CHAPTER 8 RENAL DISEASE

GLOMERULAR DISEASES
DISORDER ETIOLOGY CLINICAL COURSE PRIMARY URINE ANALYSIS OTHER SIGNIFICANT FINDINGS
Acute - Deposition of immune complexes - History of infection with Group - Hematuria dysmorphic red cells - + Anti -Streptolysin O (ASO)
Glomerulonephritis with their corresponding antibodies A beta - hemolytic - Proteinuria - + antideoxyribonuclease-B
(AGN) on the glomerular basement Streptococcus (S. pyogenes) - Hyaline and Granular antibody [anti-DNase B])
membrane that contain M protein - Granular Casts - Increased BUN
- Presents with fever, Edema, - WBCs
Hypertension, oliguria and
hematuria RBC casts are a hallmark
- Rapid onset of hematuria and characteristic of acute
edema; permanent renal damage glomerulonephritis.
seldom occurs
Rapidly Progressive - Often a complication of immune - Rapid onset with progressive - Macroscopic hematuria - Increase BUN
(Crescentic) systemic disorder - Systemic Lupus renal failure - Red cell cast - Creatinine
Glomerulonephritis Erythematosus (SLE) - Possible progression to end- - Proteinuria - eGFR
- Cresentic formations with stage renal failure
macrophages in the basement
membrane
- Deposition of immune complexes
from systemic immune disorders on
the glomerular membrane

Goodpasture’s - Attachment of antiglomerular - Follows viral infection - Macroscopic hematuria - (+) Antiglomerular basement
syndrome basement membrane - Complains of hemoptysis and - Proteinuria membrane antibody
(autoantibody), followed by dyspnea followed by hematuria - RBC casts
complement activation producing
capillary destruction
- Attachment of a cytotoxic antibody
formed during viral respiratory
infections to glomerular and alveolar
basement membranes
- Also directed to the alveolar
basement membrane (lung)
Wegener - A.k.a GRANULOMATOSIS WITH - Pulmonary symptoms, including - Hematuria - (+) Anti - neutrophilic
Granulomatosis POLYANGIITIS hemoptysis, develop first, - Proteinuria cytoplasmic antibodies
- Granuloma - producing inflammation followed by renal involvement - RBC casts (ANCA)
of the small vessels (granulomatous and possible progression to end- - Increased BUN and creatinine
vasculitis) primarily of the kidney and stage renal failure
respiratory system
- Antineutrophilic cytoplasmic auto-
antibody binds to neutrophils in
vascular walls producing damage to
small vessels in the lungs and

