NPLEX Combination ReviewNephrology / Urology

Paul S. Anderson, ND

Medical Board Review Services

Copyright MBRS

Urinalysis • Routine

– Usually consists of gross observation of the specimen, use of dipsticks and microscopic analysis of patients with suspected renal or urinary tract disorders, DM and other conditions.

• Color– Normal is straw. Hematuria, globinurias, presence of leukocytosis or

mucous, urobilinogen/conjugated bilirubin diseases and certain foods/drugs may alter urine color.

• Odor– Sweet smelling or ketogenic urine indicative of DM.– Maple syrup smell indicates congenital metabolic disease.– Musty or “mousy” odor indicates phenylketonuria.– A very pungent order may be caused by bacterial contamination.

• Turbidity– Cloudiness caused by phosphates (alkaline urine) and urates (acid

urine) is normal. Turbidity may be associated with color changes; some of these conditions need to be investigated.

Microscopic examination• RBCs: Normal range 0-2/hpf• WBCs: Normal range <5/hpf

acute/chronic inflammation 5-50/hpf >50/hpf indicates acute infection

• Epithelial cells: Normal range < 2- 5/hpf• Bacteria: Normal is negative. If positive indicative of infection

or contamination.• Crystals: Normal range none to very few, usually form after

urine stands at room temperature.• Casts:

– Hyaline 0-4/lpf. Positive especially after exercise.– RBC: pathological indicating renal hematureia, GN, Goodpastures,

bacterial endocarditis, lupus nephritis.– WBC: indicates renal infection or inflammation. – Waxy: chronic renal failure, diabetic nephropathy.– Fatty casts: indicate fatty degeneration of tubular epithelium, nephrotic

syndrome, chronic GN and degenerative tubular disease.

UrinalysisSpecific Gravity: 1.003 – 1.035. Low = Dilute.pH: 4.6-8.0 / Varies with metabolic need.

Average is about 6.0. Acid urine with E. coli, Alkaline with Proteus and Pseudomonas.

Albumen / Protein: May be normal, especially after exercise. May be + in non-renal disease (fever, ascites, liver dz…). Mostly remember that it may be indicative of RENAL DISEASE.

Glucose: Should be – on dipstick tests. + in DM. Transient + with inflammatory dz.

Ketones: Indicate Fat Catabolism. Normally negative, Urine Ketones rise BEFORE blood ketones (ketosis). + in DM, Liver dz…

UrinalysisBilirubin: Normally -. Indicates biliary

obstruction. “Dark urine, light Stool”.

Urobilinogen: Normally Trace +. Should not be absent. Increased in Liver disease, Decreased in Cholelithiasis, Severe Diarrhea…

Blood: Hemoglobin – vs – RBC’s

Hb: Extraurinary dz. (Hemolysis).

RBC’s: Genitourinary dz.

Nitrites: + in bacturia. Indicates need for culture.

Leukocyte Esterase: + for the presence of WBC’s or WBC casts. Dipstick reagent.

UrinalysisFindings: UTI

1. pH: MB Alkaline due to urea splitting bugs

2. Color: Cloudy = WBC, Green = Pseudomonas

3. Proteinuria: Low to none

4. RBC’s: MB Positive

5. WBC’s: Typically > 6/HPF

6. Nitrite:MB+ With Gram – Organisms: (e.coli, Enterobacter, Pseudomonas)

7. WBC Casts: Positive with Kidney Involvement

8. WBC Clumps MB Noted in acute infxn./Lithiasis

9. CULTURE: > 100,000 organisms / ml. Positive.

UrinalysisFindings: Lithiasis

1. RBC’s: Typically +, MB Gross hematuria

2. WBC’s: MB+, also in clumps with mucus

3. Protein: Typically -, occasionally +

4. Mucous: Positive

5. Calculi: Have patients strain urine for calculi analysis.

Test Normal Result or Range

Positive Indicates Interfering Factors

Hemoglobin Negative Burns, crushing injuries, chemical toxins, transfusion reaction with incompatible blood products

High amounts of Vitamin C, certain medicationsFalse negative results

Protein Negative to 140 mg/L

Glomerular damage Exercise, excess protein intake, cold temperatures False positive results

Glucose Negative DM, endocrine diseases, CNS disease, renal tubular disorder

High amounts of Vitamin C False negative results

Ketones Negative DM, fasting, high fever Certain medications

Nitrites Negative Urea splitting organisms, usually gram negative bacteria

High amounts of Vitamin CFalse negative results

Leukocyte Esterase

Negative UTI High amounts of Vitamin C, vaginal discharge, TrichomonasFalse positive results

