MEDICAL MANAGEMENT OF RENAL STONES

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MEDICAL MANAGEMENT OF RENAL STONES
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KIDNEY STONES Introduction

• This disease is not transmittable.
• Kidney stones can develop when certain chemicals
  in urine form crystals that stick together.
• Stones may also develop from a persistent kidney
  infection.
• Drinking small amounts of fluids.
• More frequent in hot weather

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SYMPTOMS

• Pain in the lower back part or in the lower
  abdomen, which might move to the groin. Pain may
  last from hours to minutes.
• Nausea, vomiting
• Blood in urine
• Burning during urination, foul smell in urine,
  chills, weakness and fevers for urinary tract
  infection.

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EPIDEMIOLOGY

• This disease can be found anywhere.
• This disease can strike on any age group.

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COMPARATIVE INCIDENCES OF FORMS OF URINARY
LITHIASIS

• Stone analysis in Percentage
• Form of Lithiasis India USA Japan UK
• Pure Calcium Oxalate 86.1 33 17.4 39.4
• Mixed Calcium Oxalate and 4.9 34 50.8 20.2Phosph
  ate
• Magnesium Ammonium 2.7 15 17.4 15.4Phosphate
  (Struvite )
• Uric Acid 1.2 8.0 4.4 8.0
• Cystine 0.4 3.0 1.0 2.8

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Cause of Stone Disease

• Supersaturation of urine is the key to stone
  formation
• Intermittent supersaturation - Dehydration
• Crystal aggregation
• Anatomic Abnormailities PUJ , MSK
• Bacterial Infection
• Defects in transport of Calcium and Oxalate by
  Renal epithelia

E.Coli infection increases matrix content in
urine . Proteus makes urine alkaline
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Inhibitors, Promoters of Stone Formation

• INHIBITORS
• Inhibits crystal Growth -
• Citrate complexes with Ca
• Magnesium complexes with oxalates
• Pyrophosphate - complexes with Ca
• Zinc
• Inhibits crystal Aggregation
• Glycosaminoglycans
• Nephrocalcin

• PROMOTERS
• Bacterial Infection
• Matrix
• Anatomic Abnormalities PUJ obst., MSK
• Altered Ca and oxalate transport in renal
  epithelia
• Prolonged immobilisation
• Increased uric acid levels i.e taking increased
  purine subs promotes crystalisation of Ca and
  oxalate
• ?? Nanobacteria seen in 97 of renal stones

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SOME DISEASES ASSOCIATED WITH HYPERCALCAEMIA
HYPERCALCIURIA

• Hyperparathyroidism Leukemia
• Sarcoidosis Lymphoma
• Multiple myeloma Myxedema
• Hyperthyroidism Adrenal Insufficiency
• Metastatic Malig. Neoplasm's Vit. D Intoxication

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TYPES OF KIDNEY / URETER STONES

• OXALATE (CALCIUM OXALATE)
• PHOSPHATE
• URIC ACID URATE
• CYSTINE

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Uncommon Stones

• XANTHINE STONES
• Autosomal Recessive Def. of Xanthine Oxidase
  leading to Xanthinuria
• DIHYDROXYADENINE STONE
• Def. of enzyme adenine phospo ribosyl
  transferase
• SlLICATE STONES
• Rare in humans - excess intake of Antacid
  with Mg Trisilicate
• ( Mostly in cattle due to ingestion of sand
  )
• MATRIX
• - Infection by Proteus - Radiolucent (all
  calculi have some amt ( 3) of matrix but matrix
  calculus has 65 Matrix content in calculi)

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Uncommon Stones

• TRIAMTERENE
• Anti-hypertensive used with hydroclorothiazide
  spares potassium. Mostly found as a nucleus in
  Ca-oxalate or uric acid calculus
• Indinavir Stones
• - Drug to treat AIDS (4 to13)
• Ephedrine or Guifenesin
• Cough medicine - Radiolucent

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Stones Chemical Constituents

• Whewelite Calcium Oxalate Monohydrate
  CaC2O4-H2O
• Weddelite - Calcium Oxalate dihydrate
  CaC2O4-2H2O
• Brushite Calcium Hydrogen phosphate dihydrate
  CaHPO4 2H2O
• Whitlockite - TriCalcium Phosphate Ca2(PO4)2
• Struvite Magnesium Ammonium hexahydrate
  MgNH4PO4-6H2O

