DISORDERS DETECTED THROUGH URINE

RENAL DISEASE

Disorders throughout the body can affect renal function and produce abnormalities in the urinalysis. Considering that the major function of the kidneys is filtration of the blood to remove waste products, it becomes evident that the kidneys are consistently exposed to potentially damaging substances.

General Mechanisms of Glomerular Damage

⚫ Immune complexes deposit on glomerular membranes

⚫ Mechanism

⚫ Results

⚫ Non-immunologic causes

Mechanism

Complement, neutrophils, lymphocytes, monocytes, cytokines → inflammation & damage

Results

cellular infiltration, basement membrane thickening, capillary damage

Non-immunologic causes

o Chemicals/toxins (affect tubules + glomeruli)

o Disruption of electrical charges (nephrotic syndrome)

o Amyloid deposition (chronic inflammation, acute-phase

reactants)

o Basement membrane thickening (diabetic nephropathy)

GLOMERULAR DISORDERS

⚫ Sterile inflammatory process affecting glomerulus

⚫ Urinalysis: blood, protein, casts

acute → rapidly progressive → chronic → nephrotic syndrome → renal failure

Glomerular disorder progress

Acute Post-Streptococcal Glomerulonephritis (AGN)

⚫ Cause: Group A streptococcus (M protein) → immune complex

deposition

⚫ Symptoms: sudden onset, fever, edema (periorbital), fatigue,

HTN, oliguria, hematuria

⚫ Urinary Findings: marked hematuria, proteinuria, oliguria, RBC

casts, dysmorphic RBCs, WBCs, hyaline/granular casts

⚫ Other Laboratory Results: ↑ BUN, positive anti-strep enzyme

tests

⚫ Prognosis: usually full recovery (children/young adults)

Rapidly progressive glomerulonephritis (Crescentic GN)

⚫ Cause: Immune complexes; complication of GN or SLE

⚫ Pathology: macrophages damage capillary walls → crescent

formation (macrophages, fibroblasts, fibrin)

⚫ Urinary Findings: severe proteinuria, very low GFR

⚫ Other Laboratory Results: ↑ fibrin degradation products,

cryoglobulins, IgA deposits

⚫ Prognosis: poor, often progresses to renal failure

Goodpasture syndrome

⚫ Cause: Autoantibody against "glomerular and alveolar basement"

membrane (after viral infection)

⚫ Pathogenesis: Autoimmune disorder with deposition of antiglomerular basement membrane (anti-GBM) antibodies against

type IV collagen.

⚫ Features: hemoptysis, dyspnea, hematuria → chronic GN & renal

failure

⚫ Urinary Findings: proteinuria, hematuria, RBC casts

⚫ Other Laboratory Results: detectable anti-GBM antibodies

Wegener's granulomatosis

⚫ Cause: ANCA (antineutrophilic cytoplasmic antibody) →

granulomatous vasculitis of kidney & lungs

⚫ Pathogenesis: Anti-neutrophil cytoplasmic antibodies (cANCA/PR3-ANCA) activate neutrophils → necrotizing vasculitis

in small vessels of lungs, kidneys, upper respiratory tract.

⚫ Urinary Findings: Macroscopic hematuria, protenuria, RBC

casts

⚫ Other Laboratory Results: ANCA testing

Henoch-Schonlein Purpura

⚫ Pathogenesis: Immune complex deposition (IgA) in small

vessels after infection

⚫ Symptoms: Purpura, GI bleeding, respiratory symptoms

⚫ Urinary Findings: Macroscopic hematuria, proteinuria, RBC

casts

⚫ Prognosis: >50% recover completely; others → GN/renal failure

Purpura

red skin patches = decrease in platelet that disrupts vascular integrity

Membranous GN

⚫ Cause: thickened basement membrane due to IgG immune

complex deposition

⚫ Pathogenesis: thickened basement membrane due to IgG

immune complex deposition

⚫ Urinary Findings: microscopic hematuria, ↑ proteinuria

⚫ Other Laboratory Results: risk of thrombosis

⚫ Prognosis: slow, possible remission

⚫ Associated with: SLE, Sjögren, syphilis, hepatitis B, malignancy,

drugs (gold, mercury)

Membranoproliferative GN

⚫ Cause:

o Type 1: ↑ mesangial/subendothelial cellularity → capillary

wall thickening

o Type 2: dense deposits in basement membrane

⚫ Pathogenesis: thickened basement membrane due to IgG

immune complex deposition

⚫ Urinary Findings: hematuria, proteinuria, ↓ serum complement

⚫ Prognosis: mostly children; poor prognosis

⚫ Associated with: autoimmune disorders, infections,

malignancies

Chronic Glomerulonephritis

⚫ Progression: long-term damage → ESRD

⚫ Pathogenesis: Progressive glomerular scarring → Chronic Kidney Disease (CKD)