Bilirubin Negative to 0.02 mg/dl

Liver or gall bladder disease

Certain medications, prolonged exposure to light degrades bilirubin, test urine immediately

Urobilinogen 0.1 to 1 Ehrlich unit/ml

Sensitive test for liver function, positive with hepatic damage, hemorrhage or hemolytic anemias

Certain medications, prolonged exposure to light or room temperature degrades urobilinogen, test urine immediately

pH pH 4.6 to 8; average about 6

High pH assoc. with bacterial infections or renal failures. Low pH assoc. with acidosis, dehydration or DM

Prolonged standing of sample before testing

Specific Gravity 1.001 to 1.025

Below normal: DI, absence of ADHAbove normal: DM, nephrosis

Isosthenuric 1.010 fixed specific gravity indicative of renal damage

Other Urinalysis Markers • 24 hour Creatinine clearance

– Measure of kidney function and GFR.– Required 24 hour urinary creatinine, serum creatinine and BMI to

calculate– Prior to the Levy method was the most accurate outpatient renal function

measurement

• GFR By the Levy Method– Information follows this section.

• Toxicology screen (drug screen)– Used to elicit further data in the absence of confirmatory clinical

manifestations. Rules out drug overdose or indicates drug use.

• VMA (Vanillmandelic Acid)– 24-hour urine marker for suspected pheochromocytoma. Check for

metanephrines and catecholamines.– More information in the neurology section

Other Urine Markers - 2• HCG (Human Chorionic Gonadotropin)

– Elevated during pregnancy as early as 10 days after conception.– Quantitative (Serum): MOST sensitive, will be positive earliest –

up to 3-4 days prior to urine test.– Qualitative: “Yes or No” answer. Basis of most urine / home

tests.

• Calcium (24 hour)– Hypercalciuria in conditions such as primary hyperparathyroid, bone

neoplasms, Vitamin D toxicity and various drugs.

• Uric acid (24 hour)– Elevated uric acid in gout, dehydration, renal disease, acute

inflammation, and may be drug-induced.

• Oxalate– Elevated in patients who form calcium oxalate stones.– Also increased in ethylene glycol poisoning and certain foods

(beans, strawberries, rhubarb, spinach, chocolate, etc.) that contain oxalates.

Microalbumin – 24 HR UrineReference Interval: • • Normal: 0-30 mg/day • Microalbuminuria: 30-300 mg/day • Clinical albuminuria: >300 mg/day

Use: Measurement of albumin levels in urine below the detection level of urine dipsticks. This test is useful in the management of patients with relatively early diabetes mellitus to assist in avoiding or delaying the onset of diabetic renal disease.

Antihypertensive/Diuretics

MOA Uses Adverse Effects Other

Chlorothiazide

(Hydrochloro-thiazide – HCTZ)

Inhibits sodium and chloride re-absorption in distal tubule resulting in a decrease in the glomerular filtration rate

HTNEdema

Hypokalemia, oliguria, anuria, GI disturbance, hypercalcemia, hyperglycemia, hyperuricemia, renal failure

C.I. in patients with hypersensitiv-ity to thiazide or

sulfonamide drugs

Furosemide[Lasix]

Loop diuretic, inhibits sodium and chloride re-absorption in the Loop of Henle

Edema, HTN

Hypokalemia, oliguria, anuria, GI disturbance, hypercalcemia, hyperglycemia, hyperuricemia, ototoxic, hypovolemia

ALDOSTERONE – RENIN – ANGIOTENSIN SYSTEM

Bladder Control Rx:

• Darifenacin (Enablex)

• Oxybutynin (Ditropan)

• Solifenacin (Vesicare)

• Tolterodine (Detrol)

• Trospium (Sanctura)– All are anti-muscarinic agents (a.k.a.

belladonna like activity)

Muscarinic Antagonist

MOA Uses Adverse Effects Other

“Belladonna Alkaloids”

Hyoscyamine Levsin

Belladonna alkaloid (hyoscyamus)

Diarrhea

Scopolamine Act upon Muscarinic Receptors, more potent at eyes, less potent on heart, lungs and GI

Motion Sickness prevention

CNS depression. Constipation, dry mouth, N/V, drowsiness, headache

Available in transdermal application Increases digoxin levels

GU analgesic

MOA Uses Adverse Effects

Other

Phenazo-pyridine hydrochloride[Pyridium]

Metabolizes and is eliminated via the renal system. Has a topical anesthetic effect.

