Medical management of renal stones

1. Renal Stone

2. Introduction
 The increased prevalence of kidney stone disease is
pandemic
 Nephrolithiasis has become increasingly recognized as a
systemic disorder
 Without medical treatment, nephrolithiasis is a chronic
illness with a recurrence rate greater than 50% over 10 yr

3. Epidemiology
 The worldwide prevalence of renal stone disease is
between 2 and 20%
 Racial and ethnic differences are seen in kidney stone
disease, primarily occurring in Caucasian males and least
prevalent in young African-American females
 The prevalence in Asian and Hispanic ethnicities is
intermediate
 Life time prevalence of stones: 10% in men, 5% in
women, and increasing

4. Lifetime expectancy of stones among men
aged 60–70 years in various countries

5. Composition and Relative Prevalence of
Main Renal Stone Types
Composition Relative prevalence
Calcium oxalate stones (pure) or
with small amounts of calcium
phosphate
59%
Predominantly calcium phosphate
stones
10%
Uric acid stones 17%
Struvite or infection stones 12%
Cystine and other stones 2%

6. Multiple calcium oxalate stones (0.5 x 0.5 cm) in the collecting system of a kidney
(reproduced courtesy of C F Verkoelen, Josephine Nefkens Institute, Netherlands)

7. Pathophysiological Mechanism(s) of
Calcium Stones
Etiology Prevalence Physiological
mechanism(s)
Hypercalciuria 30–60%
•1,25(OH)2D-dependent
•1,25(OH)2D-independent
•Intrinsic renal calcium leak
•Intrinsic renal phosphorus leak
•Resorptive hypercalciuria: PTH-
dependent (primary
hyperparathyroidism); PTH-independent
Hyperuricosuria 10–40%
•Exogenous: diet-induced (purine-rich
food)
•Endogenous: urate overproduction
Urine pH Unknown
•Acidic urine: diet, diarrhea, low urine
ammonium
•Alkaline urine: infection; drug-induced
defective renal acid excretion

8. Etiology Prevalence Physiological
mechanism(s)
Hypocitraturia 20–60%
•Low extracellular fluid pH: chronic
diarrhea; exercise-induced lactic acidosis;
dRTA; drug-induced
•Normal extracellular fluid pH: potassium
deficiency; excess dietary protein; urinary
tract infection
Hyperoxaluria 10–50%
•Intestinal hyperabsorption of oxalate:
imbalance between intestinal calcium and
oxalate content; diet-induced high oxalate
intake (chocolate, brewed tea, spinach,
nuts; vitamin C, >2 g/d); role
of Oxalobacter formigenes
•Primary hyperoxaluria: enzymatic
disturbances (types I, II, or undefined
primary hyperoxaluria)

9. Pathophysiological Mechanism(s) of
Non Calcium Stones
Etiology Prevalence Physiological
mechanism(s)
Uric Acid (UA) 5–10% •Low urine volume
•Hyperuricosuria
•Unduly acidic urine
Cystine <5% •Renal tubular defect in
dibasic amino acid
transport
Infection Unknown •Urease-producing
bacteria

10. Causes of non-calcium kidney stone formation. A, Uric Acid
stones; B, Cystine stones; C, Infectious stones

11. Risk Factors
 Dietary Risk Factors
 Non Lifestyle (Non Genetic) Risk Factors
 Anatomical Risk Factors
 Drugs Associated with Renal Stones

12. Dietary Risk Factors
 Low fluid intake
 High intake of animal protein
 High dietary sodium
 Excessive intake of refined sugars
 Foods rich in oxalate
 High intake of grapefruit juice, apple juice soft cola
drinks

13. Non Lifestyle (Non Genetic)
Risk Factors

14. Anatomical Risk Factors
 Obstruction of the pelviureteral junction
 Hydronephrotic renal pelvis or calices
 Calyceal diverticulum
 Horseshoe kidney
 Ureterocele
 Vesicoureteral reflux
 Ureteral stricture
 Tubular ectasia (medullary sponge kidney)

15. Drugs Associated with Renal Stones
 Decongestants: Ephedrine, Guaifenesin
 Diuretics: Triamterene
 Protease inhibitors: Indinavir
 Anticonvulsants: Felbamate, Topiramate, and
Zonisamide

