RENAL DISEASE

Mark Laurence A. Manzano

 RENAL DISEASE

• Disorders throughout the body that can affect renal function and
produce abnormalities in the urinalysis
• Diseases of the kidney are often classified into four types based
on the morphologic component initially affected: glomerular,
tubular, interstitial, or vascular.
• Initially, renal disease may affect only one morphologic
component; however, with disease progression, other
components are involved because of their close structural and
functional interdependence.
• The two most common diseases that affect the kidney are
diabetes and hypertension
 GLOMERULAR DISORDERS

• Diseases that damage the glomeruli are varied and include

immunologic, metabolic, and hereditary disorders; most often are
immune-mediated.
• Primary Glomerular Disorders (Glomerulonephritis) – specifically
affect the kidney which is often the only organ involved
• Secondary Glomerular Disorders – systemic disorders; initially and
principally involve other organs; the glomeruli become involved as a
consequence as the systemic disease progresses
• Nonimmunologic causes of glomerular damage include exposure to
chemicals and toxins that also affect the tubules, disruption of the
electrical membrane charges as occurs in the nephrotic syndrome,
deposition of the amyloid material from systemic disorders that may
involve chronic inflammation and acute-phase reactants, and the
 GLOMERULAR DISORDERS

MORPHOLOGIC CHANGES IN THE GLOMERULUS

• Four distinct morphologic changes of glomeruli are recognized; cellular
proliferation, leukocytic infiltration, glomerular basement membrane
thickening, and hyalinization with sclerosis. One or more of these
changes accompany each type of glomerulonephritis and form the basis
for characterizing glomerular diseases

PATHOGENESIS OF GLOMERULAR DAMAGE

• The primary mode of glomerular injury results from immune-mediated
processes. Circulating antigen-antibody complexes and complexes that
results from antigen-antibody reactions that occur within the glomerulus
(i.e.; in situ) play a role in glomerular damage
• Glomerular injury does not result from the immune complexes but
rather from the chemical mediators and toxic substances that they
induce. Complement, neutrophils, monocytes, platelets, and other
factors at the site produce proteases, oxygen-derived free radicals, and
 GLOMERULAR DISORDERS
PRIMARY OTHER
DISORDER ETIOLOGY CLINICAL COURSE
URINALYSIS RESULT SIGNIFICANT TESTS
Rapid onset of Macroscopic
Deposition of immune
Acute Post- hematuria and hematuria (+) ASO titer
complex formed in
streptococcal edema Proteinuria Anti-group A
conjunction of Group A
Glomerulonephriti Permanent renal Dysmorphic RBCs streptococcal
Streptococcus infection on the
s (APGN) damage seldom RBC casts enzymes
glomerular membranes
occurs Granular casts
Deposition of immune
Rapid onset with
complexes from systemic
glomerular
immune disorders (ex. SLE) on Macroscopic BUN
Rapidly Progressive damage and
the glomerular membrane hematuria Creatinine
Glomerulonephriti possible
Cellular Proliferation of Proteinuria Creatinine
