The Burden Of Visits For Fever At A Paediatric Emergency Room: A Retrospective Study On Patients Presenting At The Cantons Hospital Of Fribourg, A Peripheral Public Hospital Of Switzerland.

INTRODUCTION: Fever is the chief complaint of up to one-third of all paediatric office visits in many places. The high number of consultations at our emergency department (ED) led us to hypothesise that this increase was due to febrile paediatric patients with lower urgency seeking medical advice. METHODS: We retrospectively analysed the number and characteristics of patients 3 months to 5 years of age consulting for a body temperature of 38.5°C or higher during the 6 winter months of 2011-2012. RESULTS: Twenty-four percent of all consultations were requested by the patients included in our group. None of the 835 patients had to be hospitalised, 95% of these patients had additional respiratory or gastrointestinal symptoms, 36.7% required antibiotic therapy, and 17.6% (laryngitis and lower respiratory tract infection (RTI)) required temporary respiratory support. A total of 56.2% of patients sought advice outside of the normal working hours. CONCLUSION: The majority of patients had fever accompanied by additional symptoms justifying a medical consultation. However, most of these did not require the infrastructure of an ED for their health care problem and probably visited the ED because of the open hours.

Age at disease onset of inflammatory bowel disease is associated with later extraintestinal manifestations and complications.

INTRODUCTION: A small but increasing number of patients with inflammatory bowel disease are diagnosed during childhood or adolescence, and disease distribution and severity at onset vary according to the age at diagnosis. Clinical factors present at the time of diagnosis can be predictive of the disease course. AIM: The aim of this study was to characterize disease behavior and the cumulative complications and extraintestinal manifestations 10 years after the diagnosis and to assess their association with age at diagnosis. PATIENTS AND METHODS: Data of patients participating with the Swiss IBD cohort study registry, a disease duration of 10 years and a complete data set were analyzed. The outcome was defined as the cumulative change of disease behavior, the occurrence of extra-intestinal manifestations or complications, and the necessity for medical or surgical interventions. RESULTS: A total of 481 patients with Crohn's disease (CD) and 386 patients with ulcerative colitis (UC), grouped according to disease onset before 10, 17, 40, or after 40 years of age, were analyzed. Despite differences in sex, initial disease location, and smoking habits, at 10 years after the diagnosis, no difference was found regarding disease behavior in CD or regarding progression of disease extension in UC. Similarly, no age-of-onset-dependent cumulative need for medical or surgical therapies was found. However, higher rates of anemia and lower rates of arthralgia and osteopenia were found in both pediatric-onset CD and UC, and a tendency toward higher rates of stomatitis in pediatric-onset CD, and of primary sclerosing cholangitis and ankylosing spondylitis in pediatric-onset UC. CONCLUSION: After 10 years of disease evolution, age at disease onset is not anymore associated with disease behavior but only with a small difference in the occurrence of specific extraintestinal manifestations and complications.

Prevalence of intestinal complications in inflammatory bowel disease: a comparison between paediatric-onset and adult-onset patients.

INTRODUCTION: Intestinal complications in inflammatory bowel disease indicate active inflammation and typically result in the intensification of therapy. AIM: To analyse whether the rates of intestinal complications were associated with age at disease onset. PATIENTS AND METHODS: Data from 1506 individuals with Crohn's disease (CD) and 1201 individuals with ulcerative colitis (UC) were obtained from the Swiss inflammatory bowel disease cohort study database, classified into groups on the basis of age at diagnosis (<10, <17, <40 and >40 years of age), and retrospectively analysed. RESULTS: In CD patients, the rates of stricturing (29.1-36.2%), abdominal penetrating disease (11.9-18.2%), resectional surgery (17.9-29.8%) and perianal disease (14.7-34.0%) were correlated with disease duration, but not age at diagnosis. However, paediatric-onset CD was associated with higher rates of multiple, rectal and anal strictures and earlier colon surgery. In addition, perianal disease occurred earlier, required earlier surgical intervention, and was more often combined with stricturing and penetrating disease. Finally, anal fissures were more prevalent among younger patients. In UC patients, the rates of progression or extension of disease (0-25.8%) and colectomy (3.0-8.7%) were dependent on disease duration, but not age at disease onset. Paediatric-onset disease was associated with a higher rate of extensive colitis at diagnosis and earlier progression or extension of disease, and nonsurgically treated patients with the youngest ages at onset more frequently required antitumour necrosis factor-α treatments. CONCLUSION: The higher rates of intestinal complications, including those of the small and large bowel and in the anal region, in paediatric-onset CD patients point towards a level of inflammation that is more difficult to control. Similar findings were also evident in UC patients.

