Nephrolithiasis

Adnan Alsaka M.D.

Nephrology Fellow

Nephrolithiasis is estimated to produce medical costs of $2.1 billion per year in the US

Incidence is 0.5% Prevalence is 5.2%

More common in Asians and whites than in Native Americans, Africans, African Americans

male-to-female ratio of 3:1 Stones due to infection (struvite) are

more common in women

Most urinary calculi develop in persons aged 20-49 years

An initial stone attack after age 50 years is relatively uncommon

Pathophysiology

1- supersaturation of the urine by stone-forming constituents

Crystals or foreign bodies can act as nidi, upon which ions from the supersaturated urine form microscopic crystalline structures

Randall plaque

is deposition of stone material on a renal papillary calcium phosphate nidus

Calcium phosphate precipitates in the basement membrane of the thin loops of Henle, erodes into the interstitium, and then accumulates in the subepithelial space of the renal papilla

The subepithelial deposits, eventually erode through the papillary urothelium

Causes of Nephrolithiasis

Hypercalciuria

most common metabolic abnormality can be subdivided into absorptive,

resorptive, and renal-leak categories

Absorptive Hypercalciuria

related to increased intestinal absorption of calcium (associated with excess dietary calcium and/or overactive calcium absorption mechanisms)

the treatment may include modest dietary calcium restriction, thiazide diuretics, oral calcium binders

Resorptive hypercalciuria

related to excess resorption of calcium from bone (i.e., hyperparathyroidism)

Treatment requires parathyroidectomy

Renal-leak hypercalciuria

less common than absorptive hypercalciuria related to an inability of the renal tubules to

properly reclaim calcium in the glomerular filtrate

Usually associated with secondary hyperparathyroidism and is best managed with thiazide diuretics

Indiscriminate dietary calcium restriction is not advantageous

The reduced dietary calcium reduces the oxalate-binding sites in the gastrointestinal tract, increasing the free dietary oxalate and leading to increased oxalate absorption

Hyperoxaluria

Primary ( rare genetic disease)

Enteric

Dietary

Primary hyperoxaluria

Type I mutation of AGXT gene on chromosome 2 that

codes for alanine glyoxylate aminotransferase Type II mutation of GRHPR gene on chromosome 9 that

codes for glyoxylate reductase and hydroxypyruvate reductase.

Enteric

Due to malabsorption Associated with chronic diarrhea or short

bowel syndrome Normally, calcium binds to intestinal

oxalate reducing its absorption

Ingestion of large amount of Vitamin C

(> 2 gram/day) increase the risk of Oxalate stone

Calcium citrate is the recommended supplement because it tends to further reduce stone formation

Calcium carbonate supplementation is less expensive but does not provide citrate's added benefit

Calcium therapy works as an oxalate binder, reducing oxalate absorption from the intestinal tract.

Calcium should be administered with meals, especially those that contain high-oxalate foods.

The supplement should not contain added vitamin D because this increases calcium absorption

The optimal 24-hour urine oxalate level is 20 mg/d or less

Hyperuricosuria

predisposes to the formation of calcium-containing calculi because sodium urate can produce malabsorption of macromolecular inhibitors

can serve as a nidus for the heterogeneous growth of calcium oxalate crystals

Therapy involves potassium citrate supplementation, allopurinol, or both

Uric acid stones

Exists in equilibrium with urate at a pK of 5.5

As pH falls below 5.5, concentration of undissociated uric acid greatly exceeds that of urate

High BMI, glucose intolerance and overt DM 2 are common in uric acid stone formers

The optimal 24-hour urine uric acid level is 600 mg/d or less

Sodium and phosphorus

Elevated urinary sodium levels are almost always associated with dietary indiscretions

Decreasing the oral sodium (<2.5 gm/day) intake can decrease calcium excretion by increasing proximal calcium absorption

Hyperphophaturia

Renal phosphate leak: high urinary phosphate levels, low serum phosphate levels, high serum 1,25 vitamin D-3 (calcitriol) levels, and hypercalciuria.

This type of hypercalciuria is uncommon and does not respond well to standard therapies

Phosphate supplements are used to correct the low serum phosphate level, which then decreases the inappropriate activation of vitamin D originally caused by the hypophosphatemia

Citrate and magnesium

are important chemical inhibitors of stone formation

Hypocitraturia is one of the most common metabolic defects that predispose to stone formation

24-hour urine citrate levels of 320 mg/d is the normal threshold

Magnesium is a more recently recognized inhibitor of stone formation, and the clinical role of magnesium replacement therapy is less well defined than that of citrate

High Protein diet

The institution of a high protein diet (2 g/kg per day) adversely effects the metabolic parameters determining the risk of calcium stone formation