⚫ Urinary Findings: Hematuria, proteinuria, glucosuria, cellular,

granular, waxy, and broad casts

⚫ Other Laboratory Results: ↓ GFR, ↑ BUN & creatinine,

electrolyte imbalance

⚫ Associated with: autoimmune disorders, infections,

malignancies

Broad casts

diagnostic hallmark of CKD

IgA Nephropathy (Berger's Disease)

most common cause of glomerulonephritis

IgA Nephropathy (Berger's Disease)

⚫ Cause: IgA immune complex deposition (often after mucosal

infection or exercise)

⚫ Pathogenesis: Recurrent episodic hematuria, often following respiratory or GI infection ("synpharyngitic hematuria").

⚫ Urinary Findings: Macroscopic hematuria, protenuria, glucosuria, cellular & granular cast, waxy & broad casts

⚫ Other Laboratory Results: ↓ GFR, ↑ BUN & creatinine,

electrolyte imbalance

⚫ Associated with: autoimmune disorders, infections, malignancies

nephrotic syndrome

⚫ Pathogenesis: Damage to podocytes + shield of negativity → protein loss = hypoalbuminemia → ↓ oncotic pressure → edema, ↑ lipid synthesis = loss of immunoglobulins & clotting factors → infection + clotting risk

⚫ Manifestations: Massive proteinuria (>3.5 g/day),

Hypoalbuminemia, Hyperlipidemia

⚫ Urinary Findings: marked proteinuria, fat droplets, oval fat

bodies, RTE cells, fatty/waxy casts, microscopic hematuria

TUBULAR DISORDER

disorders affecting renal tubules such as structural damage to tubular cells, metabolic/hereditary defects interfering with reabsorption or secretion, and can lead to abnormal reabsorption of electrolytes, proteins, water, and glucose

Acute Tubular Necrosis (ATN)

⚫ Causes:

✓ Ischemic: shock trauma, sepsis, severe dehydration, cardiac failure

✓ Nephrotoxic: heavy metals, aminoglycosides, amphotericin B, hemoglobin/myoglobin, radiographic contrast agents

⚫ Pathology: Necrosis and sloughing of renal tubular

epithelial (RTE) cells → obstruction and impaired renal

function.

⚫ Urine: "Oderless Urine"

⚫ Urinary Findings: Macroscopic hematuria, protenuria,

RTE cells & casts, hyaline, granular, waxy, & broad casts

Shock

cardiac failure

ischemic

decrease in blood flow/supply

nephrotoxic

toxic substances are in the filtrate

Oderless urine

due to loss of concentrating ability

Fanconi Syndrome

⚫ Generalized failure of tubular reabsorption in the proximal

convoluted tubule

✓ Inherited: Cystinosis, Wilson's disease, glycogen storage

disease

✓ Acquired: exposure to heavy metals, outdated

tetracyclines, multiple myeloma

⚫ Pathology: loss of glucose, amino acids, phosphate, bicarbonate, uric acid.

⚫ Urinary Findings: Glucosuria with normal blood glucose, Mild

proteinuria, Very low urine pH, cystine crystals

low urine pH

loss in bicarbonate (alkalinic buffer)

Alport syndrome

⚫ Pathology: Inherited collagen defect → abnormal glomerular

basement membrane (x-linked)

⚫ Urinary Findings: Early hematuria (gross after infections,

microscopic persistent)

x-linked

males are more severe

diabetes insipidus

⚫ Neurogenic: hypothalamus fails to produce to ADH

⚫ Nephrogenic: renal tubules fail to respond to ADH

⚫ Pathology: Lack of ADH action → impaired water reabsorption in collecting ducts → excessive dilute urine.

⚫ Findings: low SG (SG < 1.005), hypotonic urine, polyuria

Diabetic Nephropathy

⚫ Glomerular basement membrane thickening

⚫ Mesangial cell proliferation + deposition of glycosylated proteins

⚫ Sclerosis of glomerular vasculature

⚫ Detection: microalbuminuria

Microalbuminuria

early sign for diabetic nephropathy

Renal Glucosuria

⚫ Cause: Isolated defect in tubular reabsorption of glucose, with

normal blood glucose levels.

⚫ Pathology: Defective sodium-glucose transporters (SGLT2) in

the proximal tubules.

Renal Glucosuria

Presence of glucose in urine due to defective tubular reabsorption of glucose.

