Rus v. Secretary of Health and Human Services

In the United States Court of Federal Claims

No 12-631V

Filed Under Seal: December 8, 2016

Reissued for Publication: January 2, 2017*

)

GRZEGORZ RUS and AGNIESZKA )

RUS, as Parents and Natural Guardians of )

A.R., a minor, )

) National Childhood Vaccine Injury Act

Petitioners, ) (“Vaccine Act”), 42 U.S.C. § 300aa–1 to

) –34 (2012).

v. )

)

SECRETARY OF HEALTH AND )

HUMAN SERVICES, )

)

Respondent. )

)

Kate Gerayne Westad, Larkin Hoffman Daly & Lindgren Ltd., Minneapolis, MN, for

petitioners.

Amy Kokot, Trial Attorney, Heather L. Pearlman, Assistant Director, Catharine E.

Reeves, Acting Deputy Director, C. Salvatore D’Alessio, Acting Director, and Benjamin C.

Mizer, Principal Deputy Assistant Attorney General, Torts Branch, Civil Division, United States

Department of Justice, Washington, DC, for respondent.

MEMORANDUM OPINION AND ORDER

GRIGGSBY, Judge

I. INTRODUCTION

Petitioners, Grzegorz and Agnieszka Rus, parents of A.R., a minor child, seek review of

the June 23, 2016, decision of the special master denying their claim for compensation under the

National Childhood Vaccine Injury Act (“Vaccine Act”), 42 U.S.C. § 300aa–1 to –34 (2012).

*

This Memorandum Opinion and Order was originally filed under seal on December 8, 2016 (docket

entry no. 90). The parties were given an opportunity to advise the Court of their views with respect to

what information, if any, should be redacted. The parties filed a joint status report on December 30,

2016, notifying the Court that they do not believe any information should be redacted (docket entry no.

92). And so, the Court is reissuing its Memorandum Opinion and Order dated December 8, 2016 without

redactions.

Petitioners allege that their minor child suffers from nephrotic syndrome, resulting from a

hepatitis A vaccination that she received on October 30, 2009. For the reasons set forth below,

the Court DENIES petitioners’ motion for review and SUSTAINS the decision of the special

master.

II. FACTUAL AND PROCEDURAL BACKGROUND1

A. Factual Background

1. A.R.’s Medical History

The medical history of petitioners’ daughter, A.R., is discussed in detail in the special

master’s June 23, 2016, decision (“Special Master’s Decision”) and can be briefly summarized

here. Rus v. Sec’y of Health & Human Servs., No. 12-631V, 2016 WL 4013709 (Fed. Cl. Spec.

Mstr. June 23, 2016). A.R. was born on August 31, 2006. Dec. at *2; Pet. Ex. 1 at 1. A.R. has

no family history of kidney or renal disease, or nephrotic syndrome. Dec. at *1; TR at 12.

Today, A.R. has nephrotic syndrome, defined by symptoms such as protein in the urine, low

blood protein levels, edema (swelling) and high cholesterol. TR at 46; Resp. Brief at n.2.

On October 30, 2009, A.R. visited her pediatrician for her 3-year well-child visit, where

she was noted to be a healthy child that was developing normally. Dec. at *1; TR at 30-32.

During this visit, A.R. received her first hepatitis A vaccination. Dec. at *1; TR at 32; Pet. Ex. 2

at 1.

On October 31, 2009, A.R. was taken to the hospital due to fever and a febrile seizure.

Dec. at *2; TR at 33-34, 40; Pet. Ex. 3 at 46. A.R.’s hospital records show that A.R. had a body

temperature of 104.1 F at the time, and that A.R. did not present with edema. Pet. Ex. 3 at 46;

TR at 39. The attending physician’s notes in A.R.’s hospital record for this visit state that “I

1

The facts recounted in this Memorandum Opinion and Order are taken from the special master’s April

25, 2016, decision in Rus v. Sec’y of Health & Human Servs., No. 12-631V, 2016 WL 4013709 (Fed. Cl.

Spec. Mstr. June 23, 2016) (“Dec.”); the transcript of the entitlement hearing before the special master

held on September 17, 2015 (“Tr.”); petitioners’ exhibits filed before the Office of Special Master (“Pet.

Ex.”); petitioners’ motion for review (“Pet. Mot.”); and respondent’s response to petitioners’ motion for

review (“Resp. Brief”). Except where otherwise noted, the facts recited herein are undisputed.

2

suspect that the child had a febrile seizure tonight, which was brought on by the fever, which is

likely secondary to her being vaccinated 2 days ago.” Pet. Ex. 3 at 46; see also Dec. at *2.

Laboratory results from tests done on November 1, 2009, show that A.R.’s albumin–a

blood protein that when low, indicates malnutrition, liver problems, or that the patient is spilling

protein into the urine–was normal. Dec. at *2; TR at 37-38; Pet. Ex. 12 at 3. In addition, these

tests show that A.R.’s total blood protein was slightly decreased, and her urine protein was

elevated. Dec. at *2; TR at 36; Pet. Ex. 12 at 3.

