Transcript Chronic Renal Failure, Proteinuria, Hematuria Jeffrey T. Reisert, DO University of New England

Chronic Renal Failure,
Proteinuria, Hematuria
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
28 JAN 2010
Contact Information
Jeffrey T. Reisert, DO
Tenney Mountain Internal Medicine
103 Boulder Point Rd., Suite 3
Plymouth, NH 03264
603-536-6355
603-536-6356 (fax)
[email protected]
Introduction

Two syndromes of renal failure
– Acute
– Chronic
End stage chronic renal failure (ESRD)
 Proteinuria
 Hematuria

Agenda

Chronic Renal Failure (CRF)
– Pathogenesis
– Complications
– Treatment

Proteinuria
– Evaluation and work-up

Hematuria
– Evaluation and work-up
Definitions-Renal failure
A brief review…..
 Spectrum of disease with declining
function/Decreased glomerular filtration
rate
 Resultant increase in nitrogenous waste
products (azotemia)
 Alteration in fluid an electrolytes

Chronic renal failureEtiologies
Most common historically was
glomerulonephritis
 Now, most commonly due to:

– Diabetes and
– Hypertension (nephrosclerosis)
Uremia
Loss of renal function with:
 Azotemia (Retention of nitrogenous wastes)
and
 Syndrome of anemia, malnutrition, and
metabolic problems)

Symptoms

Anorexia
– Loss of appetite
– Resultant weight loss
Nausea or vomiting
 Malaise
 Headache
 Itching

Evaluation
Creatinine and blood urea nitrogen follow
disease, but not symptoms
 Creatinine clearance as covered previously

Evaluation cont.

Glomerular filtration rate
– >50 normal
– 35-50 usually BUN and creatinine normal
– 20-30 usually symptoms or signs of uremia
with decreased stress threshold

Altered Na+ and water exchange with
expansion of intra and extracellular volume
Metabolic effects
Are multiple
 Covered here in no particular order

Hypothermia

Decrease in Na+ transport which is a large
source of energy/heat production
Impaired carbohydrate
metabolism
“Pseudodiabetes”
 Slower handling of glucose load due to
insulin resistance

Increased triglycerides

Etiology unknown
– Possibly due to increased hepatic synthesis
– Possibly due to decreased renal clearance

May me seen with normal total cholesterol
Volume expansion
CHF
 HTN
 Ascites
 Edema
 Typically slightly hyponatremic
 Can replace fluids as daily output + 500cc
per day (accounts for insensible loss)

Hyperkalemia


Decreased K+ excretion, typically if GFR <10 cc/min
– Aldosterone effect normally causes Na+ retention at
expense of K+ which is excreted until very late
– As a result, aldosterone causes water retention (water
follows Na+) at collecting tubule
– When GFR decreases below 10cc/min, K+ increases as
aldosterone affect is blunted
Note spironolactone is and aldosterone antagonist
– Promotes diuresis
– K+ retention
– Used to treat HTN and CHF
Hyperkalemia issues
Acidosis causes efflux of K+ from
intracellular to extra cellular fluids
 ACE inhibitors, Beta-blockers,
Cyclosporine in transplant all can lead to as
well
 May lead to cardiac arrhythmias and even
death

Hyperkalemia-Treatment






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
Sodium bicarbonate
Loop diuretic
Insulin
Dextrose
Fluids (dilutes the K+)
Albuterol
Sodium polystyrene-Ion exchange resin (PO or PR)Kaexalate®
Dialysis
Washington Manual
Hyperuricemia
? Increased gout
 Treat with allopurinol

Metabolic acidosis
Retention of metabolic acids with resultant
increased osmolar gap
 Contributes to hyperkalemia (EKG
abnormalities)
 Treatment

– Sodium bicarbonate
– Sodium citrate
– Dialysis
Calcium disorders
Generally called “Renal Osteodystrophies”
 See diagram 271-2
 Osteomalacia and osteitis fibrosa cystica
(due to hyperparathyroidism) both increase
fracture risk

Calcium disorders cont.




