Polycystic KD/Nephrolithiasis

Question 1

Polycystic Kidney Disease (PKD)

General

Answer 1

Autosomal condition characterized by fluid-filled sacs (cysts) in the kidneys that grow larger and lead to gradually loss of kidney function
Autosomal dominant (ADPDK) and recessive forms (ARPKD)

At least two genes account for the autosomal dominant disorder
ADPKD1 on the short arm of chromosome 16
Most common cause affecting 85-90% of patients

ADPKD2 on chromosome 4
Less common cause affecting 10-15% of patients
Slower progression of disease and longer life expectancy

Question 2

PKD

Autosomal dominant inheritance pattern

Answer 2

The mutated gene is a dominant gene located on a non-sex chromosomes (autosomes)

Only one mutated gene is needed to be affected by this type of disorder

Signs and symptoms appear between 30-40 years of age

Question 3

PKD

Autosomal recessive inheritance pattern

Answer 3

Two mutated genes, one from each parent is required

These disorders are usually passed on by two carriers (health is rarely affected)

Signs and symptoms can appear shortly after birth or into adolescence

Question 4

PKD

Patho

Answer 4

Increasing number and size of cysts:
Compromise blood supply to the nephrons = poor perfusion to the kidney → What happens when there is poor perfusion?
Activation of the RAAS → fluid retention & ↑ BP
Compression of the collecting system → urinary stasis and the possibility of kidney stone formation
Destruction of the normal renal architecture → flank pain and hematuria

Question 5

PKD

Clin Man

Answer 5

Renal Manifestations
Abdominal pain or flank pain
Microscopic or gross hematuria
Hypertension
Abdominal mass (enlarged kidneys that are palpable on exam)

Question 6

PKD

Complications

Answer 6

Poorly controlled hypertension

Loss of kidney function- ESRD develops by age 60 years in 50% of patients

Nephrolithiasis: 20% of patients
Stones are usually made of calcium oxalate

Renal Infection: Cysts can become infected
Flank pain, fever, leukocytosis
Urinalysis can be normal if the cyst does not communicate with the urinary tract

Development of a cerebral aneurysm (Berry aneurysm)
10-15% of patient have an aneurysm in the circle of Willis

Pregnancy complications
Associated with higher risk for preeclampsia

Question 7

PKD

Family Hx

Answer 7

Known family history
Diagnostic criteria for autosomal dominant polycystic kidney disease:
Two or more cysts in patients 30 or younger
Two or more cysts in each kidney in patients 30-59 years
Four or more cysts in each kidney in patients 60 years or older

No known family history
CT scan of the abdomen and pelvis to establish the presence of cysts in the kidney(s) and possibly the liver
Genetic testing for the ADPKD1 or ADPKD2 mutations

Don’t memorize

Question 8

PKD

Imaging

Answer 8

Ultrasound
Performed to detect the size and number of kidney cysts

CT scan or MRI
Performed if ultrasound findings are inconclusive
Can detectcysts of smaller size
Determines total kidney volume (helps assess the risk of kidney disease progression)

Question 9

PKD

Management of blood pressure

Answer 9

Use of an angiotensin-converting enzyme (ACE) or angiotensin II receptor blockers (ARB)
Target BP of < 110/75 mmHg in young, healthy individuals aged 18 to 50 years with normal GFR
Target BP of < 130/80 mmHg in all other patients

Question 10

PKD

Lifestyle Mods

Answer 10

Dietary sodium restriction
2 grams intake per day or less

Increase fluid intake
Drink > 3 L of fluid per day, unless the eGFR is < 30 or the patient is at risk for hyponatremia (taking a thiazide diuretic)
Suppress plasma vasopressin (antidiuretic hormone (ADH)) levels

Limit alcohol use

OTC acetaminophen for chronic pain; avoid use of NSAIDs

Question 11

PKD

End-stage renal disease (ESRD)

Answer 11

~half ofpatients ≥ 75 years of age
Hemodialysis orperitoneal dialysis
Kidney transplantation