After being discharged from the hospital, A.R. visited her pediatrician on November 1,

2009. Dec. at *2. During this visit, A.R.’s pediatrician noted that A.R. had a wet cough and an

upper respiratory infection. Id. On November 4, 2009, A.R. visited her pediatrician again. Id.;

TR at 42. During this subsequent visit, A.R.’s pediatrician observed that A.R. had facial

swelling. Dec. at *2. During this visit, A.R.’s pediatrician performed laboratory tests which

showed decreased albumin, decreased total blood protein, marked proteinuria2, high triglycerides

and high cholesterol. Id.; Pet. Ex. 3 at 79. It is undisputed in this matter that A.R. suffered from

diagnosable nephrotic syndrome at the time of her November 4, 2009, visit to the pediatrician.

Dec. at *8; Pet. Mot. at 10-11; TR at 47-50.

A.R. subsequently visited her pediatrician on November 5, 2009, and November 9, 2009.

Dec. at *2. During these visits, the pediatrician observed that A.R.’s facial swelling had

decreased and that she seemed to be recovering. Id. On November 11, 2009, A.R. visited a

nephrologist, Dr. Jeff Stein. TR at 171.

In January 2010, A.R.’s nephrotic syndrome went into remission. Pet. Ex. 4 at 8.

However, A.R. has experienced at least two relapses of these symptoms since that time. Dec. at

*2.

2

Proteinuria is the “[p]resence of urinary protein in amounts exceeding 0.3 g in a 24-hour urine collection

or in concentrations more than 1 g per liter in a random urine collection on two or more occasions at least

6 hours apart.” Stedman’s Medical Dictionary 730680 (updated Nov. 2014).

3

2. Nephrotic Syndrome

Nephrotic syndrome is a kidney disorder that causes, among other things, the body to

excrete too much protein into the urine. TR at 46. Nephrotic syndrome commonly involves

symptoms such as protein in the urine, low blood protein levels, edema and high cholesterol. TR

at 46; Resp. Ex. A at 2, 6.

When a person suffers from nephrotic syndrome, a breakdown in the kidney’s ability to

keep proteins in the blood and out of the urine occurs. TR at 76-78. In this regard, the

glomerular basement membrane (“GBM”) in the kidneys is responsible for keeping blood out of

the urine. Id. at 72, 76. The GBM is comprised of several different types of cells, including

podocytes and foot processes. Id. at 76–77.

3. The Entitlement Hearing

On September 25, 2012, petitioners filed a petition for vaccine compensation on behalf of

A.R. under the Vaccine Act. Dec. at *1; see generally Pet. Petition. The special master

convened an entitlement hearing on petitioners’ claim for compensation under the Vaccine Act

on September 17, 2015. Dec. at *1; see generally TR.

During the entitlement hearing, Agnieszka Rus and petitioners’ medical expert, Dr. Jan T.

Kielstein, testified on behalf of the petitioners. See generally TR. The government’s medical

expert, Dr. Bernard S. Kaplan, testified on behalf of the respondent. Id.

Ms. Rus testified that A.R. was a healthy, lively child prior to October 30, 2009. Id. at 9.

Ms. Rus further testified that A.R. did not have a family history of nephrotic syndrome. Id. at

12.

Dr. Kielstein is currently an Associate Professor of Medicine at the Department of

Internal Medicine in the Division of Nephrology and Hypertension at the Medical School in

Hannover, Germany. Pet. Ex. 13 at 1. During the entitlement hearing, Dr. Kielstein opined that

the hepatitis A vaccination caused A.R.’s nephrotic syndrome. TR at 86-87. Dr. Kielstein also

put forward two medical theories to support this opinion: (1) a specific T-cell response (the “T-

cell medical theory”) and (2) an inflammatory cykotine response to the vaccination that alters a

unspecific pathway involving angiopoietin-like 4 (“ANGPTL4 medical theory”). Id. at 72-86.

With respect to the T-cell medical theory, Dr. Kielstein testified that all vaccinations are

intended to cause an adaptive immune response, and this response occurs primarily in the T-cells

in the case of the hepatitis A vaccine. TR at 115; Dec. at *10. And so, he theorized that

nephrotic syndrome could be caused by a T-cell response to the vaccination, whereby T-cell

dysfunction results in the production of a circulating glomerular permeability factor. Pet. Ex. 12

at 5. Dr. Kielstein also theorized that the circulating glomerular permeability factor could

“directly induce[ ] foot process fusion resulting in severe alteration of the glomerular filter

system and resulting in marked proteinuria.” Id.; see also TR at 86.

