 Endocrine:

-> erythropoietin
-> activation of vitamin D

 Blood pressure regulation:

-> renin/angiotensin/aldosterone
 Urinalysis: specific gravity, urine protein, blood,
urine microscopy (RBC’s, WBC’s, bacteria,
urinary casts)

 Creatinine clearance, 24 hour urine protein, 24

hour urine volume

 Blood tests: blood urea nitrogen (BUN), and

serum creatinine
 Renal agenesis

 Polycystic kidney disease

 Renal agenesis is the failure of one (unilateral) or both
kidneys (bilateral) to develop.
 Bilateral agenesis occurs in about 1 in 4,000 live births
while the incidence of unilateral is about 1 in 500.
 Males are affected more often than females in both cases.
 In unilateral agenesis, the remaining kidney often
enlarges in compensation.
 In both types, other abnormalities are commonly present
(e.g. skeletal, cardiac, GI, respiratory, CNS)
 PKD is an inherited renal disorder which is
characterized by the development of multiple
dilations of the collecting ducts.
 This disease may be inherited either as an autosomal
dominant or as an autosomal recessive disorder.
 The autosomal recessive form is usually seen in
infants whereas the dominant form is most often
seen in adults.
 The pathogenesis of these two disorders is similar
however they are distinctly different disorders
arising from different gene mutations.
 Autosomal rec. PKD
-> diagnosed in infants
-> mutation on C6
-> 1 in 5,000-40,000
-> half die soon after birth
-> 25% survive to 10 years
-> all have hepatic fibrosis
-> may die of liver complications
 Autosomal dom. PKD
-> diagnosed in 3-5th decade
-> mutation on C16 or 4
-> 1 in 500-1,000
-> 10% of dialysis patients
-> cyst: tubular epi hyperplasia
-> cysts involve entire nephron
-> other systems: CNS, heart, GI,
liver
 Acute pyelonephritis

 Chronic pyelonephritis

 Bladder infections (cystitis)

 Bacteria: E. coli (80%), Staphylococcus,
Enterobacter, Klebsiella, Proteus

 Fungal: Candida

 Parasitic: Schistosomiasis (infects 200 million

people worldwide, rare in U.S.)
 Bacterial infection of the nephron (from the blood or
from bladder) which causes widespread inflammation in
the kidney (parenchyma, pelvis and ureters). The
inflammatory response results in arterial constriction and
edema in the affected areas.
 An ascending infection commonly occurs in the distal
tubular area of the nephrons due to the high urine
specific gravity which is inhibitory to WBC’s.
 Renal scarring and subsequent chronic disease may be
prevented by rapid treatment to limit the infection.
 Chronic pyelonephritis exhibits pathological changes in the kidney
as a result of recurring infection. These changes commonly include:
small atrophic kidneys with diffuse scarring and blunting of the
calices.
 These infections are commonly ascending and are associated with
obstruction leading to urine stasis at some level
 As a consequence of the chronic infections, chronic interstitial
inflammation develops with lymphocytic and plasma cell
infiltration of the kidney tissue.
 Fibrosis of the the interstitium (including tubules) results in
decreased function of the nephron. This is one of the leading causes
of renal failure.
 Acute glomerulonephritis

 Chronic glomerulonephritis
 Inflammation of the glomeruli.

 Causes: drugs, toxins, diabetes, autoimmune

disorders, infections, vascular disorders.

 Most common cause of chronic renal disease and

renal failure.

 May be either acute or chronic in nature.

 Acute glomerulonephritis is a disorder which
presents with an acute onset of hematuria,
proteinuria, azotemia, renal sodium and water
retention and oliguria.
 RBC casts present in the urine indicate bleeding
from glomerular capillaries.
 This disorder may be initiated directly or
indirectly by infections, inflammatory processes,
diabetes and immune system disorders.
 Once the process is initiated, inflammatory cells infiltrate
the glomerular capillaries resulting in increased
permeability, with leakage of cells and protein into the
filtrate.
 Antigen-antibody complexes may activate complement
and attract more neutrophils and macrophages. Release
of lysosomal enzymes from these cells (and ROS’s)
result in damage to glomeruli resulting in a decrease in
glomerular filtration.
 Vasoactive mediators released decrease glomerular
perfusion, further inhibiting filtration.
 Chronic GN is characterized as continuous hematuria
and proteinuria leading to a slow degeneration in
glomerular and renal function.