Decreased conversion of Vitamin D to 1,25
dihydroxyvitamin D
Decrease in serum calcium
Increased parathyroid hormone (PTH) secretion
Resultant weakness of bones
– Increased fracture risk

Aluminum excess formerly used (antacids) also
contributed historically (Alternagel, others).
Caused constipation
Phosphorus disorders
Decreased phosphorus excretion (decreased
filtration in renal failure)
 Increased secretion of PTH
 Further bone deterioration

Hyperphosphatemia treatment

Decrease serum phosphate
– Restrict diet (limit proteins, avoid dairy, limit colas)
– Calcium carbonate or calcium acetate (bind phosphate)
– Possibly aluminum (Binds Phosphate, may cause
osteomalacia)
– Sevelamer (RenaGel)

Keep calcium phosphorous product (Ca++ x phos)
below 70 else solid organs/arteries/joints calcify
(calciphylaxis)
Hypertension (HTN)

Most common complication of ESRD
– Are intertwined
Most commonly due to fluid overload
 Often requires more than one
antihypertensive
 Treat as you normally would

– Watch K+ (ACE’s, ARB’s, spironolactone)
– Watch creatinine (ACE’s and ARB’s)
Pericarditis
Toxin induced
 Loud friction rub
 Treat with dialysis

Anemia

Decreased erythropoiesis
– Bone marrow toxins
– Decreased erythropoietin
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Hemolysis
Bleeding
Hemodilution
Decreased red cell survival
Formerly a HUGE problem, that affected all
ESRD patients…….however…….
Erythropoietin
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Use if Hematocrit < 30
Typically less symptoms if HCT 34-38%
Dosed 25-50 micrograms per kg tiw, given sc or
IV
Monitor iron levels
Has revolutionized treatment of ESRD patients
Medicare guidelines determine reimbursement
– ‘spensive!
Transfusions
Try to limit
 Erythropoietin has done so
 Monitor iron levels else hemochromatosis
 Transfusion reactions

Other hematologic problems
Mild thrombocytopenia
 Platelet dysfunction
 Bruising or bleeding

Treatment of bleeding
Desmopressin-DDAVP
 Cryoprecipitate
 Estrogen
 Transfusions
 Erythropoietin

Infection risk (multifactorial)

Decreased leukocyte formation (White
blood cells)
– Particularly lymphocytes
Uremia causes a reduced inflammatory
response by all WBC’s
 Decreased nutrition, glucocorticoids and
other immune suppressants

Neuromuscular
Decreased concentration
 Drowsiness
 Insomnia
 Hiccups
 Cramps Twitches
 Peripheral neuropathy/Restless leg
syndrome

More severe neuromuscular
Stupor
 Seizure
 Coma

Gastrointestinal
Anorexia
 N/V
 Hiccups
 Uremic fetor-Bad breath
 Mucosal irritation

Dermatological
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Pallor
Yellowing-Urochromes
Uremic frost– White deposits on skin
– “Smell like a toilet”
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Bruising
Pruritus-Often refractory to dialysis
Dehydration/Dry
Conclusion:
These are VERY dynamic patients
 Lots of syndromes in chronic renal failure

Treatment CRF-General
Na+ or water restriction
 Phosphate restriction-dietician
 Protein restriction-dietician
 Blood pressure control (<120/80)

– ACE inhibitors particularly in DM
– Diuretics, alpha blockers, beta blockers
– Very important early particularly
Protein restriction
0.6 g/kg
 Works best early on
 Cardboard taste?

Transplant -vs- Dialysis
Individual based decision
 Creatinine >8 (Health Care Finance
Administration)
 Creatinine clearance <10 cc/min
 ? Living donor vs cadaver

– 3+ years wait
– Ideally life expectancy of 5 years needed to be
listed
Dialysis
In acute renal failure if appropriate,
supportive
 Chronic to alleviate symptoms of uremia
 Contraindications

– Cancer, severe CAD, CVA
Initiating Dialysis
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Patient education
Begin at right time
Hemodialysis requires shunt
– AV shunt connects artery and vein (must “ripen”)
– Artificial shunts (Gore-Tex®, others)
– or IV catheter (Subclavian or Internal Jugular approach)

Peritoneal requires catheter-Can use immediately
– History of abdominal surgery and problems may
preclude its use
Hemodialysis
Diffusion across semipermeable membrane
 Uses variable concentrations of solute
(dialysate)
 300-450 cc/min of blood flow required
 9-12 hours per week
 If using negative pressure on dialysate
side=ultrafiltration
 May even do at home!

