2.introduction
TRANSCRIPT
INTRODUCTION
INTRODUCTION:
INTRODUCTION TO URINARY SYSTEM:-
Urinary system is divided into lower and upper urinary tract. The complete
system of two kidneys, two ureters, one bladder, one urethra.
Primary function of kidney is filtration of metabolic waste product followed
by balance ,regulation of blood pressure ,acid-base balance,excretion of ingested
drugs and its metabolite ,production of RBC,rennin and erythropieotin are other
functions.
Nephron is basuc filtration unit consisting of two parts :-
a)Bowman’s capsule
b) Glomerulus (renal corpuscle )
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Blood with metabolic waste and essential component enter into glomerulus at
high pressure and get filterated The filterate then enters bowman’s capsule
followed by into the leading from bowman’s capsule. During the passage of filterate
through tube ,some of the essential component like sodium,water ,glucose,etc.are
reabsorbed and returned to the blood as per the need.some large molecule does not
filter through bowman’s capsule are directly secreted into tubule.
Introduction To Kidney
Kidney
Kidney from Gray's Anatomy
Kidneys are two organs in the abdomen of vertebrates that are shaped like
beans. They make urine (the yellow waste water that comes out of the urethra.) They
are part of the urinary system. When medical professionals discuss the kidneys, they
typically refer to the word renal. For example, renal failure is when the kidneys are
sick and do not work.
The prefix nephro- is also used in words to mean "kidneys". For example, a
nephrologist is a doctor who studies kidneys.
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Makes hormones
The kidney makes hormones. The two most important ones that it makes are
erythropoetin and renin.Erythropoetin is made by the kidneys if there is less oxygen in
the kidney. Erythropoetin tells the bone marrow to make more red blood cells. Red
blood cells carry oxygen in the blood. So this means there will be more oxygen
carried in the blood.
Renin is made by the kidney if there is low blood pressure, low volume of
blood, or too low salts in the blood. Renin tells the blood vessels to be smaller. It tells
the adrenal gland to make aldosterone (which tells the kidneys to save salts). It tells
the body to drink more water. All of this makes the blood pressure go up.
Keeps homeostasis
The kidney's most important work is keeping homeostasis. Homeostasis
means that the body keeps a stable environment inside itself. The body wants to have
the same amount of water, salt, and acid in the blood. This makes the body work
better. The kidney keeps these things constant.
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Contents
1 Makes hormones
2 Keeps homeostasis
3 Kidney diseases
4 Renal replacement
4.1 Kidney dialysis
4.2 Transplant
5 History
INTRODUCTION
If there is too much water, the kidney puts more water in the urine. If there is
not enough water, the kidney puts less water in the urine. This is why people make
less urine when they are dehydrated (have not enough water in the body and are
thirsty)(1,4,5,6).
Kidney diseases
There are many types of kidney diseases. If kidney disease makes the kidneys
not able to do but they do work in part. People can have mild renal failure and have
no symptoms. As long as it does not become worse, people may not even know they
have it. Severe renal failure means very bad failure. The kidneys do not work very
much at all. People with severe renal failure always have symptoms. They may need
special care from doctors.
The main kinds of kidney diseases are:
a) Kidney stones – this is when a solid substance forms in the urine. This stone
moves through the urinary system until it cannot go more, because it is too big
to go through. Then it stops the urine flow. This usually causes very bad pains.
After a time, the stone usually goes out or passes. If it does not go out, doctors
may have to help it.
b) Kidney infections – also called pyelonephritis. This is when a bacteria grows
in the kidney. Symptoms are back pain, vomiting, fever, and dark or bloody
urine. People with pyelonephritis need strong antibiotic medicines to kill the
bacteria.
c) Glomerulonephritis – this is a disease of the small things in the kidney that
make the urine. These are called glomeruli. Glomerulonephritis is an
autoimmune disease. It makes it so that the kidneys do not work well. It can
cause mild or severe renal failure.
d) Congenital kidney disease – this is when people are born with kidneys that do
not work right. Sometimes people are born with kidneys that are in the wrong
place, or do not have the right shape. About 1% of people are born with only
one kidney.
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e) Polycystic kidney disease - this is an inherited disorder in which cysts grow in
the kidneys, and destroy the kidney tissue until the kidneys can no longer
perform their functions.
f) Diabetic nephropathy – this is the disease diabetics get when their blood sugar
is very high for a long time. This is one of the most common causes of kidney
failure in the United States.
g) Hypertensive nephropathy – this is the disease people with hypertension (high
blood pressure) get when their blood pressure is high for a long time. Many
people have hypertensive and diabetic nephropathy together.
h) Cancer – Renal cell carcinoma is the most common kind of kidney cancer. It is
most often in adults. It is a very bad cancer. It is hard to stop it with radiation
treatments or chemotherapy.
Renal replacement
People who do not have good kidneys are very sick. If they have severe renal
failure, they cannot live unless they have a replacement for their kidneys.
Replacement is something that takes the place of something else.
There are two ways to replace the kidneys: dialysis and transplantation.
Kidney dialysis
Dialysis is when doctors use a machine and medicines to do the work that
kidneys do. There are two kinds of dialysis: hemodialysis and peritoneal dialysis.
Peritoneal dialysis is when doctors put a plastic tube into the persons
abdomen. Every day the person fills the abdomen with fluid. The extra salts, waste,
and water that the body does not need goes into the fluid. Then the fluid comes out
and takes the wastes with it. This does part of the job that kidneys do.
Hemodialysis is when doctors take blood from a person, clean the blood with a
special kind of filter, called haemodialyser, managed through a special machine, and
put it back in the person. When the blood is cleaned, water, salts, and wastes are taken
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out of it. This must be done 2-4 times every week (usually 3 times.) It takes 2-4 hours
to do this each time.
Hemodialysis and peritoneal dialysis are not perfect. They do some of the
work of the kidney, but it is not as good as a real kidney. So people who need dialysis
are not as healthy. They must take medicines also. For example, in kidney failure, the
kidneys do not make erythropoetin. So doctors have to give people erythropoetin so
they make enough red blood cells.
Transplant
A better way to do the kidneys' work is to give the person another kidney. This
is called a renal transplant. Kidney transplants are the most common organ transplant
that happens. It is more common because we have two kidneys, but only need one
kidney to live. People who are alive can donate a kidney to another person. With other
organs, the donor must be dead first.
Even transplants are not the same as kidneys people were born with. A person
who gets a renal transplants must take strong medicines to stop their body from
attacking the new kidney. Sometimes, after years, the transplanted kidney stops
working. But sometimes a patient can get a new transplanted kidney after the first one
stops working.
History
It was widely believed in Europe that the conscience was actually located in
the kidneys. This idea was taken from the Hebrew Bible. In modern times, medical
scientists have shown kidneys do not have this kind of psychological role. A KUB
is a plain frontal supine radiograph of the abdomen. It is often supplemented by an
upright PA view of the chest (to rule out air under the diaphragm or thoracic
etiologies presenting as abdominal complaints) and a standing view of the abdomen
(to differentiate obstruction from ileus by examining gastrointestinal air/water levels).
Uses
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Despite its name, a KUB is not typically used to investigate pathology of the
kidneys, ureters, or bladder, since these structures are difficult to assess (for example,
the kidneys may not be visible due to overlying bowel gas.) In order to assess these
structures with X-ray, a technique called an intravenous pyelogram is utilized.
KUB is typically used to investigate gastrointestinal conditions such as a
bowel obstruction and gallstones, and can detect the presence of kidney stones. The
KUB is often used to diagnose constipation as stool can be seen readily. The KUB is
also used to assess positioning of indwelling devices such as ureteric stents and
nasogastric tubes. KUB is also done as a scout film for other procedures such as
barium enemas.
Projection
It should include on the upright projections both right and left visualizations of
the diaphragm. In at least one projection, the symphysis pubis must be present as the
lower end of the area of interest. If the patient is large, more than one film loaded in
the Bucky in a "landscape" direction may be used for each projection. This is done to
ensure that the majority of bowel can be reviewed.
