bartter syndrome ( bs ) is a rare inherited renal tubular disorder characterized by renal salt wasting , hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism1 , 2 ) . although bs is a typical tubular disorder ,
there have been several case reports of patients who developed focal segmental glomerulosclerosis ( fsgs ) , a glomerular lesion , during the course of bs3 - 7 ) .
such cases support a possible link between the two diseases , and indicate that stimulation of the renin - angiotensin system ( ras ) and increased angiotensin ii in response to chronic glomerular hyperfiltration due to salt - losing tubulopathy may lead to secondary fsgs3 , 4 , 8) .
in addition to fsgs , several other factors have been reported to influence the renal survival of patients with bs , including recurrent episodes of dehydration during early infancy , chronic hypokalemia , long - term use of non - steroidal anti - inf lammatory drugs , nephrocalcinosis , and mutations in the bsnd gene9 - 11 ) .
however , there have been only a few case reports of patients with bs who underwent renal transplantation6 , 12 - 15 ) . here ,
we present a case of a patient with bs who developed fsgs and subsequently underwent renal transplantation due to aggravation of his renal function .
we also review previously reported cases of both diseases and cases of individuals with bs who underwent renal transplantation .
there were no perinatal problems including polyhydramnios , and the family history was unremarkable . at age
3 months , the patient visited a hospital due to recurrent febrile episodes and poor weight gain . the patient was diagnosed as bs , and potassium supplement and indomethacin medication were started . however ,
his compliance to the drug was very poor . detailed clinical and laboratory data from that time are unavailable . at age 7 , proteinuria was incidentally detected upon routine follow - up urinalysis .
a renal ultrasonography revealed diffusely increased parenchymal echogenicity without definite evidence of nephrocalcinosis or nephrolithiasis . at age 8 ,
a renal biopsy was conducted at the hospital due to persistent proteinuria ( 24-hour urine protein excretion 3,840 mg / day , serum albumin 3.4 g / dl , and serum creatinine 1.2 mg / dl ) .
his proteinuria did not respond to 4 weeks of oral prednisolone ( 2 mg / kg / day ) treatment . at age 10 ,
the patient 's height was 123 cm ( < 3rd percentile ) , weight was 36 kg ( 90 - 97th percentile ) , and blood pressure was 117/69 mmhg at the time of admission .
the laboratory examination revealed a serum creatinine level of 3.1 mg / dl , a sodium level of 138 mmol / l , a potassium level of 3.7 mmol / l , a chloride level of 103
mmol / l , a bicarbonate level of 30 meq / l , a magnesium level of 2.0
/ ml / hr ( normal range 1 - 2.5 ) , an aldosterone level of 558 pg / ml ( normal range 50 - 194 ) , and a spot urine calcium ( mg ) to creatinine ( mg ) ratio of 0.02 . additionally , the patient 's bone age was 6 years 5 months upon admission .
genetic analysis revealed a homozygous p.trp(tgg)610stop(tga ) mutation in exon 16 on the clcnkb gene .
his renal function deteriorated progressively for one year thereafter , at which point hemodialysis was started .
subsequently , the patient underwent renal transplantation successfully from a deceased donor at age 16 .
the post - transplantation course has been uneventful for more than 3 years , with complete disappearance of bs without recurrence of fsgs .
clinically , bs can be classified into two variants , antenatal / neonatal bs and classic bs according to the onset age .
genetically , bs can be classified into at least 5 subtypes according to underlying mutant genes , all of which are expressed in the tubular epithelial cells of the thick ascending limb of the loop of henle .
bs type i is caused by loss - of - function mutations of slc12a1 encoding the apical sodium - potassium - chloride cotransporter ( nkcc2 ) , while bs type ii is caused by loss - of - function mutations of kcnj1 encoding the apical inwardly - rectifying potassium channel ( romk ) , bs type iii is caused by loss - of - function mutations of clcnkb encoding the basolateral chloride channel ( clc - kb ) , bs type iv is caused by loss - of - function mutations of bsnd encoding barttin , and bs type v is caused by gain - of - function mutations of casr encoding the basolateral calcium sensing receptor ( casr)2 ) .
bs is an inherited tubular disorder ; however , our patient developed fsgs , an acquired glomerular lesion , later in the disease course .
there have been five similar case reports of bs complicated by fsgs3 - 7 ) ( table 1 ) .
in addition , there is an additional report of a patient with classic bs who developed end - stage renal disease due to glomerulopathy12 ) .
however , this patient was excluded from the review because the renal pathology was described as ' diffuse ' glomerulosclerosis . as shown in table 1 ,
patients with bs and fsgs show development of fsgs independently of gender , clinical variants of bs or genetic subtypes of bs .
one patient had nephrocalcinosis , and three patients had a history of long - term non - steroidal anti - inflammatory drug treatment prior to the onset of proteinuria .
three patients had progressed to chronic renal failure , but the rate of progression was variable .
one other patient revealed mildly decreased renal function one year after diagnosis with fsgs5 ) .
normal renal function was maintained in the remaining two patients , and , interestingly , proteinuria resolved completely in one of these patients after one year treatment with potassium supplements , spironolactone , and indomethacin3 ) .
the renal pathologic findings were described in detail in three cases , two of which had perihilar type fsgs .
the perihilar variant is common in patients with secondary forms of fsgs mediated by glomerular hyperfiltration or other adaptation after loss of renal mass8 , 16 ) .
these findings suggest that fsgs complicated by bs may be a secondary lesion due to adaptive response to chronic hyperfiltration by chronic salt - loss and resultant chronic stimulation of the renin - angiotensin system .
several case reports of gitelman syndrome complicated by fsgs support this explanation17 , 18 ) .
case reports of patients with bs who underwent renal transplantation are also rare , and the causes of esrd include progression of fsgs or other causes including complication of long - term non - steroidal anti - inflammatory drug treatment6 , 12 - 15 ) . in one of the patients , pre - emptive bilateral native nephrectomies and renal transplantation were conducted prior to the onset of esrd due to severe , clinically brittle , neonatal bs15 ) . in all of the cases ,
transplantation was successful and bs disappeared completely after transplantation as shown in our patient . in summary , bs may be complicated by fsgs due to adaptive response to chronic salt - losing nephropathy , and fsgs may cause esrd in some patients .
 bartter syndrome ( bs ) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting , hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism . 
 there have been several case reports of bs complicated by focal segmental glomerulosclerosis ( fsgs ) . here 
 , we have reported the case of a bs patient who developed fsgs and subsequent end - stage renal disease ( esrd ) and provided a brief literature review . 
 the patient presented with classic bs at 3 months of age and developed proteinuria at 7 years . 
 renal biopsy performed at 11 years of age revealed a fsgs perihilar variant . 
 hemodialysis was initiated at 11 years of age , and kidney transplantation was performed at 16 years of age . 
 the post - transplantation course has been uneventful for more than 3 years with complete disappearance of bs without the recurrence of fsgs . 
 genetic study revealed a homozygous p.trp(tgg)610stop(tga ) mutation in the clcnkb gene . in summary , 
 bs may be complicated by secondary fsgs due to the adaptive response to chronic salt - losing nephropathy , and fsgs may progress to esrd in some patients . 
 renal transplantation in patients with bs and esrd results in complete remission of bs . 