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Renal Disease
Victor Politi, M.D., FACP
Medical Director, SVCMC School of Allied
Health Professions, Physician Assistant
Program
Kidney Function
• The kidneys are bean-shaped organs, each about
the size of a fist.
• They are located near the middle of the back, just
below the rib cage.
• Every day, the kidneys process about 200 quarts of
blood to sift out about 2 quarts of waste products
and extra water.
• The waste and extra water become urine, which
flows to the bladder through tubes called ureters.
Kidney Function
• Blood enters the kidneys through arteries
that branch inside the kidneys into tiny
clusters of looping blood vessels.
– Each cluster is called a glomerulus, which
comes from the Greek word meaning filter.
– The plural form of the word is glomeruli.
– There are approximately 1 million glomeruli, or
filters, in each kidney.
Kidney Function
• The glomerulus is attached to the opening
of a small fluid-collecting tube called a
tubule.
• Blood is filtered in the glomerulus, and
extra water and wastes pass into the tubule
and become urine.
• Eventually, the urine drains from the
kidneys into the bladder through larger
tubes called ureters
Kidney Function
• Each glomerulus-and-tubule unit is called a
nephron.
• Each kidney is composed of about 1 million
nephrons.
• In healthy nephrons, the glomerular membrane
that separates the blood vessel from the tubule
allows waste products and extra water to pass into
the tubule while keeping blood cells and protein in
the bloodstream.
The Kidneys
• In addition to removing wastes, the kidneys
release three important hormones:
– erythropoietin or EPO, which stimulates the bone
marrow to make red blood cells
– renin, which regulates blood pressure
– the active form of vitamin D, which helps maintain
calcium for bones and for normal chemical balance in
the body
Kidney Disease
• Most kidney diseases attack the nephrons, causing
them to lose their filtering capacity.
• Damage to the nephrons may happen quickly,
often as the result of injury or poisoning. But most
kidney diseases destroy the nephrons slowly and
silently.
• Only after years or even decades will the damage
become apparent.
• Most kidney diseases attack both kidneys
simultaneously.
Common Causes of Kidney Disease
• Each year in the United States, nearly
100,000 people are diagnosed with kidney
failure
– Diabetes is the most common cause of kidney
failure, accounting for more than 40 percent of
new cases.
– Even when drugs and diet are able to control
diabetes, the disease can lead to nephropathy
and kidney failure.
Common Causes of Kidney Disease
• The two most common causes of kidney
disease are
– diabetes
– high blood pressure.
• Hereditary also plays a role
Diabetic Nephropathy
• Damage to the nephrons from unused glucose in
the blood is called diabetic nephropathy.
• Keeping blood glucose levels down can delay or
prevent diabetic nephropathy
• Overall, kidney damage rarely occurs in the first
10 years of diabetes, and usually 15 to 25 years
will pass before kidney failure occurs.
• For people who live with diabetes for more than
25 years without any signs of kidney failure, the
risk of ever developing it decreases.
High Blood Pressure
• High blood pressure (hypertension) is a major
factor in the development of kidney problems in
people with diabetes.
• Both a family history of hypertension and the
presence of hypertension appear to increase
chances of developing kidney disease.
• Hypertension also accelerates the progress of
kidney disease where it already exists.
High Blood Pressure
• High blood pressure can damage the small
blood vessels in the kidneys.
• Blood pressure medicines called
angiotensin-converting enzyme (ACE)
inhibitors and angiotensin receptor blockers
(ARBs) have been found to protect the
kidneys even more than other medicines
that lower blood pressure to similar levels.
High Blood Pressure
• The National Heart, Lung, and Blood
Institute (NHLBI), one of the National
Institutes of Health, recommends that
people with diabetes or reduced kidney
function should keep their blood pressure
below 130/80 mm Hg.