Renal function
Diagram showing the basic physiologic mechanisms of the kidney
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Renal function, in nephrology, is an indication of the state of the kidney and
its role in renal physiology. Glomerular filtration rate (GFR) describes the flow rate of
filtered fluid through the kidney. Creatinine clearance rate (CCr or CrCl) is the volume
of blood plasma that is cleared of creatinine per unit time and is a useful measure for
approximating the GFR.
Creatinine clearance exceeds GFR due to creatinine secretion, which can be
blocked by cimetidine.
In alternative fashion, overestimation by older serum creatinine methods
resulted in an underestimation of creatinine clearance, which provided a less biased
estimate of GFR. Both GFR and CCr may be accurately calculated by comparative
measurements of substances in the blood and urine, or estimated by formulas using
just a blood test result (eGFR and eCCr).
The results of these tests are important in assessing the excretory function of
the kidneys. For example, grading of chronic renal insufficiency and dosage of drugs
that are excreted primarily via urine are based on GFR (or creatinine clearance).
It is commonly believed to be the amount of liquid filtered out of the blood
that gets processed by the kidneys. In physiological terms, these quantities
(volumetric blood flow and mass removal) are related only loosely.
Content:
1 Indirect markers
2 Glomerular filtration rate
2.1 Measurement using inulin
3 Creatinine-based approximations of GFR
3.1 Creatinine Clearance CCr
4 Estimated values
4.1 Estimated creatinine clearance rate (eCCr) using Cockcroft-Gault formula
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4.2 Estimated GFR (eGFR) using Modification of Diet in Renal Disease (MDRD) formula
4.3 Estimated GFR (eGFR) using the CKD-EPI formula
4.4 Estimated GFR (eGFR) using the Mayo Quadratic formula
4.5 Estimated GFR for children using Schwartz formula
4.6 Importance of calibration of the serum creatinine level and the IDMS standardization effort
4.7 Cystatin C
5 Normal ranges
5.1 Chronic kidney disease stages
Indirect markers
Most doctors use the plasma concentrations of the waste substances of
creatinine and urea (U), as well as electrolytes (E), to determine renal function. These
measures are adequate to determine whether a patient is suffering from kidney
disease.
However, blood urea nitrogen (BUN) and creatinine will not be raised above
the normal range until 60% of total kidney function is lost. Hence, the more accurate
Glomerular filtration rate or its approximation of the creatinine clearance is measured
whenever renal disease is suspected or careful dosing of nephrotoxic drugs is
required.
Another prognostic marker for kidney disease is an elevated level of protein in
the urine. The most sensitive marker of proteinuria is elevated urine albumin.
Persistence presence of more than 30 mg albumin per gram creatinine in the urine is
diagnostic of chronic kidney disease (Microalbuminuria is a level of 30-299 mg/g; a
concentration of albumin in the urine that is not detected by usual urine dipstick
methods).
Glomerular filtration rate
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Glomerular filtration rate (GFR) is the volume of fluid filtered from the renal
(kidney) glomerular capillaries into the Bowman's capsule per unit time.[2] Central to
the physiologic maintenance of GFR is the differential basal tone of the afferent and
efferent arterioles (see diagram).
Glomerular filtration rate (GFR) can be calculated by measuring any chemical
that has a steady level in the blood, and is freely filtered but neither reabsorbed nor
secreted by the kidneys. The rate therefore measured is the quantity of the substance
in the urine that originated from a calculable volume of blood. The GFR is typically
recorded in units of volume per time, e.g., milliliters per minute ml/min. Compare to
filtration fraction.
There are several different techniques used to calculate or estimate the
glomerular filtration rate (GFR or eGFR).
Measurement using inulin
The GFR can be determined by injecting inulin into the plasma. Since inulin is
neither reabsorbed nor secreted by the kidney after glomerular filtration, its rate of
excretion is directly proportional to the rate of filtration of water and solutes across
the glomerular filter. Compared to the MDRD formula, the inulin clearance slightly
overestimates the glomerular function. In early stage renal disease, the inulin
clearance may remain normal due to hyperfiltration in the remaining nephrons[3].
Incomplete urine collection is an important source of error in inulin clearance
measurement.
Creatinine-based approximations of GFR
In clinical practice, however, creatinine clearance or estimates of creatinine
clearance based on the serum creatinine level are used to measure GFR. Creatinine is
produced naturally by the body (creatinine is a break-down product of creatine
phosphate, which is found in muscle). It is freely filtered by the glomerulus, but also
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actively secreted by the peritubular capillaries in very small amounts such that
creatinine clearance overestimates actual GFR by 10-20%. This margin of error is
acceptable, considering the ease with which creatinine clearance is measured. Unlike
precise GFR measurements involving constant infusions of inulin, creatinine is
already at a steady-state concentration in the blood, and so measuring creatinine
clearance is much less cumbersome. However, creatinine estimates of GFR have their
limitations. All of the estimating equations depend on a prediction of the 24-hour
creatinine excretion rate, which is a function of muscle mass. One of the equations,
the Cockcroft and Gault equation (see below) does not correct for race, and it is
known that African Americans, for example, both men and women, have a higher
amount of muscle mass than Caucasians; hence, African Americans will have a higher
serum creatinine level at any level of creatinine clearance.
A common mistake made when just looking at serum creatinine is the failure
to account for muscle mass. Hence, an older woman with a serum creatinine of 1.4
may actually have a moderately severe degree of renal insufficiency, whereas a young
muscular male, in particular if African American, can have a normal level of renal
function at this serum creatinine level. Creatinine-based equations should be used
with caution in cachectic patients and patients with cirrhosis. They often have very
low muscle mass and a much lower creatinine excretion rate than predicted by the
equations below, such that a cirrhotic patient with a serum creatinine of 0.9 may have
a moderately severe degree of renal insufficiency.
Creatinine Clearance CCr
One method of determining GFR from creatinine is to collect urine (usually
for 24-hours) to determine the amount of creatinine that was removed from the blood
over a given time interval. If one removes, say, 1440 mg in 24 hours, this is
equivalent to removing 1 mg/min. If the blood concentration is 0.01 mg/mL (1
mg/dL), then one can say that 100 mL/min of blood is being "cleared" of creatinine,
since, to get 1 mg of creatinine, 100 mL of blood containing 0.01 mg/mL would need
to have been cleared.
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Creatinine clearance (CCr) is calculated from the creatinine concentration in
the collected urine sample (UCr), urine flow rate (V), and the plasma concentration
(PCr). Since the product of urine concentration and urine flow rate yields creatinine
excretion rate, which is the rate of removal from the blood, creatinine clearance is
calculated as removal rate per min (UCr×V) divided by the plasma creatinine
concentration. This is commonly represented mathematically as
A=π r2
The common procedure involves undertaking a 24-hour urine collection, from
empty-bladder one morning to the contents of the bladder the following morning, with
a comparative blood test then taken. The urinary flow rate is still calculated per
minute, hence:
To allow comparison of results between people of different sizes, the CCr is
often corrected for the body surface area (BSA) and expressed compared to the
average sized man as mL/min/1.73 m2. While most adults have a BSA that approaches
1.7 extremely obese or slim patients should have their CCr corrected for their actual
BSA.
BSA can be calculated on the basis of weight and height.
The creatinine clearance is not widely done any more, due to the difficulty in
assuring a complete urine collection. When doing such a determination, to assess the
adequacy of a complete collection, one always calculates the amount of creatinine
excreted over a 24-hour period. This amount varies with muscle mass, and is higher in
young people vs. old, in blacks vs. whites, and in men vs. women. An unexpectedly
low or high 24-hour creatinine excretion rate voids the test. Nevertheless, in cases
where estimates of creatinine clearance from serum creatinine are unreliable,
creatinine clearance remains a useful test. These cases include "estimation of GFR in
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individuals with variation in dietary intake (vegetarian diet, creatine supplements) or
muscle mass (amputation, malnutrition, muscle wasting), since these factors are not
specifically taken into account in prediction equations."
