Altered Renal Function
Overview of Kidney Diseases
• Classified by site or cause of disease
• Organization by site:
– Prerenal
– Intrarenal (Renal)
– Postrenal
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Prerenal disease
• Results from inadequate blood flow to the
kidney
– Decreased intravascular volume
– Lesions in the renal arteries
– Hypotension
• Systemic disorders that decrease urine output
• Creatinine clearance? Plasma creatine?
BUN?
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Renal diseases
• Result from direct damage to nephron
• Glomerular disorders
• Tubulointerstitial disorders – disorders of
the medullary tubules and interstitial cells
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Postrenal diseases
• Commonly due to urinary tract obstruction
– Kidney stones
– Tumors of bladder, ureters or prostate gland
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Obstructive Disorders
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Interference with urine flow at any point
Anatomic or functional
Impedes flow proximal to blockage
Dilates urinary system
Increases risk for infection
Compromises renal function
Anatomic changes are called obstructive
uropathy
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Causes of obstruction
• Congenital malformations
• Stones
• Abdominal tumor or inflammation and
scarring
• Tumor of urinary system or prostate
• Severe pelvic organ prolapse in women
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Consequences depend on:
• Location of lesion
• Whether one or both upper urinary tracts
are involved
• Severity and completeness of blockage
• Duration of blockage
• Nature of the lesion
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Obstruction causes dilation:
• Of ureters – hydroureter
• Of renal pelvis and calyces – hydronephrosis
• Of both - ureterohydronephrosis
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There was a large renal calculus (stone) that
obstructed the calyces of the lower pole of this
kidney, leading to a focal hydronephrosis
(dilation of the collecting system). The stasis
from the obstruction and dilation led to
infection. The infection with inflammation is
characterized by the pale yellowish-tan areas
next to the dilated calyces with hyperemic
mucosal surfaces. The upper pole is normal
and shows good corticomedullary
demarcations.
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Here is a kidney with much more advanced
hydronephrosis in which there is only a thin rim of
remaining renal cortex. Such a kidney is nonfunctional and a source for ongoing infection. If this
process is unilateral, then the problem originates
from the ureteral orifice up to the pelvis. In this
case, a large "staghorn" calculus (so named
because the prominent projections of the stone into
the calyces resemble deer antlers) was present
that filled up the pelvis and calyceal system. If this
process were bilateral, then the problem would
originate in the bladder trigone or urethra (or the
prostate around the urethra) or some process
(such as a large neoplasm) that could impinge on
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both ureters
Dilation leads to:
• Enlargement and fibrosis of distal nephron
in 7 days
• Interference with distal and proximal
nephron in 14 days
• Damage to glomeruli in 28 days, also see
reduction in cortex and medulla
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• Initial tubular damage decreases the ability
to concentrate urine, causing an increase
in urine volume
• Affected kidney cannot conserve water,
sodium, or bicarb, or excrete potassium, or
hydrogen ions.
• Leads to metabolic acidosis and
dehydration.
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Recovery depends on Completeness
of blockage and duration.
Complete obstruction → damage to tubules
within hours, and irreversible damage
within 4 weeks.
• Partial recovery if removed within 56-69
days
• Partial obstruction can lead to permanent
impairment of ability to concentrate urine,
reabsorb bicarbonate, excrete ammonia,
or regulate acid-base balance.
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• Body can partially compensate if one
kidney is affected by compensatory
hypertrophy of other kidney
– No increase in number of nephrons
– Increase in size of glomerulus and
tubules
– Ability decreases with age
– Is reversible if other kidney recovers
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Relief of obstruction of partial obstruction of
both kidneys or complete obstruction of one
results in postobstructive diuresis.
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Usually mild
Restores fluid and electrolyte balance
Occasionally, can result in output of 10L/day
Can cause dehydration and electrolyte
imbalance
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Obstruction of bladder outlet or urethra
affects upper and lower tracts.
