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)
Jeffrey.T.Reisert@Hitchcock.org

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

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+ (ACEs, ARBs, spironolactone)

Watch creatinine (ACEs and ARBs)

Pericarditis
Toxin induced
Loud friction rub
Treat with dialysis

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.

Erythropoietin

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 WBCs
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

Pallor
Yellowing-Urochromes
Uremic frost White deposits on skin
Smell like a toilet

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

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
Cant 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

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

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

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

Immune suppression drugs-IV

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 cant 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 (Harrisons

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

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