Chapter 7: Renal Disease
- initial pulmonary symptoms: hemoptysis and dyspnea
Glomerular Disorders
> Immunologic Causes
- most common cause; immune complex deposition in the glomerular
membranes attract immune system components
- damage: cellular infiltration or proliferation; complement-mediated
> Non-Immunologic Causes
- exposure to chemicals and toxins
- disruption of electrical membrane charges
- deposition of amyloid material
- basement membrane thickening
A. Glomerulonephritis
- a sterile inflammatory process affecting the glomerulus
- associated urinalysis findings: blood, protein, and casts
- may progress from one form to another
1. Acute Poststreptococcal Glomerulonephritis
> Pathophysiology
- group A streptococcus: nephritogenic; contains M protein (anti-
phagocytic; cross-reactive) in the cell wall
- forms immune complexes with circulating antibodies that are
deposited on the glomerular membranes
- inflammatory reaction affects glomerular function
> Clinical Presentation and Prognosis
- common in children and young adults following respiratory infections
due to certain strains of group A streptococcus
- s/s: sudden onset; fever, edema (e.g. around the eyes), fatigue,
hypertension, oliguria, and hematuria
> Laboratory Findings
- urinalysis findings: marked hematuria, proteinuria, oliguria
- others: RBC casts, dysmorphic RBCs, hyaline and granular casts, WBCs
- urinalysis results normalize as glomerular damage subsides, except
microscopic hematuria (until membrane damage is repaired)
- BUN may be elevated in acute stages but eventually normalizes
- diagnosis: demonstration of positive anti-group A streptococcal
enzyme tests
2. Rapidly Progressive (Crescentic) Glomerulonephritis
> Pathophysiology
- a complication of another form of glomerulonephritis or an immune
systemic disorder (e.g. systemic lupus erythematosus)
- macrophages damage capillary walls; cells and plasma are released
into Bowman’s space
- crescentic formations: contains macrophages, fibroblasts, and
polymerized fibrin; causes permanent damage to capillary tufts
> Clinical Presentation and Prognosis
- a more serious form of acute glomerulonephritis; poorer prognosis;
often terminates in renal failure
- symptoms are initiated by immune complex deposition in the
glomerulus
> Laboratory Findings
- urinalysis findings: initially similar to acute glomerulonephritis;
becomes more abnormal as the disease progresses
- markedly elevated protein levels; very low glomerular filtration rates
- others: increased fibrin degradation products; cryoglobulins;
deposition of IgA immune complexes in the glomerulus
3. Goodpasture Syndrome
> Pathophysiology
- an autoimmune disorder: a cytotoxic autoantibody against the
glomerular and alveolar basement membranes may appear after viral
respiratory infections
- autoantibody: antiglomerular basement membrane antibody; can be
detected in patient serum
- capillary destruction: due to the attachment of the autoantibody to
the basement membrane and subsequent complement activation
> Clinical Presentation and Prognosis
- commonly progresses to chronic glomerulonephritis and end-stage
renal failure
> Laboratory Findings
- urinalysis findings: proteinuria, hematuria, RBC casts
4. Wegener Granulomatosis
> Pathophysiology
- a granuloma-producing inflammation of the small blood vessels of
the kidney and the respiratory system
- autoantibodies bind to neutrophils in the vascular walls; immune
response is initiated; granuloma formation is induced
> Clinical Presentation and Prognosis
- initial pulmonary symptoms; development of renal involvement
> Laboratory Findings
- urinalysis findings: hematuria, proteinuria, RBC casts
- others: elevated serum creatinine and BUN
- diagnosis: demonstration of antineutrophilic cytoplasmic antibody
(ANCA) in patient serum
- incubation of patient serum with ethanol- or formalin-fixed
neutrophils; examine using indirect immunofixation
- ethanol-fixed: antibodies form a perinuclear pattern (p-ANCA)
- formalin-fixed: granular cytoplasmic pattern (c-ANCA)
5. Henoch-Schönlein Purpura
> Clinical Presentation and Prognosis
- occurs primarily in children after upper respiratory tract infections
- s/s: appearance of raised, red patches on the skin; respiratory and
gastrointestinal symptoms (blood in sputum and stools)
- renal involvement: the most serious complication
- prognosis: complete recovery with normal renal function