• Partial obstruction can lead to over active
bladder and urine retention
• Can back up and cause hydroureter,
hydronephrosis and impaired kidney function
• Urine can be a microbiological growth medium
– infection of obstructed kidney can cause
further damage and scarring
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Hypertension can result
• Renin-angiotensin pathway in acute
unilateral obstruction
• Due to water and sodium and urea
retention in chronic bilateral partial
obstruction
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Kidney stones or renal calculi
• Masses of crystals, protein or other
substances
• Common cause of obstruction in adults
• 2-3 % of U.S. population
• Recurrence within 10 years is 50 %
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• Influenced by age, gender, race,
geographic location, season, fluid intake,
diet and occupation.
• Seen in more men than women
• Less risk if physically active and drink
adequate water
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Type of Stone
Frequency
Calcium oxalate (or phosphate)
75%
Magnesium ammonium phosphate
(struvite, or "triple phosphate")
12%
Uric acid
6%
(Gout)
Cystine
1%
Other
6%
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Get increased concentrations of
these molecules in the urine with:
• Increased renal excretion of these
molecules
• Decreased urine volume
• Change in pH of urine
– Alkaline urine increases risk of calcium
phosphate stones
– Acid urine increases risk of uric acid stones
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Size of stone determines likelihood
it will be passed.
• < 0.5mm 50 % chance
• 1 cm almost no chance ( unless ureter
dilated by previous passage)
• Develop in renal tubules, calyces, ureter or
bladder
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Clinical manifestations
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Pain (renal colic) – can determine location
Nausea / vomiting
Chills, fever
hematuria
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Treatment
• Urinalysis and analysis of stones
• Removal by surgery/ percutaneous
lithotripsy
• Drugs to dissolve stones
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Prevention of future stones
• Treat underlying metabolic disorders
• Water intake = urine output of 2 -3 L /day
• Reduction in dietary oxalates and animal
protein for uric acid stones
• Increased dietary fiber
• Do NOT decrease calcium intake –
increases risk of stones
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Urinary Tract infections
• Bacteria most common cause
• Can also be due to viruses, fungi or
parasites
• Classified by location in system or by
complicating factors
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• Cystitis – inflammation of the bladder
– Urinary frequency
– Dysuria – painful or difficult urination
– Urgency
– Lower abdominal, lower back or suprapubic
pain
• May be uncomplicated in otherwise
healthy individual
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Incidence
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Young adult women – 0.2/month
Lifetime risk in women 50%
Young adult men prevalence < 1%
High risk groups:
– Premature infants
– Sexually active women
– Women using a diaphragm or spermicide
– Diabetics
– HIV or immunosuppressive disorders
– Obstruction of lower urinary tract
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Most UTIs are caused by:
gram negative bacteria of the intestinal
tract
Escherichia coli – 80% of all uncomplicated
infections. Can form pili allowing bacterium
to adhere to bladder epithelium
Cranberry juice decreases bacterial
adhesions by epicatechin
Staphylococcus saprophyticus 10-20%
Other entreobacter species (Klebsiella,
Proteus) remaining 5%
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Treatment
• Antibiotics
• Drink normal amounts of water, but avoid
bladder irritants, such as caffeine
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Nonbacterial cystitis
• Same symptoms but without infection
• Dysfunction of external sphincter,
urethritis, or inflammation of glands near
vagina
– Tx: antibiotics, drugs to relax urethral
sphincter, retraining of voiding habits
• Interstitial cystitis – may be due to an
autoimmune reaction, mucus deficiency or
abnormal mast cells.
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Tubulointerstitial disorders
• Acute pyelonephritis (pyelo – pelvis)
– Urinary obstruction and reflux of urine most
common risk factors
– One or both kidneys may be involved
– Most common in women
– Us. E. coli, Proteus or Pseudomonas
– Proteus, Pseudomonas are urea splitters
– Us. By ascending microorganisms, but can be
carried in blood.
