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• W2104986480 abstract "Primary vesicoureteral reflux (VUR) is the commonest congenital urological abnormality in children, which has been associated with an increased risk of urinary tract infection (UTI) and renal scarring, also called reflux nephropathy (RN). In children, RN is diagnosed mostly after UTI (acquired RN) or during follow-up for antenatally diagnosed hydronephrosis with no prior UTI (congenital RN). The acquired RN is more common in female children, whereas the congenital RN is more common in male children. This observation in children might help explain the differences in the clinical presentation of RN in adults, with males presenting mostly with hypertension, proteinuria, and progressive renal failure as compared with females who present mostly with recurrent UTI and have a better outcome. Known risk factors for RN include the severity of VUR, recurrent UTI, and bladder-bowel dysfunction; younger age and delay in treatment of UTI are believed to be other risk factors. Management of VUR is controversial and includes antimicrobial prophylaxis, surgical intervention, or surveillance only. No evidence-based guidelines exist for appropriate follow-up of patients with RN. Primary vesicoureteral reflux (VUR) is the commonest congenital urological abnormality in children, which has been associated with an increased risk of urinary tract infection (UTI) and renal scarring, also called reflux nephropathy (RN). In children, RN is diagnosed mostly after UTI (acquired RN) or during follow-up for antenatally diagnosed hydronephrosis with no prior UTI (congenital RN). The acquired RN is more common in female children, whereas the congenital RN is more common in male children. This observation in children might help explain the differences in the clinical presentation of RN in adults, with males presenting mostly with hypertension, proteinuria, and progressive renal failure as compared with females who present mostly with recurrent UTI and have a better outcome. Known risk factors for RN include the severity of VUR, recurrent UTI, and bladder-bowel dysfunction; younger age and delay in treatment of UTI are believed to be other risk factors. Management of VUR is controversial and includes antimicrobial prophylaxis, surgical intervention, or surveillance only. No evidence-based guidelines exist for appropriate follow-up of patients with RN. Clinical Summary•VUR is common in children.•Renal scarring associated with VUR, also called reflux nephropathy, may be congenital or acquired in origin.•Hypertension and proteinuria are the most common complications of reflux nephropathy.•Early diagnosis and appropriate management of reflux nephropathy is important for preserving the renal function. Primary vesicoureteral reflux (VUR) is the commonest congenital urinary tract abnormality in childhood, which is diagnosed mostly after an episode of urinary tract infection (UTI). The gold standard for its diagnosis is the voiding cystourethrogram , which is graded I to V, grade V being the most severe type. Reflux nephropathy (RN) is the renal scarring that is diagnosed in patients with VUR, mostly in association with UTI. However, renal scarring can occur with UTI in the absence of a VUR, or with VUR in the absence of a UTI. Whereas the occurrence of former has been reported in the literature for a long time, the evidence for the latter is more recent and has come mostly from children with antenatally diagnosed hydronephrosis, who on postnatal evaluation are found to have VUR and renal scarring. Currently, the RN is defined as congenital (also called primary), which is a result of abnormal renal development resulting in focal renal dysplasia, or acquired, which results from pyelonephritis-induced renal injury. However, the differentiation of congenital versus acquired RN on the basis of preceding UTI can be arbitrary because the possibility of a preexisting renal scar before the UTI cannot always be ruled out. The acquired RN is seen more often in females, whereas the congenital RN occurs mostly in males. Some other important differences between acquired and congenital RN are shown in Table 1.Table 1Acquired