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24 hour urine:
Ca 380 mg/d, Uric acid 900 mg/d, Oxalate 50 mg/d, Citrate 200 mg/d,
Sodium 200 mEq/d, magnesium 119 mg/d, Volume 1800 ml/d
Over the next 2 years, he did not have recurrence of kidney stone .
History
First known stone:
6.5 cm bladder stone consisted of
Calcium Phosphate and Uric acid.
Carbon-dated 4800 B.C., it was
found in 1901 in a childs mummy
at a grave site in El Amrah, Upper
Calcium Oxalate Monohydrate
(Mummy Stone 800 AD)
Egypt.
herringlab.com Preserved in Royal Museum in
London until destroyed by
bombardment in 1941.
Stone surgery: Vedic times in
India:
Sushruta Samhita () is a
surgery textbook written in 800 BCE,
describes 300 surgical procedure, 120
surgical instruments, and 8 types of
surgery.
Detail from the panel of the Separation of Earth and Waters in the Sistine Chapel (1511)
"As regards my malady, I'm much better. We are now certain that I'm suffering from the
stone, but it's a small one and thanks to God and to the virtues of the water I'm drinking,
it's being dissolved little by little, so that I'm hopeful of being free of it" (Letter 326, 1549)
Calcium Carbonate
Calcium Citrate
Ammonium Urate
(laxative abuse)
Hereditary
Disorders
Xanthine
Polycystic kidney Disease
Medullary Sponge Kidney
Horseshoe kidney
2,8-dihydroxyadenine
adenine phosphoribosyltransferase (APRT)
Ciprofloxacin
Aminophylline Traimeterene
Phenazopyridine Phenytoin
Sulfamethoxazole
Amorphous silica
(magnesium trisilicate)
Guaifenesin
Metabolite
Methylglucamine
Iothalamate
herringlab.com
Infection?
Physico-chemical process
Physics of Crystallization
Supersaturated
Agglutination
Sodium Acid Urate
Metastable Aggregation
Nucleation
C Internalization and
cytokine activation
D Dissolution or
peritubular exit
Current Opinion in Nephrology & Hypertension. 2000; 9(4):349-355
Pathophysiology:
Plaque hypothesis
Site of stone formation
CaOX stones: Randells plaque
(Randall,1940)
Calcium apatite
in BBM of thin
Randalls plaque
limbs of Henles
loop
Laminated
microspherules
Islands of
of white apatite
crystals in the
crystals and
interstitium
black organic
matrix
Alpha trypsin
Osteopontin
inhibitor
Pathobiology of stone
formation
Brushite stones: CaHPO42H2O
Increasing in incidence
Conversion from CaOX to
brushite
High recurrent rates
Higher urinary calcium and
pH
Hard to fragment by SWL
or ultrasound
Greater tubular and
interstitial damage CKD?
Urol Res. 2010 Jun;38(3):147-60
Micro-molecular inhibitors:
Citrate
Magnesium, a weak inhibitor of CaOx
crystallization. Hypomagnesemia may
occur in enteric disorders, malnutrition
or low dietary intake.
Pyrophosphates and phosphocitrate
are inhibitors of CaP crystallization.
Citrate
Citrate, by complexing iCa, is a
powerful inhibitor of CaOx and CaP
crystal growth and aggregation.
Formation of a pH dependant Ca-
citrate-phosphate species,
independent of urinary citrate
concentration. NDT 2006 Feb;21(2):361-9
Higher excretion in women than
men.
Causes of hypocitrituria
Disorders of acid-base and electrolytes
Metabolic acidosis (Systemic or RTA)
Hypokalemia, hypocalciuria and hypomagnesuria
Diet
High protein and sodium intake
Low intake of fruit and vegetables
Drugs
Acetazolamide and topiramide (Carbonic anhydrase inhibitors)
ACE inhibitors (intracellular acidosis)
Thiazides
Genetic factors
VDR polymorphisms
NaDC-1 gene polymorphism
Macro-molecular inhibitors
Name Inhibitory Action
Tamm-Horsfall protein* Aggregation
Nephrocalcin Nucleation, growth, aggregation, attachment
Osteopontin* Nucleation, growth, aggregation
Prothrombin fragment-1 Growth, aggregation
Bikunin Nucleation, growth, aggregation, attachment
Alfa-1 microglobulin Crystallization
Calgranulin Growth, aggregation
Heparan sulfate Aggregation, attachment
Fibronectin Aggregation, attachment, endocytosis
Matrix Gla protein Crystal deposition
NHS I
Diabetes 1,371,080 1578 1.00 (reference) 1.00 (reference)
Distribution of calcium and UA stones with respect to body mass index (in kg/m 2 )
and diabetes mellitus status. BMI, body mass index; DM, diabetes mellitus.
Calcium stones UA stones.
Rule A D et al. CJASN 2011;6 (8) 2069-2075 Worcester EM J Urol. 2006 Aug;176(2):600-3
Bone disease in nephrolithiasis
Cumulative incidence of vertebral
fracture among Rochester,
Minnesota, residents following an
initial episode of symptomatic
nephrolithiasis Kidney Int. 1998;53:459464
Prevalence
Number of
Total number of patients with
Skeletal sites patients low BMD Percentage (%)
Vertebral spine 975 388 40
Hip 450 141 31
Radius 627 410 65
Adequate Analgesia
NSAIDs, e.g. ketorolac, highly effective in renal colic
Cordell (1996) Ann Emerg Med 28:151-8
NSAID compared with Opioids
Equal to or more effective than Opioids
Less Vomiting than with Opioids
Holdgate (2004) BMJ 328:1401-4
Local warming of abdomen and lower back to 42o c with
heating blanket
Kober A J (2003) Urol 170: 741-4
IV or oral fluid >2.5 Liters per day
Medical Stone Expulsion Therapy
Alpha-blockers Control Risk ratio
(95% C.I.)
Events Total Events Total
1074 1335 590 1086 1.45 (1.34, 1.57)
p=0.04