16. Clinical Features
 Urinary tract symptoms
 Pain—classic colicky loin to groin pain or renal pain
 Hematuria, gross or microscopic (occurs in 90%)
 Dysuria and strangury
 Systemic symptoms
 Restless patient, often writhing in distress
 Nausea, vomiting, or both (shared innervation of renal capsule
and intestines)
 Fever and chills (if associated infection)
 Asymptomatic
 Incidental stones (one third may become symptomatic)

17. Diagnosis
1. Medical history
2. Laboratory diagnosis
3. Radiological diagnosis

18. Medical History
 In the diagnosis of these patients, systemic and
environmental influences must be carefully identified
 Systemic abnormalities include intestinal disease,
disorders of calcium homeostasis , obesity, type II
diabetes, recurrent urinary tract infection etc
 Diet History

19. Laboratory Diagnosis
 Stone analysis
 Serum and blood testing
 Calcium, parathyroid hormone, vitamin D, electrolytes
 Urine dipstick and microscopic examination
 Urine pH
 Urine sediment examination for crystals, leukocytes, erythrocytes
bacteria
 Urine culture
 24-Hour urine collection
 Volume, creatinine, calcium oxalate, sodium, citrate, uric acid,
cystine (when indicated)

20. Radiological Diagnosis

21. Management

22. Treatment
 Conservative management
 Pharmacological treatment
 Medical expulsive therapy (MET)
 Surgical management

23. Conservative Management
 High oral fluid intake - increasing water intake to ensure a
urinary volume of approximately 2.5 liters/d
 Low dietary sodium (<100 mEq/d)
 Animal protein consumption (50–60 g/d)
 Normal calcium intake (1200 mg/d)
 Dietary oxalate restriction (<100 mg/d)
 High amounts of vitamin C

24. Pharmacological Treatment
 Pharmacological treatment is needed in most
recurrent calcium kidney stone formers as well as in
specific stone-forming populations
 It includes
 Thiazide diuretic
 Alkali treatment
 Allopurinol
 Other drugs

25. Thiazide Diuretics
 Thiazide diuretics and their analogs are commonly used
medical treatments for lowering calcium excretion in recurrent
calcium stone former
 Thiazides are effective in treating hypercalciuria and reducing
stone recurrence regardless of the underlying
pathophysiological mechanism
 The optimal effect is achieved with a low-salt diet and the
provision of sufficient potassium supplementation to avoid
hypocitraturia
 Doses of either chlorthalidone or hydrochlorothiazide should be
no more than 25 mg/day to avoid adverse effects

26. Alkali Treatment
 Potassium citrate is used either alone or in combination with
thiazide treatment in recurrent calcium or UA stone formers
 Alkali treatment is effective in lowering urinary calcium
excretion, raising urinary citrate, and reducing urinary CaOx,
CaP, and undissociated UA supersaturation
 Alkali and thiazide treatments have been shown to increase
bone mineral density in the kidney stone-forming population

27. Allopurinol Treatment
 Allopurinol—to inhibit uric acid synthesis and decrease
urinary uric acid excretion
 Allopurinol (100 to 300 mg/day) is indicated only when
hyperuricosuria is the only metabolic abnormality

28. Other Drugs
 Acetohydroxamic acid
 This treatment should only be used if surgical removal of
an infectious stone followed by eradication of infection with
antibiotics is ineffective
 This medication causes an irreversible inhibition of the
enzyme urease, therefore attenuating the rise in both
urinary pH and NH4
+
 Mercaptopropionylglycine or d-penicillamine
 Thiol-derivatives that split cystine molecules into two
cysteines and produce a highly soluble disulfide compound

29. Medical Expulsive Therapy (MET)
 MET is treatment with combination of drugs which
facilitates the spontaneous passage of ureteric calculi
 Ureteric colic is an emergency and management depends
upon the severity of obstruction and degree of renal
function deterioration
 Approximately 90% of stones <5 mm and 15% of stones
between 5 and 8 mm pass spontaneously within 4 weeks,
while 95% of those larger than 8 mm require urological
intervention

