Medical management of stones

1. DR/ MOHAMED ASHRAF MOSTAFA
MS, F.R.C.S.

2.  Nephrolithiasis is a common disorder.
 The first evidence of urinary stones was found
in an Egyptian mummy 4800 B.C
 Physiological or environmental causes of renal
calculi were identified in more than 97% of
patients with stone disease
 Low urinary volume is by far the most common
abnormality, and the single most important
factor to be corrected to avoid recurrences

3.  12% have stone in lifetime.
 12% of men will suffer from kidney stone by
age of 70
 5% of women will suffer from kidney stone by
age of 70
 50% have recurrence with in 5-10 yrs
 Highest incidence of kidney stone is in 30-45
years of age group, and incidence declines
after age of 50
 7-10 of every 1000 hospital admission is of
renal stone

4. North
America
Stone
Belt
The Afro-Asian stone-forming belt
stretches from Sudan, Egypt, Saudi
Arabia, Emirates, Iran, Pakistan, India,
Myanmar, Thailand, and Indonesia to
the Philippines
The disease affects all age groups,
from less than 1 year old to more than
70 yr old
Male-to-female ratio of 2 to 1.
The prevalence of calculi ranges from
4% to 20%

5.  Race and gender
Idiopathic stone disease occurs more
frequently in white Caucasians than in Blacks
Male > Female
 Climate and season
The incidence is higher in countries with warm or
hot climates, probably due to low urinary output
and scant fluid intake.

6.  Sodium intake , a major risk factor for stone formation
Calcium is reabsorbed passively in the proximal
tubule down the favorable concentration gradient
created by the reabsorption of sodium and water.
 Potassium-rich foods such as vegetables and
fruits has a role in the prevention of stone
formation .
 Potassium consumption augments renal tubular
phosphate absorption, which inhibits the
synthesis of 1,25-dihydroxyvitamin D. This results
in decreased intestinal absorption of calcium,
which reduces urinary calcium excretion

7.  Animal protein intake has
a great influence on stone
forming risk and the chemical
composition of urinary calculi
 The higher prevalence of
urolithiasis in Saudi Arabia
than in the USA and Europe
has been ascribed to a high
intake of animal protein,
which was 10% and 50%
higher than in the USA and
Europe, respectively.

8.  Carbohydrate consumption induces increased
urinary calcium excretion (decreased distal tubular
calcium absorption and augmented intestinal calcium
uptake).
Urinary oxalate excretion significantly increases after
administration of a glucose load .
 Obesity Increased prevalence of urolithiasis and
recurrence associated with obesity, with elevated
urinary excretion of calcium, sodium, uric acid and
oxalate . In obese patients, associated metabolic
derangements such as insulin resistance and
compensatory hyperinsulinemia may lead to the
formation of calcium containing kidney stones

9.  Autosomal recessive inheritance was defined for
cystinuria and primary hyperoxaluria. The
reported prevalence for cystinuria is 1–5% of all
patients with urolithiasis and much lower for primary
hyperoxaluria (∼2 per million populations). These
diagnoses require sophisticated procedures.
 A familial occurrence has also been suggested for
hypercalciuria . However, familial recurrence does not
necessarily imply an inherited transmission, as it may
be an effect of environmental factors shared by family
members, mainly those related to dietary habits.

11. Promoting factors Inhibiting factors
 Calcium
 Oxalate
 Urate
 Cystine
 Low urine pH
 Tamm-Horsfall
protein
 Low urine flow
 Inorganic
 Citrate
 Magnesium
 Pyrophosphate
 Organic inhibitors adsorb to
the surface of the crystal,
thereby inhibiting crystal growth
and nucleation.
Urinary Prothrombin fragment 1
Protease inhibitor: inter a inhibitor
Glycosaminoglycans, Osteopontin
(Uropontin),Renal lithostathine
 High urine flow

12.  Urinary
Lower volume
Higher calcium Higher oxalate (CaOx stones
Lower citrate
Higher pH (CaP stones)
 Anatomic
Medullary sponge kidney ,Horseshoe kidney, PUJO
 Diet
Lower fluid intake, Lower dietary calcium, Higher
oxalate
Lower potassium, Higher animal protein, Higher
sodium
Higher sucrose, Lower phytate, Higher vitamin C
 Other medical conditions
Primary hyperparathyroidism, Gout, Obesity, Diabetes
mellitus
 Family history , Two-fold higher risk