s progression to
epithelial cells inside the RBC casts Clearance
end-stage renal
Bowman’s capsule forming
failure
“crescents”
GLOMERULAR DISORDERS
 GLOMERULAR DISORDERS
PRIMARY OTHER
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
Deposition of antiglomerular Macroscopic Antiglomerular
Hemoptysis and dyspnea
Goodpasture basement membrane antibody hematuria basement
followed by hematuria,
Syndrome to glomerular and alveolar Proteinuria membrane
possible progression to ESRD
basement membrane RBC casts antibody
Anti-neutrophilic cytoplasmic
Pulmonary symptoms
autoantibody (ANCA) binds to Macroscopic Antineutrophili
including hemoptysis develop
Wegener’s neutrophils in vascular walls hematuria c cytoplasmic
first followed by renal
Granulomatosis producing damage to small Proteinuria antibody
involvement and possible
vessels in the lungs and RBC casts (ANCA)
progression to ESRD
glomerulus
Initial appearance of purpura
followed by blood in sputum
Occurs in children ff. viral Macroscopic
and stools and eventual renal
Henoch-Schoenlein respiratory infections hematuria Stool Occult
involvement
Purpura Decrease in platelets disrupts Proteinuria Blood
Complete recovery is common
vascular integrity RBC casts
but may progress to renal
failure
 GLOMERULAR DISORDERS
PRIMARY OTHER
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
Membranous Thickening of glomerular
Macroscopic Antinuclear
glomerulonephritis membrane following IgG Slow progression to nephrotic
hematuria antibody
Most common cause immune complex deposition syndrome or possible
Proteinuria HBsAg
of nephrotic associated with systemic remission
FTA-ABS
syndrome in adults disorders
Membranoproliferat Cellular proliferation affecting
ive the capillary walls of the Noticeable progression to Serum
Hematuria
glomerulonephritis glomerular basement chronic glomerulonephritis to complement
Proteinuria
(Mesangiocapillary membrane, possibly immune- nephrotic syndrome levels
glomerulonephritis) mediated
Hematuria
Marked decrease in renal Proteinuria BUN
function resulting from Noticeable decrease in renal Glucosuria Creatinine
Chronic
glomerular damage precipitated function progeressing to renal Cellular and Creatinine
Glomerulonephritis
by other renal disorders failure granular casts Clearance
Progression to renal failure Waxy and Electrolytes
broad casts
GLOMERULAR DISORDERS
 GLOMERULAR DISORDERS
PRIMARY OTHER
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
IgA Nephropathy Early stages:
Recurrent macroscopic
(Berger’s Disease) Deposition of IgA on the hematuria
hematuria following exercise
Most common cause glomerular membrane resulting Late stages: Serum IgA
with slow progression to
of chronic from increased levels of IgA similar to
chronic glomerulonephritis
glomerulonephritis chronic GN
Disruption of the electric Acute onset following
charges that produces the systemic shock
Nephrotic syndrome tightly fitting podocyte barrier Gradual progression from
resulting in massive loss of other glomerular disorders
proteins and lipids and then to renal failure