Estimated values
A number of formulae have been devised to estimate GFR or C cr values on the
basis of serum creatinine levels.
Estimated creatinine clearance rate (eCCr) using Cockcroft-Gault formula
A commonly used surrogate marker for estimate of creatinine clearance is the
Cockcroft-Gault formula, which in turn estimates GFR:[5] It is named after the
scientists who first published the formula, and it employs serum creatinine
measurements and a patient's weight to predict the creatinine clearance. [6][7] The
formula, as originally published, is:
This formula expects weight to be measured in kilograms and creatinine to be
measured in mg/dL, as is standard in the USA. The resulting value is
multiplied by a constant of 0.85 if the patient is female. This formula is useful
because the calculations are simple and can often be performed without the aid
of a calculator.
When serum creatinine is measured in µmol/L:
Where Constant is 1.23 for men and 1.04 for women.
One interesting feature of the Cockcroft and Gault equation is that it shows
how dependent the estimation of CCr is based on age. The age term is (140 - age).
This means that a 20-year-old person (140-20 = 120) will have twice the creatinine
clearance as an 80-year-old (140-80 = 60) for the same level of serum creatinine (120
is twice as great as 60). The C-G equation also shows that a woman will have a 15%
lower creatinine clearance than a man at the same level of serum creatinine.
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Estimated GFR (eGFR) using Modification of Diet in Renal Disease (MDRD)
formula
The most recently advocated formula for calculating the GFR is the one that
was developed by the Modification of Diet in Renal Disease Study Group. Most
laboratories in Australia,[9] and The United Kingdom now calculate and report the
MDRD estimated GFR along with creatinine measurements and this forms the basis
of Chronic kidney disease#Staging.[10] The adoption of the automatic reporting of
MDRD-eGFR has been widely criticised.
The most commonly used formula is the "4-variable MDRD," which estimates
GFR using four variables: serum creatinine, age, race, and gender. The original
MDRD used six variables with the additional variables being the blood urea nitrogen
and albumin levels. The equations have been validated in patients with chronic kidney
disease; however both versions underestimate the GFR in healthy patients with GFRs
over 60 mL/min. The equations have not been validated in acute renal failure.
Estimated GFR (eGFR) using the CKD-EPI formula
The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
was published in May 2009. It was developed in an effort to create a formula more
accurate than the MDRD formula, especially when actual GFR is greater than 60
mL/min per 1.73 m2.
Researchers pooled data from multiple studies to develop and validate this
new equation. They used 10 studies that included 8254 participants, randomly using
2/3 of the data sets for development and the other 1/3 for internal validation. Sixteen
additional studies, which included 3896 participants, were used for external
validation.
The CKD-EPI equation performed better than the MDRD (Modification of
Diet in Renal Disease Study) equation, especially at higher GFR, with less bias and
greater accuracy. When looking at NHANES (National Health and Nutrition
Examination Survey) data, the median estimated GFR was 94.5 mL/min per 1.73 m2
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vs. 85.0 mL/min per 1.73 m2, and the prevalence of chronic kidney disease was
11.5% versus 13.1%.
Estimated GFR (eGFR) using the Mayo Quadratic formula
Another estimation tool to calculate GFR is the Mayo Quadratic formula. This
formula was developed by Rule. in an attempt to better estimate GFR in patients with
preserved kidney function. It is well recognized that the MDRD formula tends to
underestimate GFR in patients with preserved kidney function.
The equation is: GFR = exp(1.911 + 5.249/SCr - 2.114/Scr^2 - 0.00686 * Age
-0.205 (if female))
If SCr < 0.8 mg/dL, use 0.8 for SCr
Estimated GFR for children using Schwartz formula
In children, the Schwartz formula is used. This employs the serum creatinine
(mg/dL), the child's height (cm) and a constant to estimate the glomerular filtration
rate:
Where k is a constant that depends on muscle mass, which itself varies with a
child's age:
In first year of life, for pre-term babies K=0.33 and for full-term infants
K=0.45[
For infants and children of age 1 to 12 years, K=0.55.
The method of selection of the K-constant value has been questioned as being
dependent upon the gold-standard of renal function used (i.e., creatinine clearance,
inulin clearance, etc.) and also may be dependent upon the urinary flow rate at the
time of measurement. In 2009, the formula was updated to use standardized serum
creatinine (recommend k=0.413) and additional formulas that allow improved
precision were derived if serum cystatin measured in addition to serum creatinine.
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Importance of calibration of the serum creatinine level and the IDMS
standardization effort
One problem with any creatinine-based equation for GFR is that the methods
used to assay creatinine in the blood differ widely in their susceptibility to non-
specific chromogens, which cause the creatinine value to be overestimated. In
particular, the MDRD equation was derived using serum creatinine measurements that
had this problem. The NKDEP program in the United States has attempted to solve
this problem by trying to get all laboratories to calibrate their measures of creatinine
to a "gold standard", which in this case is isotope dilution mass spectroscopy (IDMS).
At the present time in late 2009 not all labs in the U.S. have changed over to the new
system. There are two forms of the MDRD equation that are available, depending on
whether or not creatinine was measured by an IDMS-calibrated assay. The CKD-EPI
equation is designed to be used with IDMS-calibrated serum creatinine values only.
Cystatin C
Problems with creatinine (varying muscle mass, recent meat ingestion, etc.)
have led to evaluation of alternative agents for estimation of GFR. One of these is
cystatin C, a ubiquitous protein secreted by most cells in the body (it is an inhibitor of
cysteine protease).
Cystatin C is freely filtered at the glomerulus. After filtration, Cystatin C is
reabsorbed and catabolized by the tubular epithelial cells, with only small amounts
excreted in the urine. Cystatin C levels are therefore measured not in the urine, but in
the bloodstream.Equations have been developed linking estimated GFR to serum
cystatin C levels. Most recently, some proposed equations have combined creatinine
and cystatin.
Normal ranges
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The normal range of GFR, adjusted for body surface area, is similar in men
and women, and is in the range of 100-130 ml/min/1.73m2. In children, GFR
measured by inulin clearance remains close to about 110 ml/min/1.73m2 down to
about 2 years of age in both sexes, and then it progressively decreases. After age 40,
GFR decreases progressively with age, by about 0.4 - 1.2 mL/min per year.
Chronic kidney disease stages
Risk factors for kidney disease include diabetes, high blood pressure, family
history, older age, ethnic group and smoking. For most patients, a GFR over 60
mL/min/1.73m2 is adequate. But significant decline of the GFR from a previous test
result can be an early indicator of kidney disease requiring medical intervention. The
sooner kidney dysfunction is diagnosed and treated the greater odds of preserving
remaining nephrons, and preventing the need for dialysis.
The severity of chronic kidney disease (CKD) is described by six stages; the
most severe three are defined by the MDRD-eGFR value, and first three also depend
on whether there is other evidence of kidney disease (e.g., proteinuria):
Normal kidney function – GFR above 90mL/min/1.73m2 and no proteinuria
1) CKD1 – GFR above 90mL/min/1.73m2 with evidence of kidney damage
2) CKD2 (Mild) – GFR of 60 to 89 mL/min/1.73m2 with evidence of kidney damage
3) CKD3 (Moderate) – GFR of 30 to 59 mL/min/1.73m2
4) CKD4 (Severe) – GFR of 15 to 29 mL/min/1.73m2
5) CKD5 Kidney failure - GFR less than 15 mL/min/1.73m2 Some people add
CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not
yet on dialysis.
Controversies Regarding KDOQIU Classification
One problem with the KDOQI classification is that it may overlabel patients
with mildly reduced kidney function, especially the elderly, as having a disease. See
for a review of these issues by Bauer et al. and also a recent KDIGO/KDOQI position
statement here:. Kidney Disease: Improving Global Outcomes (KDIGO) held a
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controversies conference in 2009 on CKD: Definition, Classification and Prognosis
that gathered data on CKD prognosis to refine the definition and staging of CKD.