Versus Congenital Reflux Nephropathy (RN) in ChildrenClinical/Histological FeaturesAcquired RNCongenital RNTime of occurrencePostnatalPrenatalUTI before diagnosisCommonUncommonAge distributionAll pediatric age-groupsMostly in younger childrenGender distributionPredominantly femalesPredominantly malesGrade of VURAny grade, mostly high gradeMostly high gradeDysplastic features on renal histopathologyNoYesAbbreviations: UTI, urinary tract infection; VUR, vesicoureteral reflux. Open table in a new tab Abbreviations: UTI, urinary tract infection; VUR, vesicoureteral reflux. The exact mechanism for renal scarring following UTI is not known, but is believed to be mediated by immunological mechanisms, macromolecular trapping and mesangial dysfunction, vascular alterations, hypertension, and hemodynamic alterations.1Cotran R.S. Nephrology forum. Glomerulosclerosis in reflux nephropathy.Kidney Int. 1982; 21: 528-534Crossref PubMed Scopus (73) Google Scholar Renal scarring due to intrarenal reflux occurs mostly at the renal poles because of the presence of extensively fused (compound) renal papillae, which are associated with reflux.2Ransley P.G. Risdon R.A. Renal papillary morphology in infants and young children.Urol Res. 1975; 3: 111-113PubMed Google Scholar The scarring may result from a single episode of pyelonephritis, especially in young children, also called “big bang effect,”3Ransley P.G. Risdon R.A. Reflux nephropathy: effects of antimicrobial therapy on the evolution of the early pyelonephritic scar.Kidney Int. 1981; 20: 733-742Crossref PubMed Scopus (157) Google Scholar or the process may take several years. In one study, the mean time from the discovery of VUR to the appearance of renal scarring was 6.1 years.4Shindo S. Bernstein J. Arant Jr., B.S. Evolution of renal segmental atrophy (Ask-Upmark kidney) in children with vesicoureteric reflux: radiographic and morphologic studies.J Pediatr. 1983; 102: 847-854Abstract Full Text PDF PubMed Scopus (47) Google Scholar In a cohort of pediatric patients with UTI, including 68% infants, VUR was diagnosed in 33% of cases.5Wu C.Y. Chiu P.C. Hsieh K.S. Chiu C.L. Shih C.H. Chiou Y.H. Childhood urinary tract infection: a clinical analysis of 597 cases.Acta Paediatr Taiwan. 2004; 45: 328-333PubMed Google Scholar The exact incidence of RN in children or adults is not known. The diagnosis is difficult in patients who may have already undergone the natural resolution of VUR by the time RN is diagnosed. The reported incidence of RN varies from 36% to 56% in patients with UTI and VUR.6Rushton H.G. The evaluation of acute pyelonephritis and renal scarring with technetium 99m-dimercaptosuccinic acid renal scintigraphy: evolving concepts and future directions.Pediatr Nephrol. 1997; 11: 108-120Crossref PubMed Scopus (230) Google Scholar, 7Doganis D. Siafas K. Mavrikou M. et al.Does early treatment of urinary tract infection prevent renal damage?.Pediatrics. 2007; 120: e922-e928Crossref PubMed Scopus (103) Google Scholar A review of the year of publication of studies with renal scarring following UTI in children with and without VUR revealed that the rates of renal scarring in such children with first UTI have been relatively stable at 15% since 2002.8Shaikh N. Ewing A.L. Bhatnagar S. Hoberman A. Risk of renal scarring in children with a first urinary tract infection: a systematic review.Pediatrics. 2010; 126: 1084-1091Crossref PubMed Scopus (290) Google Scholar Congenital RN has been reported in 30% to 60% of mostly male children with VUR diagnosed as a result of antenatally diagnosed hydronephrosis, also called prenatal VUR.9Yeung C.K. Godley M.L. Dhillon H.K. Gordon I. Duffy P.G. Ransley P.G. The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis.Br J Urol. 1997; 80: 319-327Crossref PubMed Google Scholar, 10Ismaili K. Hall M. Piepsz A. et al.Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study.J Pediatr. 2006; 148: 222-227Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Increasing age at the diagnosis of VUR correlates with increasing incidence of renal scarring: 10% in preterm infants, 26% in children under 8 years, 47% in children older than 8 years, and 94% in adults.11Kincaid-Smith P. Becker G. Reflux nephropathy and chronic atrophic pyelonephritis: a review.J Infect Dis. 1978; 138: 774-780Crossref PubMed Scopus (58) Google Scholar, 12Bourchier D. Abbott G.D. Maling T.M. Radiological abnormalities in infants with urinary tract infections.Arch Dis Child. 