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Acute pyelonephritis
• Inflammation is usually focal, affecting
pelvis, calyces, and medulla but glomeruli
not usually involved.
• Kidney is infiltrated with wbc’s – pyuria
• Healing involves scarring and atrophy of
affected tubules
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Acute pyelonephritis
• Clinical manifestations:
– Acute onset
– Fever or chills
– Flank or groin pain
– Frequency and dysuria
• May be difficult to distinguish from cystitis
– look for white cell casts
• Treatment:
– Microorganism specific antibiotics
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Chronic Pyelonephritis
• Cause is more difficult to determine
• More likely in patients with reflux or renal
stones
• Scarring can lead to impaired urineconcentrating ability, leading to chronic renal
failure
• May be due to drug toxicity from analgesics,
such as phenacetin, aspirin, acetaminophen
• Ischemia, radiation, immune-complex disease
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Chronic Pyelonephritis
• Manifestations are often minimal– Hypertension
– Frequency and Dysuria
– Flank pain
• Diagnosis
– Urinalysis
– Intravenous pyelography, ultrasound
• Treatment
– Relieve obstruction
– antibiotics
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Normal glomerulus
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Acute pyelonephritis
At high magnification, many neutrophils are seen in the tubules and interstitium
41 in
a case of acute pyelonephritis.
Ascending bacterial infection
This is an ascending bacterial infection leading to acute
pyelonephritis. Numerous PMN's are seen filling renal tubules
across the center and right of this picture.
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Chronic pyelonephritis
Both lymphocytes and plasma cells are seen at high magnification in this case
of chronic pyelonephritis. It is not uncommon to see lymphocytes accompany
just about any chronic renal disease: glomerulonephritis, nephrosclerosis,
pyelonephritis. However, the plasma cells are most characteristic for chronic 43
pyelonephritis.
Chronic pyelonephritis
The large collection of chronic inflammatory cells here is in a patient
with a history of multiple recurrent urinary tract infections. This is
chronic pyelonephritis.
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Glomerular disorders
• Due to a change or dysfunction of the
glomerular capillaries
– Changes in membrane permeability
– Change in GFR
– Protein or blood cells in the urine
– Systemic changes – hypertension;
edema; acid-base and electrolyte
imbalances
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Glomerulonephritis
• Caused by a number of factors, most
commonly abnormal immune response
– Infection
– Toxins
– Vascular diseases
– Systemic diseases (diabetes mellitus)
• Can be diffuse, focal or segmental
• Can be membranous, proliferative,
sclerotic, or crecentic
• Often divided into acute, rapidly
progressive and chronic forms.
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Acute Glomerulonephritis
• Often associated with streptococcal
infection
• Abrupt onset 7-10 days after strept throat
or skin infection (impetigo)
– Also staphylococcus or viruses
• Strept antigens deposit in glomerular
basement membrane and attract
neutrophils and macrophages, initiating
phagocytosis and release of inflammatory
mediators that damage cells on both side
of the basement membrane.
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Poststreptococcal GN
Post-streptococcal glomerulonephritis is immunologically mediated, and the
immune deposits are distributed in the capillary loops in a granular, bumpy
pattern because of the focal nature of the deposition process.
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Proliferative GN- poststretococcal
This glomerulus is hypercellular and capillary loops are poorly defined.
This is a type of proliferative glomerulonephritis known as poststreptococcal glomerulonephritis.
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Acute Glomerulonephritis
• Symptoms occur 10-21 days after infection
– Hematuria
– Proteinuria
– Decreased GFR, oliguria
– Hypertension
– Edema around eyes, feet and ankles
– Ascites or pleural effusion
• Biopsy – immune complexes and proliferation
• Most recover without significant loss of renal
function or recurrence
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Rapidly Progressive GN
• Develops over a period of days or weeks
• Primarily adults in 50’s and 60’s
• May be idiopathic or assoc. with a proliferative
disease
• By the time of diagnosis patient has renal
insufficiency
• Proliferation of cells in Bowman’s space with
crescent formation
• Progresses to renal failure in a few weeks or months
• Hematuria is common, may see proteinuria, edema
or hypertension
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RPGN
Here is another glomerulus with epithelial crescents squashing the glomerular tufts
from all sides. RPGN may be idiopathic or may result from SLE, post-infectious
GN (as in some cases of post-streptococcal GN), from various types of vasculitis,
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and from Goodpasture's syndrome.
