Friday, 1 November 2013

Kidney stones (Renal calculus)

Kidney stones is a composed of mineral salts formed in the kidneys. Men account for the 80% of those with kidney stones and are at risk of the formings between 30 and 40 years of age. About 75% of kidney stones are calcium stones.

I. Symptoms

Some people with kidney stones may not experience any symptom at all. Renal colic is characterized by an excruciating intermittent pain, usually in the flank (the area between the ribs and hip), that spreads across the abdomen, often to the genital area and inner thigh. The pain tends to come in waves, gradually increasing to a peak intensity, then fading, over about 20 to 60 minutes. The pain may radiate down the abdomen toward the groin or testis or vulva.

Other symptoms include nausea and vomiting, restlessness, sweating, and blood in the urine. A person may have an urge to urinate frequently, particularly as a stone passes down the ureter. Chills, fever, and abdominal distention sometimes occur.(1a)
II. Causes and Risk factors
A. Causes
1. Dehydration 
Dehydration or strenuous exercise without adequate fluid can cause the forming of kidney stones as a result of low levels of urine pH (below 5.5)(1).

2. Ramadan fasting ( food restriction)
Ramadan fasting are associated with risk of kidney stones forming. In the study to evaluate the effects of fluid and food restriction in Ramadan fasting on urinary factors in kidney and urinary calculus formation, researchers at the Shahid Beheshti University of Medical Sciences, found that fasting during Ramadan has different effects on total excretion and concentrations of urinary precipitate and inhibitory factors contributing to calculus formation(2).

3. Rotavirus infection
There is a report of  4 patients with RV infection who developed postrenal renal failure induced by urinary tract obstruction with uroammoniac calculi or crystals... Uric acid stone formation was considered to have originated from the low pH caused by dehydration and the increase of urinary uric acid excretion from damaged cells(3).

4. Calcium
In the study to explore the relationship among intestinal fractional calcium absorption, calcium intake and nephrolithiasis in a prospective cohort of 9,704 postmenopausal women recruited from population based listings in 1986 and followed for more than 20 years, showed that fractional calcium absorption is higher in women with a history of nephrolithiasis. Higher intestinal fractional calcium absorption is associated with a greater risk of historical nephrolithiasis. Dietary and supplemental calcium decrease fractional calcium absorption, and may protect against nephrolithiasis(3a).

5. Gastrointestinal lipase inhibitor
Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. The use of lipase inhibitors, especially under a diet rich in oxalate alone or associated with fat, leads to a significant and marked increase in urinary oxalate and a slight reduction in uCa and uMg that, taken together, resulted in an increase in AP (CaOx) index(rat), elevating the risk of stone formation(3b).

6. High fat intake
A comparison of the dietary intake per kilogram body weight in each group was made using standard statistical procedures. None of the nutrient intakes showed a significant difference, but dietary fibre intake and the percentage of energy provided by carbohydrate were consistently higher in the control group, whereas the percentage of energy provided by fat was consistently higher in the renal stone group(3c).

7. Vitamins
In the study of a total of 1078 incident cases of kidney stones was documented during the 14-yr follow-up period. A high intake of vitamin B6 was inversely associated with risk of stone formation. After adjusting for other dietary factors, the relative risk of incident stone formation for women in the highest category of B6 intake (> or =40 mg/d) compared with the lowest category (<3 mg/d) was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake was not associated with risk. The multivariate relative risk for women in the highest category of vitamin C intake (> or =1500 mg/d) compared with the lowest category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large doses of vitamin B6 may reduce the risk of kidney stone formation in women. Routine restriction of vitamin C to prevent stone formation appears unwarranted(3d).

8. Etc.

B. Risk factors
1. Gender
If you are men, you are at higher risk to develop kidney stones. In the study to determine gender differences in the symptomatic presentation of kidney and ureteral stones among the Hispanic population and compared it with presentation in the Caucasian population, found that the male-to-female ratio of the symptomatic patients with kidney stones was 1.48 for both Hispanic and Caucasian patients. The male-to-female ratio for ureteral stones was 1.06 and 2.48 for the Hispanic and Caucasian patients, respectively (P < 0.05)(4).

2. Family history
You are more likely to develop (more) kidney stones, if one the your directed family member have itor you already have them as a result of genetic factors, environmental exposures, or others(5).

3. Hyperuricemia
If you have hyperuricemia, you are at invreased risk to develop kidney stone as the result of the elevation of uric acid levels. Uric acid stones occur in 10% of all kidney stones and are the second most-common cause of urinary stones after calcium oxalate and calcium phosphate calculi(6).