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DD of Radiolucent filling defect on IVU

• Know For Brownie Points
• Xanthine Calculus
• Hydroxyadenine Calculus
• Ephedrine Calculus
• Infection due to gas forming Org.
• Fungal Ball
• Tuberculoma
• Malacoplakia
• Hypertrophied Papilla
• Renal pseudo-tumour

• Must Know
• Uric Acid Calculus
• Matrix Calculus
• Sloughed Papilla
• Blood Clots
• TCC
• Renal Cysts
• Vascular Lesions

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OXALATE (CALCIUM OXALATE)

• ALSO CALLED MULBERRY STONE
• COVERED WITH SHARP PROJECTIONS
• SHARP MAKES KIDNEY BLEED (HAEMATURIA)
• VERY HARD
• RADIO - OPAQUE

Under microscope looks like Hourglass or Dumbbell
shape if monohydrate and Like an Envelope if
Dihydrate
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PHOSPHATE STONE

• USUALLY CALCIUM PHOSPHATE
• SOMETIMES CALCIUM MAGNESIUM AMMONIUM PHOSPHATE
  OR TRIPLE PHOSPHATE
• SMOOTH MINIMUM SYMPTOMS
• DIRTY WHITE
• RADIO - OPAQUE

Calcium Phosphate also called Brushite appears
needle-shaped under the microscope
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PHOSPHATE STONES

• IN ALKALINE URINE ENLARGES RAPIDLY TAKE
  SHAPE OF CALYCES STAGHORN

Struvite can form stag-horn and appear like
coffin lid under microscope
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CALCIUM PHOSPHATE STONES

• Hyperparathyroidism Ca P
• Renal Tubular Acidosis K CO2
• Medullary Sponge Kidney -

PTH Hormone Promotes renal production of
1-25-dihyroxycholecalciferol active Vit.D and
also increases absorption of Calcium and
decreases Phosphorus absorption from Kidneys
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URIC ACID URATE STONE

• HARD SMOOTH
• MULTIPLE
• YELLOW OR RED-BROWN
• RADIO - LUCENT (USE ULTRASOUND)

Under microscope appear like irregular plates or
rosettes
pKa of uric acid 5.75 at this pH 50 of uric
acid insoluble. If pH falls further - uric acid
more insoluble
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CYSTINE STONE

• AUTOSOMAL RECESIVE DISORDER
• USUALLY IN YOUNG GIRLS
• DUE TO CYSTINURIA -
• CYSTINE NOT ABSORBED BY TUBULES
• MULTIPLE
• SOFT OR HARD can form stag-horns
• PINK OR YELLOW - RADIO-OPAQUE

Under microscope appears like hexagonal or
benzene ring ask for first morning sample
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CYSTINE STONE - Management

• High Fluid Intake and Alkalanise Urine dissolve
  most of the smaller cystine stones
• D-Pencillamine or MPG (Mercaptopropionylglycine)
  binds to cystine that is soluble in urine
• Side effects of Pencillamine restricts it use
  Allergic rashes, GI problems- Nausea, Vomiting,
  Diarrhoea
• MPG better tolerated
• Large obstructive stones Surgery required

pKa of cystine is 8.3, hence alkalinisisation
above pH7.5 helps to dissolve the stones
Cyanide Nitroprusside Calorimeteric Test for
detecting Cystinuria. If positive do amino acid
chromatography
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Surgical Conditions and Stone Disease

• Regional ileitis and Ileal Bypass Surgery for
  Obesity can lead to increased oxalate absorption
  and stone disease
• Ileostomies, in Chr. Diarrhoea with Bicarbonate
  loss systemic acidosis and acidic urine
  increases risk of Uric Acid stones

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HISTORY

• A. IS PATIENT DRINKING ENOUGH ?
• B. PROFESSION
• C. ENQUIRE ABOUT UTI - STONES
• D. FAMILY HISTORY
• E. LONG ILLNESS - BEDRIDDEN - STONES

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MANAGEMENT OF STONES

• HISTORY
• A. FIND OUT IF DRINKING ENOUGH LIQUIDS
• (NOT DRINKING ENOUGH IMPORTANT CAUSE OF STONE
  FORMATION GROWTH)

Urinary supersaturation of salts in concentrated
urine Atleast drink 3 lts to avoid stone formation
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HISTORY (Cont...)