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

BACKGROUND: There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). METHODS: Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. RESULTS: A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). CONCLUSIONS: In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy.

Steroid Administration and Growth Impairment in Children with Crohn's Disease.

BACKGROUND: Growth impairment remains a major concern in children with Crohn's disease, but evidence remains unclear, in particular, whether steroid use is implicated. We aimed to (1) determine the frequency of temporary (TGI) and permanent (PGI) growth impairment in children administered steroids and (2) examine whether cumulative steroid administration was associated with TGI and/or PGI. METHODS: A retrospective cohort study was performed in patients with Crohn's disease (<18 yr) administered steroids at the gastroenterology clinics of Sainte-Justine Hospital, Montreal. Steroid dosage, height during follow-up, adult height (after age 20), and parental heights were ascertained. Patients with height z score <-1.64 on more than 1 occasion before age 18 were considered as patients with TGI. Patients with adult heights <8.5 cm below the expected target heights were considered as patients with PGI. Association between steroid dosage and TGI/PGI was studied using logistic regression analyses. Data from the Swiss IBD Cohort Study were analyzed for comparison. RESULTS: A total of 221 children were studied. Approximately 19% (42/221) children were deemed as TGI, and 8/137 patients (5.8%) had PGI. TGI was associated with diagnosis at younger age (P value 0.002) and steroid administration at younger age (P value 0.001), but not with steroid dosage. Final adult height was associated with target height, but not with cumulative steroid dosage. Rates of PGI in the Swiss cohort were ∼ 9.1% in steroid users and 2.7% in nonusers. CONCLUSIONS: Most children with TGI attain normal adult heights. Cumulative steroid use does not seem to be associated with either TGI or PGI in children with Crohn's disease.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS: THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

Early-onset Crohn's disease is a risk factor for smaller final height.

OBJECTIVES: Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS: Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS: Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION: Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Fecal overflow often affects children with chronic constipation that appears after the age of 2 years.

Chronic functional constipation with or without encopresis is a common problem in the pediatric population, and the prevalence of encopresis may be underestimated. The aim of this study was to assess the prevalence and risk factors for overflow incontinence in patients with chronic constipation seen at a pediatric gastroenterology consultation. A retrospective study of 270 files of patients seen between 1997 and 2012 was conducted, and a classification according to Rome III criteria was done. Among 145 (53.7%) boys and 125 (46.2%) girls, 117 had overflow incontinence (43.3%) - 41 (35%) girls and 76 (65%) boys. The first symptoms of chronic constipation appeared at a median age of 30 and 33 months in encopretic and 16 and 12 months in nonencopretic girls and boys, respectively. The first specialized consultation took place after a median disease duration of 26.5 and 24 months in encopretic and 16 and 9 months in nonencopretic girls and boys, respectively. A history of stool retention and the presence of scybala at examination, but not of pain at defecation or anal fissure, were associated with encopresis. The onset of chronic constipation after the age of 2 years, a longer disease duration, male gender, and a history of stool retention were seen as risk factors for the development of encopresis in patients with chronic functional constipation.

Coping is excellent in Swiss Children with inflammatory bowel disease: results from the Swiss IBD cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) starting during childhood has been assumed to impair quality of life (QoL) of affected children. As this aspect is crucial for further personality development, the health-related quality of life (HRQOL) was assessed in a Swiss nationwide cohort to obtain detailed information on the fields of impairment. METHODS: Data were prospectively acquired from pediatric patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by PCDAI and PUCAI. The age adapted KIDSCREEN questionnaire was evaluated for 110 children with IBD (64 with Crohn's disease 46 with ulcerative colitis). Data were analyzed with respect to established reference values of healthy controls. RESULTS: In the KIDSCREEN index a moderate impairment was only found for physical wellbeing due to disease activity. In contrast, mental well-being and social support were even better as compared to control values. A subgroup analysis revealed that this observation was restricted to the children in the German speaking part of Switzerland, whereas there was no difference compared to controls in the French part of Switzerland. Furthermore, autonomy and school variables were significantly higher in the IBD patients as compared to controls. CONCLUSIONS: The social support for children with IBD is excellent in this cohort. Only physical well-being was impaired due to disease activity, whereas all other KIDSCREEN parameters were better as compared to controls. This indicates that effective coping and support strategies may be able to compensate the burden of disease in pediatric IBD patients.