Monitor clearance
KT/ V
 Clearance x time of dialysis divided by
volume of distribution
 1-1.2 is the goal
 Check pre and post dialysis urea to calculate

Hemodialysis complications
Anemia
 Catheter related

–
–
–
–
Poor flow rates
Plugged grafts
Infection
Aneurysm
Hemodialysis complications
Disequilibrium
 Arrhythmia
 Hypotension
 Infection (Hep B must be separated, CMV,
Hep C)
 Requires heparin (bleeding,
thrombocytopenia)

Causes of death
Coronary disease (MC)
 HTN, Hyperlipidemia common
 Malnutrition
 Definitely shortens the life

– Renal failure patients often have many medical
problems to begin with
– Exception perhaps are congenital types
(polycystic kidney disease for example)
Peritoneal dialysis
Intermittent (old)
 Continuous
 Cyclic (nighttime)
 Now use longer dwell times, up to 4-6 hours
 2 litre volumes (caution pulmonary disease)
 Uses osmotic agent of dextrose

– 1.5%, 2.5%, 4.25%
Advantages of peritoneal
dialysis
No heparin
 Independence
 No vascular access

Disadvantages of peritoneal
dialysis
Longer treatment times
 Can’t use if adhesions or lung disease
 Peritonitis average 2 infections per year
 Catheter tunnel infections
 Malnutrition

Other factors
Need to be trained
 Acutely ill-hemo better
 Cost is about same---Peritoneal = hemo

Dialysis outcomes
Hemodialysis do better
 Up to 24% per year death rates
 How long should you do it for?????

Transplant

Most effective means to treat CRF
– Well being
– Cost effectiveness
Death rates in first year about 5%!
 5% rejection even in identical match

Donors
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Cadaver-In short supply, regionally
– HLA compatible
– 24-48 hour time frame to implant
Volunteer, living related donor
– Must be ABO compatible, and usually HLA compatible
– Slightly higher success than cadaver
– ?Availability
Contraindicated if cancer, infection, or ischemia
Major histocompatibility
antigens
Coded on Chromosome 6
 Typically must match all major antigens
and ABO type

Immune suppression drugs-I

Glucocorticoids (Methyl prednisolone,
prednisone)
– Initially 200-300mg per day!
– Tapered off or may continue chronically 10-15
mg/d
– Risks include diabetes, infection, GI bleed,
poor wound healing, osteoporosis, aseptic
necrosis
Immune suppression drugs-II
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
Azathioprine (Imuran)
– Inhibitor of DNA/RNA synthesis
– Decreased mitosis
– Was drug of choice for years
– 1.5-2 mg/kg/d
– Adjust to degree of renal function
– Cytopenias/Bone marrow suppression
– May be hepatotoxic
– Malignancy potential
or Mycophenolate (MMF)
– Inhibits purine synthesis (though less potent than azathioprine)
– Perhaps less toxic, though GI upset possible
Immune suppression drugs-III
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Cyclosporin
–
–
–
–
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Blocks mRNA synthesis
Decreased T cell production
No bone marrow effects
Lots of drug interactions (Calcium channel blockers,
antifungals, erythromycin, grapefruit juice)
or Tacrolimius (FK-506)
– Fungal macrolide immunosuppressant
– More potent than cyclosporine but possibly more
nephrotoxic
– May increase risk of DM
Immune suppression drugs-IV
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Serolimus (Rapamycin)
– Older fungal macrolide
Vaccinations
In preparation for transplant
 Centers have protocols
 Live vaccines are a no-no due to
immunosuppression drugs

– New zoster vaccine is live!
Acute rejection
Fever
 Swelling
 Pain

Chronic rejection
Due to nephrosclerosis
 Renal ischemia, HTN, and fibrosis all
contribute

Rejection
Elevation in serum creatinine
 Arteriogram
 Ultrasound to r/o obstruction
 Biopsy to confirm