4. Pregnancy
Although the risk is low, increased progesterone levels and decreased fluid intake during pregnancy may  be associated with the increased risk of the development of kidney stones. According to the study of 22,843 newborns or fetuses with CAs, 69 (0.30%) had mothers with KS during pregnancy. Of 38,151 matched control newborns without any abnormalities, 147 (0.39%) had KS during pregnancy. KS were associated with an adjusted prevalence odds ratio (POR) with 95% CI of 0.8, 0.6-1.0 for CAs(7).

5. Low urine pH (below 5.5) 
For uric acid crystallization and stone formation, low urine pH (below 5.5) is a more important risk factor than increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrheal states or severe dehydration(8).

6. Infection of urinary track
In the study of total of 100 kidney stone formers (59 males and 41 females) admitted for elective percutaneous nephrolithotomy who were recruited and microorganisms isolated from catheterized urine and cortex and nidus of their stones by Faculty of Associated Medical Science, Khon Kaen University, showed that from 100 stone formers recruited, 36 cases had a total of 45 bacterial isolates cultivated from their catheterized urine and/or stone matrices. Among these 36 cases, chemical analysis by Fourier-transformed infrared spectroscopy revealed that 8 had the previously classified 'infection-induced stones', whereas the other 28 cases had the previously classified 'metabolic stones'. Calcium oxalate (in either pure or mixed form) was the most common and found in 64 and 75% of the stone formers with and without bacterial isolates, respectively. Escherichia coli was the most common bacterium (approximately one-third of all bacterial isolates) found in urine and stone matrices (both nidus and periphery). Linear regression analysis showed significant correlation (r = 0.860, P < 0.001) between bacterial types in urine and stone matrices. Multidrug resistance was frequently found in these isolated bacteria. Moreover, urea test revealed that only 31% were urea-splitting bacteria, whereas the majority (69%) had negative urea test(9).

7. Water hardness 
In the study to evaluate whether the hardness of extra meal drinking water modifies the risk for calcium stones, showed that the main urinary risk factors for calcium stones, were measured in 18 patients with idiopathic nephrolithiasis, maintained at fixed dietary intake of calcium (800 mg/day), after drinking for 1 week 2 liters per day, between meals, of tap water and at the end of 1 week of the same amount of bottled hard (Ca2+ 255 mg/l) or soft (Ca2+ 22 mg/l, Fiuggi water) water, in a double-blind randomized, crossover fashion(10).

8. Obesity and diabetes
Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones(11).

9. Etc.

III. Diagnosis
If you are experience tenderness over the back and groin or pain in the genital area without an obvious cause, it can be renal colic. After a complete physical examination and recorded family history, the most common test which your doctor order is CT scan.
1. CT scan and Ultrasound
The aim of CT scan is to detect the stones or obstruction within the urinary tract.In pregnant women, CT scan can be replaced by ultrasound to reduce the risk of radiation. Helical (also called spiral) computed tomography (CT) is considered as the best to locate and reveal the degree to which the stone is blocking the urinary tract. 

2. Urinalysis 
Urinalysis is important to detect blood or pus in the urine and determine whether or not symptoms are present.
According to the study by University of Chicago Pritzker School of Medicine, Current diagnostic evaluation of recurrent Ca oxalate nephrolithiasis should be conducted while the patients follow their usual diets and includes the following:
1. Analysis of stone composition by polarization microscopy.
2. Measurement of serum Ca, phosphate, uric acid, 1,25(OH)2D3, and creatinine.
3. Twenty-four-hour urine collection for an analysis of volume, pH, and excretion of Ca, phosphorus, magnesium, uric acid, citrate, sodium, oxalate, and creatinine(12).

IV. Prevention
The do's and do not list
1. Fluid intake, protein and sodium restriction, and thiazide will be effective in ICSFs and IPSFs by decreasing urine calcium concentration and CaOx and CaP SS and may also decrease plaque formation by increased PT calcium reabsorption. Citrate may be detrimental for IPSFs if urine pH rises greatly, increasing CaP SS. Future trials should examine the question of appropriate treatment for IPSFs(13).

2.  Moderate exercise
Moderate exercise to reduce the loss of fluid. If you involve in the extreme exercise, please remember to enough fluid to avoid dehydration.