Pain with UTI

Headache nausea rash pruritus

Interferes with results of urinalysis

OTC: 95mg tablets

Rx: 100, 150 and 200mg tablets

Dosage: 200mg po tid after meals

ED Rx:• Sildenafil (Viagra)

– 25, 50 or 100mg tablets– 1 dose up to 100mg 1 hour before sexual activity

• Tadalafil (Cialis)– 2.5, 5, 10 and 20mg tablets– 1 dose daily up to 20mg without regard to timing of

sexual activity

• Vardenafil (Levitra)– 2.5, 5, 10 and 20mg tablets– 1 dose up to 20mg 1 hour before sexual activity

Nitric Oxide

Arginine

[NO Synthase] NO

Citrulline

Cytoplasmic Cyclase

cGMP GTP

Cellular Activity

+

Retina: Photoreception

Vascular Smooth Muscle: Vasodilatation

AMPA (Excitatory) receptors: probable desensitization

NO Synthase is effectively inhibited by multiple heavy metals. Mol Cell Biochem 1995 Aug-Sep;149-150:263-5

• L-Arginine PO dose– 1000 – 2000mg bid

• Magnesium Glycinate PO dose– 100-300mg bid

• Zinc PO dose– 20-50mg bid (taken in the middle of a meal to

decrease nausea!)

ED Rx:

Renal Stone Analysis

• Performed on any urinary calculi for chemical assay, evaluation and future prophylaxis.

• Urolithiasis: – 75% Ca oxalate, radiopaque(show up on X-ray); – 25% Radiolucent (no X-ray); – Proteus or Staph infection cause alkaline urine / increase crystal

formation, – Stag horn calculi = large obstructive stones in pelvis; – 6% uric acid calculi, gout, radiolucent

• OLIGURIA: urine output (<500cc/d)

• ANURIA: urine output <100cc/d

Hematuria: Important Aspects

• Presence or absence of pain– Painstone, UTI– No painrenal, prostate disease, tumor,

polycystic kidney, trauma, post exercise, BPH

– PAINLESS HEMATURIA IS CANCER UNTIL YOU PROVE IT IS NOT!

Hematuria: Important Aspects

• Gross hematuria:• Hx of menses, beets, AC’s, red clover• What part of stream noticed--

initial=urethra, bladder, terminal=prostate or higher

• Recent physical activity• Patient usually does not become anemic

Azotemia!**Increased BUN in blood

Differentiate site through Creatinine excretionTypically Kidney has to be sick to have Cre rise = to BUN

• Prerenal– Impaired renal blood flow– BUN & Cre both rise but BUN rises faster

• Healthy Kidney with low GFR• High BUN/Cre

• Intrarenal– Injury to the glomeruli, tubules, small vessels– Both high but equally so

• BUN/Cre ratio normal

• Postrenal– Obstruction– Labs tricky (BUN/Cre Normal early, rises after long oliguria).

Types of Acute Renal Failure

• Pre-renal: inadequate renal perfusion from extracellular volume.

• Post-renal: glomerular and tubular dysfunction; obstruction from calculi, prostate, tumors.

• Renal: prolonged ischemia, toxins, acute GN, tubular necrosis.

Acute Renal Failure

• Acute renal failure is sudden loss of the ability of the kidneys to excrete wastes, concentrate urine, and conserve electrolytes.

• Essentials of Diagnosis:– sudden onset of oliguria; 20-200ml/d– proteinuria; hematuria; isosthenuria sp. gr.

1.010-1.016– anorexia, nausea, vomiting, lethargy, HBP Na, Ca, HCO3

Acute Renal Failure

• decreased urine output• decreased urine volume (oliguria) or no

urine output (anuria) • ankle, feet, and leg swelling• generalized swelling, fluid retention • changes in mental status or mood

– agitation– drowsiness, lethargy– Delirium or confusion– coma

• Decreased blood flow– trauma, complicated surgery, septic shock,

hemorrhage, or burns; associated dehydration; or other severe or complicated illnesses.

• Acute arterial occlusion of the kidney and renal artery stenosis

• Over-exposure to metals, solvents, radiographic contrast materials, certain antibiotics, and other medications or substances.

• Infections such as acute pyelonephritis or septicemia

• Urinary tract obstruction

Acute Renal Failure

Acute Glomerulonephritis • Acute Nephritis:

– acute post-strep Glomerulonephritis– Red cell casts, 1-2 weeks after recovery from sore throat– Children 6-10 yrs, moderate proteinuria.