With respect to the timing associated with the T-cell medical theory, Dr. Kielstein also

testified that “we need more than a day or two for a T-cell response, and so the lowest time span

we are talking about here is about four days.” TR at 75. He acknowledged, however, that A.R.’s

nephrotic syndrome symptoms began 36-40 hours after vaccine. Id. at 49, 73-75, 107, 116.

With respect to the ANGPTL4 medical theory, Dr. Kielstein testified that ANGPTL4 is

analogous to barbed wire that covers a fence–in this case, the GBM–to help keep proteins out of

the urine. Id. at 77. Dr. Kielstein theorized that any vaccination could cause an inflammatory

response in the body that alters the production of ANGPTL4. Id. at 80-84. Specifically, Dr.

Kielstein testified that such inflammatory response may cause overproduction of a form of

ANGPTL4 lacking sialic acid residues would cause binding of ANGPTL4 to the glomerular

basement membrane, thereby inducing the development of nephrotic-range proteinuria. TR at

81-92; see also Dec. at *9; Pet. Mot. at 13-14.

In addition, to support his theory that vaccinations set off an inflammatory response that

may cause nephrotic syndrome, Dr. Kielstein offered anecdotal case reports and medical studies

finding that the meningococcal and hepatitis B vaccinations may cause relapses in cases of

established nephrotic syndrome. Pet. Ex. 15, 25. He also put forward case reports showing that

certain vaccinations, other than the hepatitis A vaccine, may cause other diseases or syndromes,

one case report demonstrating that nephrotic syndrome occurred after a hepatitis B vaccination, a

case report demonstrating that the hepatitis A vaccine allegedly caused autoimmune hepatitis and

A.R.’s medical history from October 30, 2009, onward. Pet. Ex. 12, 16-20, 22-24, 26-27. Dr.

Kielstein acknowledged, however, that he was not aware of any cases demonstrating that the

hepatitis A vaccination caused nephrotic syndrome. TR at 118.

5

Dr. Kielstein also relied upon two 2014 medical studies−Lionel C. Clement et al.,

Circulating Angiopoietin–Like 4 Links Proteinuria With Hypertriglyceridemia in Nephrotic

Syndrome, 20 Nature Medicine 37 (2014) and Sumant S. Chugh, et al., Angiopoietin–Like 4

Based Therapeutics for Proteinuria and Kidney Disease, 5 Frontiers in Pharmacology 23/1

(2014)−to support the ANGPTL4 medical theory. Dec. at *10; Pet. Ex. 34, 35. The Clement

study demonstrates that the manipulation of a certain type of ANGPTL4 is an important mediator

of nephrotic syndrome and a critical link between proteinuria and hypertriglyceridemia. Pet. Ex.

34. The Chugh study demonstrates that the manipulation of a certain type of ANGPTL4 may

improve proteinuria. Pet. Ex. 35.

The government’s medical expert, Dr. Bernard Kaplan, testified that he did not find any

evidence in the record that the hepatitis A vaccination that A.R. received on October 30, 2009,

contributed to her nephrotic syndrome.4 TR at 131. In this regard, Dr. Kaplan testified that there

is no medical literature showing that the hepatitis A vaccine precipitates nephrotic syndrome. Id.

at 132. He also offered an opinion about the medical literature relied upon by the petitioners to

support their T-Cell and ANGPTL4 medical theories. Dr. Kaplan also testified that there is no

medical literature showing that vaccines affect ANGPTL4 production. Id. at 143-44. Dr. Kaplan

further testified that there are “gaping holes” in the T-cell medical theory. Id. at 146-47; Resp.

Ex. C at 2.

Dr. Kaplan also opined that, if nephrotic syndrome was caused by an inflammatory

response to any vaccination as the petitioners suggests, diagnoses of nephrotic syndrome should

have risen over the past 50 years, as vaccinations have increased during this time period. TR at

149-50. He noted, however, that diagnoses of nephrotic syndrome have remained “absolutely

constant.” Id. at 132. And so, Dr. Kaplan concluded that the case reports and medical literature

cited by Dr. Kielstein do not demonstrate that the hepatitis A vaccination is linked to the new-

onset nephrotic syndrome. Id. at 160-61.

3

Dr. Kaplan is a pediatric nephrologist in the Division of Nephrology in the Children’s Hospital of

Philadelphia. Resp. Ex. B at 2.

6

4. The Special Master’s Decision

On June 23, 2016, the special master issued a decision denying petitioners’ claim for

compensation under the Vaccine Act. See generally Dec. In the decision, the special master

determined that petitioners had failed to prove by preponderant evidence that the hepatitis A

vaccination caused A.R.’s nephrotic syndrome under Althen Prong I. Id. at *1; see Althen v.

Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005).

