Autonomic nervous system dysregulation in children with monosymptomatic nocturnal enuresis.

AIM: To investigate the role of autonomic nervous system in subpopulations of children with enuresis. METHODS: We included 35 children with enuresis, divided in children with (17) and without nocturnal polyuria (18) and 43 healthy controls. For all participants hormones and neurotransmitters were measured. Patients and controls wore a sleep tracker device and children with enuresis underwent a 24 h blood pressure monitoring, nocturnal urine output measurement and uroflowmetry. RESULTS: Children with enuresis had lower than controls copeptin and aldosterone, with the latter being more prominent in patients without nocturnal polyuria. Dopamine was lower in patients without nocturnal polyuria compared with patients with nocturnal polyuria. Children without polyuria experienced episodes only during NREM sleep, whereas in children with polyuria episodes occurred in both REM and NREM sleep. Children with enuresis experienced a non-dipping phenomenon during sleep which was more prominent in the group without polyuria. CONCLUSION: In patients with nocturnal polyuria, nocturnal enuresis is associated with sympathetic hyperactivity which results in pressure polyuria and significantly lower systolic dipping during sleep. On the contrary, in children without nocturnal polyuria, it is mostly associated with bladder overactivity due to parasympathetic overstimulation as demonstrated by the NREM-related enuretic episodes and the lower aldosterone and dopamine levels.

The Phenotypic Variability Associated with Hepatocyte Nuclear Factor 1B Genetic Defects Poses Challenges in Both Diagnosis and Therapy.

The evolving landscape of clinical genetics is becoming increasingly relevant in the field of nephrology. HNF1B-associated renal disease presents with a diverse array of renal and extrarenal manifestations, prominently featuring cystic kidney disease and diabetes mellitus. For the genetic analyses, whole exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were performed. Bioinformatics analysis was performed with Ingenuity Clinical Insights software (Qiagen). The patient's electronic record was utilized after receiving informed consent. In this report, we present seven cases of HNF1B-associated kidney disease, each featuring distinct genetic abnormalities and displaying diverse extrarenal manifestations. Over 12 years, the mean decline in eGFR averaged -2.22 ± 0.7 mL/min/1.73 m2. Diabetes mellitus was present in five patients, kidney dysplastic lesions in six patients, pancreatic dysplasia, hypomagnesemia and abnormal liver function tests in three patients each. This case series emphasizes the phenotypic variability and the fast decline in kidney function associated with HNF-1B-related disease. Additionally, it underscores that complex clinical presentations may have a retrospectively straightforward explanation through the use of diverse genetic analytical tools.

Antibody-mediated rejection with the presence of glomerular crescents in a pediatric kidney transplant recipient: A case report.

Glomerular crescents in kidney transplantation are indicative of severe glomerular injury and constitute a hallmark of RPGN. Their concurrence with ABMR has been rarely described only in adult patients. We report a case of 10-year-old boy with compound heterozygous Fin-major Finnish-type congenital nephrotic syndrome, who had received a deceased-donor kidney transplant 5 years before onset of acute kidney injury and nephrotic range proteinuria without hematuria. Kidney allograft biopsy illustrated 6 glomeruli with global sclerosis and 6 with remarkable circumferential or segmental cellular crescents. Negative glomerular immunofluorescence for immune-complex deposits and the absence of serum ANCA eliminated the presence of immune-mediated and ANCA-positive pauci-immune crescentic glomerulonephritis. Diagnosis of ABMR was based on the high levels of HLA class II DSA and the histological evidence of glomerulitis, peritubular capillaritis, and acute tubular injury with positive linear peritubular capillary C4d staining. The patient despite plasmapheresis and enhanced immunosuppressive treatment progressed to end-stage renal disease. We conclude that glomerular crescents may represent a finding of AMBR and possibly a marker of poor allograft prognosis in pediatric patients.

Short-term antibiotic exposure affected the type and resistance of uropathogens similar to long-term antibiotic prophylaxis in children hospitalised for urinary tract infections.

