Transcript Uric Acid Stone Formation

Medical Aspects
of
Renal Stones
Dr. Mohammed Hannon Al Sodani
For 5th year medical students 2015-2016
College of Medicine , University of Baghdad
March ,31st ,2016
C.A.B.M., F.I.C.M.S.
Urinary tract calculi nephrolithiasis and nephrocalcinosis
Very common , a lifetime risk of 10%. higher in the Middle East.
- Most stones - occur in the upper urinary tract.
- composed of calcium oxalate and phosphate;
- Frequently a recurrent problem.
- 50% a recurrence within 10 years.
- recurrence increases if a metabolic or other predisposing
to stone formation is present and is not modified by treatment.
-Nephrolithiasis refers to stone formation within the renal tubules or
collecting system, although calculi are often found within the ureters
or in the bladder
- Nephrocalcinosis augmented calcium content within the Kidney
Type and frequency of renal stones in the UK
Type of renal stone
Percentage
Calcium oxalate usually with calcium phosphate
Calcium phosphate alone
Magnesium ammonium phosphate (struvite)
Uric acid
Cystine
Rarely
65
15
10–15
3–5
1–2
drugs
Aetiology
Normal urine :- has crystals (at times)
- extremely effective in maintaining a stable supersaturated
state by certain components ,Inhibitors of crystal formation ,
preventing the formation of stones.
Postulated inhibitors include;-- Inorganic :magnesium, pyrophosphate and citrate.
-- Organic ;glycosaminoglycans and nephrocalcin (an acidic protein of
tubular origin). Tamm–Horsfall protein may have a dual role in
both inhibiting and promoting stone formation
Aetiology
- Many stone-formers have no detectable metabolic defect,
‘idiopathic stone-formers’.
-Factors predisposing to stone formation in those are:- Chemical composition of urine
- Concentrated urine as a consequence of ;dehydration,
hot climate or work in a hot environment.
Impairment of inhibitors of crystallization in urine
Causes of urinary tract stone formation
Predisposing factors for kidney stones
Environmental and dietary
•Low urine volumes: Dehydration ,high temp., low fluid intake
• Diet: high protein, Hyperuricaemia , hyperuricosuria
high sodium, low calcium
• High sodium , oxalate & urate excretion
• Low citrate excretion
•Acquired causes
• Hypercalcaemia
• Ileal disease or resection (increases oxalate absorption
and urinary excretion)
RTA type I , .Infection
Causes of urinary tract stone formation
Predisposing factors for kidney stones
Congenital and inherited causes
. Familial hypercalciuria
APKD ,
Medullary sponge kidney
• Cystinuria
• Renal tubular acidosis type I (distal)
• Primary hyperoxaluria
- Drugs
Hypercalcaemia
If the GFR is normal, hypercalcaemia almost leads to hypercalciuria.
The common causes of hypercalcaemia leading to stone formation
are: - primary hyperparathyroidism most common
- vitamin D ingestion
-sarcoidosis
•Hypercalciuria the most common metabolic abnormality detected in
calcium stone-formers. Defined as 24-hour calcium excretion of >7.5
mmol in male more than 6.25 mmol in female stone-formers.
•Causes of hypercalciuria are:
- Hypercalcaemia
- Excessive dietary intake of calcium ,
- Excessive resorption of calcium from the skeleton, prolonged
immobilization or weightlessness
•Idiopathic hypercalciuria..
Hyperoxaluria
•Autosomal recessive inborn errors of glyoxalate metabolism,
increased endogenous oxalate biosynthesis associated with
calcium oxalate stone formation
- poor prognosis is owing to widespread calcium oxalate crystal
deposition in the kidneys. CRF , in the late teens or early twenties.
-Successful liver transplantation - cure the metabolic defect.
Much more common causes of mild hyperoxaluria are:- excess ingestion of foodstuffs high in oxalate, spinach, & tea
- dietary calcium restriction, with compensatory increased absorption
of oxalate
- GIT disease (e.g. Crohn’s), usually with an intestinal resection,
associated with increased absorption of oxalate from the colon
Hyperuricaemia and
hyperuricosuria
-Uric acid stones / 3–5% in the UK , 40%. ME
-primary or secondary ( increased cell turnover MPD )
-Some , have hyperuricosuria (> 4 mmol per 24 hours on a
low-purine diet) without hyperuricaemia.
•Dehydration alone may also cause uric acid stones to
form.
- Patients with ileostomies (dehydration and loss of
bicarbonate from GIT secretions results in the production
of an acid urine (uric acid is more soluble in an alkaline
than in an acid medium).
Etiology
•Some patients with calcium stones also have
hyperuricaemia and/or hyperuricosuria;
- it is believed the calcium salts precipitate upon
an initial nidus of uric acid in such patients.
•Cystinuria is a rare condition in which
reabsorption
of filtered cystine, ornithine, arginine and lysine
is defective. It is caused by mutations in the
SLC3A1
amino acid transporter gene. The
Medications associated with nephrolithiasis and
nephrocalcinosis.