Approach to Kidney Disease
• Often discovered incidentally during routine
exam
• Or patient presents with symptoms of renal
dysfunction:
–
–
–
–
HTN
Edema
nausea
hematuria
Approach to Kidney Disease
• Evaluation of patient includes:
– time estimate of disease duration
– urinalysis
– GFR glomerular filtration rate assessment
Approach to Kidney Disease
• Diagnostic Categories
– Prerenal disease
– Postrenal disease
– Intrinsic renal disease
•
•
•
•
Glomerular
Tubular
Interstitial
Vascular
Urinalysis
•
•
•
•
“Poor man’s renal biopsy”
midstream sample or by bladder cath
urine should be examined within one hour
dipstick eval - if positive findings follow by
microscopic assessment
Urinalysis
• Dipstick measures
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–
–
–
–
–
–
–
urinary specific gravity
pH
protein
hemoglobin
glucose
ketones
bilirubin
nitrites
Urinalysis
• Microscopy searches for
– all formed elements
•
•
•
•
crystals
cells
casts
infecting organisms
• Wright’s stain can detect eosinophiluria
Urinalysis
• Bland urinary sediment common especially
in
– CRD
– prerenal disorders
– postrenal disorders
• hematuria with dysmorphic red blood cells,
red blood cell casts, and mild proteinuria is
indicative of glomerulonephritis
Urinalysis
• Red blood cells are misshapen during
passage from the capillary through the
glomerular basement membrane into the
urinary space of Bowman’s capsule
Urinalysis
• Casts are composed of Tamm-Horsfall
urinary mucoprotein in the shape of the
nephron segment where they were formed
• Heavy proteinuria and lipiduria are
consistent with the nephrotic syndrome
• pigmented granular casts and renal tubular
epithelial cells alone or in casts suggest
acute tubular necrosis
Microalbuminuria and Proteinuria
• small amounts of albumin,
microalbuminuria, is a sign of deteriorating
kidney function
• As kidney function worsens, the amount of
albumin and other proteins in the urine
increases, and the condition is called
proteinuria (generally >150-160mg/24h in
adults
• Usually glomerular in origin when >1g/d
Primary reasons for development
of Proteinuria
• Functional proteinuria - benign process
from stressors (acute illness)
• Orthostatic proteinuria
– generally in people < age 30
– diagnosed by 8-hour overnight supine urinary
protein excretion - should be < 50mg
Primary reasons for development
of Proteinuria
• Overload Proteinuria
– Bence Jones proteins (multiple myeloma)
– myoglobinuria in rhabdomyolysis
– lysozymuria in some leukemias
Proteinuria
• The most reliable way to quantify
proteinuria is a 24 hour urine collection
– a finding of >150mg/24h is abnormal and
>3.5g/24 hr is consistent with nephrotic range
proteinuria
Proteinuria
• ACE inhibitors are effective by lowering
efferent arteriolar resistance out of
proportion to afferent arteriolar resistance reducing glomerular capillary pressure and
lowering urinary protein excretion
• hyperkalemia does not occur and serum
creatinine rises less than 30%
Hematuria
• Hematuria is significant if there are more
than 3 to 5 red cells per high power field
• positive dipstick tests can be caused by
vitamin C, beets, and rhubarb, bacteria, and
myoglobin
Glomerular Filtration Rate (GFR)
Based on Creatinine Measurement
• Creatinine is a waste product in the blood
created by the normal breakdown of muscle
cells during activity.
• Healthy kidneys take creatinine out of the
blood and put it into the urine to leave the
body.
• When kidneys are not working well,
creatinine builds up in the blood.
Glomerular Filtration Rate (GFR)
Based on Creatinine Measurement
• GFR is a calculation of how efficiently the
kidneys are filtering wastes from the blood.
• A traditional GFR calculation requires an injection
into the bloodstream of a substance that is later
measured in a 24-hour urine collection.
– Recently, scientists found they could calculate GFR
without an injection or urine collection.
– The new calculation requires only a measurement of the
creatinine in a blood sample.
Glomerular Filtration Rate (GFR)
Based on Creatinine Measurement
• blood will be tested to see how many
milligrams of creatinine are in one deciliter
of blood (mg/dL).
• Creatinine levels in the blood can vary, and
each laboratory has its own normal range,
usually 0.6 to 1.2 mg/dL.
Conditions affecting BUN
independently of GFR
• Increased BUN
– Reduced effective circulating blood volume
(prerenal azotemia)
– Catabolic states
– High-protein diets
– GI bleeding
– Glucocorticoids
– Tetracycline
Conditions affecting BUN
independently of GFR
• Decreased BUN
–
–
–
–
Liver dx
Malnutrition
sickle cell anemia
SIADH
Blood Urea Nitrogen (BUN)
• A deciliter of normal blood contains 7 to 20
milligrams of urea.
• If the BUN is more than 20 mg/dL, the
kidneys may not be working at full strength.
• Other possible causes of an elevated BUN
include dehydration and heart failure.