As an initial matter, the special master addressed the legal standard petitioners are

required to meet to receive compensation under the Vaccine Program. Dec. at *3. Specifically

relevant here, the special master determined that petitioners were required to prove each Althen

prong by preponderant evidence, including Althen Prong I which requires petitioners to provide

“a medical theory causally connecting the vaccination and the injury.” Id. (citing Althen, 418

F.3d at 1278). The special master also determined that, in presenting a theory causally

connecting the vaccination and the injury, “a claimant need not produce medical literature or

epidemiological evidence to establish causation under the Vaccine Act. . . .” Id. at *4. But, the

special master determined that petitioners’ causation theory must be supported by a “‘sound and

reliable’ medical or scientific explanation.” Id. at *7 (quoting Knudsen ex rel. Knudsen v. Sec’y

of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994)).

Applying the aforementioned standard, the special master determined that the petitioners

had met their burden of proof with respect to Althen Prongs II and III, but that the petitioners

failed to meet their burden with respect to Althen Prong I. Id. at *9, 12. In reaching this

conclusion, the special master found that:

In determining whether petitioner is entitled to compensation, a special master must

consider the entire record and is not bound by any particular piece of evidence.

§ 13(b)(1) (stating a special master is not bound by any “diagnosis, conclusion,

judgment, test result, report, or summary” contained in the record). Thus a special

master must weigh and evaluate opposing expert opinions, medical and scientific

evidence, and the evidentiary record in deciding whether petitioners have met their

burden of proof.

Id. at *4.

To determine whether petitioners had met their burden with respect to Althen Prong I, the

special master reviewed petitioners’ two medical causation theories, the T-cell medical theory

7

and the ANGPTL4 medical theory. The special master characterized petitioners’ T-cell medical

theory as proposing that nephrotic syndrome:

[C]ould be caused by a “specific” T-cell response to vaccination where systemic T-

cell dysfunction results in the production of a circulating glomerular permeability

factor, which directly induces podocyte foot process fusion. . . . The foot process

fusion would severely alter the glomerular filter system, resulting in proteinuria.

Id. at *5. To that end, the special master also found that the timing of the T-cell medical theory

put forward by Dr. Kielstein did not comport with the progression of A.R.’s symptoms. Id. at

*8.

In this regard, the special master noted that Dr. Kielstein testified that a T-cell response to

a vaccination would take about four days. Id. (citing TR at 75). But, the special master also

noted that Dr. Kielstein testified that the likely onset of A.R.’s nephrotic syndrome occurred

within 36 to 40 hours of the vaccination. Id. at *12 (citing TR at 73-75).

The special master also considered the petitioners’ ANGPTL4 medical theory, and he

noted that Dr. Kielstein offered anecdotal case reports, medical studies finding that the

meningococcal and hepatitis B vaccinations may cause relapses in cases of established nephrotic

syndrome, case reports showing that certain vaccinations other than hepatitis A may cause other

diseases or syndromes, one case report demonstrating that the hepatitis A vaccine allegedly

caused autoimmune hepatitis, and A.R.’s own medical progression from October 30, 2009

onward, to support this theory. Dec. at *6, 11. The special master also noted that, during the

entitlement hearing, Dr. Kielstein admitted he was not aware of any cases demonstrating that the

hepatitis A vaccination caused nephrotic syndrome. Id. at *6; TR at 118.

With respect to the Clement medical study that the petitioners put forward to support

their ANGPTL4 medical theory, the special master determined that “the Clement study appeared

to demonstrate that enhancement of ANGPTL4 reduced existing proteinuria, but did not address

how the ANGPTL4 may have been altered in the podocytes in the first place, leading to the onset

of the disease.” Dec. at *12 (citing Pet. Ex. 34).

The special master also determined that “[w]hile innate or inflammatory disruption of the

angiopoietin-like 4 pathway may, at some point, prove to be a viable theory, at the present time it

appears to be a bridge too far, too vague and too uncertain in terms of the triggering mechanism

8

and sequence of the events in this case.” Id. And so, the special master concluded that Dr.

Kielstein:

[A]cknowledged that there remains great mystery in the understanding of the

causation of this disease. Without an understanding of the causation of the disease,

it is not possible to come to a conclusion about vaccine causation or causation by a

specific vaccine such as a hepatitis A.

Id.

And so, on June 23, 2016, the special master issued a decision denying petitioners’

request for compensation. See generally Dec. Petitioners, alleging error, seek review of the

Special Master’s Decision.

B. Procedural Background

On June 22, 2016, petitioners filed a motion for review of the Special Master’s Decision.

See generally Pet. Mot. The government filed a response to petitioners’ motion for review on

August 22, 2016. See generally Resp. Brief. Petitioners’ motion for review having been fully

briefed, the Court resolves the pending motion.

III. STANDARDS FOR DECISION

A. Standard Of Review

The United States Court of Federal Claims has jurisdiction to review the record of the

proceedings before a special master and, upon such review, may:

(A) uphold the findings of fact and conclusions of law of the special master and

sustain the special master’s decision,

(B) set aside any findings of fact or conclusions of law of the special master found

to be arbitrary, capricious, an abuse of discretion, or otherwise not in accordance

with law and issue its own findings of fact and conclusions of law, or

(C) remand the petition to the special master for further action in accordance with

the court’s direction.