Clearance
Dialysis
filtration fraction
Kt/V
Pharmacokinetics
Renal clearance ratio
Renal failure
Standardized Kt/V
Tubuloglomerular feedback
Urea reduction ratio
Introduction To Kidney Stone
Urinary stones affect 10-12 % of the population in industrialized
countries.There are only a few geographical areas in which stone disease is rare, e.g.,
in Greenland and in the coastal areas of Japan. The incidence of urinary stones has
been increasing over the last years while the age of onset is decreasing With a
prevalence of > 10 % and an expected recurrence rate of 50 %, stone disease has an∼
important effect on the healthcare system Once recurrent, the subsequent relapse risk
is raised and the interval between recurrences is shortened Features associated with
recurrence include a young age of onset, positive family history, infection stones and
underlying medical conditions Epidemiological studies revealed that nephrolithiasis is
more common in men (12 %) than in women (6 %) and is more prevalent between the
ages of 20 to 40 in both sexes The etiology of this disorder is multifactorial and is
strongly related to dietary lifestyle habits or practices Increased rates of hypertension
and obesity, which are linked to nephrolithiasis, also contribute to an increase in stone
formation
Management of stone disease depends on the size and location of the stones
(see below). Stones larger than 5 mm or stones that fail to pass through should be
treated by some interventional procedures such as extracorporeal shock wave
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lithotripsy (ESWL), ureteroscopy (URS), or percutaneous nephrolithotomy (PNL)
Unfortunately, the propensity for stone recurrence is not altered by removal of stones
with ESWL and stone recurrence is still about 50 % In addition, ESWL might show
some significant side effects such as renal damage, ESWL induced hypertension or
renal impairment.
Although there are a few recent reports of beneficial effects of medical
treatments in enhancing clearance of stones in the distal ureters de facto there is still
no satisfactory drug to use in clinical therapy, especially for the prevention or the
recurrence of stones. In this regard, many plants have been traditionally used to treat
kidney stones and have been shown to be effective.The purpose of this paper is to
critically review available literature on herbal medicines and their possible role in the
management of urolithiasis. Using the key words “urolithiasis and plant extract”,
“nephrolithiasis and plant extract”, “kidney stones and plant extract”, a Medline
research revealed 116 articles published between 1 January 1966 and 1 December
2008. Only those studies were included into the present analysis which were written
in English or German and which represented original research articles. A total of 75
studies met the inclusion criteria and were further subclassified into in vitro (n = 13),
in vivo (n = 41), and clinical studies (n = 21). The included studies were further
evaluated with respect to the proximate phytochemical composition of the plant
extract and the possible mechanism of action.
Pathophyiology of Nephrolithiasis
Kidney stones are classified according to their chemical composition.
Crystallization and subsequent lithogenesis can happen with many solutes in the
urine. For crystals to form, urine must be supersaturated with respect to the stone
material, meaning that concentrations are higher than the thermodynamic solubility
for that substance. Levels of urinary supersaturation correlate with the type of stone
formed, and lowering supersaturation is effective for preventing stone recurrence
Calcium oxalate (CaOx) is the predominant component of most stones accounting for
more than 80 % of stones . The remaining 20 % are composed of struvite, cystine,
uric acid, and other stones As mentioned above, the basis for calcium stone formation
is supersaturation of the urine with stone-forming calcium salts. Metabolic
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INTRODUCTION
abnormalities such as hypercalciuria, hypocitraturia, hyperoxaluria, hyperuricosuria,
and gouty diathesis can change the composition or saturation of the urine so as to
enhance stone formation In patients who have CaOx stones, for example, urine uric
acid excretion may be elevated, often as a result of excessive protein intake.
Hyperuricosuria decreases the solubility of CaOx and promotes stone formation by
heterologous nucleation on the surface of monosodium urate levels However, patients
who have hyperuricosuric calcium stones differ from patients who have gout and uric
acid stones in having a higher urine pH and a higher uric acid level as well Since it is
beyond the scope of the present review to discuss all of these metabolic abnormalities
in greater detail, a brief summary is provided in Besides Ca or Ox, human urine also
contains other ions and macromolecules that can interact with both ions and modulate
crystallization Any cellular dysfunction that can affect various urinary ions and other
substances can also influence CaOx supersaturation and crystallization in the kidneys.
Crystal formation, particularly of calcium phosphate (CaP) and CaOx, within the
urinary tract is widespread. Since humans excrete millions of urinary crystals daily
without developing kidney stones, at least a transient development of supersaturation
is likely However, supersaturation is only one step in the process of stone formation.
For stone formation crystals need to be retained within the kidney and they should
also be located at sites from where crystals can ulcerate to the renal papillary surface
to form a stone nidus Renal injury promotes crystal retention and the development of
a stone nidus on the renal papillary surface and further supports crystal nucleation at
lower supersaturation Thus, one approach to prevent stone formation would be to stop
crystal retention. Since supersaturation is essential for the production of stones
another major therapeutic goal is the reduction of supersaturation Reactive oxygen
species (ROS) seem also to be responsible for cellular injury, therefore a reduction of
renal oxidative stress could also be an effective therapeutic approach.
Current Treatment/Prevention Option
Treatment
The accepted management of stone disease ranges from observation (watchful
waiting) to surgical removal of the stone. Various factors such as size of calculi,
severity of symptoms, degree of obstruction, kidney function, location of the stone
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and the presence or absence of associated infection influence the choice of one type of
intervention over the Stones which are smaller than 5 mm have a high probability of
spontaneous passage which can take up to 40 days During this watchful waiting
period, patients can be treated with hydration and pain medication However, stones
larger than 5 mm or stones that fail to pass are treated by interventional procedures
Open surgical procedures for the treatment of ureteric stones have gradually
disappeared in the last 30 years and have been replaced by minimal invasive
techniques such as ESWL or ureteroscopy.
ESWL is a noninvasive procedure which uses shock waves to fragment calculi
This technique is the most widely used method for managing renal and ureteral
stones. However, treatment success rates depend on stone composition, size,
properties and location of the stone as well as the instrumentation type and shock
frequency It also needs to be considered that the same forces that are directed at the
stones have deleterious effects on surrounding tissues Damage to almost every
abdominal organ system has been reported but by far the most common injury is acute
renal hemorrhage although its true incidence is unclear and poorly defined Most often
renal hemorrhage can be managed conservatively; however, in rare instances the
complications are fatal Reports of post-ESWL perirenal hematoma range from less
than 1 % to greater than 30 % Furthermore, ESWL has been associated with long-
term medical effects such as diabetes mellitus.
In addition to ESWL, other procedures such as ureteroscopy (URS) have been
developed for removal of ureteral stones. The new generations of uteroscopes are
flexible, smaller in diameter, stiffer and more durable, and have an improved tip
deflection The major drawback of URS is that it is more invasive than ESWL and the
rate of ureteric perforation and stricture formation remains around 2 to 4 %. In
contrast, the major advantage of URS is that it is cheaper and results in higher and
faster stone-free rates It remains unclear which treatment modality is better than the
other and the final decision should be based on the patient's preference, on the size
and the location of the stone, expertise of the physician and the costs of the procedure.
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Prevention
Despite the major technical achievements for stone removal in the last three
decades the problem of recurrent stone formation remains.
As mentioned earlier the recurrence rate of kidney stones is approximately 15
% in the first year and as high as 50 % within five years of the initial stone Effective
kidney stone prevention is dependent on the stone type and the identification of risk
factors for stone formation. An individualized treatment plan incorporating dietary
changes, supplements, and medications can be developed to help prevent the
formation of new stones. Regardless of the underlying etiology of the stone disease,
patients should be instructed to increase their fluid intake in order to maintain a urine
output of at least 2 L/d. A high fluid intake reduces urinary saturation of stone-
forming calcium salts and dilutes promoters of CaOx crystallization A high sodium
intake increases stone risk by reducing renal tubular calcium reabsorption and
increasing urinary calcium. Patients should be advised to limit their dietary sodium
intake to 2000-3000 mg/d A restriction of animal proteins is also encouraged since
animal proteins provide an acid load because of the high content of sulfur-containing
amino acids. Thus, a high protein intake reduces urine pH and citrate and enhances
urinary calcium excretion via bone resorption and reduces renal calcium reabsorption
Stone formers should not be advised to restrict calcium unless it has been shown that
they have an excessive intake of calcium A reduced intake of calcium leads to an
increased intestinal absorption of oxalate, which itself may account for an increased
risk of stone formation Vitamin C has been implicated in stone formation because of
in vivo conversion of ascorbic acid to oxalate. Therefore, a limitation of vitamin C
supplementation to 500 mg/d or less is recommended.
When dietary modification is ineffective, pharmacological treatment should be
initiated. The most effective hypocalciuric agents are thiazide diuretics which
hypocalciuric action enhance calcium reabsorption in the distal renal tubules
However, long-term use in up to 50 % of patients is limited because of side effects
including fatigue, dizziness, impotence, musculoskeletal symptoms, or
gastrointestinal complaints Another complication is thiazide-induced potassium
depletion, which causes intracellular acidosis and can lead to hypokalemia and
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INTRODUCTION
hypocitraturia Potassium citrate is effective in the treatment of patients who have
calcium stones and normal urinary calcium. By providing an alkali load, potassium
citrate increases urinary pH and citrate, therefore mediating the inhibitory effects of
macromolecular modulators of calcium oxalate crystallization The main limitation for
a more widespread use of alkali citrate preparations is the relatively low tolerability of
available alkali citrate preparations. Adverse effects that reduce treatment compliance
have been noted mainly in the gastrointestinal tract and include eructation, bloating,
and diarrhea In conclusion, none of the listed treatment modalities is without any side
effects. Thus, the focus should be on the development of novel strategies for the
prevention and treatment of kidney stone disease. Herbal medicines could close a gap
in this regard.
Currently Used Herbal Medicines
In vitro studies
In vitro systems for experimental nephrolithiasis can be differentiated into
systems investigating the physical chemistry of stone formation or systems that
explore the pathophysiology of renal stone disease. For the first purpose, in vitro
crystallization systems are widely used to study processes of crystal nucleation,
growth and For the latter one, cultured renal epithelial cell lines are widely accepted
as a tool to explore the mechanism of urolithiasis
From the 13 in vitro studies that met the inclusion criteria for the present
review, 7 articles focused on calcium oxalate crystallization in the presence or
absence of a particular plant extract, in 3 articles a cell culture system was used to
investigate the effects of an extract on oxalate-induced cell injury and a further 3
articles used either a combination of both techniques or included an additional in vivo
experiment.
Various herbs have been reported to inhibit CaOx crystallization. Atmani and
Khan have reported that an extract from the herb Herniaria hirsuta L., a plant that
traditionally is used in Morocco for the treatment of lithiasis, promoted the nucleation
of calcium oxalate crystals, increasing their number but decreasing their size. In a
follow-up study the authors could demonstrate that H. hirsuta could block crystal
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INTRODUCTION
binding to cultured renal cells Similar effects on calcium oxalate crystallization in
vitro have been shown for an aqueous extract from Phyllantus niruri L., a plant which
is used in traditional Brazilian medicine for the treatment of stone disease.
The authors could show that the extract interfered with the CaOx
crystallization process by reducing CaOx crystal growth and aggregation. In an earlier
study, Campos and Schor investigated the in vitro effect of P. niruri on a model of
CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited
a potent and effective non-concentration-dependent inhibitory effect on the CaOx
crystal internalization. Garimella et al. demonstrated that an extract prepared from the
seeds of Dolichos biflorus L. [now Vigna unguiculata (L.) Walp. subsp. Unguiculata]
which is used in traditional Indian Ayurvedic medicine could inhibit the precipitation
of calcium and phosphate in vitro. Several traditional Chinese medicines (TCM) or
plants that are used in Kampou medicine also have demonstrated their abilities to
inhibit calcium oxalate crystallization Dietary factors appear to affect the ability of
urine to inhibit CaOx crystallization. In this regard, lemon juice has been found to
inhibit the rate of crystal nucleation and aggregation Overall, the in vitro
crystallization experiments confirmed that prophylaxis of renal stones could be
achieved by reducing supersaturation through promotion of small crystal nucleates.
As mentioned above, in vitro studies using renal epithelial cell lines are useful
to perform mechanistic studies on urolithiasis. In this regard, oxalate, a major
constituent of CaOx stones, has been shown to exert cytotoxic effects on renal tubular
epithelial cells, attributable to increased oxidative stress within the cells Oxalate
seems to induce cell death mediated by both apoptosis and cellular necrosis, since
oxalate exposure leads to the formation of apoptotic bodies as well as induces changes
in membrane integrity, the release of cellular enzymes, and membrane-lipid
peroxidation It could be shown recently that an extract prepared from Quercus
salicina Blume/Quercus stenophylla Makino could suppress cell injury induced by
oxalate exposure by scavenging free radicals and suppressing the activation of
NADPH oxidase Similar effects were reported for epigallocatechin gallate (EGCG)
from green tea which also inhibited free radical production induced by oxalate.
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INTRODUCTION
In summary, the reported in vitro studies are promising since they have shown
an inhibition of oxalate crystallization or antioxidative action. However, the overall
limitation of all the listed studies is that the plant extracts have not been further
phytochemically characterized. As a consequence, the validity of the studies is limited
since without phytochemical characterization, quality control is difficult and
reproducibility of results questionable. In addition, only two studies addressed the
presence of oxalate in plant extracts a fact that needs to be considered for in vitro
crystallization experiments in order to exclude false negative effects. Since many
extracts contain oxalate (and/or citrate) per se, the quantitative amount of both
molecules should be taken into account for future in vitro studies.
In vivo studies
As mentioned in the previous paragraph, in vitro models relate to only one
event and one aspect of the process (e.g., crystallization studies determining
nucleation and growth). In order to understand all aspects of the pathogenesis,
including the anatomic and physiological role of kidneys, animal models are
frequently used Most of the data available on renal physiology are based on
experiments in rats, rabbits and dogs, however, rats are the animals most commonly
used for the study of nephrolithiasis [Since 80 % of all kidney stones are composed of
calcium oxalate CaOx nephrolithiasis has been studied in greater detail. Stones
formed in kidneys of humans and rats are identical at the ultrastructural level in both
the nature and the composition of their matrix thus, rat models of nephrolithiasis are
helpful experimental tools for exploring the pathophysiology of this disease. CaOx
kidney nephrolithiasis is produced in rats by the induction of acute or chronic
hyperoxaluria using a variety of agents such as sodium oxalate, ammonium oxalate,
hydroxy-L-proline, ethylene glycol, and glycolic acid. Lithogenic agents are generally
dispensed orally in food or water or by gavage but also have been injected
intraperitoneally
In plants of different ethnobotanical regions are listed for which data from
animal experiments exist and which met the inclusion criteria for the present review.
A regional distribution of the emphasis in nephrolithiasis research is noticeable, the
majority of animal studies have been performed using plants from Indian folk
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INTRODUCTION
medicine (11), followed by plants traditionally used in Japan (3), Brasil (2), Mexico
(2), Morocco (2) or China (2). From the listed herbs in Table more than one animal
study has been reported for Takusha (4 studies), Herniaria hirsuta L. (3 studies), and
Phyllantus niruri L. (2 studies).
Takusha (Alisma orientale [Sam]. Juz), one of the components of the kampo
medicine chorei-to is commonly used in Japan to cure and to prevent recurrent CaOx
kidney stones. Studies in rats receiving ethylene glycol to induce CaOx stone
formation have shown that Takusha prevented stone formation by inhibiting CaOx
aggregation In cats fed with a diet containing Takusha, a reduction of urine pH was
observed as well as reduced struvite crystal formation in cat urine.
As mentioned in the previous paragraphs, Herniaria hirsuta and Phyllantus
niruri have been shown to interfere with the CaOx crystallization process by reducing
CaOx crystal growth and aggregation in in vitro studies Atmani et al. could
demonstrate that oral administration of a Herniaria hirsuta extract to experimentally
induced CaOx nephrolithiasis in rats reduced the deposition of crystals in the kidneys.
The observed activity was unrelated to diuresis or urinary biochemical changes
Contrarily, Grases et al. reported a diuretic effect after rats received the extract for 7
days via the drinking water. The reason for this discrepancy between the two
investigations remains unclear but since in both studies the exact amount of mg
extract per kg/body weight is not clearly presented and both studies used distinct
routes of administration, it is possible that differences in the outcome are related to
dose and/or administration variations.
Studies in rats revealed that pretreatment with a Phyllantus niruri extract
significantly reduced calculous growth after ingesting the tea for three months When
P. niruri treatment was initiated on the first day after implantation of a CaOx seed
into the bladder of rats, a significant inhibition in the growth of the calculi was
observed indicating a preventive effect of the plant extract. In contrast, treatment with
the extract in the presence of a preformed calculus did not prevent further calculus
stone growth; it rather promoted the adsorption of glycosaminoglycans into the
calculi, making the stones smaller and softer These results confirmed an earlier study
and suggest that P. niruri may have a potential inhibitory effect on the development
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INTRODUCTION
of urinary calculi, probably by hindering the deposition of crystalline material on the
stone nidus. The data of both in vivo studies indicate that P. niruri probably interferes
with the biomineralization process by promoting a different interaction between the
crystal and the macromolecules of the organic matrix. The data are also in line with
results from in vitro studies in which the plant extract reduced CaOx crystal
aggregation and growth rate.
As mentioned earlier, alkali citrate increases urinary pH and citrate, therefore
inhibiting calcium oxalate crystallization The fact that any alkali citrate would be
adequate to increase urinary pH and citrate provides an interesting approach for
further research. Since certain fruit juices have high concentrations of citrate (38.3-
67.4 mmol/L) intake of these juices could also be considered for the management of
stone disease. It was shown by Grases et althat an infusion of Rosa canina L.
increased citrate excretion without changing volume, pH, or urinary concentrations of
oxalate or phosphate. Touhami et al. reported that rats treated with ethylene glycol-
ammonium chloride (EG‐AC) had large deposits of calcium oxalate crystals in all
parts of the kidney, and that such deposits were not present in rats treated with either
75 % or 100 % lemon juice [Citrus limon (L.) Burm. f.] Furthermore, calcific
parenchymatous deposits were not observed in 83 % of rats treated with 75 % or 100
% lemon juice. All rats treated with 50 % lemon juice showed fewer calcium deposits
on the kidney surface than the group that received EG‐AC alone, but treatment with
75 % and 100 % of the juice seemed to be more beneficial Unfortunately, urinary
citrate and pH were not determined in this study. However, in order to decrease
urinary pH in rats it is necessary to administer an EG dose of 2 % to induce metabolic
acidosis - but in the study of Touhami et al. EG was administered in a concentration
of 0.75 % which has been shown not to change the urinary pH value Consequently, it
is unlikely that the administration of citrate will therefore cause changes in urinary
citrate excretion. However, this remains speculative since besides the lack of
measuring urinary pH and citrate excretion the amount of citrate and other potential
active ingredients in the juice were also not determined in this study. This would have
been of interest since it has been shown that lemon juice has a high antioxidant
capacity due to its amount of citrate and flavonoids Antioxidants such as flavonoids
or other polyphenols could prevent CaOx crystal deposition in the kidney by
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INTRODUCTION
preventing hyperoxaluria-induced oxidative damage to the renal tubular membrane
which can prevent CaOx crystal attachment and subsequent development of kidney
stones.
Against this background, Tugcu et al. administered pomegranate juice (Punica
granatum L.) to stone-forming rats to investigate its possible effects on urolithiasis
and its mechanism of action. The authors could show that treatment with pomegranate
juice decreased urinary Ox excretion and CaOx deposit formation if compared with
rats receiving EG only. In addition, concentrations of malondialdehyde (MDA) and
nitric oxide (NO) were significantly lower and glutathione levels (GSH) were higher
in the kidneys of rats receiving pomegranate juice. The experiment showed that
pomegranate had protective effects on EG induced crystal deposition in rats probably
due to its antioxidative activity. Unfortunately, the juice was not further
phytochemically characterized so that the amount of ingested antioxidants remains
unclear.
In summary, although the majority of in vivo studies in rats has proven that
certain plant extracts or fruit juices decrease the excretion of urinary calcium and
oxalate and show a potential inhibitory effect on the development of urinary calculi,
the precise mechanism of action is still unclear. The prospective therapeutic
implication is also restricted by the fact that the used plant extracts have not been
further phytochemically characterized which to some degree limits the informative
value of the data because statements regarding active compounds remain speculative
at present.
Clinical trials
From the 21 clinical studies that were identified using the inclusion criteria for
this review the majority of articles (n = 9) evaluated the impact of citrus juices
(orange juice, lemon juice, grapefruit juice, apple juice or lemonade) on kidney stone
formation.
Other studies that met the inclusion criteria focused on the effect of cranberry
juice (n = 3), Hibiscus sabdariffa L. (n = 2), Phyllantus niruri L. (n = 2), Orthosiphon
grandiflorus Bold. (new: Orthosiphon stamineus Benth. or syn. Clerodendranthus
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spicatus Thunb.) (n = 1), Dolichos biflores L. [Vigna unguiculata (L.) Walp. subsp.
Unguiculata] (n = 1), Andrographis paniculata L. (n = 1), Sambucus nigra L. (n = 1),
and Solidago virgaurea L. (n = 1).
As pointed out previously, citrate is a known inhibitor of calcium-based
stones. Its presence in urine decreases the saturation of calcium oxalate and calcium
phosphate by forming soluble complexes with calcium. By its conversion through
bicarbonate citrate increases urinary pH which induces an additional citraturic
response by slowing renal citrate metabolism and impairing citrate reabsorption
However, pharmacological potassium citrate supplementation requires a rigorous
schedule of numerous tablets or liquid supplements taken routinely 3 to 4 times a day.
Patient compliance significantly decreases when medications are administered more
than once daily Patients therefore could benefit from intake of dietary citrate. Citrus
fruits and juices are a known natural source of dietary citrate. Several studies
investigated the influence of orange and grapefruit juice on urinary variables and the
risk of crystallization As observed by Wabner and Pak consumption of 1.2 L of
orange juice (Citrus aurantium var. sinensis L.) per day caused increases in urine pH
and citrate similar to a conventional dose of potassium citrate. In another investigation
the impact of orange, grapefruit [Citrus X paradisi Macfad. (pro sp.)] or apple juice
[Malus pumila P. Mill; syn: Malus domestica Borkh. (Borkh.)] on urinary
composition and crystallization was examined The authors noticed an increased pH
value and increased citrate excretion after consumption of each juice; CaOx
crystallization was significantly reduced by grapefruit and apple juice but not by
orange juice. Two additional studies investigated the effect of grapefruit juice on
urinary excretion of citrate and other urinary risk factors for renal stone formation.
Goldfarb and Asplin found that administration of grapefruit juice over a 7-day period
to healthy subjects increased mean oxalate and citrate excretion when compared to the
control group. However, no net change in the supersaturation of calcium oxalate,
calcium phosphate, or uric acid was observed in this study. Trinchieri et al. evaluated
changes in urinary risk factors after administration of a soft drink containing
grapefruit juice. In this study, urinary flow was significantly increased after both
grapefruit juice and mineral water compared to baseline. Compared to mineral water,
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grapefruit juice significantly increased urinary excretion of citrate, calcium and
magnesium.
In comparison to orange and grapefruit juice, lemon juice [Citrus limon (L.)
Burm. f.] contains the highest concentration of citrate, nearly 5 times that of oranges
So far 4 studies have investigated lemonade therapy as a potential treatment for
hypocitraturic nephrolithiasis The studies concluded that consumption of lemonade
significantly increased urinary citrate excretion and therefore could be a useful
adjunctive therapy in patients with hypocitraturia. Four ounces of lemon juice provide
5.9 g citric acid When diluted in 32 oz (960 mL) of water, lemonade could not only
promote dietary citrate but also fluids.
