomerular filtration rate

Collectively, the measure of renal function– If low, leads to azotemia– Can be estimated by serum creatinine– Affected by age, sex, weight, fluid status, and

medical condition (illnesses, nutritional status, drugs on board, etc.)

– Creatinine used as a surrogate marker as levels vary little day-to-day.

Creatinine is secreted in the proximal tubule

Assessment-Labs IIIAssessment-Labs III

Creatinine clearance– ml/min/1.73 per square meter– Reflects the glomerular filtration rate– Normal 85-125– Lower in premies– Measured or Calculated methods (next slides)

Creatinine ClearanceCreatinine Clearance

[(Urine volume (ml/min) x Urine Creatinine)Divided by Serum Creatinine] x1.73/Body Surface Area

-Involves 24 hour urine test mated with serum creatinine-Fairly accurate and easy-Once a year?

Can be measured accurately by inulin (Usually in research)…..Is filtered but not reabsorbed or secreted in the renal tubules.

Also by radionuclide markers such as I125 iothalamate or EDTA (uncommon use) because……

Creatinine Clearance EstimatesCreatinine Clearance Estimates

Cockcroft-Gault equation Men:(140-age) x (wt in kg) divided by 72 x

serum creatine For women multiply by 85% to account for

smaller muscle mass (0.85 of men’s estimate)

Use in hospitals with IV antibiotic dosing

Assessment-Labs IIIAssessment-Labs III

Fractional excretion of Na+– (Urinary Na+ x Plasma Creatinine x 100%)

divided by (Plasma Na+ x Urinary Creatinine)

AzotemiaAzotemia

Defined as excess of urea and nitrogenous compounds in blood

Due to breakdown of protein (Metabolism of carbohydrates and fats

yields water and CO2) If symptoms, use term “uremia”

Assessment-RadiographicAssessment-Radiographic

Ultrasound– Excludes obstruction– ?Small kidneys--->CRF– Advantages

Non invasive No risky contrast dye Readily available

Assessment-Radiographic IIAssessment-Radiographic II

Plain x-Ray– Flat plate (?stone)

– Pyelogram-Inject a dye, cleared through kidney

– Retrograde pyelogram-Inject dye inside urinary collection system (intravesicular, using cystoscope)

CT– Probably better but dye risk in face of rising creatinine

MRI

Assessment-Wrap upAssessment-Wrap up

Avoid contrast in ARF or CRF not on dialysis

Biopsy may be needed in ARF for intrinsic disease

Ultrasound is easy and helpful

Complications of ARFComplications of ARF

Volume overload– Decreased sodium and water excretion– Resultant weight gain, heart failure, and edema

Hyponatremia Hypocalcemia

– Paresthesias, cramps, seizures, confusion

Complications of ARF IIComplications of ARF II

Hyperkalemia, phosphatemia, magnesemia– Potassium increases 0.5mmol/l/d in uremia– Treat hyperphosphatemia with calcium or

aluminum Metabolic acidosis Hypertension (Moreso in CRF)

General treatment of ARFGeneral treatment of ARF Prevention!!! (Avoid nephrotoxins, diabetes control,

etc.) Reverse poisons (ETOH in ethylene glycol,

bicarbonate in acidosis) Restore fluid volume and electrolyte balance

(Saline/crystalloids, colloids, blood) Dialysis when needed (Acute if responsive (i.e.:

dialyzable toxin) or in CRF) Relieve obstruction (Easiest way to fix ARF!)

Acute renal failureAcute renal failure

Definitions Classifications/Types Treatment

DefinedDefined

Renal failure of recent onset (hours to days to weeks)

Typically little symptoms– Can be found on random lab test or when

suspect– If acute obstruction, symptoms (below)

ClassificationClassification

Prerenal renal failure (Renal hypoperfusion)-55%

Renal/Parenchymal/Intrinsic-45% Post renal (Obstructive)-5%

OutcomeOutcome

Usually reversible Can recover even if almost no function Nephrology opinion?

Prerenal azotemiaPrerenal azotemia

Due to renal hypoperfusion Usually reversible if restoring renal blood

flow (RBF) Parenchyma usually not damaged In severe cases, ischemia/injury

EtiologyEtiology

Hypovolemia– Fluid loss– Decreased cardiac output– Decreased systemic vascular resistance

Renal hypoperfusion– See next slides

Fluid or blood lossFluid or blood loss

Dehydration GI bleeds Burns Osmotic diuresis (i.e.: diabetes) Sequestration (i.e.: pancreatitis)

Decreased Cardiac OutputDecreased Cardiac Output

Acute MI CHF (perhaps most common among

hospital patients) Arrhythmias Pulmonary embolism (PE) Mechanical ventilator

Altered systemic vascular Altered systemic vascular resistanceresistance

Sepsis, antihypertensives, anesthetics, anaphylaxis

HypovolemiaHypovolemia

Leads to epinephrine release and subsequent vasoconstriction

Also activations of renin angiotensin system-->Vasoconstriction

Release of arginine vasopressin (AVP)