13.  Acetazolamide
 Ca- channel blockers
 Vitamin C
 Trimterene
 Ca / Vitamin D
 P- binding antacids
 Furosemide
 Theophylline

14. Risk
assessment
Family history of
stones, recurrent
stones
Bone/G.I disease
Gout
Chronic UTI
Nephrocalcinosis
Extensive
Evaluatio
n
o risk factors
No recurrent
episodes
Simplified
Evaluation

15. No risk factors
No recurrent
episodes
History
Dietary
aberration
Stones
provoking
medications
Fluid loss
UTI
Lab. Tests
Stone analysis
Serum Ca, P,
electrolytes and uric
acid
u/a , urinary
sediments(crystals)
KUB

16. Crystal identification
Calcium oxalate dihydrate
envelope shaped crystals ,
Dumbbells –shaped
monohydrate crystals
Calcium oxalate monohydrate
Needle shaped crystals

17. Uric acid crystals,
pleomorphic appears as
rhombic plates or rosettes
and form only in acid urine
“coffin lid” magnesium
ammonium phosphate
crystals form only in
alkaline urine pH > 7.0
Hexagonal
cystine crystals
pathognomonic
of Cystinuria
Crystal identification

18.  pH
< 5.5 = Gouty diathesis
> 7.5 = Infection lithiasis
 Quantitative cystine ( if suspect cystinuria )
 Culture
If suspect presence of urea- splitting
organisms: infection stones

19. Stone Type : Radiopaque Etiology
 Calcium oxalate
 Calcium phosphate
(hydroxyapatite)
 Struvite or carbonate
apatite
 Cystine
 Hypercalciuria,
hyperoxaluria, hyper
uricosuria, hypocitruria ,
hypomagnesiuria, low
urine volume
 Primary
hyperparathyroidism,
renal tubular acidosis,
sodium alkali therapy
 UTI with urea splitting
organisms
 Cystinuria

20. Stone Type : Radiolucent Etiology
 Uric acid
 Trimetrene
 Xanthine
 Silica
 Gouty diathesis,
hyperuricosuria, chronic
diarrheal syndrome,
dehydration, low urinary
pH
 Trimetrene therapy
 Xanthinuria
 Magnesium trisilicate
therapy

21.  ca, P
 K, Co2
 Uric acid
 Primary
hyperparathyroidism
 RTA
 Gouty diathesis

22.  Hypercalciuria : the excretion of urinary calcium
exceeding 200 mg in a 24 h collection
(4mg/kg/24hrs)
 Absorptive hypercalciuria
Intestinal hyperabsorption of calcium
 Renal hypercalciuria
Impairment in renal tubular reabsorption of
calcium. Unlike primary hyperparathyroidism, serum
calcium is normal and the state of
hyperparathyroidism is secondary.
 Resorptive hypercalciuria (primary
hyperparathyroidism)
Excessive resorption of bone resulting from

23.  Hyperuricosuria
Urate or uric acid may initiate calcium
oxalate
stone formation by direct induction of
heterogeneous nucleation of calcium oxalate
or by adsorption of certain macromolecular
inhibitors.
 Gouty diathesis
Formation of renal stones composed of uric acid or
calcium oxalate in patients with primary gout, either
manifesting fully with gouty arthritis and hyperuricemia
or appearing in a latent form.

24.  Hyperoxaluria
Hyperoxaluria is defined by urinary oxalate
excretion in excess of 45 mg/day.
Hyperoxaluria is usually due to intestinal
hyperabsorption of oxalate secondary to ileal
disease (enteric hyperoxaluria)
 Other causes of hyperoxaluria include:
Substrate excess (increased vitamin C
ingestion)
Low calcium intake
primary hyperoxaluria rare autosomal
disorder, characterized by enhanced conversion

25.  Hypocitraturia
Acidosis reduces urinary citrate both by
enhancing renal tubular reabsorption and
reducing the synthesis of citrate.
This mechanism accounts for the occurrence of
hypocitraturia in distal renal tubular acidosis,
enteric hyperoxaluria, hypokalemia , strenuous
physical exercise (from lactic acidosis), high
animal protein diet , and sodium excess (from
bicarbonaturia).