Question 12

Nephrolithiasis/ Urolithiasis

General

Answer 12

One of the most common conditions affecting the urinary system
Formation of a stone (calculus) anywhere along the urinary tract
Caused by the precipitation of solutes (minerals and salts) in the urine

Most common stone composition:
Calcium oxalate 70-80%
Struvite (ammonium magnesium phosphate) 5-10%
Uric acid 10%
Cystine < 5%
Calcium phosphate 5%

Most common in non-Hispanic white patients; least common in black and Asian patients

Incidence increases with age
19% of men and 9% of women will be diagnosed with a kidney stone by age 70

Question 13

Question 14

Nephrolithiasis/ Urolithiasis

RF

Answer 14

Family history

Urinary factors
pH
Alkaline urine (≥ 6.5) → calcium phosphate stones
Acidic urine (≤ 5.5) → uric acid stones
Volume
Higher urine volume is associated with a lower risk

Dietary factors
Higher consumption of animal protein and lower intake of fruits and vegetables → decreased urine pH (uric acid stones)
Sugar-sweetened beverages

High serum and urine calcium
Dehydration
Excessive concentration of urine solutes → stone formation
Loop diuretics
Inhibits calcium reabsorption → hypercalcinuria
Also has an inhibitory effect of sodium and potassium
Examples: furosemide (Lasix) and bumetanide (Bumex)

Question 15

Nephrolithiasis

Kidney Stones

Answer 15

All stones are radiopaque except uric acid stones

Calcium oxalate, uric acid, and calcium phosphate are non-infection stones
Struvite are infection stones
Cystine stone is a genetic stone; autosomal recessive defect insodium-dibasicamino acidcotransporter

Question 16

Nephrolithiasis

Staghorn calculi

Answer 16

Also referred to as coral calculi
Usually a struvite stone
Branched stones that occupy a large portion of the collecting system (renal pelvis and calyces)
Can damage the kidney and/or lead to life threatening urosepsis

Question 17

Nephrolithiasis

Medical Conditions Associated with Kidney Stones

Answer 17

Primary hyperparathyroidism (high calcium levels)
Gout (high uric acid)
Hypertension
Diabetes mellitus
Obesity
Inflammatory bowel disease (IBD)
Short gut syndrome
Gastrointestinal bypass surgery
Urinary tract infections (chronic upper urinary tract)

Question 18

Nephrolithiasis

Clin Man

Answer 18

Depends on the size, number, and location of the stone(s)
Small stones may be asymptomatic

Pain (renal colic)
Most common symptom and can be variable
Waxes and wanes in severity and develops in waves
Develops when stones initially pass into the ureter causing ureteral obstruction

Site of obstruction determines the location of pain
Upper ureteral or renal pelvis obstruction = flank pain/costovertebral angle (CVA) tenderness
Lower ureteral obstruction = radiates to the labium or ipsilateral testicle
Variable location of pain can be misleading and can mimic an acute abdomen or dissecting aneurysm

Hematuria
Gross or microscopic → trauma to the ureter
Discriminating predictor of a kidney stone in patients with unilateral flank pain

Other symptoms:
Nausea and/or vomiting
Dysuria and urinary urgency
Fever → infection

Question 19

Nephrolithiasis

Sites of Obstruction

Answer 19

Kidney stones can lodge in any of the 3 natural narrowings along the ureter:

Ureteropelvic junction(UPJ)
Junction of therenal pelvisand ureter

Ureter at thepelvic inlet
Site of ureteral crossing of the iliac vessels

Ureterovesical junction (UVJ)
Junction of the ureter andurinary bladder

Question 20

Nephrolithaisis

Complications of Obstruction

Answer 20

A lodged stone can cause obstruction and consequent proximal complications:

Acute pyelonephritis:
Obstruction of theurinary tract, which allows for proximal overgrowth ofbacteria
Inflammationof therenal pelvis → kidney parenchyma results
Presents withfever, urinary frequency, urgency,dysuria, and costovertebral angle tenderness

