we present here a case of hereditary adamts 13 deficincy presenting as recurrent acute kidney injury .
a 26-year - old male presented with history of decreased urine output , red urine for past 7 days following an episode of upper respiratory tract infection .
there was no history of edema , hypertension , flank pain , fever , and jaundice . on examination , he was conscious and alert , with pulse rate of 86 beats per minutes , blood pressure of 122/76 mmhg with no postural drop .
general physical examination was remarkable for pallor and petechial rash over lower limbs with no evidence of icterus , lymphadenopathy .
there was no hepatosplenomegaly , chest was clear to auscultation , and heart sounds were normal .
laboratory evaluation showed anemia ( hb 7.2 g / dl ) with reticulocytosis ( 7% ) thrombocytopenia ( platelet 52000 / mm ) , azotemia ( blood urea nitrogen 56 mg / dl , creatinine 5.2 mg / dl ) .
transaminases , protrombin time , and bilirubin were normal . bleeding time , clotting time , and activated partial thromboplastin time was normal .
ldh was elevated to 1540 ; serum haptaglobin was depressed to < 7.62 ( normal 30200 mg/ dl ) serum creatinine rose up to 8.8 mg / dl .
considering the diagnosis of thrombotic microangiopathy , therapy with plasmapheresis was planned but deferred as patient went into diuretic phase on the third day of illness and creatinine started declining returning to 1.5 mg / dl at day 7 . however , during follow up the persistent subnephrotic range proteinuria ( 2 - 2.5 gm / day ) , hypertension , and elevated creatinine ( 1.51.6 mg / dl ) was noted . in view of proteinuria and hypertension
patient 's past medical history was remarkable for episodes of passing red urine associated with renal failure , low platelet count , and anemia .
first , such episode was at the age of 8 years in year 1993 , associated with chicken pox that required hospitalization for approximately 2 weeks .
peritoneal dialysis was performed for 48 h after which patient had a complete recovery of the renal function .
hemoglobin had dropped to 5.7 gm requiring blood transfusion and thrombocytopenia was also noted ( platelet count 52000 ) .
recurrence of this episode occurred six times before current admission ( year 1993 , 2002 , 2003 , 2005 , 2006 , and 2009 ) ; all the three episodes were characterized by anemia , variable degree of azotemia , thrombocytopenia , and self - resolving course .
none of these episodes of aki required renal replacement therapy . in between the episodes , hemoglobin remained normal but platelet count remained low [ table 1 ] .
considering the presence of microangiopathic hemolytic anemia , thrombocytopenia , and renal failure diagnosis of recurrent aki due to tma was made .
possibility of atypical hus was investigated further with serum levels of ch 50 , complement factor h , i and mcp - all four were within the normal limits .
patient was further evaluated with level of adamts 13 ; which turned out to be very low ( less than 7%-significant deficiency is considered when the level is less than 10% ) . genetic analysis to evaluate congenital deficiency of complement pathway regulatory proteins was performed .
sequencing of scr20 of factor h ( scr20 is the hot - spot mutation region of factor h ) , scrs 1 - 4 of mcp gene ( scrs 14 are the hot - spot mutation region of mcp ) , and 13 exons of factor i gene showed no mutation in the hotspot region .
analysis by sequencing all 29 exons of adamts13 gene showed heterozygous mutation in exon 26 ( the nucleotide change 3655c > t that causes the amino acid change r1219w ) . during the molecular screening of adamts13 gene ,
a homozygous variation of adamts13 gene has been also found in the intron 8 ( 987 + 69a > c ) , but without a pathogenetic significance .
the results obtained suggest that our patient is affected by a congenital deficiency of adamts13 , determined by a heterozygous mutation of adamts13 gene .
patient showed a good response to plasma therapy in the form of normalization of platelet count ( 2.4 lac in last follow up ) , stabilization of serum creatinine to 1.4 mg / dl .
von willebrand factor ( vwf)-cleaving protease activity , or  a disintegrin and metalloprotease , with thrombospondin-1-like domains  ( adamts-13 ) is a plasma metalloprotease that cleaves vwf multimers after excretion by endothelial cells . in its absence , large vwf multimers ,
congenital adamts 13 deficiency is classically associated with inherited ttp with characteristic neurologic features , this is the first report of it presenting as recurrent acute renal failure ( without neurological features ) and later followed by hypertension , proteinuria and chronic renal insufficiency .
this is also the first report of successful use of regular plasma infusion in this setting .
although liver is the primary site for adamts 13 synthesis , local synthesis of this factor has been demonstrated in kidney which may explain kidney specific manifestations of the disease in some cases .
heterozygous mutation in exon 26 causing very low levels of adamts 13 was responsible for recurrent renal failure in our case .
this mutation has been described as a cause of adamts 13 deficiency in patients with ttp .
after repeated episodes of acute kidney injury our patient started developing chronic renal insufficiency as manifested by new onset hypertension , proteinuria and azotemia . curiously replenishing deficient adamts 13 by institution of regular monthly plasma infusions
not only prevented further aki episodes but also led to control of proteinuria , hypertension and stabilization of renal function . if adamts 13 deficiency can cause chronic kidney disease as evident in our case and in one recent case report ; it will be interesting to explore the adamts 13 deficiency as a cause of chronic kidney disease where etiology is not obvious . to conclude
, we have described a case of hereditary adamts 13 deficiency with only renal involvement at presentation ( without neurological manifestations ) in the form of recurrent aki- with hypertension , proteinuria and chronic renal insufficiency developing in long run .
 we report here a case of 26-year - old male who presented with history of recurrent acute renal failure associated with microangiopathic hemolytic anemia and thrombocytopenia . 
 adamts 13 deficiency due to mutation in the gene encoding for adamts 13 was identified as the cause . 
 after eight episodes of acute kidney injury ( aki ) , patient started developing hypertension , proteinuria , and renal insufficiency . 
 treatment with regular monthly plasma infusions prevented further episodes of aki and stabilized the renal function . 
 hypertension and proteinuria are controlled with angiotensin ii receptor blockers . 
Introduction
Case Report
Discussion