glomerulus
Henoch-Schönlein - Purpura disease occurs primarily in
purpura children after upper respiratory
infections
- A decrease in platelets disrupts
vascular integrity
IgA nephropathy - Immune complexes with IgA are
(Berger’s Disease) deposited on the glomerular
membrane
- MOST COMMON CAUSE OF
GLOMERULONEPHRITIS
Membranous - Pronounced thickening of
glomerulonephritis glomerular basement membrane
following deposition of IgG
- Associated with - SLE, Sjogrens
syndrome, Syphilis, Hepatitis B,
Gold and mercury treatments,
malignancy
Membranoproliferative - Cellular proliferation affecting the
glomerulonephritis capillary walls or the glomerular
(MPGN) basement membrane, possibly
immune mediated
Marked by 2 alterations
- Type 1 - increased cellularity in the
subendothelial cells of the mesangium
(interstitial area of Bowman’s
capsule)
- Type 2 - dense deposits in the
basement membrane
- Type 3 - both subepithelial and
subendothelial deposits
Chronic - Marked decrease in renal function
glomerulonephritis resulting from glomerular damage
(CGN) precipitated by other renal disorders
CHAPTER 8 RENAL DISEASE
- Respiratory - blood in sputum - Macroscopic hematuria - Stool occult blood
- Gastrointestinal symptom - - Proteinuria
blood on stool - RBC casts
- Appearance of red patches on
the skin
- Renal involvement is most
serious
- Initial appearance of purpura
followed by blood in sputum
and stools and eventual renal
involvement
- Most frequently seen in children - Macroscopic or microscopic - Increased serum IgA
and young adults hematuria
- Episodes of macroscopic
hematuria following infection or
strenuous exercise
- Disease progresses slowly with - Microscopic hematuria - Antinuclear antibody
possible reemission; tendency - Proteinuria - Hepatitis B surface antigen
for thrombosis - Fluorescent treponemal
antibody-absorption test (FTA-
ABS)
- Appears to be an association - Hematuria - Decreased Serum complement
with autoimmune disorders, - Proteinuria levels
infections and malignancies
- Many patients are children, and
disease has poor prognosis
- Slow progression to chronic
glomerulonephritis (CGN) or
nephrotic syndrome (NS)
- Noticeable decrease in renal - Hematuria - Increased BUN
function progression to renal - Proteinuria - Serum creatinine
failure - Glucosuria - eGFR
- Cellular and granular casts - Electrolytes
- Waxy and broad casts
 CHAPTER 8 RENAL DISEASE
The presence of broad casts is often
seen in chronic glomerulonephritis
that progresses to ESRD.
Minimal change - A.k.a Lipid nephrosis or nil disease - Occur primarily in children - Heavy proteinuria - Serum albumin
disease (MCD) - Disruption of podocytes following allergic reactions - Transient hematuria - Cholesterol
- Dysfunction of T-cell immunity and immunization and - Fat droplets - Triglycerides
(Nephrotic) - Most common cause of nephrotic possession of Human
syndrome in children Leukocyte Antigen B12 (HLA
- B12)
- Frequent complete remission
following corticosteroid
treatment
- Prognosis generally good
Focal segmental - Damage podocytes; affects only - Symptoms may be similar to the - Moderate to heavy - Drugs of abuse
glomerulosclerosis certain numbers and areas of nephritic syndrome and minimal Proteinuria - HIV tests
(FSGS) glomeruli - May resemble nephrotic - Macroscopic or microscopic
- Immune deposits, primarily IgM syndrome (NS) or minimal hematuria
(Nephrotic) and C3 change disease (MCD)
- Seen in association with abuse of
heroin and analgesics, hepatitis and
with Acquired Immune Deficiency
Syndrome
- Disruption of podocytes in certain
areas of glomeruli associated with
heroin and analgesic abuse and with
HIV and hepatitis viruses
Nephrotic syndrome - Disruption of the electrical charge of - Acute onset following systemic - Heavy proteinuria (>3.5 - Low Serum albumin
(NS) the podocytes resulting in massive shock g/day) - High Cholesterol
loss of ions, protein and lipids - Gradual progression from other - Microscopic hematuria - High Triglycerides
glomerular disorders then renal - Renal tubular cells
failure - Oval fat bodies
- Fat droplets
- Fatty and waxy casts
Alport syndrome - Genetic disorder showing lamellated - Slow progression to nephrotic - Microalbuminuria - Genetic testing
and thinning glomerular basement syndrome (NS) and end-stage - Blood glucose
membrane renal disease

TUBULAR DISORDERS
DISORDER ETIOLOGY CLINICAL COURSE PRIMARY URINE ANALYSIS OTHER SIGNIFICANT FINDINGS
Acute tubular - Damage to renal tubular cells caused - Acute onset of renal dysfunction - Microscopic hematuria - Hemoglobin
necrosis (ATN) by ischemia or toxic agents usually resolved when - Proteinuria - Hematocrit
underlying cause is corrected - Renal tubular epithelial (RTE) - Cardiac enzymes
 CHAPTER 8 RENAL DISEASE
- Disorders causing ischemic ATN cells
include shock, trauma (such as - RTE cell casts
crushing injuries), and surgical - Hyaline, granular, waxy, broad
procedures. casts

RTE cell casts and the presence of

RTE cells in the urine
sediment are characteristic for
ATN.

Fanconi syndrome - Inherited in association with cystinosis - Generalized defect in renal - Glucosuria - Serum and urine electrolytes
and Hartnup disease or acquired tubular reabsorption requiring - Possible cystine crystals - Amino acid chromatography
through exposure to toxic agents supportive therapy
Uromodulin- - Inherited defect in the production of - Continual monitoring of renal - RTE cells - Increased Serum uric acid
associated kidney normal uromodulin by the renal function for progression to renal
disease tubules and increased uric acid failure and possible kidney
causing gout transplantation
Uromodulin is a
glycoprotein and is
the only protein
produced by the
kidney—in the
proximal and distal
convoluted tubules.
Diabetic nephropathy - A.k.a as Kimmelstiel-Wilson disease
- Currently the most common cause of end-stage renal disease
- Damage to the glomerular membrane occur as a result of glomerular membrane thickening, increased proliferation of mesangial cells and increased deposition
of cellular and noncellular material within the glomerular matrix resulting in accumulation of solid substances around the capillary tufts
- This is believed to be associated with deposition of glycosylated proteins resulting from poorly controlled blood glucose levels
- The vascular structure of the glomerulus also develops sclerosis
Nephrogenic diabetes - Inherited defect of tubular response to - Requires supportive therapy to - Low specific gravity - ADH testing
insipidus (DI) ADH or acquired from medications prevent dehydration - Polyuria
Renal glycosuria - Inherited autosomal recessive trait - Benign disorder - Glucosuria - Blood glucose
- Failure to reabsorb substances from
the glomerular filtrate