Additional Tests for Kidney Disease
• Kidney Biopsy
• Renal Imaging – useful in detecting unusual
growths or blockages to the flow of urine
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Radionuclide studies
Ultrasound
Intravenous urography
CT
MRI
Arteriography & Venography
Prerenal Azotemia
• Most common cause of acute renal failure
• due to renal hypoperfusion
• can be immediately reversed
– with restoration of renal blood flow, renal
parenchymal damage does not occur
Prerenal Azotemia
• Decreased renal perfusion can occur in one
of three ways
– decrease in intravascular volume
– change in vascular resistance
– low cardiac output
Postrenal Azotemia
• Least common cause of acute renal failure
(5% of cases)
• occurs when urinary flow to both kidneys
obstructed
– each nephron has an elevated intraluminal
pressure causing a decrease in GFR
Postrenal Azotemia
• Causes include:
–
–
–
–
bladder dysfunction
bladder obstruction
obstruction of both ureters or renal pelvises
Men - benign prostatic hyperplasia most
common cause
– anticholinergic drugs - at risk
– less common causes - ureteral or urethral
stones/strictures, bilateral papillary necrosis
Intrinsic Renal Failure
• Intrinsic renal disorders account for 50% of
cases of acute renal failure
• Intrinsic or parenchymal dysfunction is
considered after prerenal and postrenal
causes have been excluded
Intrinsic Renal Failure
• Sites of injury –
–
–
–
tubules
interstitium
vasculature
glomeruli
Acute Tubular Necrosis
• ARF due to tubular damage - acute tubular
necrosis
• 85% of intrinsic acute renal failure
• Two major causes:
– ischemia - often preceded by prerenal azotemia
– toxin exposure
Acute Tubular Necrosis
• Exogenous nephrotoxins
– Up to 25% of hospitalized patients receiving
therapeutic levels of aminoglycosides sustain
some degree of acute tubular necrosis
– Nonoliguric renal failure typically occurs 5-10
days after exposure
– Aminoglycosides can remain in renal tissues for
up to one month
Acute Tubular Necrosis
• Exogenous nephrotoxins
– Gentamicin is the most toxic
– tobramycin the least
– Amphotericin B is typically nephrotoxic after a
dose of 2-3 g
– Vancomycin, acyclovir and several
cephalosporins have been known to cause acute
tubular necrosis
Acute Tubular Necrosis
• Exogenous nephrotoxins
– Radiographic contrast media
• Contrast media is the 3rd leading cause of new acute
renal failure in hospitalized patients
Acute Tubular Necrosis
• Endogenous Nephrotoxins
– heme-containing products, uric acid, and
paraproteins
– Myoglobinuria as a consequence of
rhabdomyolysis leads to acute tubular necrosis
– Necrotic muscle releases large amounts of
myoglobin which is freely filtered across the
glomerulus
Acute Tubular Necrosis
• Endogenous Nephrotoxins
– The myoglobin is reabsorbed by the renal
tubules, and direct damage can occur
– Rhabdomyolysis of clinical importance
commonly occurs with a serum creatine kinase
> 20,000-50,000 IU/L
Acute Tubular Necrosis
• Endogenous Nephrotoxins
– The globin moiety of myoglobin will cause the
urine dipstick to read falsely positive for
hemoglobin; the urine appears dark brown, but
no red cells are present
– With lysis of muscle cells, patients also become
hyperkalemic, hyperphosphatemic and
hyperuricemic
Acute Tubular Necrosis
– Endogenous Nephrotoxins
• Mainstay of treatment - hydration and diuresis as
well as alkalinization of the urine
• Massive intravascular hemolysis is seen in
transfusion reactions an in certain hemolytic
anemias
• Hyperuricemia can occur in the setting of rapid cell
turnover and lysis
– chemotherapy for germ cell neoplasms and leukemias and
lymphomas are the primary causes
Acute Tubular Necrosis
• Endogenous Nephrotoxins
– Bence Jones protein seen in conjunction with
multiple myeloma can cause direct tubular
toxicity and tubular obstruction
Interstitial Nephritis
• Accounts of 10-15% of cases of intrinsic
renal failure
• An interstitial inflammatory response with
edema and possible tubular cell damage is
the typical pathological finding
• T lymphocytes can cause direct cytotoxicity
or release lymphokines that recruit
monocytes and inflammatory cells
Interstitial Nephritis
• Drugs account for over 70% of cases
• Also occurs in infectious diseases or
immunologic disorders or idiopathic
• Most common drugs - penicillins and
cephalosporins, sulfonamides, and
sulfonamide containing diuretics, NSAIDs,
rifampin, phenytoin, allopurinol
Interstitial Nephritis
• Infectious causes - streptococcal infections,
leptospirosis, CMV, histoplasmosis, Rocky
mountain spotted fever
Glomerular Diseases
• Many diseases affect kidney function by
attacking the glomeruli, the tiny units within
the kidney where blood is cleaned.
• Glomerular diseases include many
conditions with a variety of genetic and
environmental causes, but they fall into two
major categories:
– Glomerulonephritis
– Glomerulosclerosis
symptoms of glomerular disease
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•
•
•
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proteinuria
hematuria
reduced glomerular filtration rate
hypoproteinemia
edema
Diagnosis
•
•
•
•
Urinalysis
Blood tests
Ultrasound
Kidney biopsy
Glomerulonephritis
• describes the inflammation of the
membrane tissue in the kidney that serves as
a filter, separating wastes and extra fluid
from the blood.
Glomerulosclerosis
• describes the scarring or hardening of the
tiny blood vessels within the kidney.
Glomerular disease
• Glomerular diseases damage the glomeruli, letting
protein and sometimes red blood cells leak into the
urine.
• Sometimes a glomerular disease also interferes
with the clearance of waste products by the
kidney, so they begin to build up in the blood.