1984; 59: 620-624Crossref PubMed Scopus (50) Google Scholar, 13Smellie J. Edwards D. Hunter N. Normand I.C. Prescod N. Vesico-ureteric reflux and renal scarring.Kidney Int Suppl. 1975; 4: S65-S72PubMed Google Scholar, 14Dillon M.J. Goonasekera C.D. Reflux nephropathy.J Am Soc Nephrol. 1998; 9: 2377-2383PubMed Google Scholar In a study involving otherwise healthy children and adolescents who were evaluated for newly diagnosed hypertension, dimercaptosuccinic acid (DMSA) scans revealed renal scarring in 33 (21%) of the 159 patients with a median age of 11 years; 22 patients had unilateral scarring and 11 had bilateral scarring. The study could not define whether the RN was congenital or acquired in origin and whether the hypertension was definitely the result of renal scarring.15Ahmed M. Eggleston D. Kapur G. Jain A. Valentini R.P. Mattoo T.K. Dimercaptosuccinic acid (DMSA) renal scan in the evaluation of hypertension in children.Pediatr Nephrol (Berlin, Germany). 2008; 23: 435-438Crossref PubMed Scopus (28) Google Scholar It is not clear if the VUR and its severity have a causative role in the formation of renal scars or whether it is a marker for congenital maldevelopment such as hypoplasia/dysplasia.16Patterson L.T. Strife C.F. Acquired versus congenital renal scarring after childhood urinary tract infection.J Pediatr. 2000; 136: 2-4Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Children with VUR are more likely to develop pyelonephritis (relative risk: 1.5 [95% confidence interval (CI): 1.1-1.9]) and renal scarring (relative risk: 2.6 [95% CI: 1.7-3.9]) as compared with those with no VUR, and children with VUR grades III or higher are more likely to develop scarring than children with lower grades of VUR (relative risk: 2.1 [95% CI: 1.4-3.2]).8Shaikh N. Ewing A.L. Bhatnagar S. Hoberman A. Risk of renal scarring in children with a first urinary tract infection: a systematic review.Pediatrics. 2010; 126: 1084-1091Crossref PubMed Scopus (290) Google Scholar The risk of renal scarring involving more than 25% of renal parenchyma is significantly higher in patients with grade III to IV VUR (40%) as compared with those with grade I to II VUR (14%) or no VUR (6%).17Gonzalez E. Papazyan J.P. Girardin E. Impact of vesicoureteral reflux on the size of renal lesions after an episode of acute pyelonephritis.J Urol. 2005; 173 (discussion 4–5): 571-574Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Renal cortical abnormalities are more common in children with VUR, even without a history of UTI, and the abnormalities are more common in high-grade VUR. A meta-analysis of the published data revealed that renal abnormalities (per 100 renal units) occur with a mean of 6.2% in those with grades I to III VUR and 47.9% in those with grades IV and V VUR. The abnormalities ranged from 2% to 63% (mean, 21.8%) of patients with VUR and 26% to 42% (mean, 32.3%) of the renal units.18Skoog S.J. Peters C.A. Arant B.S. et al.Pediatric vesicoureteral reflux guidelines panel summary report: clinical practice guidelines for screening siblings of children with vesicoureteral reflux and neonates/infants with prenatal hydronephrosis.J Urol. 2010; 184: 1145-1151Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar VUR-related renal scarring is more common with UTI, and the odds ratio of renal scarring with acute pyelonephritis in the presence of a VUR is 2.8 for patients and 3.7 for renal units as compared with those with no VUR.19Peters C.A. Skoog S.J. Arant B.S. et al.Summary of the AUA guideline on management of primary vesicoureteral reflux in children.J Urol. 2010; 184: 1134-1144Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar The risk of renal scarring increases with constipation and voiding dysfunction. The bladder-bowel dysfunction (BBD) increases risk of febrile UTI in children on antimicrobial prophylaxis for VUR to 44% as compared with 13% in those without BBD. The BBD delays VUR resolution at 24 months (31% with BBD and 61% without BBD), and the rate of postoperative UTI is greater in children with BBD (22% as compared with 5% without BBD).19Peters C.A. Skoog S.J. Arant B.S. et al.Summary of the AUA guideline on management of primary vesicoureteral reflux in children.J Urol. 2010; 184: 1134-1144Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar A delay in the treatment of febrile UTI is associated with increased risk of renal injury.20Smellie J.M. Poulton A. Prescod N.P. Retrospective study of children with renal scarring associated with reflux and urinary infection.BMJ. 1994; 308: 1193-1196Crossref PubMed Scopus (174) Google Scholar, 21Ataei N. Madani A. Habibi R. Khorasani M. Evaluation of acute pyelonephritis with DMSA scans in children presenting after the age of 5 years.Pediatr Nephrol (Berlin, Germany). 2005; 20: 1439-1444Crossref PubMed Scopus (57) Google Scholar A multivariate analysis of 158 children with febrile UTI and therapeutic delay of >48 hours was associated with significantly increased risk of acute lesions on renal scan.22Fernandez-Menendez J.M. Malaga S. Matesanz J.L. Solis G. Alonso S. Perez-Mendez C. Risk factors in the development of early technetium-99m dimercaptosuccinic acid renal scintigraphy lesions during first urinary tract infection in children.Acta Paediatr (Oslo, Norway). 2003; 92: 21-26Crossref PubMed Scopus (52) Google Scholar However, the Italian Renal Infection Study Trials reported that the progressive delay in antibiotic treatment of acute pyelonephritis from <1 to ≥5 days after the onset of fever was not associated with any significant increase in the risk of scarring on DMSA renal scans obtained 1 year later. The risk of scarring remained relatively constant at 30.7% ± 7%. Clinical and laboratory indices of inflammation were comparable in all groups, as was the incidence of VUR.23Hewitt I.K. Zucchetta P. Rigon L. et al.Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials.Pediatrics. 2008; 122: 486-490Crossref PubMed Scopus (114) Google Scholar In another study, early and appropriate treatment of UTI, especially during the first 24 hours after the onset of symptoms, diminished the likelihood of renal involvement during the acute phase of the infection but did not prevent scar formation.7Doganis D. Siafas K. Mavrikou M. et al.Does early treatment of urinary tract infection prevent renal damage?.Pediatrics. 2007; 120: e922-e928Crossref PubMed Scopus (103) Google Scholar Young age is believed to be another risk factor for renal scarring due to UTI, and this was highlighted in the American Academy of Pediatrics recommendations on the management of UTI in infants and young children.24American Academy of Pediatrics Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children.Pediatrics. 1999; 103: 843-852Crossref PubMed Scopus (888) Google Scholar Higher risk in infants is also acknowledged in the most recent American Urological Association (AUA) guidelines.19Peters C.A. Skoog S.J. Arant B.S. et al.Summary of the AUA guideline on management of primary vesicoureteral reflux in children.J Urol. 2010; 184: 1134-1144Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar However, scarring does occur in adult kidneys as well. Adult pig kidneys scar as quickly as those of piglets with VUR and UTI,25Coulthard M.G. Flecknell P. Orr H. Manas D. O’Donnell M. Renal scarring caused by vesicoureteric reflux and urinary infection: a study in pigs.Pediatr Nephrol (Berlin, Germany). 2002; 17: 481-484Crossref PubMed Scopus (31) Google Scholar and scarring is known to occur in adult mature kidneys transplanted into pediatric patients.26Howie A.J. Buist L.J. Coulthard M.G. Reflux nephropathy in transplants.Pediatr Nephrol (Berlin, Germany). 2002; 17: 485-490Crossref PubMed Scopus (28) Google Scholar Some recent studies have reported that the young age may not be a risk factor for renal scarring and that the risk in older children is the same21Ataei N. Madani A. Habibi R. Khorasani M. Evaluation of acute pyelonephritis with DMSA scans in children presenting after the age of 5 years.Pediatr Nephrol (Berlin, Germany). 2005; 20: 1439-1444Crossref PubMed Scopus (57) Google Scholar, 27Lin K.Y. Chiu N.T. Chen M.J. et al.Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection.Pediatr Nephrol. 2003; 18: 362-365PubMed Google Scholar, 28Benador D. Benador N. Slosman D. Mermillod B. Girardin E. Are younger children at highest risk of renal sequelae after pyelonephritis?.Lancet. 1997; 349: 17-19Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar or even higher29Coulthard M.G. Verber I. Jani J.C. et al.Can prompt treatment of childhood UTI prevent kidney scarring?.Pediatr Nephrol. 2009; 24: 2059-2063Crossref PubMed Scopus (41) Google Scholar, 30Pecile P. Miorin E. Romanello C. et al.Age-related renal parenchymal lesions in children with first febrile urinary tract infections.Pediatrics. 2009; 124: 23-29Crossref PubMed Scopus (42) Google Scholar as compared with that in the younger children. The complications of RN are well known but poorly defined because of their insidious onset and slow progression. These include hypertension, proteinuria, urine concentration defects, hyperkalemia, acidosis, and chronic kidney disease with progressive renal failure, including end-stage renal failure in some patients. Of these, hypertension and proteinuria are the commonest ones that have a significant bearing on long-term renal outcome, and both are amenable to medical intervention. The relationship between renal scarring and hypertension was first demonstrated in 1937 when the removal of a small scarred kidney cured hypertension in a 10-year-old girl with recurrent UTI and hypertension.31Butler A.M. Chronic pyelonephritis and arterial hypertension.J Clin Invest. 1937; 16: 889-897Crossref PubMed Google Scholar Hypertension occurs in 17% to 30% of pediatric patients32Faust W.C. Diaz M. Pohl H.G. Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature.J Urol. 2009; 181 (discussion 7–8): 290-297Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar and in 34% to 38% of adult patients with renal scarring.33Zhang Y. Bailey R.R. A long-term follow-up of adults with reflux nephropathy.N Z Med J. 1995; 108: 142-144PubMed Google Scholar, 34Kohler J. Tencer J. Thysell H. Forsberg L. Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi.Nephrol Dial Transplant. 1997; 12: 2580-2587Crossref PubMed Scopus (36) Google Scholar Confounding factors such as increasing frequency of primary HTN in adults makes this interpretation difficult. According to a study that did survival analysis, it was estimated that 50% of patients with unilateral and bilateral renal damage would have sustained hypertension at about 30 and 22 years of age, respectively.35Simoes e Silva A.C. Silva J.M.P. Diniz J.S. et al.Risk of hypertension in primary vesicoureteral reflux.Pediatr Nephrol (Berlin, Germany). 2007; 22: 459-462Crossref PubMed Scopus (37) Google Scholar In a follow-up lasting 15 years in pediatric patients with renal scarring, about 13% patients at age 20 to 31 years became hypertensive.36Goonasekera C.D. Shah V. Wade A.M. Barratt T.M. Dillon M.J. 15-year follow-up of renin and blood pressure in reflux nephropathy.Lancet. 1996; 347: 640-643Abstract PubMed Scopus (67) Google Scholar The plasma rennin activity may increase in some children with renal scars as they grow older, but there is no direct correlation between BP and plasma rennin activity, plasma creatinine concentration, or degree of scarring.37Savage J.M. Koh C.T. Shah V. Barratt T.M. Dillon M.J. Five year prospective study of plasma renin activity and blood pressure in patients with longstanding reflux nephropathy.Arch Dis Child. 1987; 62: 678-682Crossref PubMed Scopus (32) Google Scholar Overt proteinuria, which has been reported in 21% of adult patients with RN,34Kohler J. Tencer J. Thysell H. Forsberg L. Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi.Nephrol Dial Transplant. 1997; 12: 2580-2587Crossref PubMed Scopus (36) Google Scholar is a rare occurrence in pediatric patients. It results from glomerular and/or tubulointerstitial damage caused by immunologic injury, macromolecular trapping and mesangial dysfunction, hypertension, and glomerular hyperfiltration.1Cotran R.S. Nephrology forum. Glomerulosclerosis in reflux nephropathy.Kidney Int. 1982; 21: 528-534Crossref PubMed Scopus (73) Google Scholar Microalbuminuria, which is indicative of glomerular damage at a very early stage and precedes overt proteinuria, progressive renal damage, and renal failure, has been reported in 51% pediatric patients (mean age, 9.8 ± 4.2 years) with renal scarring.38Karlen J. Linne T. Wikstad I. Aperia A. Incidence of microalbuminuria in children with pyelonephritic scarring.Pediatr Nephrol (Berlin, Germany). 