All of the mentioned studies have shown that citrus fruit juices consumption
delivers a high citric acid load resulting in elevated urinary citrate levels. Since these
juices are also well tolerated and inexpensive they could be considered as an
alternative or at least an adjunctive therapy for hypocitraturic stone formers. The
limitation of most studies, however, is that they have been carried out in either healthy
subjects (small sample size studies) or with a larger sample size in patients but
therefore being retrospective. Thus, further research is needed in stone-forming
patients. In addition, the phytochemical composition of the administered juices
remains unclear. Furthermore, the influence of single compounds from citrus juices
has not been examined until now.
Cranberry (Vaccinium macrocarpon Ait.) juice is another juice that has been
investigated in clinical trials for its ability to influence urinary biochemical and
physicochemical risk factors associated with CaOx kidney stones. However, the
literature regarding the effects of cranberry juice on urinary stone risk factors has
yielded conflicting results. Urinary calcium has been found to be increased or
unchanged Similarly, oxalate has been reported to be either increased or decreased
and pH values have been shown to be decreased or increased The reasons for these
conflicting results might be due to the variability in the amount (330 mL-1 L per day)
of cranberry juice ingested, the source and/or the duration of intake (5 days to 2
weeks). Further, the study population was relatively small (12-24 subjects) and in all
trials healthy subjects have been used. In order to clarify the potential role of
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INTRODUCTION
cranberry juice on urinary stone risk factors, juices should be evaluated in the future
in prospective, double-blind, randomized studies in larger numbers to reach a final
conclusion.
Since compounds in cranberry juice have been shown to inhibit the attachment
of bacteria to the epithelial lining of the urinary tract the same compounds could
inhibit the attachment of CaOx crystals and stone-promoting bacteria to renal
epithelial cells. Thus, plant extracts that exert antibacterial activities could also have
antilithogenic properties by protecting epithelial cells.
In fact, Muangman et al. could demonstrate that Andrographis paniculata
tablets were beneficial in the treatment of post-ESWL urinary tract infection. In this
study post-ESWL pyuria and hematuria in patients receiving Andrographis paniculata
were significantly reduced when compared to pre-ESWL values. Other plants which
should be mentioned in this context are Arctostaphylos uva-ursi L. or Equisetum
arvense L. since they also have known antiseptic activities.
As reported formerly, for the prevention of stone formation a high fluid intake
is important because a reduced urinary volume will amplify the saturation of all
solutes. Recommended fluids include mineral water and fruit juices. Plant extracts
which increase urinary volume could therefore also be used as an adjunctive therapy.
There are a growing number of studies purporting diuretic effects with traditional
medicines. Of these, the most promising are Solidago virgaurea LSambucus nigra L.
and Hibiscus sabdariffa L. Prasongwatana et al. also report an increased uric acid
excretion and clearance after consumption of H. sabdariffa tea in study subjects with
or without a history of renal stones.
On the contrary, Kirdpon et al. found a decrease in uric acid after consumption
of a juice prepared from H. sabdariffa. An increase of uric acid excretion was also
noted after consumption of a tea prepared from Orthosiphon grandiflorus (new:
Orthosiphon stamineus Benth. or syn. Clerodendranthus spicatus Thunb.).
The authors also noticed a stone size reduction in patients which was probably
related to an increased excretion of calcium and uric acid. Recently, the authors
Yuliana et al. could show in in vitro experiments that the antilithogenic activity of O.
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INTRODUCTION
grandiflorus might be due to its diuretic activity. The authors demonstrated that
methoxyflavonoids from Orthosiphon act as antagonists at adenosine A1 receptors.
Some studies revealed that adenosine A1 receptor antagonists can induce diuresis and
sodium excretion Since adenosine A1 receptors are expressed in the afferent arterioles,
glomerulus, proximale tubules, and collecting ducts adenosine antagonists could
directly inhibit sodium reabsorption in the proximal tubules or indirectly by
promoting afferent arteriole dilatation. However, since only a very limited number of
clinical studies have been performed with these two plants the overall benefits are not
very clear yet and it is recommended that further studies are conducted to clarify the
reported effects.
As mentioned in the previous paragraph, it has been shown that Phyllantus
niruri has an inhibitory effect on CaOx crystal growth and aggregation in vitro and
prevented the increase in the size and number of formed crystals in a rat model These
results could be confirmed in a clinical trial The study revealed that if patients took
capsules containing a 2 % aqueous extract of P. niruri (450 mg capsule, 3 × d) for 3
months urinary calcium was significantly reduced in hypercalciuric patients.
Furthermore, regular self-administration (2 g per day for 3 months) of a P. nuriri
extract after ESWL for renal stones resulted in an increased stone-free rate The
authors concluded that the lack of side effects supports the use of P. niruri to improve
overall outcomes after ESWL for lower pole stones. It is worth mentioning in this
context that from all studies that were included in the present review a phytochemical
profile only exists for P. niruri.
The effects of various plants with proposed application to prevent and treat
stone kidney formation have been critically reviewed in the present article. Data from
in vitro, in vivo and clinical trials reveal that phytotherapeutic agents could be useful
as either an alternative or a complementary therapy in the management of urolithiasis.
The reviewed studies show that some possible mechanisms of action of plant
extracts include an increased excretion of urinary citrate, decreased excretion of
urinary calcium and oxalate or could be attributable to diuretic, antioxidant or
antibacterial effects. Beyond the promising data on activity and efficacy, data on
quality of extracts have to be taken into consideration as well. Unfortunately, the
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documented phytochemical characterization of all herbal preparations in the reviewed
articles is inadequate. Future scientific and clinical studies about the efficacy of herbal
extracts would highly benefit from an adequate phytochemical description of the
extract. Even though most of the reports fail to rigorously define the specific herbal
product used in in vitro, in vivo or clinical studies, investigators are increasingly
aware that significant differences in the outcome are likely to be product-specific.
It is further suggested that products used for research/clinical studies should be
characterized by the extraction solvent, drug-extract ratio and the amount of specific
marker compounds. This information should allow a more substantial discussion of
the data and would help to better explain discrepancies between the studies.
Additionally, more studies are needed which focus on the mechanism of action of the
extract and active ingredients.
The need of the hour is to develop an effective, safe and standardized herbal
preparation for the management of urolithiasis. Systematic research needs to be
undertaken, in an attempt to explore botanicals as alternative and/or complementary
medicines for the treatment of urolithiasis. In conclusion, more interdisciplinary
research between pharmacognosists, pharmacologist and clinical investigators is
needed to develop new plant-derived high-quality natural products to treat and
prevent the formation of kidney stones.[7-22,25]
Renal failure
Renal failure
Classification and external resources
ICD-10 N17.-N19.
ICD-9 584-585
DiseasesDB 26060
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INTRODUCTION
MeSH C12.777.419.780.500
A hemodialysis machine, used to physiologically aid or replace the kidneys in
renal failure.Renal failure or kidney failure (formerly called renal insufficiency)
describes a medical condition in which the kidneys fail to adequately filter toxins and
waste products from the blood. The two forms are acute (acute kidney injury) and
chronic (chronic kidney disease); a number of other diseases or health problems may
cause either form of renal failure to occur.
Renal failure is described as a decrease in the glomerular filtration rate.
Biochemically, renal failure is typically detected by an elevated serum creatinine
level. Problems frequently encountered in kidney malfunction include abnormal fluid
levels in the body, deranged acid levels, abnormal levels of potassium, calcium,
phosphate, and (in the longer term) anemia. Depending on the cause, hematuria
(blood loss in the urine) and proteinuria (protein loss in the urine) may occur. Long-
term kidney problems have significant repercussions on other diseases, such as
cardiovascular disease.