• Furthermore, loss of blood proteins like albumin
in the urine can result in a fall in their level in the
bloodstream.
Causes
• A number of different diseases can result in
glomerular disease.
– direct result of infection or drug toxic to the kidneys
– may result from a disease that affects the entire body,
like diabetes or lupus.
• Many different kinds of diseases can cause
swelling or scarring of the nephron or glomerulus.
• Sometimes glomerular disease is idiopathic.
Glomerular disease
• In normal blood, albumin acts like a sponge,
drawing extra fluid from the body into the
bloodstream, where it remains until the
kidneys remove it.
• But when albumin leaks into the urine, the
blood loses its capacity to absorb extra fluid
from the body.
– Fluid can accumulate outside the circulatory
system in the face, hands, feet, or ankles and
cause swelling.
Glomerulonephritis Causes:
Autoimmune Diseases
• When the body's immune system functions
properly, it creates protein-like substances called
antibodies and immunoglobulins to protect the
body against invading organisms.
• In an autoimmune disease, the immune system
creates autoantibodies, which are antibodies or
immunoglobulins that attack the body itself.
• Autoimmune diseases may be systemic and affect
many parts of the body, or they may affect only
specific organs or regions.
Glomerulonephritis Causes:
Autoimmune Diseases
• Systemic lupus erythematosus (SLE)
– affects many parts of the body: primarily the
skin and joints, but also the kidneys.
– women are more likely to develop SLE than
men Lupus nephritis is the name given to the
kidney disease caused by SLE, and it occurs
when autoantibodies form or are deposited in
the glomeruli, causing inflammation.
Glomerulonephritis Causes:
Autoimmune Diseases
• Goodpasture's syndrome
– involves an autoantibody that specifically
targets the kidneys and the lungs
– Often, the first indication that patients have the
autoantibody is when they cough up blood
– Lung damage in Goodpasture's syndrome is
usually superficial compared with progressive
and permanent damage to the kidneys
Glomerulonephritis Causes:
Autoimmune Diseases
• Goodpasture’s Syndrome
– rare condition that affects mostly young men
but also occurs in women, children, and older
adults
– Treatments include immunosuppressive drugs
and plasmapheresis to remove autoantibodies
Glomerulonephritis Causes:
Autoimmune Diseases
• IgA nephropathy
– form of glomerular disease that results when
immunoglobulin A (IgA) forms deposits in the
glomeruli, where it creates inflammation.
Glomerulonephritis Causes:
Autoimmune Diseases
• IgA nephropathy
– was not recognized as a cause of glomerular
disease until the late 1960s, when sophisticated
biopsy techniques were developed that could
identify IgA deposits in kidney tissue.
Glomerulonephritis Causes:
Autoimmune Diseases
• IgA nephropathy
– most common symptom hematuria
– but often a silent disease that may go
undetected for many years
– the most common cause of primary
glomerulonephritis- not caused by systemic
disease
Glomerulonephritis Causes:
Autoimmune Diseases
• IgA nephropathy
• affects men more than women
• found in all age groups
– young people rarely display signs of kidney
failure because it takes several years for disease
to progress to stage where it causes detectable
complications
Glomerulonephritis Causes:
Autoimmune Diseases
• IgA nephropathy
– Researchers funded by the National Institute of
Diabetes and Digestive and Kidney Diseases
(NIDDK) are trying to discover why these
deposits in the glomeruli are formed and
whether dietary supplements of fish oil can
inhibit IgA-induced inflammation and scarring
in the kidney.
Glomerulonephritis Causes:
Autoimmune Diseases
• Hereditary Nephritis--Alport Syndrome
– primary indicator of Alport syndrome is a
family history of chronic glomerular disease,
although it may also involve hearing or vision
impairment.
– Affects both men and women, but men are
more likely to experience chronic renal failure
and sensory loss
Glomerulonephritis Causes:
Autoimmune Diseases
• Hereditary Nephritis--Alport Syndrome
– Men with Alport syndrome usually first show evidence
of renal insufficiency while in their twenties and reach
ESRD by age 40.
– Women rarely have significant renal impairment, and
hearing loss may be so slight that it can be detected
only through testing.
– Usually men can pass the disease only to their
daughters.
– Women can transmit the disease to either their sons or
their daughters.
Glomerulonephritis Causes:
Autoimmune Diseases
• Infection-related Glomerular Disease
• Glomerular disease sometimes develops
rapidly after an infection in other parts of
the body.
Glomerulonephritis Causes:
Autoimmune Diseases
• Acute post-streptococcal
glomerulonephritis (PSGN)
– can occur after an episode of strep throat or, in
rare cases, impetigo.
– The Streptococcus bacteria do not attack the
kidney directly, but an infection may stimulate
the immune system to overproduce antibodies,
which are circulated in the blood and finally
deposited in the glomeruli, causing damage.