1996; 10: 705-708Crossref PubMed Scopus (31) Google Scholar Patients with RN also excrete in urine an increased amount of low-molecular-weight proteins such as β2-microglobin, retinol-binding protein, α1-microglobin, and N-acetyl-β-d-glucosaminase.39Tomlinson P.A. Smellie J.M. Prescod N. Dalton R.N. Chantler C. Differential excretion of urinary proteins in children with vesicoureteric reflux and reflux nephropathy.Pediatr Nephrol. 1994; 8: 21-25Crossref PubMed Scopus (52) Google Scholar, 40Miyakita H. Puri P. Urinary levels of N-acetyl-beta-D-glucosaminidase: a simple marker for predicting tubular damage in higher grades of vesicoureteric reflux.Eur Urol. 1994; 25: 135-137PubMed Google Scholar, 41Salvaggio E. Menonna N.M. Ricci R. Ferrara P. Nardini F. Beta 2 microglobulin in the diagnosis of reflux nephropathy in childhood [in Italian]. La Pediatria medica e chirurgica: medical and surgical pediatrics.Pediatr Med Chir. 1988; 10: 83-88PubMed Google Scholar, 42Goonasekera C.D. Shah V. Dillon M.J. Tubular proteinuria in reflux nephropathy: post ureteric re- implantation.Pediatr Nephrol. 1996; 10: 559-563Crossref PubMed Scopus (13) Google Scholar Microalbuminuria occurs around the same time or soon after the appearance of low-molecular-weight proteins in urine, and its excretion increases with the severity of renal scarring.39Tomlinson P.A. Smellie J.M. Prescod N. Dalton R.N. Chantler C. Differential excretion of urinary proteins in children with vesicoureteric reflux and reflux nephropathy.Pediatr Nephrol. 1994; 8: 21-25Crossref PubMed Scopus (52) Google Scholar, 42Goonasekera C.D. Shah V. Dillon M.J. Tubular proteinuria in reflux nephropathy: post ureteric re- implantation.Pediatr Nephrol. 1996; 10: 559-563Crossref PubMed Scopus (13) Google Scholar, 43Bell F.G. Wilkin T.J. Atwell J.D. Microproteinuria in children with vesicoureteric reflux.Br J Urol. 1986; 58: 605-609Crossref PubMed Scopus (24) Google Scholar RN has also been associated with focal segmental glomerular sclerosis (FSGS).44Kincaid-Smith P. Glomerular lesions in atrophic pyelonephritis and reflux nephropathy.Kidney Int Suppl. 1975; 4: S81-S83PubMed Google Scholar In a histological review of 86 pediatric nephrectomy specimens from patients with VUR (with or without apparent obstruction at the vesicoureteral junction), FSGS was found in 18 (21%) patients, 9 of whom were less than 5 years old. There was no significant association between the presence (or grade) or absence of FSGS and age at nephrectomy, gender, presence or absence of obstruction, and severity of hypoplasia and/or postnatally acquired cortical loss.45Hinchliffe S.A. Kreczy A. Ciftci A.O. Chan Y.F. Judd B.A. van Velzen D. Focal and segmental glomerulosclerosis in children with reflux nephropathy.Pediatr Pathol. 1994; 14: 327-338Crossref PubMed Scopus (26) Google Scholar FSGS is progressive and can occur in nonscarred parts of the kidney or in the normal contralateral kidney in patients with unilateral RN.46Bailey R.R. Swainson C.P. Lynn K.L. Burry A.F. Glomerular lesions in the ‘normal’ kidney in patients with unilateral reflux nephropathy.Contrib Nephrol. 1984; 39: 126-131PubMed Google Scholar The pathogenesis for FSGS in RN is not clear and has been attributed to glomerular hyperfiltration, deposition of antigen-antibody complexes, failure of mesangium to clear macromolecules, and glomerular injury due to circulating immune complexes. RN is responsible for 12% to 21% of all children with chronic renal failure.47Chantler C. Carter J.E. Bewick M. et al.10 years’ experience with regular haemodialysis and renal transplantation.Arch Dis Child. 1980; 55: 435-445Crossref PubMed Scopus (59) Google Scholar, 48Deleau J. Andre J.L. Briancon S. Musse J.P. Chronic renal failure in children: an epidemiological survey in Lorraine (France) 1975-1990.Pediatr Nephrol. 