 The continuous inflammatory state results in continuous

damage to the glomerulus by complement, lysosomal
enzymes and ROS’s.

 Chronic GN progresses to hypertension, kidney atrophy

and scarring and eventual renal failure.
 Nephrotic syndrome is a disorder caused by glomerular
disease. As a result of the disease process, increased
glomerular capillary permeability results in massive
proteinuria (>3.5 gm/day). As a result of the loss of this
protein in the urine, the patient exhibits
hypoalbuminemia, edema, hyperlipidemia and altered
immune function.
 Nephrotic syndrome is caused by a variety of glomerular
disorders including diabetic nephropathy, the most
common cause in the U.S.
 Obstructive disorders along the urinary tract interfere with the flow
of urine. These disorders may be either inherited, congenital or
acquired. Static urine is prone to infection and possibly result in
structural damage to the urinary system. The obstruction may be
acute or chronic, partial or complete.
 Obstruction may result in increased luminal pressure proximal to
obstruction as urine flows downward. This pressure may cause pain
and/or damage to the surrounding structures.
 In young children, obstruction is usually due to congenital
structural abnormalities whereas in adults, it is more often a result
of acquired conditions such as a renal stone (calculus) or a tumor.
 Calculi: Formed commonly by precipitation of
urinary salts in the renal pelvis. As a calculus moves
down the ureter, it may cause pain, obstruction
and/or result in infection.
 These calculi are informally referred to as stones and
their presence in the urinary system is called nephro-
lithiasis.
 Most stones are formed from calcium (calcium
oxalate or phosphate, ~80 of all urinary stones).
 Factors involved in stone formation include: concen-
tration of solute in urine, pH of urine and urine
volume.
 Renal cell carcinoma

 Wilm’s tumor (nephroblastoma)

 Bladder tumors
 Renal cell carcinoma makes up about 2% of all malignancies
and 85% of all renal neoplasms. It is 2-3 more common in
men than women and it’s more common in developed nations.
The five year survival rate is ~60%.
 Risk factors include: exposure to petroleum products,
asbestos, cigarette smoke, obesity, long term analgesic use,
hypertension, high protein diet, AD-PKD, long-term dialysis,
family history of RCC.
 This tumor originates in the epithelium of the PCT. It is
thought to be a result of a mutation on chromosome 3.
Hematuria and flank pain are common manifestations.
 Wilm’s tumor is the most common abdominal in
children. It is most common in 3-5 year olds. The
incidence in males and females is equal.
 Wilm’s tumor is thought to be caused by a
mutation on chromosome 11. This defect results
in abnormal growth of kidney tissue resulting in
an abdominal mass.
 Outcome is dependent upon tumor stage and
specific cell histology.
 Bladder tumors comprise ~3% of all malignant tumors.

 The risk for bladder cancer is higher for men greater than
60 years old and who smoke and/or have been
exposed to aniline dyes.

Bladder cancer is highly associated with mutations in the

p53 tumor suppressor gene.
 Acute renal failure:
- Pre-renal (decreased perfusion)
- Intra-renal (tubular necrosis)
- Post-renal (obstruction of urine flow)

 Chronic renal failure

 Acute renal failure: an abrupt decline in renal
function (<400 mL/day, oliguria). Elevated BUN
and creatinine.

 Causes: hypotension, vascular obstruction,

glomerular disease, drugs/toxins.

 May be reversible if detected and treated early.

 Chronic renal failure: the irreversible loss of
renal function over time which leads to eventual
end-stage renal failure (<10% renal function).

 Common causes: diabetes, hypertension

 Increase in BUN and creatinine as renal function

(GFR) declines below 50%.