- may progress to a more serious form of glomerulonephritis and
eventual renal failure
> Laboratory Findings
- urinalysis findings: mild/heavy proteinuria and hematuria; RBC casts
6. Membranous Glomerulonephritis
> Pathophysiology
- pronounce thickening of the glomerular basement membrane due to
deposition of IgG immune complexes
- associated disorders: systemic lupus erythematosus (SLE), Sjögren
syndrome, secondary syphilis, hepatitis B, malignancy
- others: gold and mercury treatments
> Clinical Presentation and Prognosis
- disease progression is slow, with possible remission
- nephrotic syndrome symptoms frequently develop
- tendency toward thrombosis
> Laboratory Findings
- urinalysis findings: microscopic hematuria; elevated urine protein
excretion (levels may be similar to those with nephrotic syndrome)
- diagnosis: demonstration of one of the secondary disorders
7. Membranoproliferative Glomerulonephritis (MPGN)
> Pathophysiology
- associated with autoimmune disorders, infections, and malignancies
- type 1: due to increased cellularity in subendothelial cells of the
mesangium (interstitial area of the Bowman’s capsule)
- type 2: due to extremely dense deposits in the glomerular basement
membrane
> Clinical Presentation and Prognosis
- type 1 patients: progression to nephrotic syndrome
- type 2 patients: symptoms of chronic glomerulonephritis
- most patients are children; prognosis is poor
> Laboratory Findings
- urinalysis findings: hematuria and proteinuria (usual findings)
- others: decreased serum complement levels
8. Chronic Glomerulonephritis
> Clinical Presentation and Prognosis
- s/s: gradually worsening; fatigue, anemia, hypertension, edema,
oliguria
> Laboratory Findings
- urinalysis findings: hematuria, proteinuria, glucosuria (due to tubular
dysfunction); varieties of casts (e.g. broad casts)
- others: markedly decreased glomerular filtration rate; increased BUN
and creatinine levels; electrolyte imbalance
9. Immunoglobulin A (IgA) Nephropathy (Berger Disease)
> Pathophysiology
- the most common cause of glomerulonephritis; due to IgA immune
complexes deposited on the glomerular membrane
> Clinical Presentation and Prognosis
- most frequently seen in children and young adults
- periodic episodes of macroscopic hematuria following an infection or
strenuous exercise
- recovery from macroscopic hematuria is spontaneous; asymptomatic
microhematuria and elevated IgA serum levels persist
- patients may remain asymptomatic for 20 years; gradual progression
to chronic glomerulonephritis and end-stage renal disease
> Laboratory Findings
- increased serum levels of IgA (may be a result of mucosal infection)
B. Nephrotic Syndrome
> Pathophysiology
- increased permeability of the glomerular membrane
- damage to the shield of negativity and podocytes
- passage of high-molecular-weight proteins and lipids and negatively
charged albumin into the urine
- albumin: the primary protein depleted from the circulation
- hypoalbuminemia stimulates increased lipid production by the liver
- lower oncotic pressure increases fluid loss into interstitial spaces
(edema)
- depletion of immunoglobulins and coagulation factors cause
increased risk of infection and coagulation disorders
> Clinical Presentation and Prognosis
- massive proteinuria (greater than 3.5 g/day), low levels of serum
albumin, high levels of serum lipids, pronounced edema
- acute onset: systemic shock due to circulatory disruption (pressure
and flow of blood to kidneys is decreased)
- tubular and glomerular damage occurs and may progress to chronic
renal failure
- may also be a complication of glomerulonephritis
> Laboratory Findings
- urinalysis findings: marked proteinuria, urinary fat droplets, oval fat
bodies, renal tubular epithelial (RTE) cells, epithelial, fatty, and waxy
casts, microscopic hematuria
- oval fat bodies: due to absorption of lipid-containing proteins by RTE
cells
1. Minimal Change Disease (Lipid Nephrosis)
> Pathophysiology
- some damage to podocytes and the shield of negativity
- produces little cellular change in the glomerulus; etiology is unknown
- associated conditions: allergic reactions, recent immunization,
possession of the HLA-B12 antigen
> Clinical Presentation and Prognosis
- often seen in children; edema and other symptoms of nephrotic
syndrome; prognosis is generally good
- treatment: corticosteroids
> Laboratory Findings
- urinalysis findings: heavy proteinuria and transient hematuria
