Approach to Renal Stones College of Medicine Physician Course 2013

Outline

• Epidemiology • Presentation and Pathogenesis • Contributing factors • Evaluation • Management strategies • Summary

Epidemiology • USA (NHANES data 2007-2010)

Scales et al. European Urology 2012

Incidence and Prevalence • Annual incidence 0.6-1.5%

• Prevalence 2-7%

• Lifetime risk 10-20%

• Male>Female

• Caucasians>Hispanics and Asians>African Americans

• No data available for Asia

Clinical presentation • Asymptomatic • Abdominal pain • Haematuria • Urinary tract infection • CKD/ESRD

Stone types

Pathogenesis

• Supersaturation • Imbalance of modifiers • Epithelial factors

Supersaturation

• Ratio urinary Calcium Oxalate or Calcium Phosphate concentration: solubility

• At levels <1 crystals dissolve • At levels >1 crystals can nucleate and grow

Imbalance of modifiers • Anatomical factors

o Urinary stasis - caused by ureteropelvic junction obstruction, horseshoe kidney or polycystic kidneys

• Hypercalciuria o Usually familial or idiopathic o Would a low Ca diet help?

• Calcium binds oxalate in the gut hindering its absorption therefore low Ca diet may actually result in increased Ca Oxalate stone formation!

• Hypocitraturia - increases risk of stone formation o can occur in distal RTA, hypokalaemia, carbonic anhydrase

inhibitor use (topiratmate) • Hyperuricosuria

o due to increased purine intake o promotes calcium stones by decreasing Ca Oxalate solubility

Epithelial factors

• Stones can form over regions of interstitial CaPhosphate deposits on the papillary surface (Randall’s plaques); usually in idiopathic CaOxalate recurrent stone formers

• Idiopathic CaPhosphate stones tend to form over the inner medullary collecting ducts that contain apatite or other crystals

Contributing factors • Obesity • Lower

socioeconomomic status

• Metabolic syndrome

Scales et al. European Urology 2012

Associated Factors (Ca stones)

Worcester, Coe. NEJM 2010

Worcester, Coe. NEJM 2010

Causes of renal calculi

Calcium stones Primary Hyperparathyroidism Medullary sponge kidney Distal renal tubular acidosis Uric acid stones Acidic urine (pH<5.5) UA overproduction and secretion

Struvite stones Urease-producing organisms (proteus/klebsiella) Cystine stones Cystinuria (AR disorder)

Evaluation • Comprehensive evaluation indicated for

o Multiple/recurrent stones

o Progressive calculi (increasing in size or number)

o Children, Non-caucasians

o Non calcium containing calculi

o Solitary kidney

o (Metabolic syndrome)

To Evaluate or not? • Doing something

o Uncover underlying condition e.g. primary hyperparathyroidism o Associated conditions e.g. low bone density o Tailor therapy o Follow efficacy of therapy

• Doing nothing o Recurrence rate 50-60% in 10yrs; 70-80% in 20 yrs o Empirical Rx can be effective

• Increase fluid intake • Decrease salt and protein in the diet • Alkali Rx

Imaging

Plain Xray

US

CT KUB

IVU MRI

Two separate 24 hour urine collection, while on usual diet and activities for: Urine Vol pH Calcium Oxalate Uric acid Citrate Sodium Creatinine

Treatment options for renal calculi

Symptoms

Conservative Surgical

Yes No

<7mm >7mm

Percutaneous nephrolithotomy Shock wave lithotripsy

Ureteroscopy Open/Laparoscopic surgery

Annual Imaging

Stones <5mm more likely to pass (p=0.006)

