Chronic Renal Failure, Proteinuria, Hematuria

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Chronic Renal Failure, Proteinuria, Hematuria

• Jeffrey T. Reisert, DO
• University of New England
• Physician Assistant Program
• 28 JAN 2010

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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)
• Jeffrey.T.Reisert_at_Hitchcock.org

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Introduction

• Two syndromes of renal failure
• Acute
• Chronic
• End stage chronic renal failure (ESRD)
• Proteinuria
• Hematuria

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Agenda

• Chronic Renal Failure (CRF)
• Pathogenesis
• Complications
• Treatment
• Proteinuria
• Evaluation and work-up
• Hematuria
• Evaluation and work-up

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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

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Chronic renal failure-Etiologies

• Most common historically was glomerulonephritis
• Now, most commonly due to
• Diabetes and
• Hypertension (nephrosclerosis)

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Uremia

• Loss of renal function with
• Azotemia (Retention of nitrogenous wastes) and
• Syndrome of anemia, malnutrition, and metabolic
  problems)

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Symptoms

• Anorexia
• Loss of appetite
• Resultant weight loss
• Nausea or vomiting
• Malaise
• Headache
• Itching

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Evaluation

• Creatinine and blood urea nitrogen follow
  disease, but not symptoms
• Creatinine clearance as covered previously

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Evaluation cont.

• Glomerular filtration rate
• gt50 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

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Metabolic effects

• Are multiple
• Covered here in no particular order

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Hypothermia

• Decrease in Na transport which is a large source
  of energy/heat production

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Impaired carbohydrate metabolism

• Pseudodiabetes
• Slower handling of glucose load due to insulin
  resistance

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Increased triglycerides

• Etiology unknown
• Possibly due to increased hepatic synthesis
• Possibly due to decreased renal clearance
• May me seen with normal total cholesterol

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Volume expansion

• CHF
• HTN
• Ascites
• Edema
• Typically slightly hyponatremic
• Can replace fluids as daily output 500cc per
  day (accounts for insensible loss)

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Hyperkalemia

• Decreased K excretion, typically if GFR lt10
  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

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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

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Hyperkalemia-Treatment

• Sodium bicarbonate
• Loop diuretic
• Insulin
• Dextrose
• Fluids (dilutes the K)
• Albuterol
• Sodium polystyrene-Ion exchange resin (PO or
  PR)-Kaexalate
• Dialysis
• Washington Manual

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Hyperuricemia

• ? Increased gout
• Treat with allopurinol

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Metabolic acidosis

• Retention of metabolic acids with resultant
  increased osmolar gap
• Contributes to hyperkalemia (EKG abnormalities)
• Treatment
• Sodium bicarbonate
• Sodium citrate
• Dialysis

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Calcium disorders

• Generally called Renal Osteodystrophies
• See diagram 271-2
• Osteomalacia and osteitis fibrosa cystica (due to
  hyperparathyroidism) both increase fracture risk

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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

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Phosphorus disorders

• Decreased phosphorus excretion (decreased
  filtration in renal failure)
• Increased secretion of PTH
• Further bone deterioration

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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)

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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 (ACEs, ARBs, spironolactone)
• Watch creatinine (ACEs and ARBs)

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Pericarditis

• Toxin induced
• Loud friction rub
• Treat with dialysis

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Anemia

• Decreased erythropoiesis
• Bone marrow toxins
• Decreased erythropoietin
• Hemolysis
• Bleeding
• Hemodilution
• Decreased red cell survival
• Formerly a HUGE problem, that affected all ESRD
  patients.however.

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Erythropoietin

• Use if Hematocrit lt 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!

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Transfusions

• Try to limit
• Erythropoietin has done so
• Monitor iron levels else hemochromatosis
• Transfusion reactions

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Other hematologic problems

• Mild thrombocytopenia
• Platelet dysfunction
• Bruising or bleeding

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Treatment of bleeding

• Desmopressin-DDAVP
• Cryoprecipitate
• Estrogen
• Transfusions
• Erythropoietin

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Infection risk (multifactorial)

• Decreased leukocyte formation (White blood cells)
• Particularly lymphocytes
• Uremia causes a reduced inflammatory response by
  all WBCs
• Decreased nutrition, glucocorticoids and other
  immune suppressants

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Neuromuscular

• Decreased concentration
• Drowsiness
• Insomnia
• Hiccups
• Cramps Twitches
• Peripheral neuropathy/Restless leg syndrome

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More severe neuromuscular

• Stupor
• Seizure
• Coma

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Gastrointestinal

• Anorexia
• N/V
• Hiccups
• Uremic fetor-Bad breath
• Mucosal irritation

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Dermatological

• Pallor
• Yellowing-Urochromes
• Uremic frost-
• White deposits on skin
• Smell like a toilet
• Bruising
• Pruritus-Often refractory to dialysis
• Dehydration/Dry

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Conclusion

• These are VERY dynamic patients
• Lots of syndromes in chronic renal failure

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Treatment CRF-General

• Na or water restriction
• Phosphate restriction-dietician
• Protein restriction-dietician
• Blood pressure control (lt120/80)
• ACE inhibitors particularly in DM
• Diuretics, alpha blockers, beta blockers
• Very important early particularly

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Protein restriction

• 0.6 g/kg
• Works best early on
• Cardboard taste?

