This specificity can be explained by the role of the ClCK/barritin channels in the inner ear. The secretion of the potassium ion-rich endolymph by marginal cells in the striavascularis of the inner ear is required for the normal function of the inner hair cells mediating hearing. ClCkb mutation will not effect, bcClCka exist, but barttin will effect both.A model of K+ secretion in the striavascularis of the inner ear. - K+ is taken up by basolateral NKCC1 and Na,K-ATPase and extruded through an apical K+ channel comprised of KCNQ1 and KCNE1 subunits. Na+ taken up through NKCC1 is extruded by Na,K-ATPase, whereas Cl– recycling is mediated by basolateral ClC-K1–Barttin and ClC-K2–Barttin channels.
Type I, Na-K-2Cl cotransporter at the luminal side of the tubular epithelial cells, acts like furosemide, lead to hypercalciuriaFig. 1. Transport pathways in the thick ascending limb of the loop of Henle (A) Cl–reabsorption across the luminal membrane occurs via the Na–K–2Cl– co-transporter (NKCC2). This co-transporter is driven by the low intracellular Naand Cl– concentrations generated by the basolateral Na–K-ATPase and ClC-Kb, respectively. In addition, ROMK enables functioning of NKCC2 by recycling Kback to the lumen. The lumen-positive electrical potential, which is generated by Cl– entry into the cell and Kexit from the cell, drives paracellular Ca2and Mg2transport from lumen to blood. Activation of the basolateral calcium-sensing receptor (CaSR) inhibits the luminal ROMK channel which, in turn, results in decreased NaClreabsorption and (secondary to the reduction in the intraluminal positive potential) increased urinary Ca2and Mg2excretion.
Type II, mutated protein is the potassium recycling channel, ROMK, also at the luminal sideROMK is an acronym for the Renal Outer Medullary Potassium channel. This is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells. The ATP-sensitive ROMK is involved in the regulation of renal NKCC2 cotransporter activity and net salt reabsorptionin vivo by recycling K entering cells of the TAL back to the lumen. If the ROMK channel is inactive, K levels in the lumen are then too low to permit continued Na-K-2Cl cotransport activity. Mutations in the ROMK gene on chromosome 11, resulting in Bartter syndrome has been called Bartter syndrome type II.
Type III, defective structure is the kidney-specific chloride channel at the basolateralChloride channel Kb, also known as CLCNKB is a member of the voltage-gated chloride channelsCl ion channel consists of nine members that form anion pores in plasma membraneCLCNKA and CLCNKB are closely related (94% sequence identity), tightly linked (separated by 11 kb of genomic sequence) and are both expressed in mammalian kidney.The reabsorption of NaCl in the thick ascending limb requires exit of these ions across the basolateral membrane into the blood through the chloride channel and the Na-K-ATPase pump. Dysfunction of the chloride channel thus impairs NKCC2 activity (10). Several kindreds with Bartter syndrome has been identified in whom there are large deletions and nonsense and missense mutations of the renal chloride channel gene (CLCNKB) on chromosome 1.This subset of Bartter’s syndrome is often called type III, or classic Bartter syndrome. In this distinct subset nephrocalcinosis is typically absent.In animal model, ClcNkb correlate ClCNk2 is distributed in TAL and DCTSome reports of many individuals with type III BS exhibit a mixed Bartter-Gitelmanpnenotype c/w the role of this Cl ion channel in both TAL and DCT
Bartter syndrome, infantile, with sensorineural deafness (Barttin), also known as BSND, is a human gene which is associated with Bartter syndrome.This gene encodes an essential beta subunit for CLC chloride channels. Responsible for trafficking of CLC-K to the plasma membranethese heteromeric channels localize to basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. Loss of function mutations in this gene have been associated with Bartter syndrome with sensorineural deafness.Sensorineural deafness is specific for barttin associated BS type IV….More sever form of BS than type IIIBc effects both CLCKa and b
DonorsBartter syndrome is an autosomal recessive disorder. Both parents carry at least 1 gene for the disorder. Statistically, only 1 of 4 siblings will be completely healthy. Whether carrying 1 gene for this abnormality leads to long-term problems late in life if 1 kidney is removed is unknown. Transplants from living, unrelated persons or cadavers are options for patients with ESRD.