INTERSTITIAL DISORDERS
DISORDER ETIOLOGY CLINICAL COURSE PRIMARY URINE ANALYSIS OTHER SIGNIFICANT FINDINGS
Cystitis - Ascending bacterial infection of the - Acute onset of urinary frequency - Leukocyturia - Urine culture
bladder and burning; resolved with - Bacteriuria
antibiotics - Microscopic hematuria
- Mild proteinuria
- Increased pH
 CHAPTER 8 RENAL DISEASE

The absence of pathological casts

differentiates cystitis from
pyelonephritis.
Acute pyelonephritis - Infection of the renal tubules and - Acute onset of urinary - Leukocyturia - Urine culture
interstitium related to interference of frequency, burning, and lower - Bacteriuria
urine flow to the bladder, reflux of back pain; resolved with - WBC casts
urine from the bladder, and untreated antibiotics - Bacterial casts
cystitis - Microscopic hematuria
- Proteinuria

Chronic - Recurrent infection of the renal - Frequently diagnosed in - Leukocyturia - Urine culture
pyelonephritis tubules and interstitium caused by children; requires correction of - Bacteriuria - BUN
structural abnormalities affecting the the underlying structural defect - WBC casts - Creatinine
flow of urine - Bacterial casts - eGFR
- Congenital urinary structural - Granular, waxy,broad casts
defects producing reflux nephropathy - Hematuria
are the most frequent cause of chronic - Proteinuria
pyelonephritis
Acute interstitial - Allergic inflammation of the renal - Acute onset of renal dysfunction - Oliguria - Urine eosinophils
nephritis (AIN) interstitium in response to certain often accompanied by a skin - Hematuria - BUN
medications rash - Proteinuria - Creatinine
- Resolves after discontinuation of - Leukocyturia - eGFR
medication and treatment with - WBC casts
corticosteroids
The presence of eosinophil casts
and eosinophils in the urine
sediment are characteristic for
AIN.

OTHERS

RENAL FAILURE
- May be acute or chronic
- May be a gradual progression from the original disorder to chronic renal failure or end-stage renal disease
- Progression to end -stage renal disease is characterized by:
o A marked decreased in the glomerular filtration rate (less than 25 ml/min)
o Steadily rising serum BUN and creatinine values (azotemia)
o Electrolyte imbalance
o Lack of renal concentrating ability producing an isothenuric urine
o Proteinuria
o Renal glycosuria
o And a substance of granular, waxy, and broad casts, often referred to as a telescoped urine sediment
 CHAPTER 8 RENAL DISEASE

ACUTE RENAL FAILURE

- Exhibits a sudden loss of renal function and is frequently reversible
- Broad casts are often referred to as renal failure casts.

CAUSES OF RENAL FAILURE

PRERENAL RENAL POSTRENAL
- Decreased blood pressure/ - Acute glomerulonephritis - Renal calculi
cardiac output - Acute tubular necrosis - Tumors
- Hemorrhage - Acute pyelonephritis - Crystallization of ingested
- Burns - Acute interstitial nephritis substances
- Surgery
- Septicemia

RENAL LITHIASIS
- Renal calculi (kidney stone) may form in the calcyces and pelvis of the kidney, ureters, and bladder. They may be small and be passed in the urine or large and obstruct the urinary
tract.
- LITHOTRIPSY - a procedure using high - energy shock waves, can be used to break stones located in the upper urinary tract into pieces that can be passed in the urine.
- CONDITIONS FAVORING THE FORMATION OF RENAL CALCULI:
o pH
o Chemical concentration
o Urinary stasis
- PRIMARY CALCULI CONSRITUENTS
o 75 % CALCIUM OXALATE or PHOSPHATE (frequently associated with metabolic calcium and phosphate disorders and occasionally diet)
o Magnesium ammonium phosphate (frequently accompanied by urinary infections involving urea-splitting bacteria; urine pH usually > 7.0)
o Uric acid (associated with increased intake of foods with high purine content; urine pH is acidic)
o Cystine (seen in conjunction with hereditary disorders of cysteine metabolism)
- Increased crystalluira has been noted during the summer months in persons known to form renal calculi
- Analysis can be performed chemically, but examination using x-ray crystallography provides a more comprehensive analysis
- 75% of the renal calculi are composed of calcium oxalate or calcium phosphate
- Magnesium ammonium phosphate calculi often are accompanied by urinary infections involving urea-splitting bacteria
- Uric acid calculi may be associated with increased intake of foods with high purine content and with uromodulin-associated kidney disease
- Patient management techniques include maintaining the urine at a pH incompatible with crystallization of the particular chemicals, maintaining adequate hydration to lower chemical
concentration, and suggesting possible dietary restrictions.