• Caused by inflammation of the internal kidney structures (glomeruli). – Damage to the glomeruli with subsequent impaired

filtering causes blood and protein to be lost in the urine.

– Laboratory tests may reveal anemia or indicate reduced kidney functioning, including azotemia (accumulation of nitrogenous wastes such as creatinine and urea).

– Red Cell Casts

Calculated GFR• Healthy Kidneys: 60 or higher

• Stage 1 Chronic Kidney Disease (CKD):– 90 or higher with HTN, Proteinuria, AbN Ki anatomy

• Stage 2 Chronic Kidney Disease (CKD):– 60-89 with the above

• Stage 3 Chronic Kidney Disease (CKD):– 30-59

• Stage 4 Chronic Kidney Disease (CKD):– 15-29

• Stage 5– 15 or less / Dialysis

Chronic Renal Insufficiency

• Weakness, easy fatigue, headaches, anorexia, nausea, vomiting, pruritis, polyuria, nocturia

• Hypertension, encephalopathy, retinal damage, heart failure

• Anemia, azotemia, acidosis with K, phosphate, sulfate and calcium and protein

• Low or fixed specific gravity, proteinuria, rbc’s,wbc’s, casts

• Diabetes and hypertension are the two commonest causes and account for approximately two thirds of the cases of chronic renal failure and ESRD

• Chronic renal failure results in the accumulation of fluid and waste products in the body, causing azotemia and uremia.

• Creatinine levels progressively increase. • BUN is progressively increased. • Creatinine clearance progressively decreases. • Potassium test may show elevated levels.

Chronic Renal Insufficiency

Infections of the Urinary Tract

• Urine secreted by normal kidneys is sterile until it reaches the distal urethra

• Bacteria reach urinary tract by:– Ascending route—into urethra via fecal or

vaginal contamination, instrumentation; most common

– Hematogenous route

Infections of the Urinary Tract

• Anatomic or functional obstruction is most important cause of ascending infection.

• Important antibacterial defenses:– free flow of urine– large urine volume– complete emptying of the bladder– acid pH

Infections of the Urinary Tract

• Infants—more common in males• > one year—more common in females• Later life—rare in males until BPH ensues incidence with age in women• sexual activity and parity risk in women• Majority from fecal flora e.g. E. coli,(70-90%)

Enterobacter, Klebsiella, enterococcus, Pseudomonas, Proteus– >100,000 bacteria/cc needed for diagnosis

Acute UTI (urethritis, cystitis)

• Symptoms/signs: – dysuria – turbid, foul smelling urine– Frequency– suprapubic tenderness.

• Lab findings: – uabacteriuria, – pyuria, – hematuria. (+) culture

Acute UTI

• Symptoms/signs: – headache, malaise– vomiting, chills, fever– CVA tenderness, abdominal pain.

• Lab findings: – uabacteriuria, protein, – wbc’s; leukocytosis; – blood culture usually negative.

Interstitial cystitis

• Interstitial cystitis (IC) is an inflammation (irritation with increased presence of immune cells) of the tissues of the bladder wall, with no known infectious (bacterial, viral, or fungal) cause.

• Urinary frequency (can be as often as 60 or 70 times per day)

• Urinary urgency• Urinary discomfort (dysuria) • Pain during intercourse (dyspareunia)

• Usually, cystoscopy (endoscopy of bladder) and bladder biopsy are performed. The characteristic finding of interstitial cystitis during cystoscopy is pinpoint bleeding (hemorrhage) in the lining of the bladder.

Pyelonephritis

• Medical Emergency if not resolving: May lead to Kidney Failure!

• Affects tubules and - or interstitium

• Ascending fecal flora

• Females more than males

• Compressive reasons:– Pregnancy – BPH (secondary to stasis of urine).

• Pyelo- indicates renal Pelvis.

MALE PATHOLOGIES - 1• Specific Urethritis:

– GC, males>pain, dysuria, purulent dc, frequency• Non-Specific Urethritis:

– Chlamydia, ureaplasma, E. coli, mild sx, urethral stricture, spread of infection to prostate, epididymis

• HHV / HSV: – Sexually transmitted. May be slowly or quickly symptomatic.

