Blog entry by mohammad katout

Anyone in the world

 

Vesicoureteral reflux (VUR) is the most common urologic finding in children, occurring in approximately 1 percent of newborns, and as many as 30 to 45 percent of young children with a urinary tract infection given the retrograde passage of urine from the bladder into the upper urinary tract. [1-3]

 Basically, management is mainly focused on prevention of pyelonephritis, a morbid event in itself that requires acute medical care and possible hospitalization in young infants, let alone the possible subsequent loss of renal parenchyma as a result of renal scarring resulting in a cascade of chronic kidney disease events (hypertension, proteinuria, renal insufficiency with possible ESRD). [4,5]

Even though nephrologists had been clear on the existence of VUR and its link to renal scarring and CKD, yet they had been hazy on its management in terms of clinical impact of prophylaxis and adequate medical/surgical therapeutic interventions. The ideal management of children with VUR remains a source of debate with little evidence to support many of the current management practices for children with VUR who have had 1 or 2 febrile urinary tract infections. In fact, the long-standing notion that VUR may lead to progressive CKD and potentially ESRD has been increasingly questioned and remains controversial.

Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) is a multicenter, randomized, double-blind, placebo-controlled study to determine whether daily antimicrobial prophylaxis, in the setting of prompt evaluation and treatment of UTI, is superior to placebo in preventing recurrence UTI and/or the occurrence of, or worsening, of renal scarring in children with vesicoureteral reflux (VUR).

 In their recent publication in CJASN Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial” 607 children aged 2–71 months with grade 1–4 VUR diagnosed after a first or second febrile or symptomatic UTI were enrolled in this multicenter, randomized, placebo-controlled trial . Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up99mtechnetium dimercaptosuccinic acid (DMSA) renal scans. 

Authors reported that new renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Unsurprisingly, preexisting and new renal scars occurred significantly more in “renal units” with grade 4 VUR as compared to those with low-grade or no VUR. Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). [6]

 Perhaps the most clinically relevant finding of this work that could potentially impact clinical practice is that antimicrobial prophylaxis did not decrease the risk of renal scarring whether in terms of the proportion of children (6% and 7%) or renal units (4% versus 4%) echoing the results of recent studies that evaluated the role of antimicrobial prophylaxis in reducing the risk of renal scarring (7,8).

The question remains, should we stop antimicrobial prophylaxis to VUR infants and toddlers based on the above results?

Caution is still warranted while interpreting the results of the above studies since they were not primarily designed to evaluate the role of antimicrobial prophylaxis in preventing scarring. Moreover, a short follow-up period of 1–2 years in the RIVUR Trial is not long enough to determine beyond any reasonable doubt the long-term risk for the development of renal scarring or the preventive effect of antimicrobial prophylaxis.

 

References

  1. Dillon MJ, Goonasekera CD. Reflux nephropathy. J Am Soc Nephrol 1998; 9:2377.
  2. Shah KJ, Robins DG, White RH. Renal scarring and vesicoureteric reflux. Arch Dis Child 1978; 53:210.
  3. Smellie JM, Normand IC, Katz G. Children with urinary infection: a comparison of those with and those without vesicoureteric reflux. Kidney Int 1981; 20:717.
  4. Elder JS, Peters CA, Arant BS Jr, et al. Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol 1997; 157:1846.
  5. Willi U, Treves S. Radionuclide voiding cystography. Urol Radiol 1983; 5:161.
  6. Mattoo TK, Chesney RW, Greenfield SP, Hoberman A, Keren R, Mathews R, Gravens-Mueller L, Ivanova A, Carpenter MA, Moxey-Mims M, Majd M, Ziessman HA; RIVUR Trial Investigators. Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial. Clin J Am Soc Nephrol. 2015 Nov 10. pii: CJN.05210515. [Epub ahead of print]
  7. Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, Hodson EM, Carapetis JR, Cranswick NE, Smith G, Irwig LM, Caldwell PH, Hamilton S, Roy LP; Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators: Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 361: 1748–1759, 2009
  8. Brandstro¨m P, Neve´us T, Sixt R, Stokland E, Jodal U, Hansson S: The Swedish reflux trial in children: IV. Renal damage.JUrol 184:292–297, 2010
  1. Dillon MJ, Goonasekera CD. Reflux nephropathy. J Am Soc Nephrol 1998; 9:2377.
  2. Shah KJ, Robins DG, White RH. Renal scarring and vesicoureteric reflux. Arch Dis Child 1978; 53:210.
  3. Smellie JM, Normand IC, Katz G. Children with urinary infection: a comparison of those with and those without vesicoureteric reflux. Kidney Int 1981; 20:717.
  4. Elder JS, Peters CA, Arant BS Jr, et al. Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol 1997; 157:1846.

Willi U, Treves S. Radionuclide voiding cystography. Urol Radiol 1983; 5:161.

[ Modified: Thursday, 1 January 1970, 1:00 AM ]