Glomerulonephritis Causes:
Autoimmune Diseases
• Acute post-streptococcal
glomerulonephritis (PSGN)
– sudden symptoms of edema,oliguria, and
hematuria
– Tests will show large amounts of proteinuria
and elevated levels of creatinine and urea
nitrogen in the blood, thus indicating reduced
kidney function.
– High blood pressure frequently accompanies
reduced kidney function in this disease.
Glomerulonephritis Causes:
Autoimmune Diseases
• Acute post-streptococcal
glomerulonephritis (PSGN)
– most common in children between the ages of 3
and 7, although it can strike at any age
– most often affects boys
– lasts only a brief time and usually allows the
kidneys to recover
– Rarely - kidney damage may be permanent,
requiring dialysis or transplantation to replace
renal function
Glomerulonephritis Causes:
Autoimmune Diseases
• Bacterial endocarditis
– infection of the tissues inside the heart, is also
associated with subsequent glomerular disease.
– Researchers are not sure whether the renal
lesions that form after a heart infection are
caused entirely by the immune response or
whether some other disease mechanism
contributes to kidney damage.
Glomerulonephritis Causes:
Autoimmune Diseases
• Bacterial endocarditis
– Treating the heart infection is the most effective
way of minimizing kidney damage. Chronic
renal failure can result from endocarditis, but is
not inevitable.
Glomerulonephritis Causes:
Autoimmune Diseases
• HIV
– can also cause glomerular disease.
– Between 5 and 10% of people with HIV
experience kidney failure, even before
developing full-blown AIDS.
Glomerulonephritis Causes:
Autoimmune Diseases
• HIV-associated nephropathy usually begins
with heavy proteinuria and progresses
rapidly (within a year of detection) to
ESRD.
Sclerotic Diseases
Sclerotic Diseases
• Glomerulosclerosis is scarring (sclerosis)
of the glomeruli.
• In several sclerotic conditions, a systemic
disease like lupus or diabetes is responsible.
• Glomerulosclerosis is caused by the
activation of glomerular cells to produce
scar material.
Focal segmental glomerulosclerosis
(FSGS)
• Focal segmental glomerulosclerosis
(FSGS) describes scarring in scattered
regions of the kidney, typically limited to
one part of the glomerulus and to a minority
of glomeruli in the affected region.
Focal segmental glomerulosclerosis
(FSGS)
• FSGS may result from a systemic disorder
or it may be idiopathic
• Proteinuria is the most common symptom
of FSGS
• (proteinuria is associated with several other
kidney conditions so a diagnosis of FSGS
cannot be made on the basis of proteinuria
alone)
Focal segmental glomerulosclerosis
(FSGS)
• Biopsy may confirm the presence of
glomerular scarring if the tissue is taken
from the affected section of the kidney.
• But finding the affected section is a matter
of chance, especially early in the disease
process, when lesions may be scattered.
Focal segmental glomerulosclerosis
(FSGS)
• Confirming a diagnosis of FSGS may
require repeat kidney biopsies.
• Arriving at a diagnosis of idiopathic FSGS
requires the identification of focal scarring
and the elimination of possible systemic
causes such as diabetes or an immune
response to infection.
Focal segmental glomerulosclerosis
(FSGS)
• Since idiopathic FSGS is, by definition, of
unknown cause, it is difficult to treat.
• No universal remedy has been found, and
most patients with FSGS progress to ESRD
over 5 to 20 years.
• Some patients with an aggressive form of
FSGS reach ESRD in 2 to 3 years.
Focal segmental glomerulosclerosis
(FSGS)
• Treatments involving steroids or other
immunosuppressive drugs appear to help
some patients by decreasing proteinuria and
improving kidney function.
– But these treatments are beneficial to only a
minority of those in whom they are tried, and
some patients experience even poorer kidney
function as a result.
Focal segmental glomerulosclerosis
(FSGS)
• ACE inhibitors and ARBs may also be used
in FSGS to decrease proteinuria.
• Treatment should focus on controlling blood
pressure and blood cholesterol levels,
factors that may contribute to kidney
scarring.
Nephrotic Syndrome
• Nephrotic syndrome is a condition marked
by proteinuria; low levels of protein in the
blood; swelling, especially around the eyes,
feet, and hands; and high cholesterol.
• Nephrotic syndrome results from damage to
the kidneys' glomeruli
Nephrotic Syndrome
• Nephrotic syndrome can occur with many
diseases, including the kidney diseases
caused by diabetes mellitus, but some
causes are unknown.
• Prevention of nephrotic syndrome relies on
controlling these diseases.
Nephrotic Syndrome
• Treatment of nephrotic syndrome focuses
on identifying the underlying cause if
possible and reducing high cholesterol,
blood pressure, and protein in urine through
diet, medications, or both.
• ACE inhibitors also protect the kidneys by
reducing proteinuria.
Nephrotic Syndrome
• Nephrotic syndrome may go away once the
underlying cause, if known, has been
treated.