Special Surgical ConcernsElectrolytesSpecial attention should be paid to correcting electrolyte abnormalities when patients with Bartter syndrome undergo surgical procedures.AnesthesiaThe multiple biochemical abnormalities that occur in patients with Bartter syndrome may present a challenge to anesthesiologists when general anesthesiais used. Potential problems include difficulties in fluid and electrolyte management, acid-base abnormalities, and a decreased response to vasopressors.Renal function must be monitored carefully, and dose adjustments must be made for drugs dependent on renal excretion if renal function declines. Moreover, metabolic alkalosis has been reported to alter drug protein binding for some anesthetic agents.Patients with Bartter syndrome may also have platelet dysfunction if routinely treated with nonsteroidal anti-inflammatory agents.
Bartter syndrome, originally described by
Bartter and colleagues in 1962, represents
a set of closely related, autosomal
recessive renal tubular disorders
characterized by hypokalemia,
hypochloremia, metabolic alkalosis, and
hyperreninemia with normal blood
pressure. The underlying renal abnormality
results in excessive urinary losses of
sodium, chloride, and potassium.
Bartter and Gitelman syndromes are renal
tubular salt-wasting disorders in which the
kidneys cannot reabsorb chloride in the TALH
or the DCT, depending on the mutation.
Chloride is passively absorbed along most of
the proximal tubule but is actively transported
in the TALH and the distal convoluted tubule
(DCT). Failure to reabsorb chloride results in a
failure to reabsorb sodium and leads to
excessive sodium and chloride (salt) delivery
to the distal tubules, leading to excessive salt
and water loss from the body.
Other pathophysiologic abnormalities result from
excessive salt and water loss. The renin-angiotensinaldosterone system (RAAS) is a feedback system
activated with volume depletion. Long-term stimulation
may lead to hyperplasia of the juxtaglomerular complex.
Angiotensin II (ANG II) is directly
vasoconstrictive, increasing systemic and renal
arteriolar constriction, which helps to prevent systemic
hypotension. It directly increases proximal tubular
ANG II–induced renal vasoconstriction, along with
potassium deficiency, produces a counterregulatory rise
in vasodilating prostaglandin E (PGE) levels. High PGE
levels are associated with growth inhibition in children.
High levels of aldosterone also enhance
potassium and hydrogen exchange for
sodium. Excessive intracellular hydrogen ion
accumulation is associated with hypokalemia
and intracellular renal tubule potassium
depletion. This is because hydrogen is
exchanged for potassium to maintain electrical
neutrality. It may lead to intracellular citrate
depletion, because the alkali salt is used to
buffer the intracellular acid and then lowers
urinary citrate excretion. Hypocitraturia is an
independent risk factor for renal stone
Excessive distal sodium delivery increases
distal tubular sodium reabsorption and
exchange with the electrically equivalent
potassium or hydrogen ion. This, in
turn, promotes hypokalemia, while lack of
chloride reabsorption promotes inadequate
exchange of bicarbonate for chloride, and
the combined hypokalemia and excessive
bicarbonate retention lead to metabolic
Persons with Bartter syndrome often have hypercalciuria.
Normally, reabsorption of the negative chloride ions
promotes a lumen-positive voltage, driving paracellular
positive calcium and magnesium absorption. Continued
reabsorption and secretion of the positive potassium ions
into the lumen of the TALH also promotes reabsorption of
the positive calcium ions through paracellular tight junctions.
Dysfunction of the TALH chloride transporters prevents urine
calcium reabsorption in the TALH. Excessive urine calcium
excretion may be one factor in the nephrocalcinosis
observed in these patients.
Calcium is usually reabsorbed in the DCT. Theoretically,
chloride is reabsorbed through the thiazide-sensitive sodium
chloride cotransporter and transported from the cell through
a basolateral chloride channel, reducing intracellular chloride
concentration. The net effect is increased activity of the
voltage-dependent calcium channels and enhanced
electrical gradient for calcium reabsorption from the lumen.