3. Prevent vitamin overdose as they can cause the forming of kidney stones.

4. If you live in far North with water hardness, use water filter

5. If you are over weight or obese, lose weight

6. Reduced consumption of grapefruit juice cola drinks.
Study showed that grapefruit juice and cola drinks significantly (p=0.021) increased urinary excretion of citrate (25.8+/-9.3 vs 18.7+/-6.2 mg/h), calcium (6.7+/-4.3 vs 3.3+/-2.3 mg/h, p=0.015) and magnesium (2.9+/-1.5 vs 1.0+/-0.7 mg/h, p=0.003) and in the prevention of calcium renal stones a reduced sugar content is desirable to avoid the increase of urinary calcium due to the effect of sugar supplementation(14).

7. Drink more juices (organic)
Researchers at the University of Bonn, in the study of influence of grapefruit-, orange- and apple-juice consumption on urinary variables and risk of crystallization, indicated that due to an increased pH value and an increased citric acid excretion after consumption of each juice, the RSCaOx decreased statistically significantly (P<0.05) for grapefruit juice, but not significantly for orange and apple juice. The BONN risk index yielded a distinct decrease in the crystallization risk. We showed that both grapefruit juice and apple juice reduce the risk of CaOx stone formation at a magnitude comparable with the effects obtained from orange juice(15).

7. Increased intake of fruits with high in magnesium and potassium
Grapefruit juice significantly (p=0.021) increased urinary excretion of citrate (25.8+/-9.3 vs 18.7+/-6.2 mg/h), calcium (6.7+/-4.3 vs 3.3+/-2.3 mg/h, p=0.015) and magnesium (2.9+/-1.5 vs 1.0+/-0.7 mg/h, p=0.003). Citrus fruit juices could represent a natural alternative to potassium citrate in the management of nephrolithiasis(16).

8. Reduce intake of foods containing high amount of oxalate such as spinach, rhubarb, nuts, wheat bran, etc.

9. Others
According to the study of Dietary Factors and Risk of Kidney Stone: A Case-Control Study in Southern China, researchers at the Nanfang Hospital, Guangzhou, indicated that positive associations of kidney stones include consumption of grains (odds ratio [OR] = 2.08; 95% confidence interval [CI] = 1.08, 4.02) and bean products (OR = 3.50; 95% CI = 1.61, 7.59) in women. The variable "fluid drinking" showed a significant protective effect against kidney stones in men (OR = 0.57; 95% CI = 0.36, 0.88). Consuming leafy vegetables more than 3 times per day was positively associated with stones in both men and women (OR = 2.02; 95% CI = 1.04, 3.91 and OR = 3.86; 95% CI = 1.48, 10.04, respectively)(17).

V. Treatment
A. In conventional medicine perspective
Most kidney with diameter less than 5 mm (0.20 in) may pass through the urinary tract through urination within days of the onset of symptoms
A.1. Medications
The aims of medication is to manage pain or assist the speed up the spontaneous passage of ureteral calculi
1. Analgesia
Medication used to relieve pain.
2. Expulsion therapy
a. In the study to evaluate the efficacy of alfuzosin as medical expulsive therapy for distal ureteral stone passage od a total of 76 patients with a distal ureteral calculus, showed that the overall spontaneous stone passage rate was 75%, including 77.1% for placebo and 73.5% for alfuzosin (p = 0.83). Mean +/- SD time needed to pass the stone was 8.54 +/- 6.99 days for placebo vs 5.19 +/- 4.82 days for alfuzosin. (p = 0.003). There was no difference in the size or volume of stones that passed spontaneously between the placebo and alfuzosin arms, as measured on baseline computerized tomography (4.08 +/- 1.17 and 3.83 +/- 0.95 mm, p = 0.46) and by a digital caliper after stone expulsion (3.86 +/- 1.76 and 3.91 +/- 1.06 mm, respectively, p = 0.57). When comparing the improvement from the baseline pain score, the alfuzosin arm experienced a greater decrease in pain score in the days after the initial emergency department visit to the date of stone passage (p = 0.0005)(18).

A.2. Non invasive treatment and surgery
Extracorporeal shockwave lithotripsy does not require anaesthesia and requires little analgesia so that treatment can be given on an outpatient basis, and there is no wound to heal. Only a small puncture site is needed for percutaneous endoscopic lithotomy, and with the advent of prophylactic antibiotics there are few complications. Of renal stones, about 85% can now be successfully treated by extracorporeal lithotripsy alone, and almost all of the stones too large or hard for lithotripsy can be treated endoscopically, with ultrasonic or electrohydraulic probes being used to fragment the stone(19).