• In children, 80% of cases of nephrotic
syndrome are caused by minimal change
disease, which can be successfully treated
with prednisone.
Nephrotic Syndrome
• In adults, most of the time the underlying
cause is a kidney disease such as
membranous nephropathy or focal
segmental glomerulonephritis, and these
diseases often persist even with treatment
Diabetic nephropathy
• Diabetic nephropathy is the leading cause of
glomerular disease and of ESRD in the United
States.
• Kidney disease is one of several problems caused
by elevated levels of blood glucose, the central
feature of diabetes.
• In addition to scarring the kidney, elevated glucose
levels appear to increase the speed of blood flow
into the kidney, putting a strain on the filtering
glomeruli and raising blood pressure.
Diabetic nephropathy
• Diabetic nephropathy usually takes many
years to develop.
• People with diabetes can slow down
damage to their kidneys by controlling their
blood glucose through healthy eating with
moderate protein intake, physical activity,
and medications.
Diabetic nephropathy
• blood pressure control- at a level below
130/85 mm Hg
• Blood pressure medications
– angiotensin-converting enzyme (ACE)
inhibitors and angiotensin receptor blockers
(ARBs) -particularly effective at minimizing
kidney damage
– frequently prescribed to control blood pressure
in patients with diabetes and in patients with
many forms of kidney disease
Membranous nephropathy
• also called membranous glomerulopathy
• the second most common cause of the
nephrotic syndrome (proteinuria, edema,
high cholesterol) in U.S. adults after
diabetic nephropathy
Membranous nephropathy
• Diagnosis of membranous nephropathy
requires a kidney biopsy, which reveals
unusual deposits of immunoglobulin G and
complement C3, substances created by the
body's immune system
Membranous nephropathy
• 75% of cases are idiopathic
• 25% of cases are the result of other diseases
like systemic lupus erythematosus, hepatitis
B or C infection, or some forms of cancer
Membranous nephropathy
• Drug therapies involving penicillamine,
gold, or captopril have also been associated
with membranous nephropathy
• About 20 to 40 % of patients with
membranous nephropathy progress, usually
over decades, to ESRD, but most patients
experience either complete remission or
continued symptoms without progressive
kidney failure
Membranous nephropathy
• ACE inhibitors and ARBs are generally used to
reduce proteinuria.
• Additional medication to control high blood
pressure and edema is frequently required.
• Some patients benefit from steroids, but this
treatment does not work for everyone.
• Additional immunosuppressive medications are
helpful for some patients with progressive disease.
Minimal change disease (MCD)
• Diagnosis given when a patient has the
nephrotic syndrome and the kidney biopsy
reveals little or no change to the structure of
glomeruli or surrounding tissues when
examined by a light microscope.
• Tiny drops of a fatty substance called a lipid
may be present, but no scarring has taken
place within the kidney.
Minimal change disease (MCD)
• MCD may occur at any age, but it is most
common in childhood.
• A small percentage of patients with
idiopathic nephrotic syndrome do not
respond to steroid therapy.
Minimal change disease (MCD)
• Treatment
–
–
–
–
low-sodium diet
diuretic to control edema
steroids to reduce proteinuria
ACE inhibitors and ARBs have also been used to
reduce proteinuria in patients with steroid-resistant
MCD.
– These patients may respond to larger doses of steroids,
more prolonged use of steroids, or steroids in
combination with immunosuppressant drugs, such as
chlorambucil, cyclophosphamide, or cyclosporine
RTA
• Renal tubular acidosis (RTA) is a disease
that occurs when the kidneys fail to excrete
acids into the urine, which causes a person's
blood to remain too acidic.
• Without proper treatment, chronic acidity of
the blood leads to growth retardation,
kidney stones, bone disease, and
progressive renal failure.
Types of RTA
•
•
•
•
Type I
Type II
Type III
Type IV
RTA – Type I
• Type 1 is also called classic distal RTA.
"Distal," which means distant, refers to the
point in the urine-forming tube where the
defect occurs.
• It is relatively distant from the point where
fluid from the blood enters the tiny tube (or
tubule) that collects fluid and wastes to
form urine.
RTA-Type I
• This disorder may be inherited as a primary
disorder or may be one symptom of a
disease that affects many parts of the body.
• Classic distal RTA is a complication of
diseases that affect many organ systems
(systemic diseases), like the autoimmune
disorders Sjögren's syndrome and lupus.
RTA-Type I
• Other diseases and conditions associated
with distal RTA include:
– hyperparathyroidism, a hereditary form of
deafness, analgesic nephropathy, rejection of a
transplanted kidney, renal medullary cystic
disease, obstructive uropathy, and chronic
urinary tract infections.
RTA-Type I
• A major consequence of classic distal RTA
is low blood-potassium.
• The level drops if the kidneys excrete
potassium into urine instead of returning it
to the blood supply.