FINDINGS IN NEPHROTIC SYNDROME

SERUM URINE
↓ Albumin, a1-globulins, y-globulins ↑Albumin, a1-globulins, B-globulins, y-globulins
↑a2-macroglobulins, B-globulins (B- (-)a2-macroglobulins
lipoproteins)
Oval Fat Bodies, Fatty casts, Waxy casts,
Cholesterol crystals
NEPHROTIC SYNDROME
 GLOMERULAR DISORDERS
PRIMARY OTHER SIGNIFICANT
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS RESULT TESTS
Little cellular changes in the
Heavy
Minimal change glomerulus
Frequent complete remission proteinuria Serum albumin
disease (lipoid Disruption of podocytes
following corticosteroid Transient Cholesterol
nephrosis, Nil primarily in children following
treatment hematuria Triglycerides
disease) allergic reaction &
Fat droplets
immunizations
 GLOMERULAR DISORDERS
PRIMARY OTHER SIGNIFICANT
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS RESULT TESTS
Focal Segmental Disruption of podocytes in May resemble nephrotic
Proteinuria Drugs of abuse
Glomerulosclerosis certain numbers and areas of syndrome or minimal change
Hematuria HIV tests
(FSGS) glomeruli, others remain normal disease
 GLOMERULAR DISORDERS
PRIMARY OTHER SIGNIFICANT
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS RESULT TESTS
Most common cause of ESRD
Diabetic Nephropathy Deposition of glycosylated proteins Similar to chronic Microalbuminuri
(Kimmelstiel-Wilson on the glomerular basement glomerulonephritis a Blood glucose
Disease) membranes caused by poorly (+) MIcral test
controlled blood glucose levels
Genetic disorder showing Similar to
Alport Syndrome lamellated and thinning of Slow progression to nephrotic nephrotic Genetic testing
glomerular basement membrane syndrome and ESRD syndrome
 TUBULAR DISORDERS
Disorders affecting the renal tubules include those in which tubular function is
disrupted as a result of actual damage to the tubules and those in which a metabolic
or hereditary disorder affects the intricate functions of the tubules
PRIMARY OTHER SIGNIFICANT
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS RESULT TESTS
Microscopic
hematuria
Acute of renal function Proteinuria Hemoglobin
Damage to renal tubular cells
Acute Tubular dysfunction usually resolved RTE cells, RTE Hematocrit
caused by ischemia or toxic
Necrosis when the underlying cause is casts Cardiac
agents
corrected Hyaline, enzymes
granular, waxy,
broad cast
 TUBULAR DISORDERS
PRIMARY OTHER
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
Inherited in association with Generalized defects in renal Glucosuria Serum and urine
Fanconi’s Syndrome cystinosis and Hartnup disease or tubular reabsorption requiring Possible cystine electrolytes
acquired through exposure to toxic supportive therapy crystals Amino acid
agents chromatography
Inherited defect in the production of
normal uromodulin by the renal
Uromodulin- tubules and increased uric acid Continual monitoring of renal RTE cells
associated Kidney causing gout function for progression to renal Hyperuricemia Serum uric acid
Disease (UKD) Normal uromodulin is replaced by failure and possible kidney
abnormal forms that destroy the transplantation
RTE cells
N blood glucose, ↑ Urine glucose
Renal Glucosuria Defective tubular reabsorption of Benign disorder Glucosuria Blood glucose
glucose
Neurogenic DI – failure of the
hypothalamus to produce ADH Requires supportive therapy to Low specific
Diabetes Insipidus (DI) Nephrogenic DI – renal tubules fail prevent dehydration gravity ADH testing
to respond to DI Polyuria
 INTERSTITIAL DISORDERS
Considering the close proximity between the renal tubules and the renal interstitium, disorders
affecting the interstitium also affect the tubules, resulting in the condition commonly called
tubulointerstitial disease. Most of these disorders involve infections and inflammatory conditions

The most common renal disease is a urinary tract infection (UTI). Infection may involve the lower
urinary tract (urethra and bladder) or the upper urinary tract (renal pelvis, tubules, and interstitium).
Most frequently encountered is infection of the bladder (cystitis), which can progress to a more
serious upper UTI if left untreated
 INTERSTITIAL DISORDERS
PRIMARY OTHER SIGNIFICANT
DISORDER ETIOLOGY CLINICAL COURSE URINALYSIS RESULT TESTS
WBCs, bacteria
Microscopic
Ascending bacterial infection of the Acute onset of urinary frequency and hematuria
Cystitis (Lower UTI) Urine culture
urinary bladder burning resolved with antibiotics Mild proteinuria
Increased pH
NO CAST
WBCs, Bacteria
Infection of the renal tubules and
WBC casts
interstitium related to interference of Acute onset of urinary frequency,
Acute Pyelonephritis Bacterial casts Urine culture
urine flow to the bladder, reflux of urine burning, and lower back pain resolved
(Upper UTI) Microscopic Blood culture
from the bladder (vesiculoureteral reflux) with antibiotics
hematuria
& untreated cystitis
Proteinuria
WBCs, Bacteria
WBC casts Urine culture
Frequently diagnosed in children, Bacterial casts Blood culture
Recurrent infection of the renal tubules
required correction of the underlying Hematuria BUN
Chronic Pyelonephritis and interstitium caused by structural
structural defect Proteinuria Creatinine
abnormalities affecting the flow of urine
Possible progression to renal failure Granular casts Creatinine
Waxy and broad clearance
casts
Hematuria
Acute onset of renal dysfunction often Urine eosinophils
WBC casts
Allergic inflammation of the renal accompanied by a skin rash BUN
Proteinuria
Acute Interstitial Nephritis interstitium in response to certain Resolves following discontinuation of Creatinine
WBCs (↑ Eo)
medicationa medication and treatment with Creatinine
WBC casts
costicosteroids clearance
NO BACTERIA
 VASCULAR DISORDERS