RPGN
Seen here within the glomeruli are crescents composed of proliferating epithelial cells.
Crescentic glomerulonephritis is known as rapidly progressive glomerulonephritis
(RPGN) because this disease is very progressive. There are several causes, and in this
case is due to SLE. Note in the lower left glomerulus that the capillary loops are 53
markedly thickened (the so-called "wire loop" lesion of lupus nephritis).
RPGN
This immunofluorescence micrograph of a glomerulus demonstrates positivity with
antibody to fibrinogen. With a rapidly progressive GN, the glomerular damage is so
severe that fibrinogen leaks into Bowman's space, leading to proliferation of the 54
epithelial cells and formation of a crescent.
Goodpasture Syndrome
• Antibody formation against pulmonary and
glomerular capillary basement membranes
• Activation of complement and neutrophils
damage glomerular basement membrane
• Men 20 - 30 years of age
• Pulmonary hemorrhage and renal failure
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Goodpasture Syndrome
• Treatment must begin early or prognosis is
poor
– Anticoagulants reduce fibrin content of
crescents
– Plasmapheresis with steroids and
immunosuppression therapy
– Dialysis or transplant if kidneys fail
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Goodpasture’s syndrome
This immunofluorescence micrograph shows positivity with antibody to IgG has
a smooth, diffuse, linear pattern that is characteristic for glomerular basement
membrane antibody with Goodpasture's syndrome.
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Chronic Glomerulonephritis
• Several diseases with a progressive
course leading to chronic renal failure
• Two patterns – deposition of antigenantibody complexes, or antigens specific
for GBM.
• Complement activation and phagocyte
activity damage wall of capillary and cause
proliferation of extracellular matrix,
affecting GFR
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Chronic Glomerulonephritis
• At first see increased membrane
permeability and lose cells (hematuria) or
protein into urine (proteinuria)
• Fibrin is deposited into Bowman’s space –
crescent formation
• Renal blood flow and GFR is reduced
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Chronic Glomerulonephritis
• Clinical manifestations:
– Hematuria – smoky brown-tinged urine as
opposed to pink or red
– Proteinuria > 3-5 g/day mostly albumin
– ↓ GFR leads to fluid retention and
hypertension
• After 10 – 20 years, renal insufficiency
develops and progresses to renal failure
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Chronic Glomerulonephritis
• Treatment:
– Treat underlying disease
– Steroids do not change the course of the
disease
– Correct accompanying problems such as
volume disorders, blood pressure
– Ultimately dialysis or transplant
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Nephrotic Syndrome
• Defined as excretion of 3.5 or more grams
of protein / day
• Characteristic of glomerular injury
• Also see hypoalbuminemia, edema,
hyperlipidemia
• Loss of immunoglobulins can increase
susceptibility to infections
• Decrease in vitamin D
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Nephrotic Syndrome
• Treatment:
– Diet – normal protein, low-fat, salt restricted
– Diuretics
– Immunosuppression
– Protein supplements
– Removal of glomerular membrane toxic factor
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Membranous glomerulonephritis
Here is the light microscopic appearance of membranous glomerulonephritis in
which the capillary loops are thickened and prominent, but the cellularity is not
increased. Membranous GN is the most common cause for nephrotic syndrome in
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adults. Some cases of membranous GN can be linked to a chronic infectious
disease such as hepatitis B, a carcinoma, or SLE, but many cases are idiopathic.