30. Recent findings indicate that medical expulsive
therapy can facilitate spontaneous passage for
stones up to 10 mm

31. Recommended Drugs For MET
Alpha 1 adrenergic blockers
Calcium channel blockers
Steroids

32. Alpha 1 Adrenergic Blockers
 Alpha adrenergic receptors are densely located in the
smooth muscles of ureter
 Alpha-1a-receptors predominate in bladder outlet,
prostate, and proximal urethra, whereas alpha-1d-
receptors are seen in lower ureter and detrusor muscle of
bladder
 Drugs which block these receptors cause smooth muscle
relaxation and inhibits peristalsis and relieves spasm
 Eg: Silodosin or Tamsulosin

33. Calcium channel blockers (CCBs)
 Calcium channel blockers (CCBs) cause inhibition of
calcium channels in distal ureter and decrease the
contraction and spasm caused by distal ureter calculus
 Eg: Nifidepine

34. Steroids
 Calculus in distal ureter causes inflammation and
submucosal edema which further aggravates the
obstruction due to the stone per se
 Being anti-inflammatory agents, steroids reduce the
inflammation and neutrophils-induced damage
 This class of drug, in combination with other agents,
improves stone passage and reduces stone expulsion time
 Eg: Deflazacort, Prednisolone

35. Patients receiving MET, who do not pass stones within 4
weeks, should be reffered to a urologist since delay in
definitive management may increase the rate of
complications, including renal dysfunction, urosepsis,
and intractable pain

36. Surgical Management
 Surgical management of urinary tract stones depends on their
size and site, and on any symptoms and signs
 The primary indications for surgical treatment include
 Pain
 Infection
 Obstruction
 Infection combined with urinary tract obstruction is an extremely
dangerous situation, with significant risk of urosepsis and death,
and must be treated emergently in virtually all cases

37. Contraindications
 General contraindications to definitive stone
manipulation include the following:
 Active, untreated UTI
 Uncorrected bleeding diathesis
 Pregnancy (a relative, but not absolute,
contraindication)

38. Surgical Options
 Stent placement
 Percutaneous nephrostomy
 Extracorporeal shockwave lithotripsy
 Ureteroscopy
 Percutaneous nephrostolithotomy
 Open nephrostomy

39. Stent Placement
 When used for stone disease, stents perform several
important functions
 They virtually guarantee drainage of urine from the
kidney into the bladder and bypass any obstruction
 This relieves patients of their renal colic pain even if the
actual stone remains
 Over time, stents gently dilate the ureter, making
ureteroscopy and other endoscopic surgical procedures
easier to perform later

40. Stent Placement-Drawbacks
 Stent can become blocked, kinked, dislodged, or
infected
 A KUB radiograph can be used to determine stent
position, while infection is easily diagnosed by
urinalysis
 A renal sonogram can sometimes be helpful if there
is concern for obstruction

41. Stent A is a 6-F polyurethane stent with standard proximal and distal pigtail
loops to prevent migration and fenestrations along the entire shaft length.
Stent B is a 7-F silicone stent with holes in the loops only. Stent C is a Flexima
ureteral stent . This 10-F stent has a hydrophilic coating and holes in the loops
only. Stent D is an Ultrathane Amplatz ureteral stent .This 8.5-F polyurethane-
latex stent has a hydrophilic coating and metal markers indicating shaft length
(arrowheads). Stent E is a C-Flex Towers multilength stent (Cook Urological).
This 6-F stent has a hydrophilic coating and ridges rather than fenestrations
along its length to assist with urine flow

42. Percutaneous Nephrostomy
 In some cases, drainage of an obstructed kidney is necessary
and stent placement is inadvisable or impossible
 In particular, such cases include patients with pyonephrosis who
have a UTI or urosepsis exacerbated by an obstructing calculus
 In these patients, retrograde endourological procedures like
retrograde pyelography and stent placement may exacerbate
infection by pushing infected urinary material into the obstructed
renal unit
 Percutaneous nephrostomy is useful in such situations