• Syphilis: – STD. Primary, secondary, and tertiary stages. (See micro

notes)• Penile Inflammation:

– balanitis, usu in pts. with phimosis or redudant prepuce, staph, E. coli, candida

• Penile Tumors: – condyloma acuminatum, HPV 6 & 11, benign, sexually

transmitted

MALE PATHOLOGIES - 2

• Hypospadius & Epispadius: – congenital misplacement of urethral canal ventrally or

dorsally, may be associated with undescended testicles, may cause urinary obstruction or inability to inseminate

• Phimosis: – orifice of prepuce is too small to permit retraction. Also

applies to inflammatory fusion of the foreskin to the glans.

• Paraphimosis: – prepuce is retracted & won’t replace

• Klinefelter’s: – male hypogonadism, 2 or more X chromosomes and 1 or

more Y chromosomes

• Cryptorchidism (UNDESCENDED TESTES): – usu unilateral, even if corrected have increased risk of

infertility & testicular cancer

MALE PATHOLOGIES - 3• Epididymititis & Orchitis:

– assoc, with lower UTI & prostatitis, GC or Chlamydia in men under 35; E. coli & pseundomas in men over 35; mumps 1 wk after onset

• Varicocele: – scrotal varicosity, abnormal dilation & tortuosity of pampiniform plexus of

veins, 99% left-sided, may cause infertility, sx corrected, bag of worms• Hydrocele:

– accumulation of serous fluid in scrotum, occurs developmentally in descent of testis or secondary to inflammations, painless, enlarged fluctuant scrotum

• Hematocele: – blood in scrotal sac, dt trauma or sx, spontaneous in atherosclerosis, DM,

scurvy, syphilis, tumors, will not transilluminate• Torsion:

– Medical emergency especially in pediatrics (think “inconsolable child”) due to potential loss of testicle.

• Spontaneous• Traumatic

• Seminoma: – most common tumor with cryptorchidism, best prognosis of testicular tumors,

metastasis to lymphatics, some have increased HCG

Acute Prostatitis

• Acute prostatitis is usually caused by a bacterial infection of the prostate gland.

• include gonorrhea, chlamydia in men under 35• In men older than 35, E. coli and other common

bacteria are more often the cause of prostatitis.

• Acute prostatitis often begins with chills and fever, lower abdominal discomfort, perineal pain, and burning with urination.

• Triple-void urine specimens may be collected for urinalysis and urine culture:

» #1 initial stream » #2 mid-stream » #3 after prostatic massage by examiner

Chronic Prostatitis

• Chronic prostatitis is an inflammation of the prostate gland that develops gradually, continues for a prolonged period, and typically has subtle symptoms.

• The most common causes are Escherichia coli and proteus, enterobacter, and klebsiella bacteria.

• Low-grade or subtle symptoms may include: • Low back pain• Perineal or pelvic floor pain • Testicular pain• Pain/burning with urination• Pain with ejaculation• Pain with bowel movement

Prostate• BPH/Nodular Hyperplasia:

– Discrete nodules in periurethral area middle & lateral lobes, partial or complete obstruction

– May have mild or high PSA elevation– Dihydrotestosterone causes hyperplasia

• TURP is a common Tx

• Carcinoma of Prostate: – Most common cancer of men

• Usually posterior lobe• Hematogenous spread is mainly to lumbar spine,

femur, pelvis, thoracic spine, ribs – Men with a primary male relative with the Dz and African

American males have a higher incidence

ACS Guidelines 2007 - Prostate• Both the prostate-specific antigen (PSA) blood test and digital

rectal examination (DRE) should be offered annually, beginning at age 50, to men who have at least a 10-year life expectancy. – Men at high risk (African-American men and men with a strong family of

one or more first-degree relatives [father, brothers] diagnosed before age 65) should begin testing at age 45.

– Men at even higher risk, due to multiple first-degree relatives affected at an early age, could begin testing at age 40.

• Depending on the results of this initial test, no further testing might be needed until age 45. – Information should be provided to all men about what is known and what

is uncertain about the benefits, limitations, and harms of early detection and treatment of prostate cancer so that they can make an informed decision about testing.

• Men who ask their doctor to make the decision on their behalf should be tested. – Discouraging testing is not appropriate. – Also, not offering testing is not appropriate.

Steroid Hormone SynthesisCHOLESTEROL PREGNENOLONE

PROGESTERONE

STEROIDS

Cortisol

Cortisone

Aldosterone

ANDROGENS

(DHEA)

(ASD)

TESTOSTERONE

ESTROGENS

(E1)

(E2)

(E3)

Testosterone MOA Uses Adverse Effects Other

Testosterone

Testosterone gel [1% Androgel]

All commercially available injectable forms

Can be compounded as well.