Low prevalence of behavioural and emotional problems among Swiss paediatric patients with inflammatory bowel disease.

OBJECTIVES: Whether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric IBD patients for problems with emotional and behavioural adjustment and to examine associations with clinical and demographic variables. METHODS: Data from paediatric patients with IBD enrolled in the Swiss IBD Cohort Study and the results of both the parent-rated Strengths and Difficulties Questionnaire (SDQ) and the self-reported Child Depression Inventory (CDI) were analysed. Of the 148 registered patients, 126 had at least one questionnaire completed and were included. RESULTS: The mean age of 71 patients with Crohn's disease (44 males, 27 females) was 13.4 years, and 12.8 years for the 55 patients with ulcerative or indeterminate colitis. The mean duration of disease was 1.2 and 2.7 years, respectively. The total score of the SDQ was abnormal in 11.4% of cases compared to 10% in the normal population. Abnormal sub-scores were found in 20.2% of subjects for the domain of emotional problems and in 17.1% for problems with peers. The total CDI T score indicated a significantly lower prevalence of clinical depression in IBD patients than in normal youth. No correlation between the total SDQ scores or the CDI T scores and gender, type or duration of IBD, inflammatory markers or disease scores was found. CONCLUSIONS: The prevalence of problems with behavioural and emotional adjustment among Swiss paediatric IBD patients is low and comparable to that of the normal population.

Bardet-Biedl Syndrome, Crohn Disease, Primary Sclerosing Cholangitis, and Autoantibody Positive Thyroiditis: A Case Report and A Review of a Cohort of BBS Patients.

Bardet-Biedel syndrome (BBS) is a rare autosomal recessive, genetically heterogeneous ciliopathy. Although the disease has been described in a patient with psoriasis, individuals with BBS are not known to be at risk of developing autoimmune disorders. Our objective was to describe a 14-year-old patient with BBS who presented with Crohn disease (CD), primary sclerosing cholangitis (PSC), and thyroiditis in the context of a cohort review at Sainte-Justine Hospital and to alert clinicians to the increased risk of autoimmune disorders in these patients. The cohort contained fifteen patients (9 boys), followed from 1968 to 2009 during a median period of 12 years (range 9 months-26 years). Three of the 15 patients (20%) developed a chronic autoimmune disease: one had juvenile rheumatoid arthritis; a second one had type 1 diabetes mellitus in association with Hashimoto thyroiditis and psoriasis; a third one developed CD, PSC, and Hashimoto thyroiditis. As chronic autoimmune diseases occurred in 20% of our cohort of children with BBS, it is appropriate to keep this association in mind during the followup.

Patient satisfaction with the services of a pediatric digestive tract endoscopy unit: validation and application of a questionnaire.

Global satisfaction is the result of satisfaction with sequential connected caregiving activities administered according to current quality standards. We assessed patients' satisfaction with diagnostic digestive endoscopy via a questionnaire, asking for the state of information, organizational issues, anxiety, pain and discomfort, and medication side effects. A total of 157 patients completed the questionnaire before and after the procedure, and the endoscopy nurse filled it during the procedure. Despite a high rate of global satisfaction, the questionnaire disclosed several items to improve: Patient information on medication intake before digestive endoscopy was insufficient. Patients would have appreciated more detailed description on the type of sedation during the procedure. While the amnesic effect of our sedation was good, the analgesic effect was less optimal. These results suggest that the questionnaire is a valid tool to assess both patients' satisfaction and quality of care in a pediatric endoscopy unit and that patient satisfaction does not necessarily reflect quality of care.

The mutation spectrum in RECQL4 diseases.