- others: normal BUN and creatinine results
2. Focal Segmental Glomerulosclerosis (FSGS)
> Pathophysiology
- due to damaged podocytes; affects only certain numbers and areas
of glomeruli, others remain normal
- associated with abuse of heroin and analgesics and with AIDS
> Clinical Presentation and Prognosis
- symptoms are similar to nephrotic syndrome and minimal change
disease
> Laboratory Findings
- urinalysis findings: heavy proteinuria and microscopic hematuria
(most consistent findings)
- others: immune deposits (IgM and C3) in undamaged glomeruli
Tubular Disorders
A. Acute Tubular Necrosis (ATN)
- the primary disorder associated with damage to the renal tubules
- damage to RTE cells: caused by ischemia or toxic substances
> Pathophysiology
- actual damage to the tubules
- metabolic or hereditary disorders affecting tubular function
a. Ischemic Acute Tubular Necrosis
- ischemia: decreased blood flow causing a lack of oxygen presentation
- causes: shock, trauma (e.g. crushing injuries), surgical procedures
- shock: a general term for a severe condition that decreases blood
flow throughout the body
- causes of shock: cardiac failures, sepsis (e.g. toxigenic bacteria),
anaphylaxis, massive hemorrhage, contact with high-voltage
electricity
b. Acute Tubular Necrosis Due To Exposure To Nephrotoxic Agents
- aminoglycoside antibiotics, amphotericin B (antifungal agent),
cyclosporine, radiographic dye, organic solvents (e.g. ethylene glycol),
heavy metals, toxic mushrooms
- others: filtration of large amounts of hemoglobin and myoglobin
> Clinical Presentation and Prognosis
- may present as an acute complication of an ischemic event or more
gradually during exposure to toxic agents
- complete recovery is facilitated by correcting underlying causes and
managing the symptoms
> Laboratory Findings
- urinalysis findings: mild proteinuria, microscopic hematuria;
presence of RTE cells and RTE cell casts containing tubular fragments
consisting of three or more cells
- other casts: hyaline, granular, waxy, and broad casts
B. Hereditary and Metabolic Tubular Disorders
- systemic conditions affecting or overriding the tubular reabsorptive
maximum (Tm) for particular substances
- failure to inherit a gene or genes required for tubular reabsorption
1. Fanconi Syndrome
> Pathophysiology
- the disorder most frequently associated with tubular dysfunction
- generalized failure of tubular reabsorption in the proximal
convoluted tubules
- affected substances: glucose, amino acids, phosphorus, sodium,
potassium, bicarbonate, and water
- dysfunction of the transport of filtered substances across tubular
membranes
- disruption of cellular energy needed for transport
- changes in tubular membrane permeability
- may be inherited with cystinosis and Hartnup disease
- acquired through exposure to toxic agents (heavy metals and
outdated tetracycline)
- a complication of multiple myeloma and renal transplant
> Laboratory Findings
- urinalysis findings: glycosuria and mild proteinuria
- urinary pH may be very low due to failure to reabsorb bicarbonate
- others: normal blood glucose
2. Alport Syndrome
> Pathophysiology
- an inherited disorder of collagen production affecting the glomerular
basement membrane
- inherited as a sex-linked or autosomal genetic disorder
- males inheriting the X-linked gene are more severely affected than
females inheriting the autosomal gene
> Clinical Presentation and Prognosis
- males younger than age 6 may exhibit macroscopic hematuria and
continue to exhibit microscopic hematuria during respiratory
infections; abnormalities in hearing and vision may develop
- prognosis: ranges from mild symptoms to persistent hematuria and
renal insufficiency in later life to nephrotic syndrome and end-stage
renal disease
> Laboratory Findings
- urinalysis findings: hematuria (macroscopic or microscopic)
- glomerular basement membrane has a lamellated appearance with
areas of thinning; no evidence of glomerular antibodies is present
3. Uromodulin-Associated Kidney Disease
> Pathophysiology
- uromodulin (Tamm-Horsfall protein): a glycoprotein; the only protein
produced by the kidney; the primary protein found in normal urine
- produced by proximal and distal convoluted tubules
- forms the matrix of urinary casts
- an inherited disorder caused by an autosomal mutation in the gene
that produces uromodulin (UMOD gene, chromosome 16)
- decrease in production of normal uromodulin and is replaced by the