MALIGNANCIES
- Nuclear Matrix Proteins (NMPs) - Detection of Bladder Cancer
- Also referred to as nuclear skeletal proteins and nuclear mitotic apparatus proteins
- 236 kDa proteins needed for correct mitotic spindle formation
- A number of tumor - associated NMPs has been identified, each specific for one of five tumor types (bladder, prostate, breast, colon, and bone0
 CHAPTER 8 RENAL DISEASE
- NMP22 - best studied NMP and is strongly associated with transitional cell carcinoma of the bladder
o Which functions as a nuclear mitotic apparatus protein involved with chromosomal separation during mitosis
o Amount of this protein in malignant transitional epithelial cells is 10 - 20 times that in normal cells

METABOLIC DISEASES

 OVERFLOW: Results from the disruption of a normal metabolic pathway that causes increased plasma concentrations of the nonmetabolized substances
 RENAL: Caused by malfunctions in the tubular reabsorption mechanism

OVERFLOW METABOLIC RENAL

- Phenylkeonuria - Infantile tyrosinemia - Hartnup disease
- Tyrosinemia - Melanuria - Cytinuria
- Alkaptonuria - Indicanuria
- Maple syrup urine - 5 - Hydroxyindoleacetic
disease acid
- Organic acidemias - Porphyria
- Cytinosis
- Porphyria
- Mucopolysaccharidoses
- Galctosemia
- Lesh - Nyhan disease

PHENYLALANINE - TYROSINE DISORDERS

 PHENYLKETONURIA - failure to inherit the gene for PHENYLALANINE HYDROXYLASE production
 TYROSYLURIA - deficiency in Tyrosine transaminase or p - hydroxyphenylpyruvate oxidase
 ALKAPTONURIA - Failure to inherit the gene for HOMOGENTISIC ACID OXIDASE
 MELANURIA - overproliferation of melanin producing cells (melanocytes)

 GUTHRIE TEST or GUTHRIE’s MICROBIAL INHIBITION ASSAY

o Most well -known test for PKU
o Blood from heel stick is placed on filter paper disks
o Disks are placed into the culture media incorporated with beta - 2 thienylalanine which serves as inhibitor for Bacillus subtilis
o POSITIVE RESULT: GROWTH OF THE ORGANISM

BRANCHED - CHAIN AMINO ACID DISORDERS

 MAPLE SYRUP URINE DISEASE - Accumulation of Leucine, Isoleucine & Valine in blood and urine
 ORGANIC ACIDEMIAS
o ISOVALERIC ACIDEMIA
o PROPIONIC ACIDEMIA
o METHYLMALONIC ACIDEMIA
 CHAPTER 8 RENAL DISEASE
TRYPTOPHAN DISORDERS
 INDICANURIA
o Can be due to intestinal disorders (obstruction, presence of abnormal bacteria, malabsorption syndrome)
o Rare inherited disorder that can exhibit indicanuria; HARTNUP DISEASE (blue diaper syndrome)
 ARGENTAFFINOMA - increased 5 - HIAA (hydroxyindoleacetic acid) - metabolite of serotonin

CYSTINE DISORDERS
 CYSTINURIA - defect in renal tubular transport of amino acids Cystine, Ornithine, Lysine & Arginine (COLA)
 CYSTINOSIS - inborn error of metabolism where cysteine crystals deposit in many areas of the body
 HOMOCYSTINURIA - defect in the metabolism of METHIONINE leading to increased hmocystine

MUCOPOLYSACCHARIDE DISORDERS
 Inherited disorders which results in accumulation of the incompletely metabolized polysaccharide portions in the lysosomes of connective tissues cells and their increased
excretion in urine
o HURLER - mucopolysaccharides accumulate in the cornea; skeletal structure abnormality and severe mental retardation
o HUNTER - skeletal structure abnormality and severe mental retardation
o SANFILLIPO - mental retardation only
o CTAB (cetyltrimethylammonium bromide) test will yield WHITE TURBIDITY

PURINE DISORDERS
 LESCH - NYHAN DISEASES
o There is massive excretion of uric acid crystals in the urine
o Caused by the failure to inherit gene to produce HYPOXANTHINE GUANINE PHOSPHORIBOSYL TRANSFERASE
o “ORANGE SAND” in diaper