A.3. Recurrent treatments
2.1. Recurrent cystine renal stones
In the report of using ureterorenoscopy (URS) for the treatment of recurrent renal cystine stones. From 2003 to 2007, 10 patients (4 males and 6 females) with one or multiple recurrent renal cystine stones underwent URS. Overall, 21 procedures have been performed. Mean maximum diameter of stones was 11.2 mm (range 5-30 mm). Either 8-9.5 F semirigid or 7.9 F flexible ureteroscopes were used. In 6 cases, stones were removed using a basket; in 9 procedures laser lithotripsy with flexible scope was performed; in 6 cases renal calculi were pulled down in the ureter using flexible instrument and then shattered with laser introduced by semirigid instrument. Stone-free status was defined as the absence of any residual fragment. A complete stone clearance was obtained in 15 out of 21 procedures (71%). In 5 cases (24%) significant residual fragments occurred; in the remaining case (5%) URS was ineffective. In 5 out of these unsuccessful procedures, stone clearance was obtained with auxiliary treatments. The last patient has not been treated yet(20).

2.2. In general
Patients with kidney stones are highly motivated to prevent recurrence and were more amenable to fluid intake change than to another dietary or pharmaceutical intervention. Barriers preventing fluid intake success aligned into 3 progressive stages.
a. Stage 1 barriers included not knowing the benefits of fluid or not remembering to drink.
b. Stage 2 barriers included disliking the taste of water, lack of thirst and lack of availability.
c. Stage 3 barriers included the need to void frequently and related workplace disruptions.
Tailoring fluid intake counseling based on patient stage may improve fluid intake behavior(21).

B. In herbal medicine perspective
1. Asparagus racemosus Willd
In the study of the ethanolic extract of Asparagus racemosus Willd. for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days, showed that the histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment(22).

2. Goldenrod
Investigations in molecular pharmacology could show new mechanisms responsible for the biological effect of natural product from goldenrod extracts. The use of such herbal preparations with a rather complex action spectrum (anti-inflammatory, antimicrobial, diuretic, antispasmodic, analgesic) is especially recommended for treatment of infections and inflammations, to prevent formation of kidney stones and to help remove urinary gravel. This therapy is safe at a reasonable price and does not show drug-related side-effects, according to the study of the Institut für Pharmazie der Freien Universität Berlin, Berlin(23).

3. Other herbs
In the study of the effects of seven plants with suspected application to prevent and treat stone kidney formation (Verbena officinalis, Lithospermum officinale, Taraxacum officinale, Equisetum arvense, Arctostaphylos uva-ursi, Arctium lappa and Silene saxifraga) in female Wistar rats, showed that beneficial effects caused by these herb infusions on urolithiasis can be attributed to some disinfectant action, and tentatively to the presence of saponins. Specifically, some solvent action can be postulated with respect to uric stones or heterogeneous uric nucleus, due to the basifying capacity of some herb infusions. Nevertheless, for all the mentioned beneficial effects, more effective and equally innocuous substances are well known(24).

4. Etc.

C. In the traditional Chinese medicine perspective 
C.1. According to the article of Chinese medicine Hospital for Chronic and Difficult diseases(25), traditional Chinese medicine defined kidney stones is a condition caused by
1. Qi stagnation
a. The aim of the herbal treatment is to Promotethe circulation of qi, inducing diuresis, relieving strangury and removing the stones.
b. Herbal formula: Modified Pyrrosia Decoction 
Lysimachia, Pyrrosia leaf, Plantago seed, Cluster mallow fruit, Oriental water plantain rhizome, Citron fruit, Vaccaria seed, Radish seed and Rhubarb.
2. Damp-Heat Pattern
a. The aim of the herbal formula is to clear heat and dampness, relieve strangury and remove the stones.
b. Herbal formula: Modified Eight Health Restoring Powder
Lysimachia, Prostrate knotweed, Chinese pink herb, Talc, Phellodendron bark, Capejasmine fruit and Plantago seed , Rhubarb and Licorice root tip
  3. Kidney deficiency
a. The aim of the herb used to treat kidney stones as a result of kidney deficiency is to tonify qi, reinforce the kidney, relieve stranguria and remove the stones.  
b. Herbal formula: Modified Kidney-Reinforcing Decoction
Prepared rehmannia root, Wolfberry fruit, Dogwood fruit, Achyranthes root,  Bighead atractylodes. Rhizome eucommia bark, Cinnamon bark, Pilose asiabell root, Lysimachia and Climbing fern spore
C.2. Chinese herbal formula Wu Ling San (Poria, Rhizoma Alismatis, Polyporus, Cortex Cinnamomi, Rhizoma Atractylodis Macrocephalae (stir-baked))
In  the study to determine the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg), found that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula(26).

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