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นิ่วในไต
นิ่วในไต
1.
(kidney stone disease, nephrolithiasis)
5-10
(Tropical/ subtropical regions)
20
10-16
(lithotripsy)
(surgery)
25 3
39 2
(first episode)
2 (calcium stones)
80 (calcium oxalate, CaOx)
(calcium phosphate, CaP)
(non- calcium stones)
15-20 (uric acid stone)
(infection stone struvite) (cystine stone)
(mixed stone)
(pure stone)
1 256
Geographic regions
All regions
Stone composition NE N C S
Freq. % Freq. % Freq. % Freq. % Freq. %
n 256 103 81 47 25
Pure stones 103 40.23 37 35.92 29 35.80 24 51.06 13 52.00
CaOx 54 21.09 19 18.45 18 22.22 13 27.66 4 16.00
UA 36 14.06 12 11.65 11 13.58 8 17.02 5 20.00
CaP 5 1.95 2 1.94 0 0 1 2.13 2 8.00
MAP 8 3.13 4 3.88 0 0 2 4.26 2 8.00
Mixed stones 153 59.77 66 64.08 52 64.20 23 48.94 12 48.00
CaOx+CaP 122 47.66 52 50.49 46 56.79 15 31.91 9 36.00
CaOx+UA 12 4.69 6 5.83 3 3.70 2 4.26 1 4.00
CaOx+others 8 3.13 4 3.88 2 2.47 1 2.13 1 4.00
Others 11 4.30 4 3.88 1 1.23 5 10.64 1 4.00
Stone types regarding to the major crystalline component
CaOx 189 73.83 77 74.76 68 83.95 29 61.70 15 60.00
CaP 14 5.47 7 6.80 1 1.23 3 6.38 3 12.00
UA 41 16.02 13 12.62 12 14.81 11 23.40 5 20.00
MAP 12 4.69 6 5.83 0 0 4 8.51 2 8.00
CaOx: calcium oxalate, UA: uric acid, CaP: calcium phosphate, MAP: magnesium ammonium
phosphate (infection stone), other mix stone type (xanthine, ammonium urate and calcium
carbonate), NE: northeastern, N: northern, C: central, S: southern.
2.
(intrinsic risk factors) (extrinsic risk
factors) (metabolic risk factors)
2.1
2.1.1 (genetics): (relative risk)
2.5
32
48.6 32
(BMI) 55.6 2 60 2
2 144
Variable/ Risk factor Frequency Percentage P value
Stone recurrence 0.637
First episode 74 51.39
Recurrence episode 70 48.61
Family history <0.001*
Negative 98 68.06
Positive 46 31.94
Nutritional status 0.059
BMI < 23.0 64 44.44
BMI 23.0 80 55.56
Water intake 0.001*
< 2 liters/day 86 59.72
> 2 liters/day 58 40.28
* indicates statistical significance of proportion test (P < 0.05).
50 Rice/Carbohydrate
Animal protein
Percent of patients Vegetables
40 Fruits
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
Daily consumption (serving/day)
1
144
2.2.2
2.2.3
Beryllium renal tubular acidosis
2.2.4
2.2.5
2.3
Alanine-glyoxalate aminotransferase (AGT)
autosomal recessive
50
lysosomal enzymes
alkaline phosphatase N-acetyl--glucosaminidase (NAG)
2.3.2 (hypercalciuria)
4 1 200
3
(absorptive hypercalciuria) (resorptive
hypercalciuria) (renal hypercalciuria)
(supersaturation)
3
(PTH)
(calcitonin)
2.3.4 (hyperphosphaturia)
0.311.3
900
pH
2.3.5 (hypocitraturia)
ATP
320 19-63
80-90 200
acetazolamide carbonic anhydrase
fluorocitrate
hydroxycitrate
2.3.6 (dehydration)
2-3
2
(supersaturation)
3
(calcium stones)
(non-calcium stones)
Stone Type
Metabolic abnormality Cutoff Calcium Non-calcium P value
(n=46) (n=19)
Hypercalciuria >200 mg/d 2.17% 0% 0.0473*
Hyperoxaluria >0.45 mmol/d 17.39% 10.53% 0.5653
Hyperphosphaturia >0.9 g/d 2.17% 21.05% 0.3338
Hyperuricosuia >600 mg/d 39.13% 42.11% 0.6239
Hypocitraturia <250 mg/d 86.96% 86.47% 0.1943
Hypokaliuria <30 mEq/d 76.09% 63.16% 0.4887
Hypomagnesiuria <50 mg/d 52.17% 52.63% 0.6548
* indicates statistical significance of proportion test (P < 0.05)
3.
(stone/calculi formation) (crystal formation)
(supersaturation) (stone
promoters/ lithogenic substances) (Ca) (Ox) (P)
(UA)
(crystal retention) (stone
inhibitors/ stone modulators) (citrate)
(magnesium) (pyrophosphate)
glycosaminoglycans (GAGs), Tamm-Horsfall protein (THP), Nephrocalcin, urinary
prothrombin fragment-1 (UPTF1), osteopontin (OPN), bikunin (BK) albumin
(crystal retention/
crystal deposit) (renal tubular injury/ dysfunction/
damage) stone nidus (a base for stone growth)
renal papilla (cell debris)
(heterogeneous crystal
nucleation) stone nidus
renal interstitium Randalls plaque
Randalls plaque
Randalls plaque
(normal renal mineral handling)
Randalls plaque renal papilla
nidus
(chronic/ persistent
supersaturation)
(internalization/ endocytosis)
renal interstitium
reactive oxygen species (ROS)
(oxidative stress) ROS
14
Millions
P = 0.003
14
Millions
P = 0.738
12
12
(arbitrary unit/g Cr)
10
(arbitrary unit/g Cr)