• B. ASK ABOUT THEIR PROFESSION DEHYDRATION -
  STONES CAN FORM e.g.
• MARATHON, NEAR A FURNACE,
• BRICK - LAYER, LABOURERS WEAVERS
• TRUCK BUS DRIVERS

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HISTORY (Cont...)

• C. ENQUIRE ABOUT UTI STONES
• D. FAMILY HISTORY
• E. LONG ILLNESS BEDRIDDEN STONES

Zero Gravity state astronauts on long space
flights more prone to stones
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CLINICAL FEATURES

• 1. PAIN IN 75 OF THE CASES RENAL COLIC IF
  SEVERE AND ACUTE
• A) KIDNEY STONE FIXED PAIN IN THE LOIN
• B) URETERIC STONE PAIN RADIATES LOIN TO GROIN

Both Stomach Kidney supplied by celiac ganglion
hence nausea vomiting common in renal colic
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CLINICAL FEATURES (Contd....)

• 2) HAEMATURIA
• CAN BE FRANK
• OR ONLY FOUND ON DIP - STICK OR LAB.
• 3) PYURIA - IF INFECTION, CAN HAVE PUS IN URINE

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ON EXAMINATION

• 1. ACUTE PRESENTATION
• ABDOMEN TENSE AND RIGID
• TENDERNESS PRESENT IN THE LOIN
• 2. IN ROUTINE PRESENTATION
• NO FINDINGS IN ABDOMEN

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INVESTIGATIONS

• 1. FULL BLOOD COUNT TO CHECK FOR ANAEMIA, IF
  GOING FOR SURGERY
• 2. SERUM ELECTROLYTES PLUS UREA / CREATININE /
  CALCIUM / URIC ACID / PHOSPHATE

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INVESTIGATIONS (Cont...)

• 3. 24-HOURS URINE FOR ELECTROLYTES (Only if
  recurrent stone former)
• CALCIUM / OXALATE / URIC ACID / CYSTINE /
  CITRATE

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INVESTIGATIONS (Cont...)

• 4. PLAIN KUB X-RAY OF ABDOMEN (Mandatory)
• 5. IVU (INTRA VENOUS UROGRAM) OR IVP
• 6. ULTRASOUND (Mandatory)

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INVESTIGATIONS

• IVU OR IVP - Not Mandatory
• 1 in 40,000 patients die due to anaphylactic
  reaction to contrast
• Useful for radio-lucent stones to detect
• Congenital Anomalies in Urinary tracts

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INVESTIGATIONS (Cont...)

• 7. CT TO LOOK AT UNUSUAL ANATOMY OF THE
  KIDNEY
• To differentiate cause of acute colic stone
  or anuria suspected due to stone disease
• 8. DMSA OR DTPA OR MAG3 RENOGRAM - TO STUDY
  FUNCTION OF EACH KIDNEY.

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Bilateral Ureteric Calculus in a patient
presenting with Anuria
Helical or Spiral CT provides 3D reconstruction.
Helical refers to path the X ray follows on
Gantry. These are rapidly performed and do not
require contrast agents for reconstruction.
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MANAGEMENT OF UROLITHIASIS

• Non-invasive approach to urinary calculus
  -HALLMARK for last 20 yrs.
• Lithotripters
• 1.Extra Corporeal Shock wave
• 2.Intra Corporeal
• Better fiber optics Miniaturisation of
  Telescopes
• Accessories - Innovative variety

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Diet Fluid Advice

• High Fluid Intake
• Restrict Salt (Na)
• Oxalate Restrict
• Avoid high intake of Purine food
• Increased citrus fruits may help
• If hypercalciuria restrict Ca intake

Role of Potassium Citrate in preventing Cal
Oxalate stone ds KCit lowers urinary calcium
whereas Na Citrate does not lower Calcium due to
Sodium load
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LIQUIDS