Stimulates testosterone receptive tissues

Delayed puberty, androgen deficiency postpartum breast pain, and palliative treatment for female breast cancer

Prostatic hyperplasia, reduced sperm count, hyperlipidemia, atherosclerosis, cholestatic hepatitis, hirsutism, hypercalcemia

Most toxic forms (cypionate, propionate)

Contraindicated in breast feeding women, during pregnancy, and in male patients with breast or prostate cancer.

Class 3 drug: highly monitored

Methyltestosterone Short acting form that stimulates testosterone receptive tissues

Hypogonadism, postpubertal cryptorchidism, breast cancer in females and post-partum breast engorgement

“ “

Androgen Rx:• Testosterone 30mg Buccal

– 1 buccal system qd to bid

• Testosterone Transdermal 2.5 or 5mg / day patches– 1 to 2 patches applied daily

• Testosterone Gel 1% 25 or 50mg / dose– 25 to 100mg qd

• Testosterone Pump 1.25G / pump– Up to 4 – 6 pumps applied daily

Kidney Stones

Nephrolithiasis

• One of the most painful urologic disorders– Calcium stones most common– Uric acid stone much less common

• Once a patient has a stone they have a greater risk of recurrence

Kidney Stones• The calcium may combine with other substances such as oxalate (the

most common substance), phosphate, or carbonate to form the stone. • Oxalate is present in certain foods. Diseases of the small intestine

increase the tendency to form calcium oxalate stones.Symptoms:– flank pain or back pain on one or both sides– nausea, vomiting– urinary frequency/urgency– blood in the urine– abdominal pain– urination, painful– Fever and chills

• Stones or obstruction of the ureter may appear on: – kidney ultrasound– IVP (intravenous pyelogram– abdominal X-rays or CT

Renal Stone Analysis

• Performed on any urinary calculi for chemical assay, evaluation and future prophylaxis.

• Urolithiasis: – 75% Ca oxalate, radiopaque(show up on X-ray)– – 25% Radiolucent (no X-ray)

– Proteus or Staph infection cause alkaline urine / increase crystal formation

– Stag horn calculi = large obstructive stones in pelvis

– 6% uric acid calculi, gout, radiolucent

Interstitial Nephritis

• Acute– It may be a temporary lesion, most often

associated with the effects of various medications on the kidney, or it may be chronic and progressive.

– Medications commonly associated with interstitial nephritis include antibiotics such as penicillin, ampicillin, methicillin, sulfonamide medications, and others.

– Interstitial nephritis causes reduction in kidney function, ranging from mild dysfunction to acute kidney failure.

Interstitial Nephritis• Symptoms 

– increased or decreased urine output – fever – mental status changes, ranging from drowsiness to confusion to coma – nausea, vomiting – rash (sometimes) – swelling of the body, any area

• weight gain (from fluid retention) – blood in the urine

• Signs and tests – An examination may reveal edema or fluid overload, or signs of volume depletion, with abnormal

sounds heard when listening with a stethoscope to the heart or lungs. The blood pressure commonly is high.

– A urinalysis shows small amounts of protein and sometimes red blood cells, renal tubular cells, and other abnormalities. The excretion of protein in the urine is not as severe as with nephrotic syndrome.

– WBCs and WBC casts in the urine (particularly eosinophils) are often seen. – CBC may demonstrate eosinophilia (higher than normal eosinophil count). – Urine specific gravity and osmolality show there is a failure to concentrate urine even when water intake

is restricted. – Urine pH may show a failure to acidify urine appropriately. – Arterial blood gases and blood chemistry may show metabolic acidosis. – BUN and creatinine levels are used to assess level of kidney functioning. – RBC - urine shows increased red blood cells indicating kidney disease. – A kidney biopsy confirms the diagnosis of interstitial nephritis and is used to evaluate the extent of

damage to the kidney.

Hereditary Chronic NephritisAlport syndrome

• An inherited (usually X-linked) disorder:• Involves damage to the kidney

– Hematuria– and in some families, loss of hearing. – The disorder may also include eye defects.

• The cause is a mutation in a gene for collagen formation.

• The disorder causes chronic glomerulonephritis with ultimate destruction of the glomeruli.

Polycystic Kidney Disease • An inherited kidney disorder which enlarges the

kidneys and interferes with their function because of multiple cysts on the kidneys.

• Cysts in the kidneys are associated with• aneurysms of the blood vessels in the brain• diverticula of the colon• cysts in the liver, pancreas, and testes.