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Transplant -vs- Dialysis

• Individual based decision
• Creatinine gt8 (Health Care Finance
  Administration)
• Creatinine clearance lt10 cc/min
• ? Living donor vs cadaver
• 3 years wait
• Ideally life expectancy of 5 years needed to be
  listed

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Dialysis

• In acute renal failure if appropriate, supportive
• Chronic to alleviate symptoms of uremia
• Contraindications
• Cancer, severe CAD, CVA

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Initiating Dialysis

• 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

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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
  sideultrafiltration
• May even do at home!

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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

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Hemodialysis complications

• Anemia
• Catheter related
• Poor flow rates
• Plugged grafts
• Infection
• Aneurysm

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Hemodialysis complications

• Disequilibrium
• Arrhythmia
• Hypotension
• Infection (Hep B must be separated, CMV, Hep C)
• Requires heparin (bleeding, thrombocytopenia)

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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)

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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

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Advantages of peritoneal dialysis

• No heparin
• Independence
• No vascular access

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Disadvantages of peritoneal dialysis

• Longer treatment times
• Cant use if adhesions or lung disease
• Peritonitis average 2 infections per year
• Catheter tunnel infections
• Malnutrition

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Other factors

• Need to be trained
• Acutely ill-hemo better
• Cost is about same---Peritoneal hemo

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Dialysis outcomes

• Hemodialysis do better
• Up to 24 per year death rates
• How long should you do it for?????

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Transplant

• Most effective means to treat CRF
• Well being
• Cost effectiveness
• Death rates in first year about 5!
• 5 rejection even in identical match

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Donors

• 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

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Major histocompatibility antigens

• Coded on Chromosome 6
• Typically must match all major antigens and ABO
  type

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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

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Immune suppression drugs-II

• 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

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Immune suppression drugs-III

• Cyclosporin
• 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

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Immune suppression drugs-IV

• Serolimus (Rapamycin)
• Older fungal macrolide

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Vaccinations

• In preparation for transplant
• Centers have protocols
• Live vaccines are a no-no due to
  immunosuppression drugs
• New zoster vaccine is live!

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Acute rejection

• Fever
• Swelling
• Pain

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Chronic rejection

• Due to nephrosclerosis
• Renal ischemia, HTN, and fibrosis all contribute

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Rejection

• Elevation in serum creatinine
• Arteriogram
• Ultrasound to r/o obstruction
• Biopsy to confirm

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Death/Outcome

• MC remains atherosclerosis
• Higher cancer risk
• Bacterial infections

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Syndromes in renal disease

• Proteinuria
• Hematuria

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Proteinuria

• Protein in the urine
• A clinical continuum of diseases
• Generally screening not recommended
• Except perhaps DM and HTN

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Proteinuria-Types

• Glomerular
• Most cases detected
• Larger proteins such as albumen (69,000 molecular
  weight)
• Tubular
• Usually lower MW proteins (lt25,000) not usually
  detected on dipstick
• Overflow
• I.e. Myeloma producing large amounts of
  immunoglobulin

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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

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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

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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

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Pathogenesis-II

• Less than 1000mg protein is common in ATN
• Injured proximal tubules and cant reabsorb
  filtered protein
• If glomerular damage, typically excrete 1000-3000
  mg/day

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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

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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)

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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

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Potential for confusion

• Blood
• Semen ?
• Great story

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Assessment-Part II

• Urinary sediment (?casts)
• Ultrasound (?PKD)
• CT
• Biopsy
• Serology

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Treatment of proteinuria

• Treat hypertension
• ACE inhibitors
• ARBS
• Protein restriction
• Treat edema (loop diuretics)
• Treat cholesterol (?statin)
• ?Anticoagulants

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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)

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Differential

• Stones
• Tumor (Bladder, kidney, prostate)
• Tuberculosis
• Trauma or exercise
• Prostatitis in men, Cystitis or urethritis in
  women
• Menstruation
• Anticoagulation

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See figure 47-3 (Harrisons textbook)
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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 gt50y/o)
• Retrograde pyelogram

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Clues

• If pyuria think infection
• Microscopic exam
• Rule out malignancy

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Glomerular diseases

• Typically need biopsies for diagnosis
• IgA Nephropathy (Most common of these)
• Hereditary nephritis
• Thin basement membrane disease

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Glomerulonephritis

• Hematuria
• Red cell casts, proteinuria
• Usually need biopsy to confirm

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Questions???

• ?

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Summary-Clinical pearls

• Look for postrenal renal failure
• Monitor electrolytes/fluid
• Know how to treat emergencies
• Know appropriate use of dialysis

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Where to get more information

• Harrisons or Cecils textbooks of internal
  medicine
• Spend some time in a dialysis center