In Gitelman syndrome, dysfunction of
the sodium chloride cotransporter
(NCCT) leads to hypocalciuria and
hypomagnesemia. In the last several
years, the understanding of magnesium
handling by the kidney has improved
and advances in genetics have allowed
the differentiation of a variety of
While patients the variants that make
up Bartter syndrome may or may not
havehypomagnesemia, this condition is
pathognomonic for Gitelman syndrome.
The mechanism of the impaired
magnesium reabsorption is still
unknown; studies in NCCT knockout
mice demonstrate increased apoptosis
of DCT cells, which would then lead to
diminished reabsorptive surface area.
The ClC-Kb channel is found in the basolateral membrane of
the TALH, while the barttin subunits of ClC-Ka and ClC-Kb are
found in the basolateral membrane of the marginal cells of the
cochlear stria vascularis.
In the inner ear, an Na-K-2Cl pump, called NKCC1, on the
basolateral membrane increases intracellular levels of sodium,
potassium, and chloride. Potassium excretion across the
apical membrane against a concentration gradient produces
the driving force for the depolarizing influx of potassium
through the ion channels of the sensory hair cells required for
hearing. The sodium ion is excreted across the basolateral
membrane by the Na-K-adenosine triphosphatase (ATPase)
pump, and the ClC-K channels allow the chloride ion to exit to
associated with type IV
Bartter syndrome, a
neonatal form of the
disease (see Etiology),
is due to defects in the
barttin subunit of the
ClC-Ka and CIC-Kb
Mutations in only the
ClC-Kb subunit, as
occurs in type III Bartter
syndrome, do not result
in sensorineural deafnes
Defects in either the sodium chloride/potassium
chloride cotransporter or the potassium channel
affect the transport of sodium, potassium, and
chloride in the thick ascending limb of the loop of
Henle (TALH). The result is the delivery of large
volumes of urine with a high content of these
ions to the distal segments of the renal
tubule, where only some sodium is reabsorbed
and potassium is secreted.
Familial and sporadic forms of Bartter and
Gitelman syndromes exist. When
inherited, these syndromes are passed on as
autosomal recessive conditions.
Normal transport mechanism
Normal transport mechanisms in
the thick ascending limb of the
loop of Henle. Reabsorption of
sodium chloride is achieved with
the sodium chloride/potassium
chloride cotransporter, which is
driven by the low intracellular
sodium, chloride, and
potassium. Low concentrations
are maintained by the
basolateral sodium pump
triphosphatase), the basolateral
chloride channel (ClC-kb), and
the apical potassium channel
Neonatal (type I and type II)
An autosomal recessive mode of inheritance is
observed in some patients with neonatal
Bartter syndrome, although many cases are
At least 2 genotypes have been identified in
neonatal Bartter syndrome. Type I results from
mutations in the sodium chloride/potassium
chloride cotransporter gene (NKCC2; locus
SLC12A1 on chromosome bands 15q15-21).
Type II results from mutations in
the ROMK gene (locus KCNJ1 on
chromosome bands 11q24-25).
Type I neonatal
gene result in
Type II neonatal
Mutations in the
result in an
the cell back
into the tubular
inhibition of the
Classic (type III) Bartter
Some patients have an autosomal
recessive mode of inheritance in classic
Bartter syndrome, although many cases
In classic Bartter syndrome, the defect in
sodium reabsorption appears to result from
mutations in the chloride-channel gene (on
band 1p36). The consequent inability of
chloride to exit the cell inhibits the sodium
chloride/potassium chloride cotransporter.
Mutations in the
channel lead to
an inability of
chloride to exit
the cell, with
inhibition of the
Increased delivery of sodium
chloride to the distal sites of
the nephron leads to salt
wasting, polyuria, volume
contraction, and stimulation
of the renin-angiotensinaldosterone axis. These
effects, combined with
biologic adaptations of
segments, specifically the
distal convoluted tubule
(DCT) and the collecting
duct, result in hypokalemic
The hypokalemia, volume
contraction, and elevated
angiotensin levels increase
intrarenal prostaglandin E2
(PGE2) synthesis, which
contributes to a vicious
cycle by further stimulating
the renin-aldosterone axis
and inhibiting sodium
chloride reabsorption in the
Type IV Bartter syndrome
Studies have identified a novel
type IV Bartter syndrome.[10, 23,
24] This is a type of neonatal
Bartter syndrome associated
with sensorineural deafness
and has been shown to be
caused by mutations in
the BSND gene.[23, 25,
26] BSND encodes barttin, an
essential beta subunit that is
required for the trafficking of
the chloride channel ClC-K
(ClC-Ka and ClC-Kb) to the
plasma membrane in the TALH
and the marginal cells in the
scala media of the inner ear
that secrete potassium ion ̶
rich endolymph. Thus, lossof-function mutations in barttin
cause Bartter syndrome with
In contrast to other Bartter types, the
underlying genetic defect in type IV is
not directly in an ion-transporting
protein. The defect instead indirectly
interferes with the barttin-dependent
insertion in the plasma membrane of
chloride channel subunits ClC-Ka and
Type V Bartter syndrome
Other observations have identified type V
Bartter syndrome. This is another type of
neonatal Bartter syndrome that is associated
with sensorineural deafness, but it is not
caused by mutations in the BSND gene. Type
V Bartter syndrome has been shown to be a
digenic disorder resulting from loss-of-function
mutations in the genes that encode the
chloride channel subunits ClC-Ka and ClCKb. The specific genetic defect includes a
large deletion in the gene that encodes ClC-Kb
(ie, CLCNKB) and a point mutation in the gene
that encodes ClC-Ka (CLCNKA).
Summary of Pathophysiology
Hypokalemic salt-losing tubulopathies_Zelikovic_Nephrology Dialysis Transplant_2003
A summary of currently identified genotype-phenotype
correlations in Bartter syndrome is in the table below. For
completion, the genetic defect found in Gitelman syndrome
(the thiazide-sensitive sodium chloride cotransporter,
encoded by the gene NCCT) is also included.
Bartter Syndrome Genotype-Phenotype Correlations
Bartter type I
Bartter type II
Bartter type III
Bartter type IV
Neonatal with deafness
Bartter type V
CLCNKB and CLCNKA
Neonatal with deafness
Cascade of events
Renin/aldosterone secretion / JGA hyperplasia
autonomous hyperreninemic hyperaldosteronism
Enhanced K and H secertion at the collecting tubule
Hypokalemia and metabolic alkalosis result
Bartter syndrome is rare, and estimates of its occurrence vary
from country to country. In the United States, the precise
incidence is unknown.
In Costa Rica, the frequency of neonatal Bartter syndrome is
approximately 1.2 cases per 100,000 live births but is higher if
all preterm births are considered. No evidence of consanguinity
was found in the Costa Rican cohort.
In Kuwait, the prevalence of consanguineous marriages or
related families in patients with Bartter syndrome is higher than
50%, and prevalence in the general population is 1.7 cases per
In Sweden, the frequency has been calculated as 1.2 cases per
1 million persons. Of the 28 patients Rudin reported, 7 came
from 3 families; the others were unrelated.
Neonatal Bartter syndrome can be
suspected before birth or can be
diagnosed immediately after birth. In the
classic form, symptoms begin in
neonates or in infants aged 2 years or
younger. Gitelman syndrome is often not
diagnosed until adolescence or early
Neonatal Bartter syndrome
Maternal polyhydramnios, secondary to fetal
polyuria, is evident by 24-30 weeks' gestation.
Delivery often occurs before term. The newborn has
massive polyuria (rate as high as 12-50 mL/kg/h).
The subsequent course is characterized by lifethreatening episodes of fluid loss, clinical volume
depletion, and failure to thrive. Volume depletion
increases thirst, and the normal response is to
increase fluid intake.
A subset of patients with neonatal Bartter syndrome
(types IV and V) develop sensorineural deafness.
Classic Bartter syndrome
Patients have a history of maternal
polyhydramnios and premature delivery.
Symptoms include the following:
Tendency for volume depletion
Failure to thrive
Linear growth retardation
Other symptoms, which appear during
late childhood, include fatigue, muscle
weakness, cramps, and recurrent
Developmental delay and minimal brain
dysfunction with nonspecific
electroencephalographic changes are
Neonatal Bartter syndrome
Patients are thin and have reduced muscle
mass and a triangularly shaped face, which
is characterized by a prominent forehead,
large eyes, protruding ears, and drooping
mouth. Strabismus is frequently present.
Blood pressure is within the reference
A subset of patients with Bartter syndrome
(types IV and V) develop sensorineural
deafness, which is detectable with
Classic Bartter syndrome
The patient's facial appearance may be similar to
that encountered in the neonatal type. However, this
finding is infrequent.
Patients with Gitelman syndrome tend to have milder
symptoms than do those with Bartter syndrome and
to present in adolescence and early adulthood.
Often, patients have minimal symptomatology and
lead relatively normal lives.
Consider possible renal tubular disorder if
patients, especially dehydrated infants and young
children, are found to have hypokalemia and a high
serum bicarbonate concentration that do not correct
with potassium and chloride replacement treatment.
Clinical and biochemical features of Gitelman's
syndrome and the various types of Bartter's
Conditions to consider in the differential diagnosis of Bartter
syndrome include the following:
Hyperprostaglandin E syndrome
Familial hypomagnesemia with hypercalciuria/nephrocalcinosis
Activating mutations of the CaSR calcium-sensing receptor
Congenital chloride diarrhea
Gullner syndrome - Familial hypokalemic alkalosis with proximal
Morbidity and mortality
Significant morbidity and mortality occur if
Bartter syndrome is untreated. With
treatment, the outlook is markedly
improved; however, long-term prognosis
remains guarded because of the slow
progression to chronic renal failure due to
Sensorineural deafness associated with
Bartter syndrome IV is due to defects in the
barttin subunit of the ClC-Ka and CIC-Kb
A review of 61 cases of Bartter syndrome reported 29 with
nephrocalcinosis, a condition that is often associated with
Renal failure is fairly uncommon in Bartter syndrome. In a
review of 63 patients, 5 developed progressive renal
disease requiring dialysis or transplantation.
In 2 reports of patients who underwent biopsies before
developing end-stage renal disease (ESRD), 1 patient
had interstitial nephritis, and the other had mesangial and
One report relates the case of a patient developing
reversible acute renal failure from rhabdomyolysis due to
Short stature/growth retardation
Nearly all patients with Bartter syndrome
have growth retardation. In a review of
66 patients, 62 had growth
retardation, often severe (below the fifth
percentile for age). Treatment with
potassium, indomethacin, and growth
hormone (GH) has been effective.
Other complications in Bartter syndrome
include the following:
Cardiac arrhythmia and sudden death May result from electrolyte imbalances
Failure to thrive and developmental delay Common in untreated patients
Significant decrease in bone mineral
density - Has been documented in patients
with either the neonatal or classic form
The severity and site of the mutation determines the age at
which symptoms first develop. Completely dysfunctional
mutations in the receptors and ion channels in the thick
ascending limb of the loop of Henle (TALH) are probably not
compatible with life.
Most cases of Bartter syndrome are discovered in infancy or
early adolescence. Bartter syndrome can also be diagnosed
prenatally, when the fetus develops polyhydramnios and
intrauterine growth retardation. Many of the neonates are
born prematurely. Children diagnosed early in life usually
have more severe electrolyte disorders and symptoms.
Because of Bartter syndrome's heterogeneity, patients with
minimal symptomatology may be discovered relatively late.
An electrocardiogram (ECG) may reveal changes
characteristic of hypokalemia, such as flattened T waves and
prominent U waves.
Although renal biopsy is not usually required, histologic
findings may be useful in confirming the diagnosis of Bartter
In neonatal and classic Bartter syndrome, the cardinal finding
is hyperplasia of the juxtaglomerular apparatus. Less
frequently, hyperplasia of the medullary interstitial cells is
Glomerular hyalinization, apical vacuolization of the proximal
tubular cells, tubular atrophy, and interstitial fibrosis may be
present as a consequence of chronic hypokalemia.
Initiate timed urine collection to determine potassium levels. In hypokalemia, normal
kidneys retain potassium. Elevated urinary potassium levels with low blood
potassium levels suggest that the kidneys are having problems retaining potassium.
Next, initiate timed urine collection to determine aldosterone levels. Aldosterone levels
should be high in volume-replete patients. If urinary aldosterone levels are high
despite volume replacement, there is an abnormal stimulation of aldosterone.
Patients with primary hyperaldosteronism in a volume-replete state usually have
normal to high blood pressure. Low or low-normal blood pressure with high
aldosterone excretion suggests that the primary problem is something else and that
the aldosterone response is secondary to the undiagnosed primary abnormality.
Next, initiate a timed urine collection to determine chloride levels.
Extrarenal volume depletion is a possible reason for low blood
pressure, high aldosterone excretion, and potassium loss. In this
case, the kidneys retain sodium and chloride, and urinary chloride
concentrations should be low.
High urine chloride levels with low blood pressure, high aldosterone
secretion, and high urinary potassium levels are found only with
long-term diuretic use and Bartter or Gitelman syndrome. If diuretic
abuse is suspected, a urine screen for diuretics can be ordered.
Otherwise, the diagnosis is Bartter or Gitelman syndrome.
Patients with Bartter syndrome have high urinary excretion of
calcium and normal urinary excretion of magnesium.
In patients with Gitelman syndrome, the opposite is true, with tests
showing low urinary excretion of calcium and high urinary excretion
Hyperuricemia is present in 50% of patients with Bartter syndrome,
whereas in Gullner syndrome, hypouricemia, secondary to impaired
proximal tubular function, is present.
Complete blood count
Polycythemia may be present from hemoconcentration.
Mutations in the different transporters cause Bartter syndrome. The
older methods of determining the presence of mutations require
more detailed physiologic investigations, including determination of
serum magnesium levels and further urine collections to assess
calcium, magnesium, and PGE2 levels.
In Bartter syndrome, urine calcium excretion is high, leading to
nephrocalcinosis, while serum magnesium levels are normal.
With the transporter mutations that cause Gitelman syndrome,
hypomagnesemia is common and is accompanied by hypocalciuria.
Genetic analysis has become the preferred methodology for
determining if a mutation in one of the transporters has occurred. An
analysis of the genes for the transporters shows multiple problems
leading to abnormal gene function, including missense, frame-shift,
loss-of-function, and large deletion mutations. (Not all mutations
lead to a marked loss of function.)[3, 4, 5, 6, 19, 20]
If the diagnosis is being made
prenatally, assess the amniotic fluid. The
chloride content may be elevated in either
Gitelman or Bartter syndrome.
Glomerular filtration rate
The glomerular filtration rate (GFR) is
preserved during the early stages of the
disease; however, it may decrease as a result
of chronic hypokalemia. One
study, however, hypothesizes that GFR is
affected more by secondary
hyperaldosteronism than by hypokalemia.
Neonatal Bartter syndrome can be diagnosed best
prenatally by ultrasonography. The fetus may have
polyhydramnios and intrauterine growth retardation.
Amniotic chloride levels may be elevated.
After birth, especially if the disease is diagnosed in
older patients who have hypercalciuria, consider a
renal ultrasonogram or flat plate of the abdomen for
nephrocalcinosis. Sonographic findings include
diffusely increased echogenicity, hyperechoic
pyramids, and interstitial calcium deposition.
Because continued calcium loss may affect
bones, dual-energy radiographic absorptiometry
scans to determine bone mineral density may be
advisable in older patients.
Nephrocalcinosis can occur and is often
associated with hypercalciuria. It can be
diagnosed with abdominal radiographs,
intravenous pyelograms (IVPs), renal
ultrasonograms, or spiral computed
tomography (CT) scans.