Mutations in the RECQL4 gene can lead to three clinical phenotypes with overlapping features. All these syndromes, Rothmund-Thomson (RTS), RAPADILINO and Baller-Gerold (BGS), are characterized by growth retardation and radial defects, but RAPADILINO syndrome lacks the main dermal manifestation, poikiloderma that is a hallmark feature in both RTS and BGS. It has been previously shown that RTS patients with RECQL4 mutations are at increased risk of osteosarcoma, but the precise incidence of cancer in RAPADILINO and BGS has not been determined. Here, we report that RAPADILINO patients identified as carriers of the c.1390+2delT mutation (p.Ala420_Ala463del) are at increased risk to develop lymphoma or osteosarcoma (6 out of 15 patients). We also summarize all the published RECQL4 mutations and their associated cancer cases and provide an update of 14 novel RECQL4 mutations with accompanying clinical data.

13C-labeled mixed triglyceride breath test (13C MTG-BT) in healthy children and children with cystic fibrosis (CF) under pancreatic enzyme replacement therapy (PERT): a pilot study.

The MTG-BT estimates the hydrolysis of triacyl-glycerols by pancreatic lipase, and appears attractive for monitoring exogenous lipase requirements in patients with exocrine pancreatic insufficiency. To assess the test's discrimination capacity and repeatability, 9 CF patients with PERT and 10 healthy children underwent the (13)C-MTG-BT twice, at a 2- to 4-week interval. The test distinguished well between patients with severe exocrine pancreatic insufficiency (SEPI) and healthy subjects. However, within-subject variability for postprandial per thousand(13)C-enrichment and postprandial % dose recovery (PDR) was high in both groups. Therefore, the (13)C-MTG-BT seems useful to distinguish between SEPI and normal exocrine pancreatic function, but requires further development to improve its repeatability.

Interface hepatitis is associated with a high incidence of late graft fibrosis in a group of tightly monitored pediatric orthotopic liver transplantation patients.

Chronic graft dysfunction, manifesting with elevated liver enzymes and histological features of interface hepatitis (IH), is being increasingly recognized as a long-term problem after liver transplantation. The aim of this study was to characterize our group of post-orthotopic liver transplantation (OLT) patients with respect to clinical, laboratory, and histological signs of IH. A retrospective study of charts and liver biopsy specimens from patients transplanted between 1986 and 1999 was used. Histological features of IH were found in 29/119 patients at a median interval of 23.9 months (95% confidence interval -28.2 to 52.6) after OLT. All patients with IH had risk factors for chronic rejection, such as steroid-resistant rejection, acute rejection later than 3 months post-OLT, female receiver of male graft, or pretransplant cytomegalovirus (CMV)-positive serology with a CMV-negative donor liver. None of the 29 had features favoring a diagnosis of de novo autoimmune hepatitis, but 4 had isolated hypergammaglobulinemia, and 4 had non-organ-specific autoantibodies without hyperimmunoglobulin G. Sixteen of 29 patients also had features of chronic rejection, such as foam cell arteriopathy, loss of bile ducts, or pericentral fibrosis. After abnormal biopsy, all but 1 patient were switched to tacrolimus. During a median follow-up of 12 years, death occurred in 5, retransplantation occurred in 7, and definite cirrhosis occurred in 4. In conclusion, IH was detected in 24.4% of our patients and was associated with a high degree of fibrosis development. Most likely, IH represents a form of chronic rejection directed against periportal hepatocytes.

An immunohistochemical evaluation of C4d deposition in pediatric inflammatory liver diseases.

C4d is a marker of the activated complement cascade used to assess the humoral component of rejection, mostly in kidney allograft transplants. The role of C4d deposition has recently been addressed in hepatic allograft but has never been tested in a series of inflammatory liver diseases without previous liver transplantation. The aim of this study was to compare the immunohistochemistry profile of C4d deposition in a pediatric population, between a cohort of patients with autoimmune hepatitis (AIH) and a series of patients with chronic viral hepatitis B or C. Immunohistochemical analysis was performed on 64 liver biopsies. C4d deposition was observed in 25 (83%) of 30 AIH biopsies examined, in 6 (40%) of 15 hepatitis C biopsies, and in 17 (89%) of 19 hepatitis B biopsies. No expression of C4d was observed in 4 noninflammatory liver specimens used as negative controls. In the AIH group, a staining of the periportal sinusoids was often observed, as well as focal periductal reinforcement. Centrolobular vein staining was observed in the 3 hepatitis groups with a higher frequency in viral hepatitis B biopsies. Regardless of the etiology, lymphoid aggregates demonstrated an accentuation of the staining. These results confirm a role for a humoral immune response in pediatric autoimmune as well as in viral hepatitis. The relative ratios of positive cases imply that this immunostaining does not represent a strong diagnostic criterion in the differentiation between viral hepatitis and AIH. However, differences in the pattern of the staining were observed, depending on the etiology of the disease. The high prevalence of C4d reactivity in viral hepatitis strongly suggests that C4d does not represent a useful marker in the differentiation between acute rejection and viral hepatitis relapse in liver transplants.