Protein restriction reduce Ca oxalate formation by:

less acidic urine reduces the formation of UA stones

less acidic urine favors the trivalent form of the citrate anion, which is less able to bind the Na/citrate cotransporter in PT

Reduction of daily acid load reduces bone buffering (calcium resorption) to reduce ca excretion

Struvite Stones

form in chronic upper urinary tract infection due to a urease-producing organism

are composed of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite

Normal urine is undersaturated with ammonium phosphate, and struvite stone occurs only when ammonia production is increased and the urine pH is elevated to decrease the solubility of phosphate

Struvite Stones

may grow rapidly over a period of weeks to months can develop into a staghorn calculus involving the entire renal collecting system

Cystine stones

only develop in patients with cystinuria (an autosomal recessive disorder)

due to the poor solubility of cystine in the urine

Autosomal recessive or dominant Increased excretion of COAL (cystine,

ornithine, arginine, lysine)

Cystine superstauration occurs at cystine concentration > 250 mg/L

its solubility will gradually increase as pH increases from 6.5 to 7.5

The hallmark of treatment is water, water and more water.

Cystine crystals

Phosphate crystals

Uric acid crystals

Calcium oxalate

Obstructive Uropathy

refers to obstruction of the urinary tract at any point from the renal pelvis to the distal urethra

The acute or chronic loss of kidney function resulting from obstruction is termed obstructive nephropathy

The likelihood of functional impairment

depends on The duration of the obstruction

Whether it is partial or complete

Whether it involves one or both functioning kidneys

Dilated urinary tract without obstruction 1- Pregnancy is the most common cause

occurring in 50% of women in 3rd trimester

due to reduced peristalsis movement and ureteral relaxation due to progesterone

It is not a cause of renal failure

Dilated urinary tract without obstruction

2- Vesicoureteral reflux 3- high urine flow rate 4- Acute pyelonephritis

Effects on glomerular filtration

The first 2-3 hours: the release of Prostaglandin from Macula

densa in response to distal tubular flow will lead to vasodilation

GFR is maintained because the increase in tubular pressure is offset by increase in tubular blood flow

After 4-5 hours:

Intra-tubular pressure falls as sodium and water are reabsorbed

The release of Angiotensin II from Macula densa

in response to decreased distal sodium delivery and promotes vasoconstriction

Renal blood flow and GFR both fall in the subsequent 12-24 hours

Tubular functions during obstruction Early on, urine indices are suggestive of a

pre-renal insult due to enhanced absorption of sodium and water in response to decreased distal delivery

With more prolonged obstruction, FENA >1 as sodium reabsorption falls

Natriuresis follows the release of obstruction down-regulation in the number and activity

of sodium transport proteins throughout the nephron

reduced activity of NA/K ATPase Release of prostaglandin by inflammatory

cells

Question 1

In industrialized countries, what is the most common type of urinary stone?

A- Calcium phosphate B- Calcium oxalate C- Ammonio magnesium phosphate (struvite) D- Uric acid E- Cystine

Question 1

In industrialized countries, what is the most common type of urinary stone?

A- Calcium phosphate B- Calcium oxalate C- Ammonio magnesium phosphate (struvite) D- Uric acid E- Cystine

Question 2

A 48-year-old woman is admitted to the hospital for intravenous

hydration and analgesics after experiencing her third bout of renal colic in the past year. Previous intravenous pyelograms revealed recurrent right- and left-sided 3-mm caliceal stones. A current sonogram shows a 3-mm right caliceal stone and a 2-mm distal ureteral stone. Physical examination of the heart and lungs is unremarkable. Abdominal examination reveals right flank tenderness. Which of the following is the LEAST likely diagnosis?

Hyperparathyroidism Gout Rheumatoid arthritis Sarcoidosis Renal tubular acidosis

Question 2

3. A 48-year-old woman is admitted to the hospital for intravenous hydration and analgesics after experiencing her third bout of renal colic in the past year. Previous intravenous pyelograms revealed recurrent right- and left-sided 3-mm caliceal stones. A current sonogram shows a 3-mm right caliceal stone and a 2-mm distal ureteral stone. Physical examination of the heart and lungs is unremarkable. Abdominal examination reveals right flank tenderness. Which of the following is the LEAST likely diagnosis?

Hyperparathyroidism Gout Rheumatoid arthritis Sarcoidosis Renal tubular acidosis

Question 3

A 44-year-old male patient has passed his second Ca Oxalate urinary stone. He was told to increase his fluid intake and referred to your evaluation. A 24-hour urine collection reveals the following:

Volume 2500 ml Sodium 250 mEq Calcium 240 mg Uric Acid 700 mg Oxalate 25 mg Citrate 350 mg

What treatment do you recommend? A- Increase fluid intake B- Thiazide diuretic C- Reduce sodium intake D- Allopurinol E- Urocit-K

Thank you