26. Non-calcareous stones represent approximately 20% of all
stone occurrences.
Uric acid stones
 Gouty diathesis
 Purine overproduction, such as myeloproliferative
states, glycogen storage disease and malignancy.
 Chronic diarrheal syndromes (e.g. ulcerative colitis,
regional enteritis) or jejunoileal bypass surgery may
cause uric acid lithiasis by inducing net alkali deficit and
lowering urine volume (thereby reducing urinary pH and
augmenting urinary concentration of uric acid,
respectively)

27.  Cystine stones
 Cystinuria is an inborn error of
metabolism characterized by a
disturbance in renal and intestinal
handling of dicarboxylic acids, including
cystine. Stone formation, occurring in a
minority of patients, is the result of an
excessive renal excretion of cystine and
its low solubility in urine.

28. Infection (struvite) stones
 Infection of the urinary tract with urea-splitting
organisms (Proteus, Klebsiella, Pseudomonas,
and Staphylococcus) may be associated with
renal stones composed of struvite (magnesium–
ammonium phosphate) or calcium carbonate
apatite.
 The resulting alkalinity of the urine augments
dissociation of phosphate to form triphosphate
ions which reduce the solubility of struvite.

30.  Increase fluid intake to maintain a urine output of
more than 2000 ml/day.
 Limit dietary oxalate intake — spinach,
rhubarb, peanuts, cashews, and almonds.
 Limit salt intake
A low sodium diet (to 80 to 100 meq/day) can
enhance proximal sodium and calcium reabsorption,
leading to a reduction in calcium excretion
 Restricted intake of animal protein

31.  Restricted intake of animal protein and salt, combined
with a normal calcium intake, provide greater protection
than the traditional low-calcium diet in the long term
prevention of stone recurrence.
 Severe calcium restriction is inappropriate in patients
with recurrent nephrolithiasis as reduced calcium diet
could be potentially dangerous by affecting the calcium
balance, leading to osteoporosis particularly in older
women but also in males.


32.  Limit sucrose and fructose intake
Sucrose intake increases urine calcium
independent of calcium intake. Fructose intake
also increases the risk of stone formation
 Increase fruit and vegetable intake — This
benefit is primarily the result of increasing
citrate excretion

33.  High dose vitamin C appears to increases
urine oxalate High dose supplements should
be avoided in those with higher urine oxalate
excretion.
 Phytate appears to decrease the risk of stones
in women .
 Weight control may be helpful in preventing
stone recurrence .

34. Thiazide such as hydrochlorothiazide or
chlorthalidone
 Thiazide is ideally indicated for the treatment of
renal hypercalciuria. This diuretic has been shown
to correct the renal leak of calcium by augmenting
calcium reabsorption in the distal tubule, and by
causing extracellular volume depletion and
stimulating proximal tubule reabsorption of
calcium.
 The full benefit may not be seen unless sodium
intake is also restricted

35.  If the urine calcium does not fall as desired or
the thiazide is not well tolerated.
- 40 to 60 meq of alkali per day as
potassium bicarbonate or potassium
citrate (citrate is rapidly metabolized to
bicarbonate)
- Orthophosphate may reduce the excretion of
calcium and increase the excretion of inhibitors
of crystallization (such as pyrophosphate).
 Potassium citrate for hypocitraturia

36.  Rx:
K3Cit 20-40meq bid
Allopurinol 300mg/day for serum uric
acid > 8mg/dl
urinary uric acid > 800mg/day

37.  Rx:
Acetohydroxamic acid ( e.g. lithostat)
a urease inhibitor 250 mg tid/qid
Antibiotics
Stone removal

38.  Positive quantitative test for cystine
 Cystine on stone analysis
 Rx:
K3Cit 10-20 meq bid to maintain urine pH
between 6.5-7.0
If urinary cystine concentration is > 300mg/l,
Tiopronin (e.g. Thiola ) or D-pencillamine
300mg tid
Adjust dose to keep cystine < 200mg/l

39.  Dietary Aberrations that have a role in stone
disease include Low fluid intake, High Ca
intake, High oxalate diet, Sodium excess, High
Animal protein intake and Low citrus fluid intake
 Every effort should be done to detect
underlying abnormalities in stone disease
patients .
 Preventive measures to decrease recurrence of
stones include increase fluid intake, limitation
of dietary oxalate. Restriction of salt and
protein animal intake and to limit sucrose and
fructose


40.  Drug therapy is indicated if the stone disease
remains active (as evidenced by the formation of new
stones, enlargement of old stones, or the passage of
gravel)
 Initial drug therapy varies with the metabolic abnormality
that is present:
 Thiazide diuretics for reducing urinary calcium
excretion
 Allopurinol for hyperuricosuria
 Potassium citrate for hypocitraturia