42 U.S.C. § 300aa–12(e)(2).

The special master’s determinations of law are reviewed de novo. Andreu ex rel. Andreu

v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1373 (Fed. Cir. 2009). The special master’s

findings of fact are reviewed for clear error. Id.; see also Broekelschen v. Sec’y of Health &

9

Human Servs., 618 F.3d 1339, 1345 (Fed. Cir. 2010) (“We uphold the special master’s findings

of fact unless they are arbitrary or capricious.”) (citation omitted). In addition, a special master’s

findings regarding the probative value of the evidence and the credibility of witnesses will not be

disturbed so long as they are “supported by substantial evidence.” Doe v. Sec’y of Health &

Human Servs., 601 F.3d 1349, 1355 (Fed. Cir. 2010) (citation omitted); see also Burns v. Sec’y

of Health & Human Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (holding that the decision of

whether to accord greater weight to contemporaneous medical records or later given testimony is

“uniquely within the purview of the special master”). This “level of deference is especially apt

in a case in which the medical evidence of causation is in dispute.” Hodges v. Sec’y of Health &

Human Servs., 9 F.3d 958, 961 (Fed. Cir. 1993). And so, the Court will “not substitute its own

judgment for that of the special master if the special master has considered all relevant factors,

and has made no clear error of judgment.” Lonergan v. Sec’y of Health & Human Servs., 27

Fed. Cl. 579, 580 (1993).

B. Vaccine Injury Claims

Pursuant to the Vaccine Act, the Court shall award compensation if a petitioner proves,

by a preponderance of the evidence, all of the elements set forth in 42 U.S.C. § 300aa–11(c)(1),

unless there is a preponderance of evidence that the illness is due to factors unrelated to the

administration of the vaccine. 42 U.S.C. § 300aa–13(a)(1). A petitioner can recover either by

proving an injury listed on the Vaccine Injury Table (“Table”), or by proving causation-in-fact.

See 42 U.S.C. §§ 300aa–11(c)(1)(C); Althen, 418 F.3d at 1278. And so, to receive compensation

under the National Vaccine Injury Compensation Program, a petitioner must prove either that:

(1) the petitioner suffered a “Table Injury” that corresponds to one of the vaccinations in

question within a statutorily prescribed period of time or, in the alternative, (2) the petitioner’s

illnesses were actually caused by a vaccine. See 42 U.S.C. §§ 300aa–13(a)(1)(A), 300aa–

11(c)(1)(C)(i-ii), 300aa–14(a); see also Moberly v. Sec’y of Health & Human Servs., 592 F.3d

1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec’y of Health & Human Servs., 440 F.3d 1317, 1320

(Fed. Cir. 2006).

In addition, in Table and non-Table cases, a petitioner bears a “preponderance of the

evidence” burden of proof. 42 U.S.C. §§ 300aa–13(a)(1)(A); Althen, 418 F.3d at 1278 (citing

Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)). And so,

10

a petitioner must offer evidence that leads the “trier of fact to believe that the existence of a fact

is more probable than its nonexistence before [he] may find in favor of the party who has the

burden to persuade the [judge] of the fact’s existence.” Moberly, 592 F.3d at 1322 n.2 (brackets

existing) (internal quotation omitted); see also Snowbank Enter. v. United States, 6 Cl. Ct. 476,

486 (1984) (holding that mere conjecture or speculation is insufficient under a preponderance

standard).

To establish a prima facie case when proceeding on a causation-in-fact theory, as

petitioners seek to do in this matter, a petitioner must “prove, by a preponderance of the

evidence, that the vaccine was not only a but-for cause of the injury but also a substantial factor

in bringing about the injury.” Shyface, 165 F.3d at 1352. “[T]o show that the vaccine was a

substantial factor in bringing about the injury, the petitioner must show ‘a medical theory

causally connecting the vaccination and the injury.’” Id. at 1352-53 (quoting Grant v. Sec’y of

Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992) (per curiam)). In other words,

“[t]here must be a ‘logical sequence of cause and effect showing that the vaccination was the

reason for the injury,’” id. at 1353 (quoting Grant, 956 F.2d at 1148), and “[t]his ‘logical

sequence of cause and effect’ must be supported by a sound and reliable medical or scientific

explanation.” Knudsen, 35 F.3d at 548 (quoting Jay v. Sec’y of Health & Human Servs., 998

F.2d 979, 984 (Fed. Cir. 1993)); see also 42 U.S.C. § 300aa–13(a)(1) (“The special master or

court may not make such a finding based on the claims of a petitioner alone, unsubstantiated by

medical records or by medical opinion.”). However, medical or scientific certainty is not

required. Knudsen, 35 F.3d at 548-49.

