Urolithiasis

Presented By :

Aamir Sharif HO at Hijaz Hospital

Overview• Introduction• Conditions causing stone formation• Types of kidney stones

• Calcium salts• Uric acid• Mg ammonium PO4

• Cystine• Other (xanthine, etc.)

• Laboratory investigations• Comparison Between Urosinal Syrup

& Zyloric Tablets

Urolithiasis

• Urolithiasis is the condition where urinary stones are formed or located anywhere in the urinary system

• The term nephrolithiasis (or "renal calculus") refers to stones that are in the kidney,

• Ureterolithiasis refers to stones that are in the ureter.• The term cystolithiasis (or vesical calculi) refers to stones

which form or have passed into the urinary bladder.• Stones are Composed of metabolic products present in

glomerular filtrate• These products are in high conc.

Near or above maximum solubility

Conditions causingkidney stone formation

High conc. of metabolic products in glomerular filtrate

Changes in urine pHUrinary stagnationDeficiency of stone-

forming inhibitors in urine

High conc. of metabolic products in glomerular filtrate is due to:

Low urinary volume (with normal renal function) due to restricted fluid intake

Increased fluid loss from the body

Increased excretion of metabolic products forming stones

High plasma volume (high filtrate level)

Low tubular reabsorption from filtrate

Changes in urine pH is due

to:

• Bacterial infection

• Precipitation of salts at different pH

Urinary stagnation is due to:

• Obstruction of urinary flow

Deficiency of stone-forming inhibitors:

Citrate, pyrophosphate, glycoproteins inhibit growth of calcium phosphate and calcium oxalate crystals

In type I renal tubular acidosis, hypocitraturia leads to renal stones

Kidney Stone type

Population Circumstances Details

Calcium oxalate

80% when urine is alkaline (ph>5.5)

Some of the oxalate in urine is produced by the body. Calcium and oxalate in the diet play a part but are not the only factors that affect the formation of calcium oxalate stones. Dietary oxalate is an organic molecule found in many vegetables, fruits, and nuts. Calcium from bone may also play a role in kidney stone formation.

Calcium phosphate

5-10% when urine is alkaline (high pH)

: staghorn in renal pelvis (large)

Uric acid 5-10% when urine is persistently acidic

Diets rich in animal proteins and purines: substances found naturally in all food but especially in organ meats, fish, and shellfish.

Struvite 10-15% infections in the kidney

Preventing struvite stones depends on staying infection-free. Diet has not been shown to affect struvite stone formation.

Cystine 1-2% rare genetic disorder

Cystine, an amino acid (one of the building blocks of protein), leaks through the kidneys and into the urine to form crystals.

Calcium salt stones

80% of kidney stones contain calcium

The type of salt depends on• Urine pH• Availability of oxalate

General appearance:• White, hard, radioopaque• Calcium PO4: staghorn in

renal pelvis (large)• Calcium oxalate: present in

ureter (small)

Calcium oxalate stones

Calcium salt stones

Causes of calcium salt stones: Hypercalciuria:

• Increased urinary calcium excretion• Men: > 7.5 mmols/day• Women > 6.2 mmols/day• May or may not be due to hypercalcemia

Hyperoxaluria:• Causes the formation of calcium oxalates without

hypercalciuria• Diet rich in oxalates• Increased oxalate absorption in fat malabsorption

Primary hyperoxaluria:• Due to inborn errors• Urinary oxalate excretion: > 400 mmols/day

Calcium salt stones Treatment:

• Treatment of primary causes such as infection, hypercalcemia, hyperoxaluria

• Oxalate-restricted diet• Increased fluid intake• Acidification of urine (by dietary

changes)• Calcium salt stones are formed in

alkaline urine

Uric acid stones

• About 8% of renal stones contain uric acid

• May be associated with hyperuricemia (with or without gout)

• Form in acidic urine• General appearance:

• Small, friable, yellowish• May form staghorn• Radiolucent (plain x-rays

cannot detect)• Visualized by ultrasound

or i.v. pyelogram

Uric acid stones Treatment:

• Purine-restricted diet

• Alkalinization of urine (by

dietary changes)

• Increased fluid intake

Mg ammonium PO4 stones

About 10% of all renal stones contain Mg amm. PO4

Also called struvite kidney stones Associated with chronic urinary tract

infection• Microorganisms (such as from

Proteus genus) that metabolize urea into ammonia

• Causing urine pH to become alkaline and stone formation

• Commonly associated with staghorn calculi

• 75% of staghorn stones are of struvite type

Mg ammonium PO4 stones Treatment:

• Treatment of

infection

• Urine acidification

• Increased fluid intake

Cystine stones

• A rare type of kidney stone• Due to homozygous cystinuria• Form in acidic urine• Soluble in alkaline urine• Faint radio-opaqueTreatment:

• Increased fluid intake• Alkalinization of urine (by dietary

changes)• Penicillamine (binds to cysteine to form

a compound more soluble than cystine)

Laboratory investigationsof kidney stones

If stone has formed and removed:

Chemical analysis of stone helps to:• Identify the cause• Advise patient on prevention

and future recurrence

Laboratory investigationsof kidney stones

If stone has not formed:• This type of investigation identifies causes

that may contribute to stone formationSerum calcium and uric acid analysisUrinalysis: volume, calcium, oxalates and

cystine levelsUrine pH > 8 suggests urinary tract

infection (Mg amm. PO4)Urinary tract imaging:Ultrasound and i.v. pyelogram

Comparison Between Urosinal Syrup & Zyloric Tablet

Urosinal Syrup Zyloric Tablet

Name of the product Urosinal  Zyloric Tablets

 Composition Barley Salt 500 mgPotassium Nitrate500 mgSolanum nigrum (Leaves)125 mgSolanum nigrum Berries 62.5 mgPreservativesBaseQ.S

Allopurinol 100 mg , ExcipentsLactoseMaize StarchPovidoneMagnesium StearatePurified Water

 Pharmaceutical form Syrup:120 ml (Tablets) 100 & 300 mg

Indications Urinary Bladder Ailments, Kidney Disorders, Liver Disorders, Urinary Retention

indicated for reducing urate/uric acid formation in conditions where urate/uric acid deposition has already occurred (e.g. gouty arthritis, skin tophi, nephrolithiasis) or is a predictable clinical risk (e.g. treatment of malignancy potentially leading to acute uric acid nephropathy).

Name of the product Urosinal  Zyloric Tablets

Pharmacodynamic It lowers the level of uric acid in the body, and alleviates gout and rheumatism.Mechanism not known

Allopurinol is a xanthine-oxidase inhibitor. Allopurinol and its main metabolite oxipurinol lower the level of uric acid in plasma and urine by inhibition of xanthine oxidase, the enzyme catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. In addition to the inhibition of purine catabolism in some but not all hyperuricaemic patients, de novo purine biosynthesis is depressed via feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase. Other metabolites of allopurinol include allopurinol-riboside and oxipurinol-7 riboside.

Name of the product

Urosinal  Zyloric Tablets

Pharmacokinetics Not Known Allopurinol is active when given orally and is rapidly absorbed from the upper gastrointestinal tract.

Allopurinol is negligibly bound by plasma proteins and therefore variations in protein binding are not thought to significantly alter clearance.

Estimates of bioavailability vary from 67% to 90%.

Peak plasma levels of allopurinol generally occur approximately 1.5 hours after oral administration of Zyloric, but fall rapidly and are barely detectable after 6 hours.

Approximately 20% of the ingested allopurinol is excreted in the faeces.Elimination of allopurinol is mainly by metabolic conversion to oxipurinol by xanthine oxidase and aldehyde oxidase, with less than 10% of the unchanged drug excreted in the urine.

Allopurinol has a plasma half-life of about 1 to 2 hours

Name Of The product Urosinal Zyloric Tablets

Dosage Children:2.5 ml (half a teaspoonful) mixed with milk or Sharbat Bazoori in the morning and in the evening.Adults:5 ml (one teaspoonful) mixed with milk or sharbat Bazoori in the morning and in the evening

Children: Children under 15 years: 10 to 20 mg/kg bodyweight/day up to a maximum of 400 mg daily.Use in children is rarely indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.Adults: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used. i.e 100mg/day

 Contraindications Not Reported Zyloric should not be administered to individuals known to be hypersensitive to allopurinol or to any of the components of the formulation.

Name Of The product Urosinal Zyloric Tablets

Interaction with other medicinal products

Not Known Salicylates and uricosuric agents decrease its activityChlorpropamide increased risk of prolonged hypoglycaemic activityTheophylline: Inhibition of the metabolism of theophyllineFrequency of skin rash increases patients receiving ampicillin or amoxicillin concurrently with allopurinol

Side Effects No side effects reported Skin reactions are the most common reactions and may occur at any time during treatment.They may be pruritic, maculopapular, sometimes scaly, sometimes purpuric and rarely exfoliative, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN)