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The Other Reflux

March 1, 2011

If you watch television, you have heard about GER or gastroesophageal reflux, what most folks call heartburn. In pediatric nephrology, we chat about vesicoureteral reflux (VUR), a condition recognized for 50 years but poorly understood.

What is VUR?

Click for Source (Cincinnati Children's Hospital)

Like GER, VUR involves fluid backing up in the wrong direction. When we pee, the bladder squeezes urine out. Generally the contraction of the bladder wall should close off the ureters so that the only escape route for the urine is the urethra and the outside world. With VUR, the ureters remain open and urine can back up into the ureters.

VUR has 5 grades based on findings from voinding cystourethrograms (see figure). For this study, the bladder is filled with dye via a catheter and x-rays taken to determine where the dye goes. If normal, it stays in the bladder and exits with voiding. If it backs up into the ureter but does not reach the kidney, the diagnosis is grade I VUR. With grade II, the urinary tract looks normal but dye reaches into the pelvis, the upper part of the ureter that is inside the kidney. With grade III and higher, the components of the urinary collecting system show varying amounts of enlargment.

With VUR, a couple of bad things can happen. First, urine that refluxes into the ureters immediately flows back into the bladder where it can sit and grow bacteria. Second, with grade II or higher, any bladder infection that occurs is more likely to ascend to the kidney and cause potential damage, including scars. End-stage kidney failure may be associated with VUR, but treatment does not appear to ameliorate the risk of progressive kidney damage.

Treatment of VUR

Since the 1960s, opinion-based recommendations and suboptimal studies supported the use of prophylactic antibiotics in VUR. Initial studies showed that scars in the kidney could be prevented as well by prophylaxis as by surgical repair of the reflux. Professional societies echoed this endorsement, but only recently have appropriate, randomized, prospective studies been performed. These five studies form the basis of an editorial commentary and meta-analysis in the December issue of Pediatric Nephrology:

Evidence for and against urinary prophylaxis in vesicoureteral reflux Mattoo TK. Pediatr Nephrol (2010) 25:2379-2382  DOI  10.1007/s00467-010-1632-9

Five studies made the grade for analysis, only one of which included a placebo-control arm; in the others, patients randomized to no treatment knew they were not getting antibiotics. In all of the studies, patients had a history of urinary tract infection, so we will look at the efficacy of antibiotics for preventing future UTI’s:

Click to embiggen

On their own, each of these studies showed minimal, if any, benefits for antibiotics, and the meta-analysis relative risk of 0.82 (95% confidence interval: 0.62-1.08; p=0.16) confirms this overall impression. One study from Australia found that boys with grade III reflux significantly benefited from low-dose trimethoprim-sulfa, the highest grade of reflux in the study.

So What Should We Do?

The treatment of VUR remains in flux. High-grade reflux (III or higher) associated with documented infection probably warrants prophylaxis at this time. Most pediatric nephrologists I know have not used suppressive antibiotics with grade I reflex for many years. Grade II VUR associated with infection can probably be safely managed without prophylaxis. If more infections occur, a trial of antibiotics could be in order.

Of course, none of this addresses every patient with VUR. Many children get imaged for reflux because of genetic syndromes, congenital renal anomalies, or siblings with the condition, but the kid in question has never had a urinary tract infection. Is prophylaxis of benefit in these conditions? We don’t know, and the available studies do not address these issues. Clearly, more work lies ahead if we truly want to know what we should do, not merely what we think we should do.

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