• Moderate Amounts High Amounts
  
• Apple Juice Cocoa
• Beer Fresh Tea
• Coffee
• Cola
• FOODS
• Almonds, Asparagus, Cashew Nuts, Currants,
  Greens, Plums, Raspberries, Spinach

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Principles of Medical Management

• Monitor stone burden with periodic KUB
• Instruct patient on adequate water consumption (
  enough to produce 2L of urine in 24 hrs.)
• Instruct in low oxalate and modified calcium diet
• If hypercalcuric, treat with hydrochlorothiazide
  (monitor urinary Ca)

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Principles of Medical Management 2

• If hyperuricosuric
• allopurinol if serum uric acid elevated
• alkalinize urine if serum level is normal
• If active Ca stone former not aided by diet, HCTZ
  added to K-citrate
• If magnesium ammonium phosphate stone, after
  reduction of burden treat aggressively with
  antibiotics

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Anatomic Evaluation

• Necessary to decide on how to best treat
• size and location of stone
• number of stones
• anatomy of kidney, ureter
• is stone overlying bone
• condition of involved kidney

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Principles of Stone Prevention

• Prevent supersaturation
• water! water and more water enough to make 2L of
  urine per day
• prevent solute overload by low oxalate and
  moderate Ca intake and treatment of hypercalcuria
• replace solubilizers i.e... citrate
• manipulate pH in case of uric acid and cystine
• Flush! forced water intake after any dehydration

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Urine citrate

• Hypocitriuria is one of the most remarkable
  Feature of renal tubular acidosis and kidney
  stone Formation
• Hypocitriuria is a frequent finding in
  individuals with Recurrent stone formation.
• Presence of citrate in urine is an inhibitor of
  stone formation.

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Emergency Department Care

• Intravenous access - for analgesics and
  antiemetics
• Intravenous hydration is controversial.
• May hasten passage of the stone
• Others feel exacerbates the pain of renal colic
• IV hydration should be given in dehydration or
  with a borderline serum creatinine level who must
  undergo IVP
• Strain urine for stone collection
• Ref J Endourol. Oct 200620(10)713-6

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ED Care Analgesics Antiemetics

• Analgesia should be provided promptly.
• The pain of renal colic is mediated by PGE2.
  NSAIDs inhibit formation of this mediator
• NSAIDs have been proven in multiple studies to be
  as effective as opioid analgesics, with fewer
  adverse effect
• Opioid analgesics can be added in cases of
  incomplete pain control
• Antiemetics should be administered as needed
• Ref Arch Intern Med. Jun 27 1994154(12)1381-7
  
• Am J Emerg Med. Jan 199917(1)6-10

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ED Care - Expulsive therapy

• Multiple prospective randomized controlled
  studies in the urology literature have
  demonstrated that patients treated with oral
  alpha-blockers have an increased rate of
  spontaneous stone passage and a decreased time to
  stone passage
• The best studied of these is tamsulosin, 0.4 mg
  administered daily
• Ref J Urol. Dec 2003170(6 Pt 1)2202-5
• J Urol. Jul 2005174(1)167-72
• J Urol. Aug 2004172(2)568-71

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ED Care - Expulsive therapy

• CCBs in combination with oral steroids have also
  proven efficacious in multiple studies. The most
  common regimen is 30-mg slow-release nifedipine
  daily plus oral corticosteroid such as
  prednisolone
• A systematic review found that medical expulsive
  therapy using either alpha antagonists or CCBs
  augmented the stone expulsion rate for moderately
  sized distal ureteral stones
• Ref Ann Emerg Med. Nov 200750(5)552-63

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ED Care - Expulsive therapy

• A systematic review found that medical expulsive
  therapy with alpha antagonists for 28 days
  increased the rate and decreased the time to
  stone passage decreased the rates of
  hospitalization and ureteroscopy
• Ref Ann Pharmacother. Jul-Aug 200640(7-8)
  1361-8

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Ca-oxalate, ca-phosphate, and ca-urate are
associated with

• Hyperparathyroidism - Treated surgically or with
  orthophosphates if the patient is not a surgical
  candidate
• Increased gut absorption of calcium - The most
  common identifiable cause of hypercalciuria,
  treated with calcium binders or thiazides plus
  potassium citrate