Calcium Stone Formation
- Loop diuretics , Vitamin D , Corticosteroids
- Calcium supplements
- Antacids (calcium and non calcium antacids)
- Theophylline Acetazolamide* Amphotericin B*
Uric Acid Stone Formation
Salicylates Probenecid Allopurinol ( xanthine stones)
Melamine (in contaminated infant formula and milk products)
Medications That May Precipitate into Stones
Acyclovir (if infused rapidly intravenously)
Triamterene Indinavir Nelfinavir
Urinary tract calculi and nephrocalcinosis
- In developed countries, most calculi occur in healthy
young men in whom investigations reveal no clear
predisposing cause.
•Urinary concretions vary greatly in size
- particles like sand anywhere in the urinary tract,
- large round stones in the bladder.
Staghorn calculi fill the whole renal pelvis and branch into
the calyces ( they are usually associated with infection and
composed largely of struvite.
Radio-opaque bilateral staghorn calculi visible during IVU. The
intravenous pyelogram demonstrates that, while some dye is
being excreted by the right kidney, there is little function on
the left.
14
Clinical assessment;-The most common presentation is with renal colic,
Acute loin pain radiating anteriorly and often to the
groin ,together with haematuria, is typical of ureteric
obstruction ( stone becomes impacted in the ureter) most
commonly due to calculi ( D.Dx sloughed renal papilla, tumour
or blood clot )
- radiates round the flank to the groin and often into the testis
or labium (sensory distribution of the L1)
- The pain steadily increases in intensity /peak in a few
minutes.
- The patient is restless and generally tries unsuccessfully to
obtain relief by changing position or pacing the room.
- pallor, sweating and often vomiting.
Clinical assessment;- It is usually constant during attacks, although slight fluctuations in
severity may occur
-Contrary to general belief, attacks rarely consist of intermittent
severe pains coming and going every few minutes.
-Subsequent to colic there may be intermittent dull pain in the loin or
back.
•Asymptomatic Stone Disease
-Even large staghorn calculi may be asymptomatic
-- Obstructive uropathy may also be painless;
-therefore, nephrolithiasis should always be considered in the
D.Dx of unexplained renal failure.
- In the recent outbreak of melamine-associated nephrolithiasis in
Chinese infants, the majority presenting to a screening clinic had no
Investigations and management
Investigations
Dx of renal colic is usually made easily from the
history and by finding red cells in the urine.
Investigations are required to confirm
- the presence, number & site of the stone,
- is stone overlying bone ,
- degree of obstruction &
- the condition” of involved kidney
-90% of stones contain calcium / seen on a plain
abdominal X-ray.
Investigations and management
Investigations
When the stone is in the ureter an IVU shows delayed
excretion of contrast from the kidney and a dilated
ureter down to the stone
- IVU the most commonly used, but spiral CT gives the
most accurate assessment and will identify nonopaque stones (e.g. uric acid).
•Ultrasound may
- show dilatation of the ureter if the stone is
obstructing urine flow.
- The stone may also cast an acoustic shadow.
Urine crystals. A, calcium oxalate B, Uric acid crystals:
C, A typical hexagonal cystine crystal. D, Coffin lid crystals
of magnesium ammonium phosphate (struvite).
Investigations and management
- Patients with a first renal stone should have a minimum set of
investigations
- the yield of more detailed investigation is low, and hence usually
reserved for those with;- recurrent or multiple stones,
- complicated
- unexpected presentations (e.g. in the very young).
- Chemical analysis of stones is helpful.
- Since most stones pass spontaneously through the urinary tract,
urine should be sieved for a few days after an episode of colic in
order to collect the calculus for analysis
Radiopaque renal calculi.
A, X-ray ;-multiple stones in the Rt kidney, ureter& bladder.
B, X-ray left staghorn calculus & a single bladder
stone.
Stone in the right renal pelvis.
Helical (spiral) CT scanshowing a single stone in the right renal
pelvis. There is no hydronephrosis.
Obstructive uropathy resulting from nephrolithiasis in AKI
A, X-ray a stone in Rt upper ureter& small stone in Lt lower ureter
B, IVU bilateral hydronephrosis caused by ureteral obstruction.
Unilateral obstruction. IVU of
a patient with
a stone (not visible) at
the lower end of the
right ureter. This film,
taken
2 hours post-contrast
injection,
demonstrates
persistence of
contrast
medium in the right
kidney, pelvicalyceal
system and ureter,
whereas only a
small amount remains
visible in the normal
left pelvicalyceal
Radiolucent urate
calculi.
Antegrade
pyelogram
showing
multiple
radiolucent
urate stones
obstructing the
lower
ureter.
Investigations for renal stones
Management
General Treatment ;- Intervention for stone removal may be required
when pain, obstruction, and infection due to nephrolithiasis do not
respond to conservative management.