Cystitis

⚫ Cause: Ascending bacterial infection of the urinary bladder

⚫ Manifestation: Acute onset of urinary frequency and burning; inflammation to the bladder mucosa

⚫ Findings: WBCs, Bacteria, Microscopic hematuria, no casts

Cystitis

E. coli, Proteus, Klebsiella

Acute pyelonephritis

⚫ Cause: Ascending infection from bladder

⚫ Manifestation: Infection of the renal tubules & interstitum

⚫ Findings: WBCs, Bacteria, Microscopic hematuria, WBC cast, bacterial cast

Chronic Pyelonephritis

⚫ Cause: Recurrent or persistent infections due to structural abnormalities

⚫ Pathology: Progressive tubulointerstitial scarring and loss of renal parenchyma → renal insufficiency.

⚫ Manifestation: repeated history of UTI

⚫ Findings: WBCs, Bacteria, Microscopic hematuria, WBC cast, bacterial cast, granular cast, waxy & broad cast

Acute interstitial nephritis

⚫ Cause: Allergic/hypersensitivity reaction to drugs (common

culprits: antibiotics [penicillins, cephalosporins], NSAIDs,

diuretics), infections, or autoimmune diseases.

⚫ Pathology: Inflammatory infiltration of the renal interstitium, predominantly eosinophils and lymphocytes.

⚫ Findings: WBCs, Microscopic hematuria, Increased eosinophils, WBC cast, proteinuria

Phenylketonuria (PKU)

⚫ Pathophysiology: Inability to convert phenylalanine → tyrosine

⚫ Manifestations: Severe mental retardation if untreated;

Microcephaly, seizures, eczema, fair skin/hair (↓ melanin

synthesis)

⚫ Screening Test:

◼ B. Subtilis is cultured with beta-2-thienylalanine (TE) and

inhibits the growth of B. subtilis. Phenylalanine counteracts

the action of beta-2-TE.

⚫ Confirmatory test: Ion exchange HPLC

⚫ Treatment: Dietary restriction of phenylalanine

Phenylketonuria

most well-known aminoaciduria

Phenylalanine hydroxylase

Defective enzyme of Phenylketonuria

Mousy/Musty odor

Odor of phenylketonuria (as well as in sweat and breath)

Guthrie bacterial inhibition test

Screening test for Phenylketonuria

Tyrosyluria/Tyrosinemia

⚫ Defective enzyme:

◼ Type 1 - Hepatorenal tyrosinemia

◼ Type 2 - Oculocutaneous tyrosinemia

◼ Type 3 - Neurologic tyrosinemia

Type 1 - Hepatorenal tyrosinemia

furamarylacetoacetate hydrolase deficiency

Type 2 - Oculocutaneous tyrosinemia

tyrosine aminotransferase deficiency

Type 3 - Neurologic tyrosinemia

p-hydroxyphenylpyruvic acid dioxygenase deficiency

Rancid butter odor

Odor of Tyrosyluria

Nitroso-napthol test

screening test for tyrosyluria

Orange-red

(+) Nitroso-napthol color

Alkaptonuria

⚫ Screening: Ferric chloride test = (+) transient blue color

⚫ Confirmatory: Gas chromatography/mass spectrometry

homogentisic acid oxidase

defective enzyme of alkaptonuria

Alkaline

alkaptonuria urine darkens after becoming _______________ from standing at room temperature

Melanuria

⚫ Cause: Excess melanin in urine (often due to melanoma)

⚫ Mechanism: Tumors secrete 5,6-dihydroxyindole → oxidized to melanin

Air Exposure

melanuria Urine: darkens upon ________

Ferric Chloride Test = (+) gray/black precipitate

screening test for melanuria

Maple Syrup Urine Disease (MSUD)

⚫ Urine: Caramelized sugar/maple syrup/ curry urine odor

⚫ Screening Test: 2,4-dinitrophenylhydrazine (DNPH) = (+) yellow

turbidity/precipitate

⚫ Confirmatory: GCMS

Branched-chain alpha-ketoacid dehydrogenase

defective enzyme in MSUD

Maple Syrup Urine Disease

Most common inborn error of metabolism in the Philippines

Hartnup disease

⚫ Defect: Transport of neutral amino acids (e.g., tryptophan) in intestine & kidney → tryptophan deficiency → ↓ niacin synthesis

Indigo blue

Hartnup urine: color upon air exposure

"Blue diaper syndrome"

manifestation of Hartnup disease

Obermayer's test = (+) indican

screening test for Hartnup

Lesch-Nyhan disease

⚫ Pathophysiology: Defective purine salvage pathway → ↑ uric acid production

hypoxantine guanine phosphoribosyltransferase (HGPRT)

defective enzyme of Lesch Nyhan

severe gouty arthritis

manifestation of Lesch Nyhan (self-mutilation behavior - biting lips/fingers)

orange-sand like

Lesch Nyhan urine deposits in diapers (urate crystals)