• Since potassium helps regulate nerve and
muscle health and heart rate, low levels can
cause extreme weakness, cardiac
arrhythmias, paralysis, and even death.
RTA-Type I
• Untreated distal RTA causes growth
retardation in children and progressive renal
and bone disease in adults.
• Restoring normal growth and preventing
kidney stones, another common problem in
this disorder, are the major goals of therapy.
RTA-Type I
• If acidosis is corrected with sodium bicarbonate or
sodium citrate, then low blood-potassium, salt
depletion, and calcium leakage into urine will be
corrected.
• Alkali therapy also helps decrease the
development of kidney stones.
• Potassium supplements are rarely needed except in
infants, since alkali therapy prevents the kidney
from excreting potassium into the urine.
• Type 2 is called proximal RTA. The word
"proximal," which means near, indicates
that the defect is closer to the point where
fluid and wastes from the blood enter the
tubule.
RTA- Type II
• This form of RTA occurs most frequently in
children as part of a disorder called
Fanconi's syndrome.
• The symptoms of Fanconi's syndrome
include high levels of glucose, amino acids,
citrate, and phosphate in the urine, as well
as vitamin D deficiency and low bloodpotassium.
RTA- Type II
• Proximal RTA can also result from inherited
disorders that disrupt the body's normal
breakdown and use of nutrients.
– Examples include the rare disease cystinosis (in
which cystine crystals are deposited in bones
and other tissues), hereditary fructose
intolerance, and Wilson's disease.
RTA- Type II
• Proximal RTA also occurs in patients treated with
ifosfamide, a drug used in chemotherapy.
• A few older drugs--such as acetazolamide or
outdated tetracycline--can also cause proximal
RTA.
• In adults, proximal RTA may complicate diseases
like multiple myeloma, or it may occur in people
who experience chronic rejection of a transplanted
kidney.
RTA- Type II
• When possible, identifying and correcting the
underlying causes are important steps in treating
the acquired forms of proximal RTA.
• The diagnosis is based on the chemical analysis of
blood and urine samples.
• Children with this disorder would likely receive
large doses of oral alkali, such as sodium
bicarbonate or potassium citrate, to treat acidosis
and prevent bone disorders, kidney stones, and
growth failure.
RTA- Type II
• Correcting acidosis and low potassium
levels restores normal growth patterns,
allowing bone to mature while preventing
further renal disease.
• Vitamin D supplements may also be needed
to help prevent bone problems.
RTA- Type III
• Type 3 is rarely used as a classification
today because it is now thought to be a
combination of type 1 and type 2.
RTA- Type IV
• Type 4 RTA is caused by another defect in the
distal tubule, but it is different from classic distal
RTA and proximal RTA because it results in high
levels of potassium in the blood instead of low
levels.
• Either low potassium (hypokalemia) or high
potassium (hyperkalemia) can be a problem
because potassium is important in regulating heart
rate.
RTA- Type IV
• It occurs when blood levels of the hormone
aldosterone are low or when the kidneys do
not respond to it.
• Aldosterone directs the kidneys to regulate
the levels of sodium, potassium, and
chloride in the blood.
• Type 4 RTA is distinguished by a high
blood-potassium level.
RTA- Type IV
• Hyperkalemic distal RTA may result from
sickle cell disease, urinary tract obstruction,
lupus, amyloidosis, or transplantation.
RTA- Type IV
• Aldosterone's action may be impeded by drugs, including
– diuretics such as spironolactone or eplerenone
– ACE inhibitors and angiotensin receptor blockers (ARBs)
– trimethoprim
– heparin
– pentamidine
– NSAIDs
– some immunosuppressive drugs
RTA- Type IV
• To treat type 4 RTA successfully, patients may
require alkaline agents to correct acidosis as well
as medication to lower the potassium in their
blood.
• If treated early, most people with RTA will not
develop permanent kidney failure.
• Therefore, the goal is early recognition and
adequate therapy, which will need to be
maintained and monitored throughout the patient's
lifetime.
Amyloidosis and Kidney Disease
• In recent years, researchers have discovered that
different kinds of proteins can form amyloid
deposits and have identified several types of
amyloidosis.
• Two of these types are closely related to kidney
disease.
– primary amyloidosis, abnormal protein production
occurs as a first step and can lead to kidney disease
– Dialysis-related amyloidosis (DRA), on the other hand,
is a result of kidney disease
Amyloidosis and Kidney Disease
• One common sign of kidney amyloidosis is
the presence of abnormally high levels of
protein in the urine, a condition known as
proteinuria.
Amyloidosis and Kidney Disease
• No effective treatment has been found to
reverse the effects of amyloidosis.
• Combination drug therapy with melphalan
(cancer drug) and prednisone may improve
organ function and survival rates by
interrupting the growth of the abnormal
cells that produce amyloid protein.
Inherited and Congenital Kidney
Diseases
• Some kidney diseases result from hereditary
factors.