1994; 8: 472-476Crossref PubMed Scopus (71) Google Scholar According to the 2008 North American Pediatric Renal Trials and Collaborative Studies report, RN is the fourth commonest cause for chronic kidney disease in 8.4% of the children and is the primary pathology in 5.2% of transplanted patients and 3.5% of dialysis patients.49NAPRTCSThe Annual Report of North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).in: The EMMES Corporation, Rockville, Maryland2008Google Scholar In the CKID study that involved a cohort of 586 children aged 1 to 16 years with an estimated GFR of 30 to 90 mL/min/1.73 m2, RN was the underlying cause for CKD in 87 (14.8%) patients. This constituted 19% of the patients with nonglomerular etiology for CKD.50Susan L. Furth AG, Jerry-Fluker J, et al. Metabolic abnormalities, CVD risk factors and GFR decline in children with CKD. Clin J Am Soc Nephrol. In press.Google Scholar Unlike pediatric patients in whom a diagnosis of renal scarring is prompted mostly by the occurrence of UTI, the diagnosis in adults is either a carryover diagnosis from the pediatric age group or is a result of pregnancy-related complications, recurrent UTI, hypertension, proteinuria, renal calculi, or renal failure. RN in adults shows a more marked differentiation in clinical presentation between the males and the females. As shown in Table 2, adult males with RN generally present with hypertension, proteinuria, and renal failure, whereas the females present mostly with UTI and pregnancy-related complications. The males have a poorer outcome as compared with females; this difference was previously explained on the basis of more insidious onset and hence delayed diagnosis in males and the UTI-prompted earlier diagnosis in females, and the dilution of severe cases because of earlier presentation of females due to recurrent UTI and pregnancy-related complications.51Williams D.G. Reflux nephropathy.Q J Med. 1990; 77: 1205-1207Crossref PubMed Scopus (6) Google Scholar However, given the knowledge gained from pediatric patients, it is possible that the adult males most probably have congenital RN as compared with acquired RN in adult females.Table 2Reflux Nephropathy in AdultsClinical/Laboratory FeaturesMalesFemalesUTIUncommonFrequentPlasma creatinineHigherNormalEnd-stage renal failureMore commonLess commonVURHigh grade/bilateralLow grade/unilateralProteinuriaFrequent/severeInfrequent/Less severeHypertensionMore commonLess commonAbbreviations: UTI, urinary tract infection; VUR, vesicoureteral reflux. Open table in a new tab Abbreviations: UTI, urinary tract infection; VUR, vesicoureteral reflux. In a study that assessed renal function 16 to 26 years after the first UTI with renal scarring in childhood and compared it with an age-matched cohort, the total GFR remained unchanged, but the individual GFR of the scarred kidneys decreased significantly. The decrease in GFR was significant in those with bilateral renal scarring. The median urine albumin/creatinine ratio was 1.2 mg/mmol compared with 0.6 in those with no scarring.52Wennerstrom M. Hansson S. Jodal U. Sixt R. Stokland E. Renal function 16 to 26 years after the first urinary tract infection in childhood.Arch Pediatr Adolesc Med. 2000; 154: 339-345Crossref PubMed Scopus (105) Google Scholar In another study on 293 adults (mean age at presentation 31 ± 13.4 years) with RN, females outnumbered males by a ratio of 5:1. The commonest presenting complaints for both genders were UTI (65%), hypertension (20%), and proteinuria (6%). However, UTI as a presenting complaint was significantly more common in females as compared with males (72% vs 31%), whereas proteinuria was significantly more common in males (20% vs 4%). Hypertension was also more common in males (29% vs18%), but the difference was not significant. VUR was present in 65% females and 75% of males. Of the 147 patients who were followed for a mean period of 6.9 ±" @default.
• W2104986480 created "2016-06-24" @default.
• W2104986480 creator A5048077398 @default.
• W2104986480 date "2011-09-01" @default.
• W2104986480 modified "2023-10-10" @default.
• W2104986480 title "Vesicoureteral Reflux and Reflux Nephropathy" @default.
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