Contents
1 Classification
a) 1.1 Acute kidney injury
b) 1.2 Chronic kidney disease
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INTRODUCTION
c) 1.3 Acute-on-chronic renal failure
2 Symptoms
3 Causes
a) 3.1 Acute renal failure
b) 3.2 Chronic kidney disease
c) 3.3 Genetic predisposition
4 Diagnostic approach
a) 4.1 Measurement for CKD
b) 4.2 Use of the term uremia
5 References
6 External links
Classification
Renal failure can be divided into two categories: acute kidney injury or
chronic kidney disease. The type of renal failure is determined by the trend in the
serum creatinine. Other factors which may help differentiate acute kidney injury from
chronic kidney disease include anemia and the kidney size on ultrasound. Chronic
kidney disease generally leads to anemia and small kidney size.
Acute kidney injury
`Acute kidney injury (AKI), previously called acute renal failure (ARF), is a
rapidly progressive loss of renal function, generally characterized by oliguria
(decreased urine production, quantified as less than 400 mL per day in adults,[1] less
than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); body water and body
fluids disturbances; and electrolyte derangement. AKI can result from a variety of
causes, generally classified as prerenal, intrinsic, and postrenal. An underlying cause
must be identified and treated to arrest the progress, and dialysis may be necessary to
bridge the time gap required for treating these fundamental causes.
Chronic kidney disease
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INTRODUCTION
Chronic kidney disease (CKD) can develop slowly and initially, show few
symptoms. CKD can be the long term consequence of irreversible acute disease or
part of a disease progression.
Acute-on-chronic renal failure
Acute kidney injuries can be present on top of chronic kidney disease, a
condition called acute-on-chronic renal failure (AoCRF). The acute part of AoCRF
may be reversible, and the goal of treatment, as with AKI, is to return the patient to
baseline renal function, typically measured by serum creatinine. Like AKI, AoCRF
can be difficult to distinguish from chronic kidney disease if the patient has not been
monitored by a physician and no baseline (i.e., past) blood work is available for
comparison.
Symptoms
Symptoms can vary from person to person. Someone in early stage kidney
disease may not feel sick or notice symptoms as they occur. When kidneys fail to
filter properly, waste accumulates in the blood and the body, a condition called
azotemia. Very low levels of azotaemia may produce few, if any, symptoms. If the
disease progresses, symptoms become noticeable (if the failure is of sufficient degree
to cause symptoms). Renal failure accompanied by noticeable symptoms is termed
uraemia.
Symptoms of kidney failure include:-
High levels of urea in the blood, which can result in:
Vomiting and/or diarrhea, which may lead to dehydration
Nausea
Weight loss
Nocturnal urination
Foamy or bubbly urine
More frequent urination, or in greater amounts than usual, with pale urine
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INTRODUCTION
Less frequent urination, or in smaller amounts than usual, with dark coloured
urine
Blood in the urine
Pressure, or difficulty urinating
Unusual amounts of urination, usually in large quantities
A build up of phosphates in the blood that diseased kidneys cannot filter out
may cause:
Itching
Bone damage
Muscle cramps (caused by low levels of calcium which can cause
hypocalcaemia)
A build up of potassium in the blood that diseased kidneys cannot filter out
(called hyperkalemia) may cause:
Abnormal heart rhythms
Muscle paralysis
Failure of kidneys to remove excess fluid may cause:
Swelling of the legs, ankles, feet, face and/or hands
Shortness of breath due to extra fluid on the lungs (may also be caused by
anemia)
Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys
and sometimes the liver, can cause:
Pain in the back or side
Healthy kidneys produce the hormone erythropoietin which stimulates the
bone marrow to make oxygen-carrying red blood cells. As the kidneys fail,
they produce less erythropoietin, resulting in decreased production of red
blood cells to replace the natural breakdown of old red blood cells. As a result,
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INTRODUCTION
the blood carries less hemoglobin, a condition known as anemia. This can
result in:
Feeling tired and/or weak
Memory problems
Difficulty concentrating
Dizziness
Low blood pressure
Other symptoms include:
Appetite loss, a bad taste in the mouth
Difficulty sleeping
Darkening of the skin
Causes
Acute renal failure
Acute kidney failure usually occurs when the blood supply to the kidneys is
suddenly interrupted or when the kidneys become overloaded with toxins. Causes of
acute failure include accidents, injuries, or complications from surgeries in which the
kidneys are deprived of normal blood flow for extended periods of time. Heart-bypass
surgery is an example of one such procedure.
Drug overdoses, whether accidental or from chemical overloads of drugs such
as antibiotics or chemotherapeutics, may also cause the onset of acute kidney failure.
Unlike in chronic kidney disease, however, the kidneys can often recover from acute
failure, allowing the patient to resume a normal life. People suffering from acute
failure require supportive treatment until their kidneys recover function, and they
often remain at increased risk of developing future kidney failure.[7]
Amongst the accidental causes of renal failure is there also the crush
syndrome, when large amounts of toxins are suddenly released in the blood
circulation after a long compressed limb is suddenly relieved from the pressure
obstructing the blood flow through its tissues, causing ischemia. The resulting
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INTRODUCTION
overload can lead to the clogging and the destruction of the kidneys. It is a reperfusion
injury that appears after the release of the crushing pressure. The mechanism is
believed to be the release into the bloodstream of muscle breakdown products –
notably myoglobin, potassium and phosphorus – that are the products of
rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions).
The specific action on the kidneys is not fully understood, but may be due in part to
nephrotoxic metabolites of myoglobin.
Chronic kidney disease
CKD has numerous causes. The most common is diabetes mellitus. The
second most common is long-standing, uncontrolled, hypertension, or high blood
pressure. Polycystic kidney disease is another well-known cause of CKD. The
majority of people afflicted with polycystic kidney disease have a family history of
the disease. Other genetic illnesses affect kidney function as well.
Overuse of common drugs such as aspirin, ibuprofen, and acetaminophen can
also cause chronic kidney damage.[8]
Some infectious diseases such as hantavirus can attack the kidneys, causing
kidney failure.
Diagnostic approach
Measurement for CKD
Chronic kidney failure is measured in five stages, which are calculated using a
patient’s GFR, or glomerular filtration rate. Stage 1 CKD is mildly diminished renal
function, with few overt symptoms. Stages 2 and 3 need increasing levels of
supportive care from their medical providers to slow and treat their renal dysfunction.
Patients in stages 4 and 5 usually require preparation of the patient towards active
treatment in order to survive.Stage 5 CKD is considered a severe illness and requires
some form of renal replacement therapy (dialysis) or kidney transplant whenever
feasible.
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Glomerular filtration rate.A normal GFR varies according to many factors,
including sex, age, body size and ethnicity. Renal professionals consider the
glomerular filtration rate (GFR) to be the best overall index of kidney function.
Use of the term uremia
Before the advancement of modern medicine, renal failure was often referred
to as uremic poisoning. Uremia was the term used to describe the contamination of
the blood with urine. Starting around 1847, this term was used to describe reduced
urine output, that was thought to be caused by the urine mixing with the blood instead
of being voided through the urethra. The term uremia is now used to loosely describe
the illness accompanying kidney failure.
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Medicinal Plants Used In Treatment Of Kidney Diseases:-
Sr.no PLANT NAME FAMILY LOCAL NAME
1. Abutilon indicum Linn Malvaceae Kanghi
2. Aerva lanata Linn Amarnthaceae Chaya
3. Boerhaavia Diffusa
Linn
Nyctaginaceae Punarnava
4. Cynodon Dactylon Linn Poaceae Hari Doob
5. Fragaria Vesca Linn Rosaceae Strawberry
6. Daucus Carota Apiaceae Gajar
7. Equisetum Debile Equisetaceae Jode tode ji ghas
8. Gomphrena Celosiodes Amaranthaceae Kasia
9. Ricinus Communis Euphorbiaceae Castor Oil
10. Tribulus Terrestris Linn Zygophylloceae Gokhuru
11. physalis Alkekengi linn Rosaceae Strawberry Tomato
12. Zea Mays linn Poaceae Makka
13. Trianthema
Portulacastrum
Ficodae Bishkarpa
14. Musa balbiasiana Colla Musaceae Kela
15. Crataeva Nurvala Capparaceae Varuna
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INTRODUCTION
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