High rate of complicated idiopathic gallstone disease in pediatric patients of a North American tertiary care center.

AIM: To assess spectrum and etiology of gallstones and biliary sludge in the pediatric population of a North American tertiary care centre. METHODS: Retrospective review of abdominal ultrasounds recorded at Saint Justine Hospital over a period of 24 mo (8/2003 to 8/2005) in patients < 19 years of age. Patients < 2 years of age were analyzed separately. RESULTS: The presence of gallstones was noted in 127 patients. In 107 it was a new diagnosis, in 48/105 (45.7%) patients > 2 years of age idiopathic gallstone disease was found. These 48 patients represent 2.1% of the population who required ultrasound for abdominal pain. Complicated gallstone disease occurred in 28/48 with idiopathic disease, mainly adolescent girls. Patients with hemolytic disorders, cystic fibrosis, oncologic diseases or kidney transplantation and gallstones were asymptomatic and stones were detected during routine abdominal ultrasound. Twenty two patients < 2 years of age not consulting for abdominal pain had gallstone disease of diverse etiology. Biliary sludge was seen in 84 patients, 78.5% on total parenteral nutrition. In 4 patients, sludge progressed to gallstones. CONCLUSION: Idiopathic gallstone disease and its rate of complication are more frequent in our cohort than expected from previous studies. Adolescent girls with abdominal pain and idiopathic gallstones require special attention for complicated disease course.

Recurrent pancreatitis in mitochondrial cytopathy.

Diabetes mellitus and exocrine insufficiency are the commonest pancreatic manifestations of mitochondrial diseases. In contrast, pancreatitis has rarely been described in mitochondrial syndromes. We report on a patient with Kearns-Sayre syndrome and recurrent episodes of acute pancreatitis for which no explanation could be found other than the associated mitochondrial dysfunction. Interestingly, pharmacological disruption of mitochondrial metabolism in various models as well as in patients can cause pancreatitis, further supporting this association. A diagnosis of pancreatitis should be considered in any patients with mitochondrial disease and recurrent abdominal pain.

Normal glomerular filtration rate in long-term follow-up of children after orthotopic liver transplantation.

BACKGROUND: Cyclosporine A (CyA) and tacrolimus are the principal immunosuppressive agents used for OLT in children. However, progressive deterioration of renal function from calcineurin inhibitor toxicity after OLT has been widely reported. The aim of this study was to assess long-term renal function in children after OLT. METHODS: We reviewed all OLT patients surviving >1 year at Sainte Justine Hospital from 1987 to 2003. The GFR (ml/min/1.73 m) was measured yearly by the Tc-99m DTPA single injection technique RESULTS: In all, 101 OLT patients (27 tyrosinemia, 33 biliary atresia, 5 fulminant hepatic failure, 36 miscellaneous) were studied. Median age at OLT was 35 months (range 6-178 months) in tyrosinemia group and 58 months (range 1-226 months) in the "Others" (P = NS), median pediatric end-stage liver disease score was respectively 3 (range -9 to 21) and 15 (-9 to 35), (P=0.001), and median follow-up was 6 (range 1-14) and 6 (range 1-17) (P = NS) years, respectively. Median annual GFR values in tyrosinemia fluctuated between 61 and 104 ml/min/1.73 m, with an improving tendency, and 94-121 ml/min/1.73 m in the Others. GFR did not differ on CyA vs. tacrolimus treatment. The median duration of therapy with calcium-channel blocker in the tyrosinemia group was 5 (1-13) vs. 2 (1-13) years in the Others. CONCLUSIONS: Median GFR remained normal in most nontyrosinemia patients (Others). Tyrosinemia patients remained stable at a lower GFR. CyA administration in three daily doses and prolonged calcium-channel blocker therapy may have contributed to this stability. Impairment of kidney function was associated with congenital kidney disease, toxic kidney injury, and portal hypertension.