Renal hypoperfusionRenal hypoperfusion

Renal vasoconstriction due to epinephrine ACE inhibitors Cyclooxygenase inhibitors (i.e.: NSAID’s)-

Also lead to volume depletion Hyperviscosity syndromes

Hepatorenal syndromeHepatorenal syndrome

Cirrhosis leads to intrarenal vasoconstriction

Sodium retention Precipitated by bleeding, paracentesis,

diuretics, vasodilation, cyclooxygenase inhibitors

Prerenal azotemia-Prerenal azotemia-AssessmentAssessment

Symptoms– Thirst, dizzy

Signs– Low blood pressure, tachycardia, orthostasis– Low UOP

Lab evaluationLab evaluation

Urine volume Urine microscopy

– Hyaline/bland casts due to concentrated urine

Intrinsic renal failureIntrinsic renal failure

Renovascular obstruction-Large vessel disease

Glomerular or microvascular diseases

Renovascular obstructionRenovascular obstruction

Obstructed renal artery (Atherosclerosis, thrombus)

Renal vein obstruction (Thrombosis, external compression)

Glomerular diseasesGlomerular diseases

Glomerulonephritis Vasculitis Acute tubular necrosis Ischemic or nephrotoxic Interstitial nephritis Renal allograft rejection Will expand in later section

VasculitisVasculitis

Kidneys are one of several very vascular organs Hemolytic uremic syndrome Thrombotic thrombocytopenic purpura Disseminated intravascular coagulation Toxemia Accelerated HTN Lupus ?Include sickle cell disease

Acute tubular necrosisAcute tubular necrosis

Most susceptible area of the nephron to ischemia is the renal tubule

Ischemia from prerenal azotemia (Most common)– Prerenal azotemia is the most common cause of

intrinsic renal failure Toxin induced Often see casts (covered later)

IschemiaIschemia

Hypoperfusion Resultant injury or ischemia Cortical necrosis Either recover (tubules regenerate) or

develop irreversible failure

NephrotoxinsNephrotoxins

Radiocontrast (Intrarenal vasoconstriction) Aminoglycosides (Decrease GFR) Cyclosporin Chemotherapy (Cisplatin) Solvents (ethylene glycol) Others

Endogenous nephrotoxinsEndogenous nephrotoxins

Rhabdomyolysis (Due to crush, injury, ETOH)

Hemolysis (toxic to renal tubule) Uric acid (Same thing that causes gout) Myeloma (Plasma cell malignancy) Hypercalcemia (Causes renal

vasoconstriction)

Interstitial NephritisInterstitial Nephritis

Allergic (Antibiotics such as beta-lactams), NSAID’s, diuretics

Infection (Bacterial-pyelonephritis, viral-CMV, Fungus-Candidiasis)

Infiltration (Lymphoma, leukemia, sarcoidosis)

Idiopathic

Intrinsic renal failureIntrinsic renal failure

Symptoms-Often none May have history of nephrotoxin exposure Signs-Azotemia on lab testing Nephritic syndrome (Oliguria, edema,

HTN, Urine sediment)– This suggests a glomerulonephritis or vasculitis

Intrinsic renal failure-Lab Intrinsic renal failure-Lab evaluationevaluation

Microscopy– Muddy brown casts (ischemia and nephrotoxic)– Red cell casts (acute glomerular injury or

nephritis)– White cell casts (interstitial nephritis)– Eosinophilic casts (allergic nephritis)– Often no casts– Hematuria

Intrinsic renal failure-Lab Intrinsic renal failure-Lab evaluationevaluation

Proteinuria due to impaired reabsorption at the proximal tubules

Guided by etiology (i.e.: sedimentation rate if vasculitis)

Intrinsic renal failure-Intrinsic renal failure-TreatmentTreatment

Treat cause Remove insult Support, hope, and pray

ExamplesExamples

Glucocorticoids in vasculitis and allergic interstitial nephritis)

Control blood pressure

Postrenal renal failurePostrenal renal failure

Urinary outflow obstruction Single kidney or urethral obstruction--

>Anuria

Etiologies of postrenal Etiologies of postrenal azotemiaazotemia

Prostate disease Neurogenic bladder

– I.e.: spinal cord injuries Anticholinergics Blood clots Stones Tumor or other extrarenal obstruction

Postrenal signs and Postrenal signs and symptomssymptoms

Bladder distension Abdominal pain-colic Renal distension (ultrasound) History of risk factors (prostate disease,

stones, etc.)

Treatment of obstructionTreatment of obstruction

Urologist Fix plumbing May need nephrostomy tube or suprapubic

catheter placed

Miscellaneous treatment Miscellaneous treatment wrap-upwrap-up

Loop diuretics may restore diuresis Dopamine may promote sodium and water

excretion Dialysis when needed

Wrap-up II--Dialysis UseWrap-up II--Dialysis Use

?BUN > 100 Uremia Hypervolemia Hyperkalemia Acidosis Toxins

– Multiple

– Include digoxin, others

More……More……

…to come in next slide set