Nephritic Syndrome
• Alteration of filtration leads to loss of rbc’s
• Also decreased GFR
– Decreased urine output
– Azotemia (increased nitrogenous wastes in
the blood)
– Renal tubules undergo disuse atrophy and
scarring
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Renal Failure
• Acute renal failure – abrupt decrease in renal
function
– Increase in BUN and creatinine
– Usually oliguria (output < 30 ml/hour or 400
ml/day)
– Most cases are reversible if diagnosed and treated
early
• Prerenal most common cause – failure to
restore blood volume or pressure and oxygen
can lead to acute tubular necrosis or acute
cortical necrosis
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Acute tubular necrosis
The tubular vacuolization and dilation here is a result of ethylene glycol poisoning.
This is representative of acute tubular necrosis (ATN), which has many causes.
ATN resulting from toxins usually has diffuse tubular involvement, whereas ATN
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resulting from ischemia (as in profound hypotension from cardiac failure) has
patchy tubular involvement.
Acute Renal Failure
• Intrarenal acute renal failure
– Usually due to acute tubular necrosis
• Usually caused by ischemia most often
after surgery (40 -50 %)
• Also sepsis, burns, obstetrical
complications, antibiotics, radiocontrast
media, other toxic substances
– Whatever the cause, get decreased
GFR and oliguria
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Acute Renal Failure
• Postrenal acute renal failure
– Usually due to urinary tract obstruction that
affects both kidneys
– Characterized by several hours of anuria
with flank pain, followed by polyuria
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Acute Renal Failure
• Clinical symptoms of ARF are divided into three
stages:
Stage1 Oliguria:
↓urine vol.about 25 % of normal to anuria
can last 1-3 weeks
↑BUN, plasma creatinine
↑ K+ (hyperkalemia) and electrolyte imbalance
fluid retention and edema
congestive heart failure
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Stage 2 Diuresis:
3-4 L/day of urine
Tubules still damaged, but recovering
Can lose too much Na+ and K+
May see extracellular volume depletion
Stage 3 Recovery
May take 3-12 months for plasma
creatinine to return to normal
About 30 % never regain normal kidney
function.
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Acute Renal Failure
• Treatment
– Prevention if possible
– Maintain individual’s life until renal function is
recovered
• Correct fluid and electrolyte imbalances
• Treat infections
• Maintain nutrition and cardiac function
• Remember drugs and/or medications are
not excreted!
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Chronic Renal Failure
• Progressive and irreversible loss of
nephrons
• Slow development (years)
• Alterations in salt and water balance not
apparent until renal function is less than
25% of normal.
• Common causes:
– Chronic glomerulonephritis
– Chronic pyelonephritis
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Chronic Renal Failure
• Clinical manifestations are often described using the
term uremia –symptoms due to accumulation of
toxins in plasma.
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hypertension
Anorexia
Nausea
Vomiting
Diarrhea
Weight loss
Pruritis (itching)
Edema
Anemia
Neurologic changes
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Chronic Renal Failure
• Diagnosis is by increased BUN and serum
creatinine; imaging will show small
kidneys, and can be confirmed by biopsy
• Management includes:
– Diet control – restrict proteins, potassium
– Evaluate fluid and sodium levels
– Treat with erythropoietin as needed.
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End stage kidney
The microscopic appearance of the "end stage kidney" is similar regardless of cause,
which is why a biopsy in a patient with chronic renal failure yields little useful information.
The cortex is fibrotic, the glomeruli are sclerotic, there are scattered chronic
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inflammatory cell infiltrates, and the arteries are thickened. Tubules are often dilated
filled with pink casts and give an appearance of "thyroidization."
Atrophy
There is a relatively normal kidney at the left with only a few scattered, shallow
cortical scars and one fairly large pale tan-yellow scar in the upper pole. The left
kidney is atrophic because of renal arterial occlusion. Such a situation can lead to
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hypertension (Goldblatt kidney).