Preventon of Renal Stones

Preetham Boddana

Renal Consultant

26 Feb 2014

Outline

• Epidemiology

• Evidence for medical management

• Pathophysiology

• Preventon of stones by medical management

Epidemiology

• Prevalence of kidney stones 8.5%

• Male-to-female rato 3:1 to < 2:1

• Increases with age

• Whites>black, asian or hispanic etnicity

Clinical Risk Factors

• occupaton

• family history

• diet

• hydraton

• small bowel disease (i.b.d.)

• medical conditons causing hypercalcuria

• medical conditons causing aciduria

STONE MANAGEMENT

OPTIONS

Open surgery

Percutaneous nephrolithotomy

Ureteroscopy

Shock wave lithotripsy

Medical therapy

Metabolic Evaluaton

• Stone passage ≠ stone formaton

• Focused history for stone risk formers

• Urine analysis

• Stone analysis

NEPHROLITHIASIS

Peak incidence age 30 - 60

Gender (Male : Female) 3 : 1

Family history 3 - fold risk

Body size risk with weight

Recurrence afer frst stone:

Year 1 10 - 15%

Year 5 50 - 60%

Year 10 70 - 80%

NATURAL HISTORY & RISK FACTORS

Placebo/

Potassium

Conservatve Citrate

Stone formaton 0.54 0.25 0.52 0.02 rate (no/pt/yr)

Reducton in stone 54% 96%

formaton rate

Remission rate 61% 96%

MEDICAL MANAGEMENTOF NEPHROLITHIASIS

Preminger & Pak, 1985

IMPACT OFMEDICAL THERAPY

Pre-On

Duraton (yr/pt) 3.0 3.7

Surgery rate (no/pt) 0.21 0.01

Patents requiring 58% 2%Surgery

NEED FOR STONE REMOVAL

Preminger & Pak, 1985

SELECTIVE MEDICAL THERAPY

Sto

ne

Fo

rmat

ion

Rat

e

IMPACT OF MEDICAL RX

Pre-Rx On K-Citrate

0

1

2

3

4

5

6 Chronic Diarrh ea

RT A

Hyp erurico su ria

IdiopathicHyp oci tUric Aci d

Conditons causingkidney stone formaton

• High conc. of metabolic products in glomerular fltrate

• Changes in urine pH

• Urinary stagnaton

• Defciency of stone-forming inhibitors in urine

Conditons causingkidney stone formaton

• Defciency 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

Pathogenesis of Renal Stones

• 99% of renal stones are composed of:

– calcium oxalate 75% (mono or di hydrate)

– calcium hydroxyl phosphate (15%)(apatte)

– magnesium ammonium phosphate 10% (struvite)

– uric acid 5%

– cystne 1%

Calcium stone risk factors: 1) Hypercalciruia

• (>250mg/day in women, and >300mg/day in men)

– Seen in up to ½ of idiopathic calcium stone formers

– 3 types of hypercalciuria

• Absorptve: (most common form)

– increase in intestnal calcium absorpton from gut

• Resorptve: (5% of patents with recurrent stones)

– Secondary to primary hyperparathyroidism

– Risk of recurrent stones returns to baseline about 10 years afer parathyroidectomy

• Renal: (2%)

– Increased excreton of calcium secondary to defect in renal tubular calcium reabsoropton

Calcium stone risk factors: 2) Hyperuricosuria

• (>750mg/day in women, 800mg/day in men)

– UA is end product of purine metabolism

– Uric acid is thought to act as a nidus for calcium stone formaton

– In most of these pts, a high purine diet is responsible rather than defect in uric acid metabolism

Calcium stone risk factors: 3) Hypocitraturia

• (<320mg/day)

– Citrate thought to be a principal inhibitor of stone formaton by actng in tubular lumen by

combining with calcium to form soluble complex

– Women excrete more citrate and thus have lower incidence of stone formaton than men

– Chronic metabolic acidosis limits citrate excreton (by enhancing proximal reabsorpton)

• chronic diarrhea,

• RTA,

• carbonic anhydrase inhibitors

Calcium stone risk factors: 4) Hyperoxaluria

• (>45mg/day)

– 1) Enteric hyperoxaluria

• Decolonisaton of Oxalobacter formigenes,

• Low calcium diet

• Small bowel disease or surgical resecton,

– malabsorpton of faty acids and bile saltsincrease in oxalate absorpton from:

» Increased free Ca to bind with oxalate (Ca is bound to faty acids in the intestnal lumen)

» increased colonic permeability to oxalate

Principles of Medical Management

• instruct patent on adequate water consumpton ( enough to produce 2L of urine

in 24 hrs.)

• if hypercalciuric treat with hydrochlorothiazide (monitor urinary Ca)

Principles of Medical Management (2)

• if hyperuricosuric

– allopurinol if serum uric acid elevated

– alkalinize urine if serum level is normal

• if actve Ca stone former not aided by diet, hctz add K citrate

• if magnesium ammonium phosphate stone afer reducton of burden treat

aggressively with antbiotcs.

Principles of Stone Preventon

• Prevent supersaturaton

– 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 cystne

Drug therapy for calcium stones

• Hypercalciuria: thiazide diuretcs

– Thiazide therapy can lower calcium excreton by as much as 150mg/day

• Hyperuricosuria: allopurinol or K citrate

– Raising the urine pH above 6.0 will convert insoluble uric acid to much more soluble urate salt

• Hypocitraturia: K citrate

– Alkalinizing urine enhances citrate excreton

Drug therapy for calcium stones (cont)

• Hyperoxaluria

– Aim to diminish intestnal oxalate absopton (high fuid, K citrate, oral calcium carbonate, low

fat, low oxalate diet)

– Possible drug therapy pending

• Pyridoxine may reduce producton of oxalate

• Cholestyramine reduces intestnal absorpton of oxalate

• Probiotc treatment with Oxalobacter has been shown to decrease urinary oxalate concentraton ,

Treatment of Uric Acid Stones

• Hydraton, dietary purine moderaton (lower meat, poultry, fsh)

• Alkalinizaton urine with K citrate to maintain urine pH between 6.0-7.0

• If nocturnal urine pH falls, acetazolamide

• Can add allopurinol

Cystne stones

• Treatment

– High fuid intake

– Urine alkalinizaton

– Sodium restricton

• Penicillamine, topronin, and captopril

– Cystne is formed from linkage of two cysteine

molecules by a disulfde bond. These meds by

decrease availability by forming complexes with

cysteine.

cysteine

cysteine

Disulfde bond

THANK YOUTHANK YOU