1. MEDICAL MANAGEMENT OF RENAL STONES

2. 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

3. 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.

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

5. COMPARATIVE INCIDENCES OF FORMS OF URINARY LITHIASIS
Stone analysis in Percentage
Form of Lithiasis India USA Japan UK
Pure Calcium Oxalate
Mixed Calcium Oxalate and Phosphate
Magnesium Ammonium Phosphate (Struvite )
Uric Acid
Cystine

6. 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

7. Inhibitors, Promoters of Stone Formation
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

8. SOME DISEASES ASSOCIATED WITH HYPERCALCAEMIA & HYPERCALCIURIA
Hyperparathyroidism Leukemia
Sarcoidosis Lymphoma
Multiple myeloma Myxedema
Hyperthyroidism Adrenal Insufficiency
Metastatic Malig. Neoplasm's Vit. D Intoxication

9. TYPES OF KIDNEY / URETER STONES
OXALATE (CALCIUM OXALATE)
PHOSPHATE
URIC ACID & URATE
CYSTINE

10. 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)

11. 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

12. 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

13. 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

14. 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

15. 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

16. PHOSPHATE STONES
IN ALKALINE URINE ¯ ENLARGES RAPIDLY ¯ TAKE SHAPE OF CALYCES ¯ STAGHORN ®
Struvite can form ‘stag-horn’ and appear like coffin lid under microscope

17. 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

18. 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

19. 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

20. 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

21. 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

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

23. 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

24. HISTORY (Cont...)
B. ASK ABOUT THEIR PROFESSION DEHYDRATION - STONES CAN FORM e.g.
MARATHON, NEAR A FURNACE,
BRICK - LAYER, LABOURERS & WEAVERS
TRUCK & BUS DRIVERS

25. 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

26. 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

27. 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

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

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

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

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

32. 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

33. 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.

34. 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.

35. 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

36. 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

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

38. 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)
Not all patients with renal stones require treatment. If the stone is metabolically inactive (has remained unchanged in location, size and number, not produced any symptoms) then it may be reasonable to observe. Observation should include: a periodic KUB to determine if the stone is changing, urine culture to detect presence of unsuspected infection and continuous exhortations on the part of the MD to encourage adequate water intake and adherence to a low oxalate and moderate calcium diet. The patient needs to consume enough water to produce 2,000cc’s of urine in a 24 hour period. It has been shown that at this rate of urine production the occurrence of ss is reduced and that the ensuing dieresis will “flush out” intraductal crystalline clumps. Obviously this will require far more water consumption i the hot weather when there is increased extra-renal fluid loss.
Patient who are hypercalciuric should first be tried on a low calcium diet. There are 2 types of hypercalcuria type 1 where the hypercalcuria is refractory to dietary restriction of calcium and type 2 where the hypercalcuria can be controlled. If the patient’s hypercalcuria can not be controlled by dietary restriction it is reasonable to try hydrochlorothiazide at a dose of 25 mgs BID. After 3-4weeks of HCTZ the 24 hour Ca should be repeated and if still high increase the dose of HCTZ. Potassium citrate is also helpful in inhibiting the stone formation process by forming a chelate with Ca and removing it from being available to bind with oxalate. K citrate also has the advantage of providing K+ in patients receiving HCTZ.

39. 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
The patient with hyperuricosuria can be treated with allopurinol which will lower the serum and urinary uric acid level. Also very effective control of uric acid stones can be achieved with oral alkalization agents. The simplest one to use is sodium bicarbonate. Sodium bicarbonate is available in 600mg size tablets. Patients are instructed in the use of pH paper and measure their urine pH at each voiding. The untreated uric acid stone former will always have a low urinary pH in the range of 5. Patients should be started off with a bicarbonate dose of 1.2 to 1.8 gms Q 4 hours. The goal is to get the urine pH to If the pH is 6 then the next bicarbonate dose should be increased by i tablet (600mgs). If the pH is higher than 7.0 the bicarbonate dose should be decreased by 600mgs. Maintaining the urine pH at 7.0 will dissolve most uric acid stones and prevent the formation of new ones.
Patients with struvite (magnesium ammonium phosphate) stones often have an associated urea splitting infection. It is important after reducing the stone burden to treat these infections very aggressively otherwise they will continue to produce a very alkaline pH and cause further struvite stone formation.

40. 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
The patient with chronic or recurrent stone formation should have evaluation of the anatomy of their urinary tract since there may be an underlying anatomic abnormality predisposing to stone formation. Examples of these would be: ureteropelvic junction obstruction, horseshoe kidney, ectopic kidney and malrotated kidney.
If there is normal renal function then the most helpful study is the IVU. This will provide the needed information about the renal anatomy and will also delineate the size, location and presence of obstruction.

41. 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
From the information presented above you can see that the mainstay to stone prevention is to prevent urinary ss by consuming enough water to produce 2,000ccs of urine per day. Prevention of solute overload by controlling the oxalate intake. Calcium intake should not be eliminated altogether but should be limited to about the equivalent of no more than 240ccs of milk per day. In the case of uric acid stone formers one should avoid eating large amounts of red meat “organ” meats which contain large amounts of purines. The replacement of solubilizers such as citrate can be helpful and should be tried in the unresponsive Ca stone former who is failing treatment with HCTZ.
Stone patients must continuously be reminded that even though they may have been successfully managed for a period of months or years that it is still important for them to remain on treatment indefinitely since the causes for their stone problem have not been removed.

42. 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.

43. 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 2006;20(10):713-6

44. 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 1994;154(12):1381-7
Am J Emerg Med. Jan 1999;17(1):6-10

45. 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 2003;170(6 Pt 1):2202-5
J Urol. Jul 2005;174(1):167-72
J Urol. Aug 2004;172(2):568-71

46. 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 2007;50(5):552-63

47. 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 2006;40(7-8):1361-8

48. 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

49. 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

50. 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

51. 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

52. 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

53. 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

54. 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

55. 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 2003;62(4):748
Urol Clin North Am. Feb 2003;30(1):123-31
Urology. Jan 2004;63(1):175-6

56. 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

57. 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

58. 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

59. 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.

60. THANK YOU !