In Althen, the Federal Circuit addressed the three elements that a petitioner must provide

to prove causation-in-fact:

(1) a medical theory causally connecting the vaccination and the injury; (2) a

logical sequence of cause and effect showing that the vaccination was the

reason for the injury; and (3) a showing of a proximate temporal relationship

between vaccination and injury.

Althen, 418 F.3d at 1278. All three prongs “must cumulatively show that the vaccination was a

‘but-for’ cause of the harm, rather than just an insubstantial contributor in, or one among several

possible causes of, the harm.” Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355

(Fed. Cir. 2006). In addition, if a petitioner establishes a prima facie case, the burden shifts to

11

the respondent to show, by a preponderance of the evidence, that the injury was caused by a

factor unrelated to the vaccine. See 42 U.S.C. § 300aa–13(a)(1)(B); Shalala, 514 U.S. at 270-71.

But, regardless of whether the burden of proof ever shifts to the respondent, the special master

may consider the evidence presented by the respondent in determining whether the petitioner has

established a prima facie case. See Stone v. Sec’y of Health & Human Servs., 676 F.3d 1373,

1379 (Fed. Cir. 2012) (“[E]vidence of other possible sources of injury can be relevant not only to

the ‘factors unrelated’ defense, but also to whether a prima facie showing has been made that the

vaccine was a substantial factor in causing the injury in question.”); de Bazan v. Sec’y of Health

& Human Servs., 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is

permitted to offer evidence to demonstrate the inadequacy of the petitioner’s evidence on a

requisite element of the petitioner’s case[-]in-chief.”).

IV. LEGAL ANALYSIS

Petitioners enumerate three objections to the special master’s decision. See generally Pet.

Mot. First, petitioners argue that the special master erred as a matter of law by holding

petitioners to a higher burden of proof than required under the Vaccine Act to prove the causal

relationship between the vaccination and the injury under Althen Prong I. Pet. Mot. at 2, 17.

Second, petitioners argue that the special master “failed to consider the medical and scientific

evidence contained in the record as a whole” in evaluating their claim under the first prong of

Althen. Id. at 2. Finally, petitioners also argue that the special master erred in finding that

petitioners’ expert, Dr. Kielstein, testified that there was “great mystery in the understanding of

the causation of” nephrotic syndrome. Id. at 3 (quoting Dec. at *12).

The government counters that the special master’s decision to deny compensation in this

case is reasonable, in accordance with law and supported by the record evidence. See generally

Resp. Brief. For the reasons discussed below, the Court agrees. And so, the Court SUSTAINS

the decision of the special master.

A. The Special Master Applied The Correct Burden Of Proof

As an initial matter, the record demonstrates that the special master correctly applied the

law in determining the burden of proof that petitioners must meet to satisfy the medical theory

prong of Althen. In their motion for review, petitioners argue that the special master imposed too

high of a burden of proof on petitioners to prove “a medical theory causally connecting the

12

vaccination and the injury.” Pet. Mot. at 2; 15 (citing Althen, 418 F.3d at 1278). The Court

reviews the special master’s determination of law de novo. Andreu, 569 F.3d at 1373.

The record evidence shows that the special master correctly applied the burden of proof

for petitioners’ vaccine injury claim. In his decision, the special master determined that

petitioners were required to prove each prong under the Federal Circuit’s decision in Althen v.

Secretary of Health and Human Services by a preponderance of the evidence. Dec. at *7 (citing

Althen, 418 F.3d at 1278). The special master also determined that, in putting forth their theory

causally connecting the vaccination and the injury the petitioners “need not produce medical

literature or epidemiological evidence to establish causation under the Vaccine Act.” Id. at *4.

In addition, the special master concluded that petitioners’ medical theories in this case must be

supported by a “‘sound and reliable’ medical or scientific explanation” under Althen Prong I. Id.

at *7 (quoting Knudsen, 35 F.3d at 548).

The special master’s decision correctly states the legal standard under the Federal

Circuit’s decision in Althen. Althen, 418 F.3d at 1278. And so, the special master did not err as

a matter of law in determining the burden of proof for the petitioners’ claim in this action.

The record evidence also shows that the special master correctly applied this burden of

proof to the medical theories put forward by the petitioners to support their vaccine injury claim.

In this regard, the special master determined that petitioners’ T-cell medical theory−that

nephrotic syndrome could be caused by a T-cell response to the vaccination−did not fit within

the timeline that the petitioners’ medical expert identified for the onset of A.R.’s symptoms.

Dec. at *12. Specifically, Dr. Kielstein testified during the entitlement hearing that it would take

approximately four days for a T-cell reaction to occur after a vaccination. Id. (citing TR at 73-

75). But, as the special master noted in his decision, Dr. Kielstein acknowledged in his

testimony that A.R.’s nephrotic syndrome symptoms first occurred just 36-40 hours after A.R.

received the hepatitis A vaccination. Id.