•Surgical management of stones includes
- extracorporeal shock wave lithotripsy
- endoscopic or percutaneous surgical removal of stones
The risk for development of renal impairment varies with types of
stone, and this must be considered in planning management
-The immediate treatment of renal pain or renal colic is ;-bed rest and application of warmth to the site of pain.
- Powerful analgesia, morphine (10–20 mg), pethidine (100 mg) IM
- or diclofenac as a suppository (100 mg).
Management
-Patients are advised to drink 2 L per day +/- IV fluids (no benefit
from forced diuresis)
- Size of stone dictates outcome
Diameter (mm)
% of stones passing spontaneously
<4
90
4-6
50
>6
10
- may require endoscopic surgical intervention.
- All stones are potentially infected and surgery should be covered
with appropriate antibiotics
Management
-Immediate action is required if there is anuria or
pyonephrosis (severe Infection occurs in the stagnant
urine proximal to the stone).
-Attempts to develop drugs that dissolve stones ???
unsuccessful.
•ESWL EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY most stones
can now be fragmented by shock waves generated outside the body
are focused on the stone, breaking it into small pieces which can
pass easily down the ureter. This requires free drainage of the distal
urinary tract.
- Large stones, or stones which do not pass spontaneously through
the urinary tract, may require surgical removal and/or fragmentation
by extracorporeal shock wave lithotripsy
Indications for intervention
• Obstructive anuria or severe infection(pyonephrosis)
→ Emergency percutaneous nephrostomy only
• Severe pain or solitary kidney → Urgent ESWL or surgery
• Pain and failure of the stone to move
→ Elective ESWL or surgery
management
•Urate stones can be prevented by allopurinol,
•Stones formed in cystinuria can be reduced by penicillamine therapy.
• attempt to alter urine pH with
ammonium chloride (low pH discourages phosphate stone formation)
sodium bicarbonate (high pH discourages urate and cystine stone
formation).
Measures to prevent calcium stone formation
•Diet Fluid prevent supersaturation
- Water! Water and more water enough to make at least 2 L UOP/day
(intake 3–4 L / distributed throughout the day (especially before bed)
•Sodium Restrict intake
•Protein Moderate, not high
•Calcium Plenty in diet (because calcium forms an insoluble salt with
dietary oxalate, lowering oxalate absorption and excretion)
• Avoid supplements away from meals (increase calcium
excretion without reducing oxalate excretion)
•Oxalate Avoid rich in oxalate (spinach, rhubarb)
•N.B. Citrate supplementation is of unproven value
Measures to prevent calcium stone formation
•Drugs
•Thiazide diuretics
Reduce calcium excretion
Valuable in recurrent stone-formers
and patients with hypercalciuria
•Allopurinol
If urate excretion high (unproven except for uratestones)
•Avoid
Vitamin D supplements as increase calcium absorption
and excretion
Vitamin C hypersupplementation as this increases oxalate
excretion
Foods High in Oxalate and Purine
•High Purine Foods (avoid in setting of hyperuricosuria)
-Organ meats: liver, kidney, brains, heart Shellfish
- Meat: beef, pork, lamb, poultry
- Fish sardines , tuna, carp
-Certain vegetables: cauliflower, peas, spinach, mushrooms, lima
and kidney beans, lentils
•High Oxalate Foods (avoid in setting of hyperoxaluria)
Green beans Beets Green onions Leeks Leafy greens , spinach,
•Cocoa Chocolate Black tea
•Berries: blackberries, blueberries, strawberries, raspberries,
•Orange peel Lemon peel Dried figs
•Nuts, peanut
Nephrocalcinosis augmented calcium content within the Kidney
Deposits of calcium may be present throughout the renal
parenchyma, giving rise to fine calcification within the renal
parenchyma (nephrocalcinosis),
Medullary Nephrocalcinosis (the majority)
- calcification tends to occur in the area of the renal pyramids,
- Elevated urinary Ca++, phosphate, and oxalate, any of
•hypercalcemia or hypercalciuria.
•Instead of stone formation, smaller parenchymal calcifications
are deposited in the medulla ,usually bilateral and relatively
symmetric
Urinary tract calculi and nephrocalcinosis
•Cortical Nephrocalcinosis
- usually the result of dystrophic calcification, which follows
parenchymal tissue destruction rather than the precipitation of
excessive urinary constituents.
- typically asymmetric & is usually localized to the renal cortex.
- secondary to infarction, neoplasm, and infection.
-cortical nephrocalcinosis
Transplant rejection, cortical necrosis, tuberculosis, ethylene
glycol toxicity, and chronic GN - RTA, - hyperparathyroidism,
- vitamin D intoxication
Nephrocalcinosis. Dense cortical and medullary calcification in the
shrunken kidneys (oxalosis and longstanding renal failure )
Medullary nephrocalcinosis. Plain radiograph;bilateral metastatic medullary nephrocalcinosis
Distal RTA
Cortical nephrocalcinosis. Non–contrast-enhanced CT scan ;cortical nephrocalcinosis in the right kidney ( cortical
necrosis).