Because kidney function is directly dependent on receiving 25% of the cardiac output, any
disruption in the blood supply will affect renal function. Likewise, any changes in the
vasculature of the kidney directly affect the close interrelationship and interdependence of the
blood vessels with the renal interstitium and tubules. Therefore, disorders that alter the blood
vessels or the blood supply to the kidney can cause renal disease

Atherosclerosis of the intrarenal arteries causes a reduction in renal blood flow, whereas
hypertension, polyarteritis nodosa, eclampsia, diabetes, and amyloidosis often cause
significant changes in the renal arterioles and glomerular capillaries such that severe and fatal
renal ischemia can result

Hypertension is a frequent finding in many kidney disorders when the role of the kidneys in
blood pressure control is compromised by disease
 RENAL FAILURE

• ↓ glomerular filtration rate (<25 mL/min)

• Azotemia (↑ BUN, Creatinine)
• Electrolyte imbalance
• (-) renal concentrating ability  Isosthenuria
• Proteinuria
• ↑ Telescoped sediment
• Simultaneous appearance of the elements of acute/chronic glomerulonephritis and nephrotic
syndrome
• ↑ cells and casts (RBC, granular, waxy, broad, fatty), lipid droplets, oval fat bodies
 RENAL FAILURE
ACUTE KIDNEY INJURY (ACUTE RENAL FAILURE)
• Sudden loss of the ability of the kidney to remove waste and concentrate urine without losing
electrolytes which is due to many possible causes; ischemic acute tubular necrosis is the most
common cause
• Patient accumulate urea and other nitrogenous waste products and have decreased glomerular
filtration rates
 RENAL FAILURE
CHRONIC RENAL FAILURE
• Progression occurs in four stages:
DIMINISHED RENAL RESERVE GFR drops to about 50% of normal
RENAL INSUFFICIENCY GFR drops from 20-50%; azotemia, anemia,
hypertension begins
RENAL FAILURE GFR <20%; kidneys cannot regulate volume and solute
concentration; metabolic acidosis, hyperkalemia,
edema develop
END-STAGE RENAL DISEASE GFR <5% of normal; glomerular scarring and reduction
of renal capillaries
Tubular atrophy and fibrosis; loss of kidney mass
Dialysis or transplantation may be required for survival
Critical renal functions are lost
 RENAL LITHIASIS

• Renal calculi (kidney stones) ay form in the calyces and pelvis of the kidney,
ureters, and bladder
• Most common cause of upper urinary tract obstruction
• Upper renal stones are common in Western industrialized countries, whereas
bladder stones are uncommon
• Conditions favoring the formation of renal calculi
1. pH
2. Chemical concentration
3. Urinary stasis
Primary urinalysis findings: MICROSCOPIC HEMATURIA
 RENAL LITHIASIS
METHODS FOR ANALYSIS OF CALCULI COMPOSITION OF RENAL CALCLI
• Optical crystallography 80% CALCIUM OXALATE or a mixture of oxalate and
calcium phosphate
• Radiograph diffraction 3-10% Mixed calcium phosphate, magnesium
each ammonium phosphate, and uric acid
• Infrared spectroscopy 1-2% Cystine stones
• Electron beam analysis
• Mass spectroscopy
 RENAL LITHIASIS
CAUSES OF VARIOUS CALCULI COMPOSITION
COMPOSITION CONDITIONS COMPOSITION CONDITIONS
a. Idiopathic hypercalciuria MAGNESIUM Alkaline infection with urea-spitting
AMMONIUM
b. Primary hyperparathyroidism PHOSPHATE bacteria (especially Proteus, also
c. Bone disease HEXAHYDRATE Pseudomonas, enterococci (Brunzell)
CALCIUM d. Excessive milk, alkali, or vitamin D
COMPOSITION intake a. Gout
e. Renal tubular acidosis b. Polycythemia
f. Sarcoidosis c. Leukemia
g. berylliosis d. Lymphoma
URIC ACID
e. Liver disease
a. Oxaluria AND URATE
f. Acid isohydria
b. Incomplete catabolism of g. Theophylline and thiazide therapy
CALCIUM carbohydrates h. Conditions associated with rapid
OXALATE c. Isohydria at pH 5.5 to 6.0 protein catabolism
d. Excessive glycogen breakdown
e. Primary hyperthyroidism a. Transient acute phases of chronic renal
disease
a. Same conditions as for calcium oxalate CYSTINE b. Heavy metal nephrotoxicity
CALCIUM
b. Alkaline infection (urea-splitting) c. Aminoaciduria
PHOSPHATE
c. Persistently alkaline urine d. Renal tubular acidosis syndromes
 RENAL LITHIASIS
VALUES OF pH CAN BE ASSOCIATED WITH CALCULI FORMATION
pH <5.5 Uric acid, cystine, or xanthine calculi
pH 5 to 6 Calcium oxalate and apatite calculi
pH >7 Magnesium ammonium phosphate or calcium phosphate calculi

