Carlos A. Cuello GarciaMD, PhD candidateStudent No. 1352724 Health Research Methodology ProgramDepartment of Clinical Epidemiology and Biostatistics

HRM 777 Methods for Diagnostic and Prognostic Research

URINARY TRACT INFECTIONS AND VESICOURETERAL REFLUX DURING INFANCY AND THEIR ROLE IN THE PROGNOSIS OF RENAL DAMAGE AND END-STAGE RENAL DISEASE

DERIVATION OF A PROGNOSTIC MODEL

Prognosis research question

Hamilton, OntarioJune 18, 2015

• Among otherwise healthy infants (<36 months of age)

with a first febrile urinary tract infection (UTI), does

the use of several prognostic factors built into a

prognostic model, help predict the probability of renal

damage and end-stage renal disease (ESRD) during

childhood and adolescence?

Research question

renal scars

VUR

recurrent UTI

renal damage?

CKD, ESRD?

Urinary Tract Infection

(UTI)

THE PROBLEM

Exclude

First examination for febrile infants 1 to 24 months old

• UA (leukocyte esterase, nitrites, gram stain) • ±Urine culture, CBC, other tests based on initial assessment

Management protocol

• Renal US within the first 24 hours • DMSA scan within the first 48 hours • ±VCUG at day 30 after first day of fever (if necessary) • CBC, urine culture, serum creatinine + BUN, PCT, and CRP) • ±Hospitalization, antibiotics, antipyretics as necessary

UTI suspected

UTI confirmed

First full follow-up assessment

DMSA for the diagnosis of renal damage VCUG, renal US, other tests if indicated. Medical ± surgical treatments? other diagnoses?

Second full follow-up assessment

DMSA for the diagnosis of renal damage Evaluation of glomerular filtration rate (for CKD / ESRD) VCUG, renal US, other tests if indicated. Medical ± surgical treatments? other diagnoses?

Protocol overview

no

yes

3 years post-first

UTI

*

UA, urinalysis; CBC, complete blood count; UTI, urinary tract infection; US, ultrasound; DMSA,

Technetium 99m dimercapto-succinic acid scan; VCUG, voiding cystourethrogram; BUN, blood urea

nitrogen; PCT, procalcitonin; CRP, C-reactive protein; ESRD, end-stage renal disease.

no

yes

5 years post-first

UTI * ?

Telephonic brief interview with parents / caregivers at least every 6 m*

RENAL DAMAGE

0/1

bacteria type♀♂ antibiotics

VUR I VUR II VUR III VUR IV VUR V

family history

prenatal hydronephrosis

abnormal anatomy

PCT

C-reactive protein

nitrites

initial temperature

THE MODEL

relapsing UTI

• Multivariable logistic regression to obtain coefficients

• Imputation • Internal validation ‣ discrimination by bootstrapping & using C-index

Moons 2015

• We’re still uncertain if UTIs in infancy ± VUR ± renal scars cause CKD / ESRD, and how strong the association is.

• Limitations

‣ Physicians still have problems diagnosing CKD (overdiagnosis?)

‣ It might require a very long time, and lots of patients

COMMENTARY