10
MUC2 intensity
MUC1 intensity
8
8
6
6
4
4
2
2
0
0
-1 0 1 2 -1 0 1 2
Healthy Nephrolithiasis
A. Healthy Nephrolithiasis B.
4 MUC1 (A) MUC2 (B)
(nephrolithiasis) (healthy control)
Millions
Spearman's rho = 0.871
P < 0.001
12
0
0 2 4 6 8 10 12 14
Millions
Urinary MUC1 intensity (arbitrary unit/g Cr)
5 Scatter plot MUC1 MUC2
(Spearmans rho = 0.871, P < 0.001)
225 225
B PAS intensity- NL
175 175
PAS Intensity (arbitrary unit)
150 150
125 125
100 100
75 C D 75
50 50
25 25
0 0
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 70 73 76 79
Fractions
ETC
Inflammation
L/M/P L/M/P
ECM proteins Fibrosis
Degradation of ECM
Myofibroblast
Interstitium
Interstitial
MCP-1
Profibrotic damage
IL-6
cytokines
OPN F
(e.g., TGF-)
ANGII
Oxidative stress Crystal
Inflammatory
mediators Mac deposition
STONE NIDUS
O2- OH- ONOO- FORMATION
3
- -
O2 OH ONOO
-
RTC
Renal tubular
4. Stone matrix
2 (inorganic
composition) (organic composition/ organic matrix)
2-3
(cellular biomolecules) GAGs
organic matrix 64% 6
crystal
nucleation, crystal-to-cell interaction, crystal aggregation, nidus formation stone growth
transmission electron microscopy (adhesion)
discontinuous coat 10-20 nm anionic
4.2 Proteins
20
stone matrix albumin, - and -globulin THP
albumin CaOx, UA, struvite cystine
albumin CaOx CaP THP
THP (loose interaction) THP
stone matrix
Tamm-Horsfall protein (THP): THP (glycoprotein)
Tamm Horsfall THP 80 kDa (616 amino acid
residues) 30% THP (aggregate)
polymeric form polymerization THP Ca ions high
ionic strength/osmolality pH THP
urinary casts THP 20-
100 mg/day THP
THP
THP CaOx CaP THP
4.3 Lipids
mineralized tissues 7-14% 2-6%
(dentin) 12-22% (enamel) 10.2% supragingival calculi
calcification crystal
nucleation, aggregation calcified tissues
(protein-to-lipid ratio)
UA struvite CaOx CaP cholesterol,
cholesterol ester triacylglycerides struvite CaOx, CaP
UA phospholipids glycolipids glycolipids
glucocerebrosides phospholipids sphingomyelin
(crystal formation)
5.
3
5
2
(stone recurrence) (stone growth)
2
200
700
900
50
320
150
pH 5.5 7.0
(calyceal stones) (< 5 .)
107
5 48.5 % 50 %
(stone free)
5.1.1
< 10 . (50-60 %) stone free
rate SWL 79.9 % (63 %-90 %)
stone free rate PCNL SWL
SWL
(Staghorn stones)
calyces
(Struvite stones) cystine, calcium
oxalate monohydrate
30 %
PCNL SWL PCNL
SWL OSS SWL OSS
PCNL PCNL
3 ports
5.1.2
SWL cystine brushite
SWL calcium oxalate monohydrate, hydroxyapatite, struvite, calcium
oxalate dihydrate uric acid (cystine, brushite, calcium
oxalate monohydrate) SWL (< 15 . )
PCNL
5.2
. (SWL)
13 25
2 3
.
39
allopurinal, thiazide, orthophosphate, triponin, acetohydroxamic acid,
5.2.2
3 21 63
glutathione ( 7)
2
Fractional Excretion of Mg (%) 3.50 1.93 3.32 1.89 2.84 1.46 3.25 1.24 3.25 0.86 3.64 2.19
U - NAG 5.31 3.53 3.22 2.5 3.71 2.13 4.76 4.23 5.04 3.56 3.4 2.41
P- MDA (uM) 2.50 1.25 1.91 1.01 2.85 1.67 2.56 1.07 3.82 1.77 2.66 0.94
R GSH (umole/gHb) 6.95 2.35 7.48 2.40* 7.27 1.30 6.16 1.71** 6.44 1.73 7.00 1.68
11/24/2007
U MDA (uM) 7.81 4.41 3.59 3.40 8.70 7.40 4.93 3.51 7.97 5.44 6.66 5.85
3 (* = P < 0.05 , ** =
7
6.
6.1. 8
24 2
6.2.
6.2.1.
pH
6.2.2
6.2.3.
150
6.2.4
6.2.5
800-1200
6.2.6. 30
4. 500
5.
6.
2
7.
1. Aihara K, Byer KJ, Khan SR. Calcium phosphate-induced renal epithelial injury and stone
formation: involvement of reactive oxygen species. Kidney Int. 2003; 64:1283-91.
2. Boonla C, Thummaborworn T, Tosukhowong P. Urolithiasis in Udon Thani Hospital : A rising
prevalence of uric acid stone. Chula Med J. 2006 Feb; 50(2):77-90.
3. Cao LC, Honeyman T, Jonassen J, Scheid C. Oxalate-induced ceramide accumulation in
Madin-Darby canine kidney and LLC-PK1 cells. Kidney Int 2000; 57(6): 2403-11.
4. Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest 2005; 115(10): 2598-608.