20% incidence of spontaneous passage

Only 7.1% required intervention eventually

Ureteric obstruction Koh LT et al. BJUI 2011

Chandrashekar K et al. AJM 2012

Recurrence prevention

• Fluid intake

• Dietary restrictions? o Low animal protein, Na, oxalate with normal Ca intake vs low Ca and

oxalate intake 36,37

o Low sodium diet can decrease excretion of both calcium and oxalate

• Thiazides

• Potassium citrate

Clinical trials in pharmacotherapy

Sakhaee et al.J Clin Endocrinol Metab, June 2012

Preventative measures

Worcester, Coe. NEJM 2010

Fluid intake

• Ensuring a urine volume of >2L/day was associated with reduced urinary supersaturation of CaOxalate and reduced stone recurrence

Borghi et al. J Urol 1996

Dietary contributory factors

• High animal protein diet • High salt diet • High oxalate containing foods • Low calcium diet • Excessive Vit C and D • Excessive fructose intake

Dietary interventions • Low calcium diet? • In men with recurrent

calcium oxalate stones and hypercalciuria, restricted intake of animal protein and salt, combined with a normal calcium intake, provides greater protection than the traditional low calcium diet

Borghi et al. NEJM 2002

Thiazide diuretics

• Decreases urine calcium excretion and reduces rates of Ca stones by >50% in a 3 year period1,2,3,4

• Concurrent low salt diet (attenuates urinary calcium excretion) and sufficient potassium (to avoid hypocitraturia)5

1Borghi et al. J Cardio Phamacol 1993 2Ettinger et al. J Urol 1988 3Laerum et al. Acta Med Scand 1984 4Fernandez-Rodriguez et al. Actas Urol Esp 2006 5Pak et al. AJM1985

Potassium Citrate • Reduces stone recurrence among patients with

hypocitraturia1,2

• Can be safely combined with a thiazide • Lowers urinary calcium excretion, raises urinary

citrate and reduces urinary CaOxalate, CaPhosphate and undissociated uric acid supersaturation3.

1Ettinger et al. J Urol 1997 2Barcelo et al. J Urol 1993

3Sakhaee et al. KI 1983

Allopurinol

• Decreases stone recurrence in patients with idiopathic CaOxalate stones with hyperuricosuria

• Should be paired with a reduction in purine intake

Approach to evaluation & Rx of kidney stones First stone Recurrent stone

24 Urine Collection

High/N Calcium

Blood test

Uric Acid >750mg/day (women)

>800mg/day (men) Oxalate <40mg/day

Citrate <550mg/day (women) <450mg/day (men) Calcium

>250mg/day (women) >300mg/day (men)

Urine Vol <2L High PTH

Hyperparathyroidism

Bicarbonate

RTA

Progressive calculi (increasing in size or number) Children, Non-caucasians Non calcium containing calculi Solitary kidney xt

Increase fluid intake Aim UV >2L/day Lower salt intake

Thiazide

Urine pH <6.5

Potassium Citrate Low oxalate diet ↑Calcium in diet

↓Purine diet Weight loss Allopurinol

UTI? Rx UTI

Imaging Imaging

Low/Low N

Yes

No

No

Yes Labs

Summary • Renal stones is increasing in incidence • First timers may not need to be evaluated, however • Further evaluation is necessary in certain circumstances

o Multiple/recurrent stones o Progressive calculi (increasing in size or number) o Children, Non-caucasians o Non calcium containing calculi o Solitary kidney o Metabolic syndrome

• In the acute setting medical therapy can be attempted (if stones are <7mm) and surgical options pursued if needed

• General advice to increase fluid intake, salt/oxalate/animal protein restriction and normal calcium diet is applicable to most patients

• Further treatment options can be tailored based on biochemical findings

• Follow-up is required to avoid long term sequelae from chronic renal calculi

Recommended reading

• Elaine M. Worcester and Fredric L. Coe.Calcium Kidney Stones.NEJM 2010;363:954-63.

• Khashayar Sakhaee, Naim M. Maalouf, and Bridget Sinnott. Kidney Stones 2012: Pathogenesis, Diagnosis, and Management. J Clin Endocrinol Metab 97: 1847–1860, 2012.