abnormal form
- abnormal uromodulin is still produced by tubular cells and
accumulates in the cells; tubular cells are destroyed
> Clinical Presentation and Prognosis
- the mutation also causes an increase in serum uric acid
- affected individuals develop gout as early as teenage years before the
onset of detectable renal disease
- eventual need for renal monitoring and renal transplantation
4. Diabetic Nephropathy
> Pathophysiology
- the most common cause of end-stage renal disease
- glomerular membrane damage: glomerular membrane thickening;
increased proliferation of mesangial cells; increased deposition of
cellular and noncellular material within the glomerular matrix
(accumulation of solid substances around capillary tufts)
- deposition of glycosylated proteins due to poorly controlled blood
glucose levels
- glomerular vascular structure develops sclerosis
> Clinical Presentation and Prognosis
- treatment: modification of diet and strict control of hypertension to
decrease progression of renal disease
> Laboratory Findings
- urinalysis findings: microalbuminuria (for monitoring)
5. Nephrogenic Diabetes Insipidus
> Pathophysiology
- inability of the renal tubules to respond to ADH
- neurogenic diabetes insipidus: failure to produce ADH
- urine concentration is regulated in the distal convoluted tubules and
collecting ducts in response to ADH produced by the hypothalamus
- inherited as a sex-linked recessive gene or acquired from medications
- implicated medications: lithium and amphotericin B
- a complication of polycystic kidney disease and sickle cell anemia
> Laboratory Findings
- urinalysis findings: low specific gravity, pale yellow color
- others: possible false-negative results for chemical tests
6. Renal Glycosuria
> Pathophysiology
- an autosomal recessive trait; affects only the reabsorption of glucose
- the number of glucose transporters in the tubules are decreased or
the affinity of transporters for glucose is decreased
- renal threshold for glucose: 160-180 mg/dL (in normal conditions)
> Laboratory Findings
- increased urine glucose with normal blood glucose levels
Interstitial Disorders
- tubulointerstitial disease: disorders affecting the interstitium also
affect the tubules due to their close proximity
- most disorders involve infections and inflammatory conditions
A. Urinary Tract Infection (UTI)
- the most common renal disease
- lower urinary tract: urethra and bladder
- upper urinary tract: renal pelvis, tubules, and interstitium
- cystitis: infection of the bladder; most frequently encountered UTI
- can progress to a more serious upper UTI if left untreated
- often seen more often in women and children
- s/s: urinary frequency and burning
- urinalysis findings: numerous WBCs and bacteria; mild proteinuria
and hematuria; increased pH
B. Pyelonephritis
- presence of WBC casts in pyelonephritis differentiates it from cystitis
1. Acute Pyelonephritis
> Pathophysiology
- pyelonephritis: infection of the upper urinary tract
- acute pyelonephritis most frequently occurs due to ascending
movement of bacteria from a lower UTI
- ascending movement of bacteria is enhanced by conditions
interfering with downward flow of urine or emptying of the bladder
- obstructions: renal calculi, pregnancy, vesicoureteral reflux
- vesicoureteral reflux: reflux of urine from bladder back into ureters
> Clinical Presentation and Prognosis
- s/s: sudden onset; urinary frequency, burning on urination, lower
back pain
- treatment: appropriate antibiotic therapy; removal of underlying
conditions
> Laboratory Findings
- urinalysis findings: similar to those seen in cystitis; numerous WBCs
and bacteria; mild proteinuria and hematuria
- WBC casts: indicates infection within the tubules
- observe sediments for presence of bacterial casts
2. Chronic Pyelonephritis
> Pathophysiology
- congenital urinary structural defects producing reflux nephropathy:
the most frequent cause of chronic pyelonephritis
- results in permanent damage to renal tubules; possible progression
to chronic renal failure
> Clinical Presentation and Prognosis
- often diagnosed in children; may not be suspected until tubular
damage has become advanced
> Laboratory Findings
- urinalysis findings: similar to those seen in acute pyelonephritis
- others; granular, waxy, and broad casts; increased proteinuria and
hematuria; renal concentration is decreased
C. Acute Interstitial Nephritis (AIN)
