Lower urinary tract dysfunction in children with chronic kidney disease : before an after renal transplantation

Chronic kidney disease (CKD) in children is a complex condition with the risk of progression to end-stage renal disease (ESRD) requiring dialysis or renal transplantation. Children with CKD and pediatric renal transplant recipients face a variety of complications, such as side effects of the treatment and concerns about deterioration of graft function. Urinary tract infections (UTIs) are common complications that may harm renal function. In the general population lower urinary tract (LUT) dysfunction is a major risk factor for UTI, but less is known about LUT dysfunction in children with CKD or a renal transplant. The overall aim of this thesis was to evaluate LUT function in children with CKD before and after renal transplantation, and to study the role of LUT dysfunction in relation to UTIs. An additional aim was to gain knowledge about associations between LUT dysfunction and health related quality of life (HRQoL) in children with CKD before and after transplantation.

All studies were cross-sectional and included 40 children with CKD stages 3–5 (Studies III and IV), 68 children with a renal transplant (Studies I and II), and 59 children (Study V) with CKD stage 3–5 (n=23), or with a renal transplant (n=36). The documents and investigations used to evaluate LUT function were bladder diaries/questionnaires, uroflowmetry, bladder ultrasound (for measuring post-void residual urine), and, in Study IV, cystometry. The glomerular filtration rate (GFR) was assessed by the renal clearance of inulin or iohexol, or estimated by the plasma level of cystatin C. The history of UTI was obtained by reviewing the medical records. Two questionnaires, the Kidscreen-27 and Disabkids-37, were used for self-ratings of HRQoL and the modified Symptom Inventory for assessing associated subjective symptoms (Study V).

One or more signs of LUT dysfunction were found in 72.5% of children with CKD and in 72% of those with a renal transplant. Signs of LUT dysfunction were observed in all (100%) of the children with CKD along with underlying urological disorders and in 59% with non-urological disorders (p = 0.0074). Regarding LUT function in children with a renal transplant, no significant difference was found in groups with and without urinary tract malformations (74% vs. 71%, NS). In children with CKD, 47.5% had a bladder capacity larger than expected and the large bladder was often combined with reduced bladder sensation. A discontinuous urinary flow was found in 20% and 15% had residual urine. Corresponding figures in children with a renal transplant were 26%, 50% (17.6%, with a tower pattern excluded), and 32%. UTIs were more common in children with CKD and signs of LUT dysfunction than in those without (55% vs. 0%, p = 0.0012). In children with a renal transplant, recurrent UTIs were equally common in children with and without LUT dysfunction (35% vs. 42%, NS). Recurrent UTIs were, however, associated with a faster deterioration of GFR than in those without UTIs (p = 0.02). Children with CKD or a renal transplant with or without signs of LUT dysfunction reported a similar HRQoL, except those with incontinence, who reported lower HRQoL. Girls and older children rated well-being lower, as did those with a renal transplant. The entire study population perceived poorer well-being than healthy children, but similar to those with chronic conditions other than CKD.

In conclusion, LUT dysfunction is common in children with CKD stages 3–5 and pediatric renal transplant recipients, not only in children with urological disorders but also in those with non- urological disorders. Earlier UTIs and LUT dysfunction seem to correlate in children before, but not after a renal transplantation. The findings in this thesis contribute to our knowledge about LUT dysfunction in children with CKD stage 3–5 and pediatric renal transplant recipients, but also to our knowledge about the association between HRQoL and LUT dysfunction as well as possible impact of CKD status, sex and age. Further research is needed before general recommendations for possible interventions can be given.

List of scientific papers

I. Herthelius M, Öborn H. Bladder dysfunction in children and adolescents after renal transplantation. Pediatr Nephrol. 2006 May;21(5):725-8. Epub 2006 Mar 25.
https://doi.org/10.1007/s00467-006-0018-5

II. Herthelius M, Öborn H. Urinary tract infections and bladder dysfunction after renal transplantation in children. J Urol. 2007 May;177(5):1883-6.
https://doi.org/10.1016/j.juro.2007.01.054

III. Öborn H, Herthelius M. Lower urinary tract symptoms in children and adolescents with chronic renal failure. J Urol. 2010 Jan;183(1):312-6.
https://doi.org/10.1016/j.juro.2009.09.002

IV. Öborn H, Herthelius M. Bladder function in children with moderate to severe chronic kidney disease. [Submitted]

V. Öborn H, Forinder U, Herthelius M. Impact of lower urinary tract dysfunction on health-related quality of life in children with chronic renal disease before and after renal transplantation. [Submitted]