AIM: We investigated the impact of any antibiotic exposure on unusual and resistant pathogens in children with a urinary tract infection (UTI). METHODS: This was a retrospective cohort study of 695 children (54% female) hospitalised with 711 UTI episodes at Heraklion University Hospital, Greece, from January 2007 to December 2017. Three groups were studied: no previous antibiotic exposure, ongoing prophylaxis and short-term exposure to antibiotics in the last six months. RESULTS: The median age at hospitalisation was 0.8 years (range 25 days to 15.9 years). Previous short-term exposure and prophylaxis were important determinants of non-Escherichia coli (E. coli) (OR 2.05, 95% CI 1.25-3.36, P = .0017 and OR 3.84, 95% CI 2.32-6.34, P < .0001, respectively) and extended-spectrum beta-lactamase-positive uropathogens (OR 2.43, 95% CI 1.36-4.32, P = .0025 and OR 2.63, 95% CI 1.31-5.33, P = .0070, respectively). Short-term antibiotics in the last 30 days or intravenous antibiotics were mostly associated with non-E. coli pathogens (OR 6.71 and OR 2.55, respectively). The most important determinants of E. coli resistance were short-term antibiotics for ampicillin (OR 2.58) and prophylaxis for cotrimoxazole (OR 2.64). CONCLUSION: Recent short-term exposure to antibiotics and ongoing prophylaxis both had a significant impact on the type and resistance of uropathogens.

Vascular endothelial growth factor-A gene polymorphism is associated with congenital renal lesions in children with urinary tract infections.

AIM: This study investigated the relationship between vascular endothelial growth factor-A (VEGF-A)-460C/T functional gene polymorphism and renal parenchymal lesions, vesicoureteral reflux and other urinary tract abnormalities in children with a urinary tract infection (UTI). METHODS: VEGF-A-460C/T gene polymorphism was investigated with restriction length polymorphism analysis in 76 children with their first UTI and in 63 controls without infections. Genotype and allele frequencies were compared between children with UTIs and controls and between different groups with UTIs. RESULTS: The VEGF-A-460C/T genotype frequencies differed significantly between those with and without renal parenchymal lesions in the UTI cohort. Allele C homozygosity was significantly more common in those with renal parenchymal lesions (36.6% versus 8.7%, p = 0.007). A separate analysis showed that allele C was associated with lesions compatible with hypodysplasia, rather than with focal ones associated with infections, with an odds ratio of 11.55 and 95% confidence interval of 3.03-43.9 (p = 0.0001). No significant differences in genotypes or allele frequencies were found between children with and without reflux or other urinary tract anomalies. CONCLUSION: In children with UTIs, C allele polymorphism of the VEGF-A gene was associated with hypodysplastic renal parenchymal lesions, which were possibly congenital and existed before the infection.

Acute focal bacterial nephritis, pyonephrosis and renal abscess in children.

BACKGROUND-AIM: Acute focal bacterial nephritis (AFBN), renal abscess and pyonephrosis are uncommon and not fully addressed forms of urinary tract infection (UTI) which may be underdiagnosed without the appropriate imaging studies. Here, we review the characteristics and outcome of these renal entities in children managed at a single medial centre. PATIENTS AND METHODS: The medical files of all children hospitalized for episodes of AFBN, renal abscess and pyonephrosis during a 10-year period (2003-2012) were reviewed. RESULTS: Among the 602 children hospitalized for UTI, 21 presented with AFBN, one with abscess and three with pyonephrosis. All 25 children (13 girls), ranging in age from 0.06 to 13.4 years, were admitted with fever and an impaired clinical condition, and 18 had urological abnormalities. More than one lesion, often of different types, were identified in 11 episodes. Urine cultures from 13 episodes grew non-Escherichia coli pathogens and those from two episodes were negative. Antibiotics were administered for 14-60 days, and emergency surgery was required in three cases. During follow-up, 13 patients underwent corrective surgery. Permanent renal lesions were identified in 16 patients. CONCLUSIONS: AFBN, renal abscess and pyonephrosis should be suspected in children with severe presentation and urological history. Appropriate imaging is crucial for management planning. Prognosis is often guarded despite appropriate treatment. Based on the results of this study we propose a management algorithm.

Incidence and morbidity of urinary tract infection in a prospective cohort of children.

AIM: Information on the epidemiology of childhood urinary tract infections (UTIs) is scarce and mostly based on retrospective data. This study investigated incidence rates, morbidity and risk factors for UTIs in a prospective cohort of children. METHODS: We explored UTIs in a representative cohort of 1049 neonates from birth to 6 years of age, using maternal interviews that were verified by hospital records. The majority (88.2%) completed the first-year, and more than half (56.2%) completed the 6-year follow-up. RESULTS: By 6 years of age, more than 10% of our sample had been affected by UTIs. The cumulative incidence for the first year of life was 3.77%, without significant differences between genders, and for one to 6 years, it was 6.81% and 5.7 times higher in girls than boys. Clinical information was available for 63 children: 25 were hospitalised, 16 suffered recurrences, 10 received prophylaxis, eight had urinary tract malformations, three required surgery, and two had impaired renal function. CONCLUSION: UTIs affected approximately 4% and 10% of children by the ages of one and 6 years, respectively, and their incidence was related to gender and age. Morbidity was considerable, recurrences were common, and despite advances in management, long-term consequences may still be encountered.