43. Extracorporeal Shockwave
Lithotripsy (ESWL)
 ESWL has been an established form of treatment for upper
urinary tract stones since the early 1980s
 It is non-invasive and can be performed as an outpatient
procedure under local anesthesia or sedation
 ESWL has therefore been accepted as a standard treatment
for renal stones measuring less than 2 cm
 A shock wave is generated by a source external to the patient
that propagates through the body before being focused on a
kidney stone

44.  SWL is limited somewhat by the size and location of the
calculus
 A stone larger than 1.5 cm in diameter or one located in the
lower section of the kidney is treated less successfully
 Fragmentation still occurs, but the large volume of fragments
or their location in a dependent section of the kidney precludes
complete passage
 In addition, results may not be optimal in large patients,
especially if the skin-to-stone distance exceeds 10 cm

45.  Being a noninvasive and safe treatment, complications of
ESWL occur in only 3% to 7% of the patients who undergo
this procedure
 The complications are usually mild, and life-threatening
complications are extremely rare
 The incidence of clinically significant hematoma formation
after ESWL is reported in less than 1% of the cases in the
literature
 Moreover, hepatic hematoma after ESWL is extremely rare

46. Ureteroscopy
 Along with SWL, ureteroscopic manipulation of a
stone is a commonly applied method of stone removal
 A small endoscope, which may be rigid, semirigid, or
flexible, is passed into the bladder and up the ureter
to directly visualize the stone
 Ureteroscopy is especially suitable for removal of
stones that are 1-2 cm, lodged in the lower calyx or
below, cystine stones, and high attenuation ("hard")
stones

47.  The typical patient has acute symptoms caused by a
distal ureteral stone, usually measuring 5-8 mm
 Stones smaller than 5 mm in diameter generally are
retrieved using a stone basket
 Whereas tightly impacted stones or those larger than 5
mm are manipulated proximally for SWL or are
fragmented using an endoscopic direct-contact
fragmentation device

48. Two calculi in a dependent calyx of the kidney (lower pole) visualized
through a flexible fiberoptic ureteroscope

49. Percutaneous Nephrostolithotomy
 Percutaneous nephrostolithotomy allows fragmentation
and removal of large calculi from the kidney and ureter
 Because of their increased morbidity these procedures
are generally reserved for large and/or complex renal
stones and failures from the other treatment
 It is especially useful for stones larger than 2 cm in
diameter
 Percutaneous access to the kidney typically involves a
sheath with a 1-cm lumen, which will admit relatively large
endoscopes with powerful and effective lithotrites

50.  In some cases, a combination of SWL and a
percutaneous technique is necessary to completely
remove all stone material from a kidney
 This technique, called sandwich therapy, is reserved
for staghorn or other complicated stone cases
 In such cases, experience has shown that the final
procedure should be percutaneous nephrostolithotomy

51. Open Nephrostomy
 Open nephrostomy has been used less and less often
since the development of SWL and endoscopic and
percutaneous techniques
 it now constitutes less than 1% of all interventions
 Disadvantages include longer hospitalization, longer
convalescence, and increased requirements for blood
transfusion

52. References
 J Clin Endocrinol Metab. 2012 June; 97(6): 1847–1860. Kidney Stones 2012:
Pathogenesis, Diagnosis, and Management
 Nephron Clin Pract 2010;116:c159–c171An update and practical guide to renal
stone management.
 BMJ. 2004 Jun 12;328(7453):1420-4.Kidney stones
 Cleve Clin J Med.2009 Oct;76(10):583-91. Nephrolithiasis: treatment, causes,
and prevention
 CJEM. 2007 Nov;9(6):463-5.Myth: nephrolithiasis and medical expulsive therapy.
 F1000 Med Rep. 2009 Jul 8;1. pii: 53. doi: 10.3410/M1-53. Recent advances in
management of ureteral calculi
 RadioGraphics, 22, 1005-1022. Complications of ureteral stent placement.
 J Urol. 2010 Mar;51(3):212-5. Epub 2010 Mar 19. Life-threatening complication
after extracorporeal shock wave lithotripsy for a renal stone: a hepatic
subcapsular hematoma
 Nephrolithiasis Treatment & ManagementAuthor: J Stuart Wolf Jr, MD, FACS;
Chief Editor: Bradley Fields Schwartz, DO, FACS