> Pathophysiology
- inflammation of the renal interstitium followed by inflammation of
the renal tubules
- primarily associated with an allergic reaction to medications
occurring within the renal interstitium (medication may bind to
interstitial proteins)
- implicated medications: penicillin, methicillin, ampicillin, NSAIDs,
cephalosporins, sulfonamides, thiazide diuretics
- NSAIDs: non-steroidal anti-inflammatory drugs
> Clinical Presentation and Prognosis
- symptoms develop approximately 2 weeks following administration
of the offending medication
- frequent initial symptoms: fever and presence of a skin rash
- s/s: rapid onset; oliguria and edema
- treatment: discontinue offending medication; administer steroids to
control inflammation
- others: supportive renal dialysis (until inflammation subsides)
> Laboratory Findings
- urinalysis findings: hematuria (may be macroscopic), mild to
moderate proteinuria, numerous WBCs, WBC casts without bacteria
- others: decreased renal concentrating ability; decreased glomerular
filtration rate
- confirmatory diagnosis: differential leukocyte staining for presence
of increased eosinophils
Renal Failure
- progression to end-stage renal disease
- marked decrease in glomerular filtration rate (less than 25 mL/min)
- rising BUN and creatinine values (azotemia)
- electrolyte imbalance and lack of renal concentrating ability
(isosthenuric urine)
- proteinuria and renal glycosuria
- telescoped urine sediment: granular, waxy, and broad casts
A. Acute Renal Failure (ARF)
> Pathophysiology
- sudden loss of renal function; frequently reversible
- causes: decreased blood flow into the kidney (prerenal), acute
glomerular and tubular disease (renal), and renal calculi or tumor
obstructions (postrenal)
> Clinical Presentation and Prognosis
- general characteristics: decreased glomerular filtration rate, oliguria,
edema, and azotemia
> Laboratory Findings (Urinalysis)
- prerenal origin: presence of RTE cells and casts (ATN)
- renal origin: RBCs (glomerular injury); WBC casts with or without
bacteria (interstitial infection or inflammation)
- postrenal origin: normal or abnormal urothelial cells possibly
associated with malignancy
Renal Lithiasis
- renal calculi: kidney stones; forms in the calyces and pelvis of the
kidney, ureters, and bladder
- renal lithiasis: calculi vary in size and shape (staghorn calculi resemble
the shape of renal pelvis; smooth and round stones from the bladder)
> Pathophysiology
- factors affecting renal calculi formation: pH, chemical concentration,
and urinary stasis
- clumps of crystals in freshly voided urine suggest conditions
promoting calculus formation
- increased crystalluria has been noted during the summer months in
persons known to form renal calculi (stone formers)
- comprehensive chemical analysis via x-ray crystallography
> Chemical Composition of Renal Calculi
- majority (75%) of renal calculi are composed of calcium oxalate or
calcium phosphate
- others: magnesium ammonium phosphate (struvite), uric acid, and
cystine crystals
a. Calcium Calculi
- associated with metabolic calcium and phosphate disorders,
occasionally diet
b. Magnesium Ammonium Phosphate Calculi (Struvite)
- accompanied by urinary infections involving urea-splitting bacteria
- urine pH is higher than 7.0
c. Uric Acid Calculi
- associated with increased intake of foods with high purine content
and with uromodulin-associated kidney disease
- urine pH is acidic
d. Cystine Calculi
- seen in conjunction with hereditary disorders of cystine metabolism
> Clinical Presentation and Prognosis
- small calculi: passed in urine; causes severe pain radiating from the
lower back to the legs
- larger calculi: cannot be passed in urine; may not be detected until
onset of symptoms related to urinary obstruction
- lithotripsy: a procedure using high-energy shockwaves used to break
stones in the upper urinary tract into pieces which are passed in urine
- stone may also be removed surgically
- patient management: maintenance of urine pH incompatible with
crystallization of particular chemicals
- adequate hydration to lower chemical concentration
- suggestion of possible dietary restrictions
> Laboratory Findings
- urinalysis findings: microscopic hematuria due to irritation of tissue
by the moving calculus
- microscopic hematuria: the primary finding in urine specimens from
patients passing or being in the process of passing renal calculi