Given this, the special master appropriately determined that petitioners had not shown, by

a preponderance of the evidence, that their T-cell medical theory could causally connect the

hepatitis A vaccination that A.R. received on October 30, 2009 to the onset of A.R.’s nephrotic

syndrome. Id. at *8, 12. And so, the special master did not err as a matter of law in reaching this

conclusion.

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The special master also properly applied the legal standard under Althen in considering

the petitioners’ ANGPTL4 medical theory. In this regard, the record evidence shows that the

special master determined that the medical literature upon which the petitioners relied to support

this medical theory did not link any vaccines to dysfunction in the ANGPTL4. Id. at *11. The

special master also noted that the government’s expert, Dr. Kaplan, testified that “in spite of

“hundreds of millions of vaccines” administered worldwide over the last 50 years,” the

prevalence of nephrotic syndrome has remained “absolutely constant.” Dec. at *11 (quoting TR

at 132). And so, the special master concluded that the absence of a correlation between the

increase in the number of vaccinations and the prevalence of nephrotic syndrome cast doubt

upon the petitioners’ ANGPTL4 medical theory. Dec. at *11.

Given the lack of evidence to support either of petitioners’ medical theories, the special

master found that “[t]he bigger problem is that there seems to be a genuine lack of understanding

about the cause of this disease entity among nephrologists even though nephrotic syndrome has

been studied for many years.” Id. And so, the special master reasonably concluded there was

insufficient evidence for the petitioners to meet their burden of proof under Althen Prong I. Id. at

*12.

B. The Special Master Appropriately Considered

The Medical And Scientific Evidence In The Record

Petitioners’ argument that the special master erred by failing to consider the medical and

scientific evidence contained in the record is similarly unsupported by the evidence. Pet. Mot. at

2. As discussed above, the special master’s findings of fact are reviewed for clear error. Andreu,

569 F.3d at 1373; see also Broekelschen, 618 F.3d at 1345. In addition, the special master’s

findings regarding the probative value of the evidence and the credibility of witnesses will not be

disturbed so long as they are “supported by substantial evidence.” Doe, 601 F.3d at 1355

(citations omitted); see also Burns, 3 F.3d at 417.

The record evidence shows that special master properly considered the medical literature

relied upon by the petitioners in reaching his decision. Dec. at *11. In particular, the special

master specifically considered the Chugh medical study put forward by the petitioners, and the

special master noted in his decision that, “Chugh reported that “the central role played by

[angiopoietin-like 4] in nephrotic syndrome . . . suggests that manipulating [angiopoietin-like 4]

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related pathways in the context of therapeutics has a high chance of success.” Id. at *10 (citing

Pet. Ex. 35).

The special master also considered the Clement medical study, which the petitioners also

advanced to support their claim. In this regard, the special master acknowledged that the

Clement medical study “demonstrated that angiopoietin-like 4 is an important biological

mediator of nephrotic syndrome and is a critical link between proteinuria and

hypertriglyceridemia.” Id. at *10 (citing Pet. Ex. 34). The special master ultimately determined,

however, that neither the Clement nor the Chugh medical study linked the hepatitis A

vaccination−or any vaccine−to dysfunction in the ANGPTL4. Dec. at *11-12. And so, the

special master reasonably concluded that the medical literature relied upon by the petitioners did

not support their ANGPTL4 medical theory.

The record evidence also shows that the special master appropriately considered Dr.

Kielstein’s expert reports and testimony in support of the petitioners’ claim. See generally Dec.;

Pet. Mot. at 7-8; TR at 24-118; Pet. Ex. 14-20, 22-27, 32-35. For example, the special master

notes in his decision that Dr. Kielstein attempted to relate the medical theories discussed in the

Chugh and Clements medical studies to A.R.’s case in his testimony. Dec. at *11 (citing TR at

83).

With respect to the ANGPTL4 medical theory, the special master also notes in his

decision that Dr. Kielstein testified that the high fever that A.R. experienced during her October

31, 2009, visit to the emergency room suggested a cytokine response that could have been

secondary to the hepatitis A vaccine. Dec. at *11. The special master further notes, however,

that Dr. Kielstein testified that he did not know whether a cytokine response could have caused

A.R.’s symptoms, “because we are making the data, looking at that, and this is a very fascinating

field.” Id.; TR at 84. And so, the evidentiary record shows that the special master reasonably

concluded that Dr. Kielstein was unable to link the hepatitis A vaccination to A.R.’s nephrotic

syndrome. Dec. at *11.

In addition, the record evidence demonstrates that the special master considered the case

reports that the petitioners put forward to support their medical theories. Specifically, the special

master noted in his decision that Dr. Kielstein provided case reports demonstrating that vaccines

other than the hepatitis A vaccine may cause nephrotic syndrome. Dec. at *6; see also Pet. Ex.