PHYSICAL CHARACTERISTICS OF RENAL CALCULI

RENAL CALCULI INFORMATION/DESCRIPTION
Major constituent of renal calculi
CALCIUM OXALATE Very hard, dark in color with rough surface
URIC ACID/URATE Associated with increased intake of foods with high purine content and with UKD
Seen in hereditary disorders of cystine metabolism
CYSTINE Yellow-brown, greasy, resembles on old soap; least common calculi (1-2%)
PHOSPHATE CALCULI Pale and friable
Accompanied by urinary infections involving urea-splitting bacteria
TRIPLE PHOSPHATE Branching/staghorn calculi resembling antlers of a dear
RARE CALCULI
a. Sulfonamide calculi
b. Silica calculi – ingestion of silica over a long period of time
c. Triamterene calculi – insoluble diuretic; mustard-colored stones
d. Adenine calculi – associated with inherited enzyme deficiency and hyperuricemia
e. Xanthine calculi – associated with a genetic disorder with an absence of xanthine oxidase
RENAL LITHIASIS
 RENAL LITHIASIS
Nephrocalcin, osteopontin (uropontin), citrate, Tamm-
Horsfall protein (uromodulin), chondroitin sulfate,
NATURAL INHIBITORS OF CALCULI FORMATION
calgranulin, bikunin, prothrombin F1 fragment, heparan
sulfate, pyrophosphate, and CD59

ANALYSIS OF RENAL CALCULI

1. Wipe off stone(s) and describe in terms of size (mm), shape, color, and hardness (texture)
2. Powder stone and dissolve in a small amount of concentrated HCl
a. Foaming on contact with HCl = carbonate
b. Acid extract + sodium cyanide + sodium nitroprusside = magenta color (cystine)
c. Acid extract + ammonium molybdate + ferrous ammonium sulfate + H2SO4 = blue color (phosphate)
d. Acid extract + NaOH + p-nitrobenzeneazoresorcinol = blue precipitate (Mg)
e. Acid extract + NaOH + clacein + KOH = pale yellow color (calcium)
f. Acid extract + NaOH + mercuric iodide + potassium iodide = orange-brown color (ammonium)
g. Acid extract + NaOH + neocuproine + Hac + CuSO4 = yellow-orange color (uric acid)
h. Acid extract + MnO2 = black sediment which settles and bubbles which appear from the bottom of the tube
(oxalate)
3. For each cation (Ca, NH4, Mg), there is an anion (Oxalate, PO4, CO3); NH4 should accompany Mg
 RENAL LITHIASIS
PREVENTION AND TREATMENT OF RENAL CALCULI
Increase fluid intake and modify diet to eliminate excess in certain solutes
PREVENTION
Oral medications, eliminating causative agents (urea-splitting bacteria)
Extracorporeal shockwave lithotripsy (ESWL) – use of sound waves to break up
stone in vivo
TREATMENT
Cystoscopy – if stone is located in the lower third of the ureter or in the bladder
Percutaneous nephrolithotomy – if ESWL is unsuccessful