• Up to 50% of people with polycystic kidney disease also have cysts on the liver.

Polycystic Kidney Disease• The disease is slowly progressive, eventually resulting in end-stage kidney failure. It

is also associated with liver disease, including infection of liver cysts. – An autosomal recessive form of polycystic kidney disease also exists and appears in

infancy or childhood; it tends to be very serious and progresses rapidly, resulting in end-stage kidney failure and causing death in infancy or childhood.

• Examination may show high blood pressure – Kidney / abdominal masses palpated during examination– Abdominal tenderness over the liver and enlarged liver. – There may be heart murmurs or other signs of aortic insufficiency or mitral insufficiency.

• A urinalysis is nonspecific, but it may show urine protein or blood in the urine. • A CBC may show decreased or increased RBCs and hematocrit.

• Cerebral angiography may show associated aneurysms. • Polycystic kidney disease, and associated cysts on the liver or other organs, may

show on: – abdominal ultrasound – abdominal CT scan – abdominal MRI scan – IVP

• In a family with several affected members, genetic linkage tests can be performed to determine with fair reliability whether a person at risk carries the gene for ADPKD.

Single Renal Cysts

• Often a cause of “painless hematuria”

• Found incidentally on imaging

• Most commonly not cancerous

• Follow with follow up U/A and Imaging

Nephrotic Syndrome

• A constellation of signs and symptoms including:

• protein in the urine (exceeding 3.5 grams/day)• low blood protein levels• high cholesterol levels and • swelling (edema). • The urine may also contain fat which is visible

under the microscope.

Nephrotic Syndrome• Nephrotic syndrome is caused by various

disorders which damage the kidneys, particularly the basement membrane of the glomerulus. – (Membranous GN)– This immediately causes abnormal excretion of

protein in the urine.

• Symptoms– General edema (around the eyes feet and ankles)– Ascites– Foamy appearance of the urine – Weight gain (unintentional) from fluid retention

Nephrotic SyndromeCauses, incidence, and risk factors of Membranous GN• Membranous nephropathy is caused by thickening of the capillary wall of the

glomerular basement membrane (the deepest membrane) by immune complexes. – The cause is not known.– It is one of the most common causes of nephrotic syndrome, which is the most common

presentation of the disease. – It may also appear as asymptomatic excretion of protein in the urine. – Glomerular filtration rate is usually nearly normal, and examination of sediment in the urine

may be unremarkable or may show oval fat bodies, and hyaline, granular, and fatty casts.– Membranous nephropathy may be a primary renal disease of uncertain origin, or it may be

associated with other conditions. • Risks include systemic disorders such as Hepatitis B, malaria, malignant solid tumors, non-

Hodgkin's lymphoma, systemic lupus erythematosus, syphilis, and others. • Risks also include exposure to substances or medications, including gold, mercury,

penicillamine, trimethadione, skin-lightening creams, and others.

• Tests to rule out various causes may include: – glucose tolerance test – antinuclear antibody – rheumatoid factor – cryoglobulins – complement levels – Hepatitis B and C antibodies – VDRL serology – serum protein electrophoresis – kidney biopsy

IgA Nephropathy (Buerger’s Disease)

• “Primary Recurrent Hematuria”– an immune complex glomerulopathy in which

deposition of IgA with C3 and fibrin-related antigens occurs in a granular pattern in the glomerulus

– Macro and microscopic hematuria, mild proteinuria are usually the only signs

– Disease progresses over 2 to 3 decades with glomeruli destruction, loss of renal function and hypertension.

IgA Nephropathy (Buerger’s Disease)

• Dx made by renal biopsy– Mostly a clinical Dx though– See posted document on Buerger Dz

• IgA also found in skin capillaries.

• Similar deposits may be seen in – Henoch-Schölein purpura– SLE– eclampsia

– as well as other causes of glomerular disease

IgA Nephropathy (Buerger’s Disease)• Risk factors include having a personal or family history of IgA

nephropathy or Henoch Schonlein purpura (a form of vasculitis that affects many parts of the body, and may cause a kidney lesion that is identical to the lesion of Berger's disease).

• Berger's disease can occur in persons of all ages, but most often affects males in their teens to late 30s

• Prognosis:– IgA nephropathy progresses slowly. In many cases, it does not progress

at all. – High blood pressure, large quantities of protein in the urine, and

increased BUN or creatinine levels indicate a higher risk for progression of the disorder.