Hydronephrosis:
Obstruction causes proximal accumulation ofurine
Results in the dilation of therenal pelvis and calyces (visible on imaging)

Question 21

Nephrolithiasis

Labs

Answer 21

Nephrolithiasis should be suspected in patients with renal colic or flank pain with or without gross hematuria

Labs
BMP
Assess kidney function (BUN and creatinine)
Urine pregnancy test
Urinalysis
To evaluate for hematuria and signs of urinary tract infection
Pyuria and positive nitrites – concurrent urinary tract infection
Urine microscopic
Evaluates for the presence and shape of crystals

Question 22

Nephrolithiaisis

Imaging

Answer 22

Diagnostic imaging
Determines if a kidney stone is present and to assess for obstruction (hydronephrosis)
Stone size and location
Helps to predict the likelihood of spontaneous passage
Guide management

Recent passage of a ureteral stone can also be seen:
Pyeloureteral dilatation
Perinephric stranding

Modalities
CT scan of the abdomen and pelvis without contrast (gold standard)
IV contrast can decrease sensitivity for small stones (> 2 mm)
If a patient is pregnant, an ultrasound of the kidneys and bladder is preferred
Abdominal x-ray (KUB): can detect large stones

Question 23

Nephrolithiasis

tx

Answer 23

Many patients can be managed with hydration (reverses precipitation) and pain management until the stone passes (≤ 5 mm)
Hospitalization for patients that:
Cannot tolerate oral intake
Have uncontrolled pain or fever

Strain urine
Done for several days to capture the stone for analysis

Urology consultation
Patients with concomitant urinary tract infection
Obtain a urine culture
Prompt treatment with antibiotics
Acute kidney injury
Anuria
Bilateral ureteral obstruction
Single-functioning kidney

Question 24

Nephrolithiasis

Pain control

Answer 24

NSAIDs
Initial choice for pain control
Ketorolac (Toradol) 15-30 mg IV
Relief in 10-30 minutes

Opioids
Stone passage
Smaller and more distal stones are more likely to pass without intervention
≤ 5 mm pass spontaneously
≥ 10 will not pass
Alpha adrenergic blocker
Ureteral stones > 5 mm and < 10 mm
Tamsulosin (Flomax) 0.4 mg PO once daily for up to 4 weeks

Question 25

Nephrolithiasis

Surgical management

Answer 25

10-20% of all kidney stones require surgical removal
Indications:
Pain
Infection
Urinary obstruction

Surgical options
Ureteroscopy (with stent)
Treatment of choice for the majority of middle and distal ureteral stones; can also be used to manage proximal ureteral stones
Modality of choice for patients with obesity, who are pregnant, or have a bleeding disorder
Stents are sometimes placed to help prevent ureteric obstruction and pain from passage of a stone

Stents can be uncomfortable and patient are more likely to have lower urinary tract symptoms (dysuria, frequency, urgency and hematuria)

Question 26

Shock wave lithotripsy

Answer 26

Shock wave lithotripsy
High-intensity acoustic pulses
Not suitable for patients with obesity, pregnant patients, patients with uncontrolled bleeding disorders, or patients with abnormal anatomy

Question 27

Percutaneous nephrolithotomy

Answer 27

Surgical procedure with skin incision to retrieve the kidney stone
Reserved for large (> 20 mm) or complex stones (Staghorn stones)

Question 28

Stone-Specific Management

Calcium oxalate andcalcium phosphate stones

Answer 28

Low-sodium diet to increase concomitantsodium andcalcium reabsorptionin proximal tubules
Citrate to dissolvecalcium oxalate crystals
Thiazide diuretics to increasecalcium reabsorption in the distal tubule

Question 29

Stone-Specific Management

Struvite stones

Answer 29

Antibiotic therapy to eliminate the causative microbe
Proteus mirabilis
Proteus vulgaris
Morganella morganii

Question 30

Stone-Specific Management

Uric acid stones

Answer 30

Urine alkalinization withpotassium citrate to dissolve uric acid crystals
Allopurinol to decrease uric acid production

Question 31