Death/Outcome
MC remains atherosclerosis
 Higher cancer risk
 Bacterial infections

Syndromes in renal disease
Proteinuria
 Hematuria

Proteinuria
Protein in the urine
 A clinical continuum of diseases
 Generally screening not recommended

– Except perhaps DM and HTN
Proteinuria-Types

Glomerular
– Most cases detected
– Larger proteins such as albumen (69,000 molecular
weight)

Tubular
– Usually lower MW proteins (<25,000) not usually
detected on dipstick

Overflow
– I.e.: Myeloma producing large amounts of
immunoglobulin
Physiology
Typically large proteins stay in the blood,
never entering the urine side of the
glomerulus
 Small proteins can cross, but are usually
reabsorbed in the proximal tubule

Physiology-II

Normal excretion is 30-150 mg/day
– A maximum of 30mg is albumen
– The remainder are other proteins (particularly
tubular proteins---Tamm-Horsfall proteins and
also IgA, urokinase, etc.
– Accurate measurement requires 24 hour urine
collection
Pathogenesis
If endothelium of vessels is damaged, or
renal epithelium cells are damaged the
space created allows proteins to spill out
 Low albumen levels can develop with
weight loss
 Edema
 Hyperlipidemia

Pathogenesis-II

Less than 1000mg protein is common in
ATN
– Injured proximal tubules and can’t reabsorb
filtered protein

If glomerular damage, typically excrete
1000-3000 mg/day
Pathogenesis-III

Multiple myeloma
– Plasma cell tumors that secrete/ spill light chain
(Bence Jones) proteins into urine
– Often test negative on dip stick, positive on 24
hour urine
– I.e.: Must test for if you suspect
Nephrotic syndrome
Greater than 3500mg/d with:
 Hypoalbuminemia (urine loss and decreased
synthesis)
 Edema (Decreased osmotic pressure)
 Hyperlipidemia (Decreased protein
stimulates synthesis)
 Also can get hypercoagulability (Loss of
Antithrombin III, Proteins C and S)

Assessment

Dip stick-Good screen for larger proteins in
larger quantities
– Specific, but not sensitive
Microalbumen-Special dipstick to detect
small amount of protein
 Albumen to creatinine ratio (? New gold
standard)
 24 hour urine collection-Best measure

Potential for confusion
Blood
 Semen ?

– Great story……
Assessment-Part II
Urinary sediment (?casts)
 Ultrasound (?PKD)
 CT
 Biopsy
 Serology

Treatment of proteinuria
Treat hypertension
 ACE inhibitors
 ARBS
 Protein restriction
 Treat edema (loop diuretics)
 Treat cholesterol (?statin)
 ?Anticoagulants

Hematuria

Definition
– 2-5 red cells per high power field
– Dipsticks positive at 1-2 RBC/hpf

Types
– Gross (?menses)
– Microscopic (? For sediment)

Screening not recommended (for healthy
people)
Differential
Stones
 Tumor (Bladder, kidney, prostate)
 Tuberculosis
 Trauma or exercise
 Prostatitis in men, Cystitis or urethritis in
women
 Menstruation
 Anticoagulation

See figure 47-3 (Harrison’s
textbook)
Work-up


UA
Urine cytology
– First morning urine specimen
– Requires preservative
– Spin in centrifuge and look for cancer cells




Young…….IVP
Ultrasound (or CT)
Cystoscopy (yield higher if >50y/o)
Retrograde pyelogram
Clues
If pyuria think infection
 Microscopic exam
 Rule out malignancy

Glomerular diseases
Typically need biopsies for diagnosis
 IgA Nephropathy (Most common of these)
 Hereditary nephritis
 Thin basement membrane disease

Glomerulonephritis
Hematuria
 Red cell casts, proteinuria
 Usually need biopsy to confirm

Questions???

?
Summary-Clinical pearls
Look for postrenal renal failure
 Monitor electrolytes/fluid
 Know how to treat emergencies
 Know appropriate use of dialysis

Where to get more information
Harrison’s or Cecil’s textbooks of internal
medicine
 Spend some time in a dialysis center