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Ca-oxalate, ca-phosphate, and ca-urate are
associated with

• Renal calcium leak - Treated with thiazide
  diuretics
• Renal phosphate leak - Treated with oral
  phosphate supplements
• Hyperuricosuria - Treated with allopurinol, low
  purine diet, or alkalinizing agents such as
  potassium citrate

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Ca-oxalate, ca-phosphate, and ca-urate are
associated with

• Hyperoxaluria - Treated with dietary oxalate
  restriction, oxalate binders, vitamin B-6, or
  orthophosphates
• Hypocitraturia - Treated with potassium citrate
• Hypomagnesuria - Treated with magnesium
  supplements

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Struvite (magnesium ammonium phosphate) stones

• Struvite stones are associated with chronic UTI
  with gram-negative rods capable of splitting urea
  into ammonium, which combines with phosphate and
  magnesium
• Underlying anatomical abnormalities that
  predispose patients to recurrent kidney
  infections should be sought and corrected

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Struvite (magnesium ammonium phosphate) stones

• Usual organisms include Proteus, Pseudomonas, and
  Klebsiella species
• Escherichia coli is not capable of splitting urea
  and, therefore, is not associated with struvite
  stones
• UTI does not resolve until stone is removed
  entirely
• Urine pH is typically greater than 7

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Uric acid stones

• Associated with urine pH less than 5.5, high
  purine intake (eg, organ meats, legumes, fish,
  meat extracts, gravies), or malignancy
• Approximately 25 of patients with uric acid
  stone have gout - serum and 24-hour urine sample
  should be sent for creatinine and uric acid
  determination
• If serum or urinary uric acid is elevated, the
  patient may be treated with allopurinol 300 mg
  daily
• Patients with normal serum or urinary uric acid
  are best managed by alkali therapy alone

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Cystine stones

• Treated with low-methionine diet (unpleasant),
  binders such as penicillamine or
  a-mercaptopropionylglycine, large urinary
  volumes, or alkalinizing agents
• A 24-hour quantitative urinary cystine
  determination helps to titrate the dose of drug
  therapy to achieve a urinary cystine
  concentration of less than 300 mg/L

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Drug-induced stone disease

• A number of medications or their metabolites can
  precipitate in urine causing stone formation
• These include indinavir atazanavir guaifenesin
  triamterene silicate (overuse of antacids
  containing magnesium silicate) and sulfa drugs
  including sulfasalazine, sulfadiazine,
  acetylsulfamethoxazole, acetylsulfasoxazole, and
  acetylsulfaguanidine
• Ref Urology. Oct 200362(4)748
• Urol Clin North Am. Feb 200330(1)123-3
  1
• Urology. Jan 200463(1)175-6

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Potassium-magnesium-citrate

• Potassium citrate reduces urinary saturation of
  calcium by complexing with calcium in urine and
  thus reduces urinary calcium
• Citrate also inhibits spontaneous nucleation of
  calcium oxalate and calcium phosphate
• Due to its alkalinising effect it increases
• dissolution of uric acid and thus reduce
  uric acid stone formation

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Magnesium

• It forms complex with oxalate and reduces
  supersaturation of urine with calcium oxalate
• It increases pH of urine and thus inhibit stone
  Formation
• Magnesium has direct inhibitory influence on
  Calcium phosphate crystal growth.
• Magnesium also prevents intestinal absorption of
  Oxalate 1

1. Am J Ther,2006 Mar-Apr 13(2) 101-8
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CONCLUSION

• As compared to potassium citrate , Potssium
  magnesium citrate cause more
• Rise in urinary pH
• Rise in urinary citrate level
• Rise in urinary magnesium level
• Reduction in undissociated uric acid level
• Equally effective in correcting thiazide induced
  hypokalemia

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• Potassium magnesium citrate based medical
  prophylaxis is effective for preventing
  recurrence of urinary stones like calcium
  oxalate, hypercalciuria, hyperuricosuria and
  hypocitriuria
• Regular prophylaxis effectively prevent stone
  recurrence regardless of stone composition,
  metabolic abnormalities and stone free status.

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• THANK YOU !