Bacterial and Host Genetic Risk Factors in Acute Pyelonephritis

NCT01137929 | Withdrawn

• 1 other identifier: Genes-APN
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

No single host or pathogen trait identified by previous research can be correlated with all cases of childhood acute pyelonephritis or APN (i.e., kidney/upper urinary tract infections) and APN-associated renal scarring (the outcome with the highest morbidity), making it difficult for physicians to determine which patients will be affected. Our proposal is to comprehensively study the relationships between the clinical manifestations of urinary tract infections (UTIs), the host risk factors and immune response, and the microbial species that cause these conditions. The result of the study will be a clinical severity score to personalize diagnostic and treatment strategies for infants with UTI, with the goal of decreasing the morbidity of APN/renal scarring and improving patient outcomes.

Conditions

Vesicoureteral Reflux

Keywords

Vesicoureteral reflux; Kidney; Renal Scar; Urinary tract infection

Outcome Measures

Primary Outcomes (1)

• Incidence of acute pyelonephritis lesions

  Children under two years of age will undergo a 99m-Tc-DMSA renal scan for the detection of acute pyelonephritis lesions within 72 hours of presentation to the ED for evaluation of a fever and positive urine culture. Based on finding the characteristic lesions (such as preservation of the renal contour but with diminished photopenia. This outcome measure will be aggregated with other bacterial and host related risk factors in order to identify the salient ones that result in morbidity from bladder infection.

  < 72 hours after presentation with fever and positive urine culture

Secondary Outcomes (1)

• Incidence of renal cortical scarring

  At least 6 months

Study Arms (6)

With APN, With VUR, With Renal Scar

This group of children who present with a febrile UTI will be found to have APN on DMSA renal scan and will also have VUR by VCUG and a renal scar on follow-up DMSA renal scan.

With APN, With VUR, Without Renal Scar

This group of children who present with a febrile UTI will be found to have APN on DMSA renal scan and will also have VUR by VCUG and NO renal scar on follow-up DMSA renal scan.

With APN, without VUR, with Renal Scar

This group of children who present with a febrile UTI will be found to have APN on DMSA renal scan but who will NOT have VUR by VCUG; however they will have a renal scar on follow-up DMSA renal scan.

With APN, Without VUR, Without Renal Scar

This group of children who present with a febrile UTI will be found to have APN on DMSA renal scan and will NOT have VUR by VCUG, NOR will they have a renal scar on follow-up DMSA renal scan.

Without APN, With VUR

This group of children who present with a febrile UTI will be found NOT to have APN on DMSA renal scan and will also have VUR by VCUG. They will not undergo a second DMSA scan since the first one is normal.

Without APN, Without VUR

This group of children who present with a febrile UTI will be found NOT to have APN on DMSA renal scan and will also NOT have VUR by VCUG, NOR a renal scar on follow-up DMSA renal scan.

Eligibility Criteria

• Age: 2 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

We will identify infants ≤ 2 years to be of particular risk for UTIF and renal scarring by virtue of a variety of risk factors, including age, gender, race, and underlying genetic risk factors and bacterial phenotypes.

You may qualify if:

• UTIF: A UTIF will require the presence of
• (1) fever and/or symptoms consistent with UTI,
• (2) pyuria based on urinalysis, and
• (3) culture-proven infection with a single organism. Specifically, the study definition of UTIF will require:
• Fever: A documented temperature of at least 100.4 °F or 38°C, measured anywhere on the body either at home or at doctor's office.
• Positive dipstick analysis: Pyuria on urinalysis (\>10 WBC/mm3 (uncentrifuged specimen) OR \>5 WBC/hpf (centrifuged specimen), OR \>1+ leukocyte esterase on dipstick).
• Culture documentation of UTI: Evidence of bacteria (\>5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen). Bag collected specimens will not be acceptable

Sponsors & Collaborators

• Hans Pohl: lead

Biospecimen

Retention: SAMPLES WITH DNA

Urine samples: Urine is routinely collected at the time of presentation with fever to diagnose UTI and an aliquot of this urine sample will be frozen for microbial genomic and metagenomic sequencing and analysis, that will allow us to identify unique/pathogenic/virulence factors in the genomes of these bacterial species when compared to non-pathogenic strains that have been subject to whole genome sequencing. Blood: DNA samples will be obtained at the time of renal scanning from the study subjects. The genomic DNA is used in PCR reactions and the resulting PCR products are screened for single nucelotide polymorphisms. Although we will be performing a genome wide association study, we will be particularly curious as to the behavior of SNP's among certain previously described candidates for the risk of renal scarring such as TLR2, TLR4, TGF-beta, and TNF-alpha. DNA samples will be stored for possible use in other future association studies.

MeSH Terms

Conditions

Vesico-Ureteral Reflux; Urinary Tract Infections

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 7, 2010
• Study Start: November 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: October 2, 2014

Record last verified: 2014-10