• Polycystic kidney disease (PKD), for
example, is a genetic disorder in which
many cysts grow in the kidneys.
• PKD cysts can slowly replace much of the
mass of the kidneys, reducing kidney
function and leading to kidney failure.
Inherited and Congenital Kidney
Diseases
• Some kidney problems may show up when a child
is still developing in the womb.
– Examples include autosomal recessive PKD, a rare
form of PKD, and other developmental problems that
interfere with the normal formation of the nephrons.
• The signs of kidney disease in children vary. A
child may grow unusually slowly, may vomit
often, or may have back or side pain.
• Some kidney diseases may be "silent" for months
or even years.
Inherited and Congenital Kidney
Diseases
• The first sign of a kidney problem may be
high blood pressure, anemia, or blood or
protein in the child's urine.
• Further tests include additional blood/ urine
tests, radiology studies or biopsy
Inherited and Congenital Kidney
Diseases
• Some hereditary kidney diseases may not be
detected until adulthood.
• The most common form of PKD was once called
"adult PKD" because the symptoms of high blood
pressure and renal failure usually do not occur
until patients are in their twenties or thirties.
• With advances in diagnostic imaging technology,
cysts in children and adolescents are usually
detected before any symptoms appear.
How do kidneys fail?
• Many factors that influence the speed of
kidney failure are not completely
understood.
• Researchers are still studying how protein
in the diet and cholesterol levels in the
blood affect kidney function.
Acute Renal Failure
• Acute renal failure is worsening of renal
failure over hours to days
• Acute renal failure results in the retention of
nitrogenous wastes (urea nitrogen) and
creatinine in the blood - called azotemia
Acute Renal Failure
• Some kidney problems happen quickly, like an
accident that injures the kidneys.
– Losing a lot of blood can cause sudden kidney failure.
– Some drugs or poisons can make the kidneys stop
working.
• These sudden drops in kidney function are called
acute renal failure (ARF).
• ARF may lead to permanent loss of kidney
function. But if the kidneys are not seriously
damaged, acute renal failure may be reversed.
Chronic Renal Failure
• Most kidney problems, however, happen
slowly. “Silent" kidney disease may go on
for years.
• Gradual loss of kidney function (months to
years) is called chronic kidney disease
(CKD) or chronic renal insufficiency/failure
(CRF).
Chronic Renal Failure
• Some forms of CRF can be controlled or
slowed down
– For example, diabetic nephropathy can be
delayed by tightly controlling blood glucose
levels and using ACE inhibitors and ARBs to
reduce proteinuria and control blood pressure.
Chronic Renal Failure
• CRF cannot be cured.
• Partial loss of renal function means that
some portion of the patient's nephrons have
been scarred, and scarred nephrons cannot
be repaired.
• In most cases, CRF leads to ESRD.
Chronic or Acute ?
• Differentiating between the two types of
renal disease (Acute or Chronic) is
important for diagnosis, treatment and
outcome.
Chronic or Acute ?
• Oliguria is unusual in Chronic renal
insufficiency
• Anemia (from low renal erythropoietin
production) is rare in the initial period of
acute renal failure
• Small kidneys are most consistent with
chronic renal failure
• Normal - Large kidneys are seen in both
ESRD
• Complete and irreversible kidney failure is
called end-stage renal disease, or ESRD.
• If the kidneys stop working completely, the
body fills with extra water and waste
products. This condition is called uremia.
Uremia
• Untreated uremia may lead to seizures or
coma and will ultimately result in death.
• If the kidneys stop working completely,
dialysis or kidney transplant are the only
options
Dialysis
• There are two major forms of dialysis
– Hemodialysis
– Peritoneal dialysis
Hemodialysis
• Hemodialysis is the most common method
used to treat advanced and permanent
kidney failure
• Became a practical treatment for kidney
failure in the 1960s
Peritoneal Dialysis
• In the 1980s, PD first became a practical
and widespread treatment for kidney failure
• Types of PD
– Continuous Ambulatory Peritoneal Dialysis
(CAPD)
– Continuous Cycler-Assisted Peritoneal Dialysis
(CCPD)
– Nocturnal Intermittent Peritoneal Dialysis
(NIPD)
Hemodialysis
• In hemodialysis, blood is sent through a
machine that filters away waste products.
• The clean blood is returned to the body.
• Hemodialysis is usually performed at a dialysis
center three times per week for 3 to 4 hours.
Peritoneal Dialysis
• In peritoneal dialysis, fluid is put into the abdomen. This
fluid, called dialysate, captures the waste products from the
blood.
• After a few hours, the dialysate containing the body's
wastes is drained away.
• Then, a fresh bag of dialysate is dripped into the abdomen.
• Patients can perform peritoneal dialysis themselves.
• Patients using continuous ambulatory peritoneal dialysis
(CAPD), the most common form of peritoneal dialysis,
change dialysate four times a day
Questions