– About 25% of people with IgA nephropathy develop end-stage renal failure within about 25 years.

Henoch-Schonlein Purpura

• kids 3-8 yrs

– Purpuric skin lesions on extensor surface of extremities & buttock

– IgA precipitation after respiratory infection

– Hematuria recurrences for yrs

Goodpasture’s SyndromeAnti-glomerular BM Nephritis

• A form of rapidly progressive glomerulonephritis.

– Goodpasture’s involves a progressive decrease in the kidney's ability to function properly, accompanied by a cough with bloody sputum.

– Antibodies collect in both the kidney glomerulus and the alveoli in the lungs, causing both glomerulonephritis and bleeding in the lungs.

Goodpasture’s SyndromeAnti-glomerular BM Nephritis

• Symptoms – Hematuria– Dark colored urine – Decreased urine output – Foamy urine – Cough with bloody sputum (coughing up blood) – Difficulty breathing after exertion – Weakness – Nausea/vomiting – Nonspecific chest pain – Pale skin

• Signs and labs:– Hypertension– Pulmonary rales– A skin rash may be observed in some cases.– A CBC often indicates anemia. – Serum iron and ferritin may be low. – BUN and creatinine levels increase as kidney function decreases. – A urinalysis may show protein, blood, casts, or other abnormality. – Serum antibody to normal human glomerular basement membrane is positive. – Sputum stain may indicate macrophages that contain iron pigments. – A chest X-ray shows fluid in the lung tissues. – A lung needle biopsy shows immune system deposits.

Summary: Renal / Urinary Cancers:• Adenocarcinoma / Hypernephroma:

– Cigarette, pipe, & cigar smokers; upper kidney pole, solitary, unilateral– Metastasize to lung & bone before sx appear – Painless hematuria

• Wilm’s Tumor: – Common primary renal tumor in kids, genetic, age 2-5 yrs, – Large abd mass – painless hematuria– good prognosis with tx

• Malignant Ureteric Tumors: – Primary rare (normally metastatic dz.) transitional cell CA– obstruction – painless hematuria

• Tumors of Bladder: – Risk factors; Industrial solvents, > cigarette smoking. – Transitional cell tumors, benign papilloma; 90% transitional cell carcinoma,

squamous cell carcinoma, – Painless hematuria– HCG in urine is marker of aggressive tumor– tends to recur after excision

Renal Cell Carcinoma

• A kidney cancer that involves cancerous changes in the cells of the renal tubules:

– The most common type of kidney cancer in adults.

– A history of smoking greatly increases the risk for developing renal cell carcinoma.

– Hematuria is the single most common symptom and leads to anemia

Renal Cell Carcinoma• Symptoms

– Hematuria – Abnormal urine color (dark, rusty, or brown) – Flank pain – Back pain – Abdominal pain – Weight loss, more than 5% of body weight

• Emaciated, thin, malnourished appearance – Enlargement of one testicle – Ascites

• Additional symptoms that may be associated with this disease: – Vision abnormalities – Paleness – Excessive hair grown (females) – Constipation – Cold intolerance

Embryonic TumorsNephroblastoma (Wilms Tumor)

• Wilms' tumor is one of the most common tumors of the abdomen in children and the most common type of kidney tumor.

• The exact cause of tumor formation in most children is unknown.

• Peak incidence in second year of life• Symptoms

• Abdominal pain • Swelling in the abdomen• Blood in the urine (occurs in less than 1/4 of children)

Nephroblastoma (Wilms Tumor)• It is associated with certain birth defects including urinary tract abnormalities, absence of the iris

(aniridia), and hemihypertrophy (enlargement of one side of the body).

• It is more common among some siblings and twins, which suggests a possible genetic cause.

• The tumor may become quite large, but usually remains encapsulated - It may spread to other body tissues, especially the lungs.

• The frequency of disease occurrence is estimated to be about 1 out of 200,000 to 250,000 children. The peak time of occurrence is at 3 years old, and Wilms' tumor is rare after the age of 8 years.

• Symptoms– Abdominal pain – Swelling in the abdomen (abdominal hernia or mass) – Blood in the urine (occurs in less than 1/4 of children) – Fever – Loss of appetite – Nausea – Vomiting – General discomfort or uneasiness (malaise) – Blood pressure, high – Constipation – Increased growth on only one side of the body (hemihypertrophy) – Note: Abnormal urine color may also be associated with this disease. A missing iris of the eye (aniridia)

is a birth defect that is sometimes associated with Wilms' tumor.