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15-20, 22. The special master also noted in his decision that two of the case reports provided by

petitioners show that diseases other than nephrotic syndrome have occurred following

vaccinations other than the hepatitis A vaccination. Dec. at *6; see Pet. Ex. 23-24. But, as the

special master correctly concluded in his decision, none of these case reports show that the

hepatitis A vaccination causes nephrotic syndrome. Dec. at *6, 11; see also Pet. Ex. 15-20, 22-

24, 27.

Lastly, the record before the Court makes clear that the special master afforded

appropriate weight to all of the evidence discussed above. The special master notes in his

decision that Dr. Kielstein testified that “he was not aware of any case reports showing the

development of nephrotic syndrome following a Hep A vaccine, and he was not aware of any

medical literature where the authors assert a causal connection between Hep A and nephrotic

syndrome.” Id. at *6 (citing TR at 118). In addition, the special master noted that Dr. Kielstein

also testified that “the existing literature was a ‘low-quality database,’ as the studies are not

‘prospective, randomized studies.’” Id. (quoting TR at 65). Given Dr. Kielstein’s testimony, it

was certainly reasonable for the special master to afford limited weight to the medical literature

and case studies advanced by the petitioners. And so, the Court will not disturb the special

master’s findings regarding the probative value of this evidence. Doe, 601 F.3d at 1355.

In sum, given the evidence in the record, it is not surprising that the petitioners do not

point to any specific medical or scientific evidence that the special master failed to consider in

deciding their vaccine injury claim. See generally Pet. Mot. Nor do petitioners demonstrate that

the special master failed to properly weigh this evidence in reaching his decision on that claim.

And so, the evidentiary record here demonstrates that the special master did not err in

considering the medical and scientific evidence to support petitioners’ claim.

C. The Special Master Correctly Characterized Dr. Kielstein’s Testimony

As Conveying That The Cause Of Nephrotic Syndrome Remains Unknown

Lastly, petitioners’ final challenge–that the special master erred in characterizing Dr.

Kielstein’s testimony as conveying that there was “great mystery in the understanding of the

causation of [nephrotic syndrome]”–is equally without evidentiary support. Dec. at *12; Pet.

Mot. at 12-13.

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In this regard, the record evidence shows that Dr. Kielstein made several statements in his

expert reports and during his expert testimony that support the special master’s factual finding

that there is uncertainty about the causes of nephrotic syndrome. See TR; Pet. Ex. 12, 30, 31.

Specifically, the record before the Court shows that Dr. Kielstein states in his expert report dated

August 15, 2014, that “the exact underlying cause of [nephrotic syndrome] is not fully

understood.” Pet. Ex. 12. In his supplemental expert report, dated March 6, 2014, Dr. Kielstein

also states that “[u]nraveling the pathophysiology of minimal change nephritic [sic] syndrome is

an ongoing endeavor.” Pet. Ex. 30.

Dr. Kielstein expressed a similar view during the entitlement hearing. For example, the

following exchange occurred during Dr. Kielstein’s testimony about the petitioners’ ANGPTL4

medical theory:

THE COURT: And are you suggesting that the injury [the inflammatory response

to the vaccination] causes some loss of the angiopoietin-like 4?” . . .

DR. KIELSTEIN: “The question is can we, from the data we have, identify the

single mechanism that is – that is inducing that [the nephrotic syndrome]? I’m not

able to do that. What I am doing is to offer possible explanations. . . .”

TR at 80-81.

Dr. Kielstein’s own testimony and expert reports make clear that Dr. Kielstein

represented to the Court that the cause of nephrotic syndrome remains undetermined. Given this,

the special master did not err in characterizing Dr. Kielstein’s testimony as conveying that there

remains “great mystery in the understanding of the causation of this disease.” Dec. at *12. And

so, the Court will not set aside the findings of the special master.

V. CONCLUSION

In sum, the record evidence in this case demonstrates that petitioners have not

demonstrated that the special master erred in considering their vaccine injury claim. To the

contrary, the record evidence in this matter demonstrates that the special master’s decision was

reasonable, supported by the evidence and in accordance with law.

And so, for the foregoing reasons, the Court DENIES petitioners’ motion for review and

SUSTAINS the decision of the special master.

The Clerk is directed to enter judgment accordingly.

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Each party to bear their own costs.

Some of the information contained in this Memorandum Opinion and Order may be

considered privileged, confidential, or sensitive personally-identifiable information that should

be protected from disclosure. Accordingly, this Memorandum Opinion and Order shall be

FILED UNDER SEAL. The parties shall review the Memorandum Opinion and Order to

determine whether, in their view, any information should be redacted prior to publication. The

parties shall also FILE, by December 30, 2016, a joint status report identifying the information,

if any, that they contend should be redacted, together with an explanation of the basis for each

proposed redaction.

IT IS SO ORDERED.

s/ Lydia Kay Griggsby

LYDIA KAY GRIGGSBY

Judge

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