Since first described in 1962, several types of medical
treatment have been used, including the following:
Sodium and potassium supplements - Used for the
Aldosterone antagonists and diuretic spironolactone - Are
mainstays of therapy
Angiotensin-converting enzyme (ACE) inhibitors - Used to
counteract the effects of angiotensin II (ANG II) and
Indomethacin - Used to decrease prostaglandin excretion
Growth hormone (GH) - Used to treat short stature
Calcium or magnesium supplements - May occasionally be
needed if tetany or muscle spasms are present
Reports associated with Bartter syndrome in
pregnant women are limited because Bartter
syndrome is a rare disease. Complications related
to electrolyte loss (eg, hypokalemia,
hypomagnesemia) responded well to
supplementation. Fetuses were unaffected and
carried to term.
In Rudin's report of 28 pregnant patients, no
problems were noted except asymptomatic
hypokalemia. In another study, of 40 patients, 30
reported normal pregnancies and terminated by
normal parturition; however, many of the patients
who were pregnant probably had Gitelman
For patients initially diagnosed in the hospital, the goal is to
stabilize the patient sufficiently for discharge. This includes
stabilization of potassium and other electrolytes, as well as volume
and, perhaps, acid-base parameters.
Contact a nephrologist or pediatric nephrologist whenever a
patient fitting the clinical picture of Bartter or Gitelman syndrome is
identified. The specialist can assist with the initial diagnosis and
carry out periodic outpatient evaluation of growth, development,
renal function, serum electrolytes, and response to therapy.
Patients initially need frequent outpatient follow-up care until the
metabolic abnormalities caused by the renal tubular transporter
mutation are stabilized with medications. The length of time to
stability depends on the severity of the mutation and the degree of
Bartter and Gitelman syndromes, by themselves, do
not lead to chronic renal insufficiency; however, in
patients with these syndromes who develop endstage renal disease (ESRD) for other
reasons, transplants from living relatives are an option
and result in normal urinary handling of
sodium, potassium, calcium, and magnesium.
Reports of renal transplants from living relatives in
ESRD patients with Bartter syndrome suggest that
many endocrinologic abnormalities in Bartter
syndrome improve or normalize after transplantation.
Because the genetic abnormality in Bartter syndrome
may be found only in the kidneys (which is certain in
Na-K-Cl cotransporter but may not be the case for
some of the other mutations), transplantation corrects
the problem by replacing unhealthy kidneys with
One approach to the management of severe
Bartter syndrome involves preemptive
nephrectomy and renal transplantation. The
rationale for this approach lies in the fact that
Bartter syndrome is an incurable genetic
disease, and the poorly controlled forms may
result in frequent life-threatening episodes of
dehydration and electrolyte imbalances.
Preemptive bilateral nephrectomies and
successful kidney transplantation prior to the
onset of ESRD has resulted in correction of
metabolic abnormalities and excellent graft
Diet and Activity
Adequate salt and water intake is necessary to
prevent hypovolemia, and adequate potassium
intake is essential to replace urinary potassium
losses. Patients should consume foods and
drinks that contain high levels of potassium
(eg, tomatoes, bananas, orange juice).
With growth retardation, adequate overall
nutritional balance (protein-calorie intake) is
important. Whether other dietary supplements
(eg, citrate, magnesium, vitamins) are helpful
is not clear.
No restriction on general activity is
required, but precautions against
dehydration should be taken. Patients
should avoid strenuous exercise
avoided because of the danger of
dehydration and functional cardiac
abnormalities secondary to potassium
early diagnosis and appropriate treatment
may improve growth and neurointellectual
sustained hypokalemia and
hyperreninemia can cause progressive
tubulointerstitial nephritis, resulting in endstage-renal disease.
With early treatment of the electrolyte
imbalances the prognosis is good.
Bone age is appropriate for chronological
age, and pubertal and intellectual
development are normal with treatment.
The disease does not recur in the patient
with a transplanted kidney.
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