Long-term resistance trends of uropathogens and association with antimicrobial prophylaxis.

BACKGROUND: The aim of this study was to identify long-term resistance trends of uropathogens and determine the effect of prophylaxis in a pediatric patient population. MATERIALS AND METHODS: A total of 638 uropathogens were isolated from urine samples collected from children hospitalized for urinary tract infection during the 12-year study period (1997-2008) and analyzed. RESULTS: The most frequent uropathogen identified was Escherichia coli (69 %), followed by Klebsiella spp. (9.7 %), Pseudomonas aeruginosa (6.7 %), Enterococcus spp. (5.6 %), and Proteus spp. (4.4 %). High resistance rates were observed for common agents used for empiric treatment, such as amoxicillin, cotrimoxazole, and ceftriaxone. Resistance increased over time for nitrofurantoin, ceftriaxone, and piperacilin-tazobactam (chi-square for trend p < 0.0002, p < 0.0034 and p < 0.014, respectively) and decreased for cefuroxime (p < 0.016) and gentamicin (p < 0.014). The use of prophylaxis was related to an increased proportion of non-E. coli pathogens (46.9 vs. 26.9 %; odds ratio 2.4, 95 % confidence interval 1.61-3.55; p < 0.0001), as well as to increased resistance of non-E. coli pathogens, and was a major risk factor associated with resistance to amoxiclav (p < 0.005), cotrimoxazole (p < 0.0001), cefuroxime (p < 0.0001), ceftriaxone (p < 0.0001), gentamicin (p < 0.0001), and nitrofurantoin (p < 0.0001). CONCLUSIONS: Our findings point to considerable changes in the long-term resistance patterns of uropathogens and an association of prophylaxis with resistance. Our results suggest the need for continuous surveillance, re-evaluation of empiric regimens and further assessment of the role of prophylaxis in the treatment of urinary tract infection.

The role of the autonomic nervous system in nocturnal enuresis.

INTRODUCTION: Nocturnal enuresis (NE) is common in children, but its pathophysiology is still not fully understood. Despite the recognition of three major pathways, nocturnal polyuria, nocturnal bladder dysfunction and sleep disorders, their inter-relations remain elusive. The autonomic nervous system (ANS) which is greatly involved in both diuresis and sleep might have an important role in NE. METHODS: A comprehensive electronic search of Medline database was performed, to identify articles reporting on the role of the autonomic nervous system (ANS) in enuretic children regarding sleep regulation, cardiovascular function and diuresis-related hormones and neurotransmitters. RESULTS: Of an initial total of 646 articles, 45 studies were finally selected for data extraction according to inclusion criteria, published between 1960 and 2022. Of these studies 26 reported on sleep regulation, 10 on cardiovascular functions and 12 on ANS-associated hormones and neurotransmitters. Evidence on parasympathetic or sympathetic overstimulation in enuretic individuals is suggesting that NE could be attributed to a dysregulation of ANS. Sleep studies have shown increased rapid eye movement sleep time in polyuric enuretic children pointing to sympathetic overactivity, whereas patients with overactive bladder have non-rapid eye movement related enuretic episodes, potentially associated with parasympathetic stimulation. Twenty-four-hour blood pressure monitoring demonstrated "non-dipping" phenomenon, suggesting sympathetic involvement, whereas heart-rate analysis showed parasympathetic hyperfunction. Nocturnal lower levels of arginine-vasopressin, angiotensin II and aldosterone in polyuric children with NE as compared to non-polyuric and controls and potential involvement of dopamine and serotonin in sleep and micturition suggest that ANS-associated hormones and neurotransmitters have a role in the pathogenesis of NE. CONCLUSION: Summarizing the existing data we suggest that ANS dysregulation related either with sympathetic or parasympathetic overactivity may provide a unifying model in understanding the pathogenesis of NE in different enuretic subpopulations. This observation provides new insights in future research and new potential treatment options.

Urine IL-8 concentrations in infectious and non-infectious urinary tract conditions.

Urine IL-8 concentrations are known to be elevated in urinary tract infection (UTI), as well as in vesicoureteral reflux (VUR) even in the absence of infection. In this study we further investigated urine IL-8 in infants with congenital anomalies of the kidneys and urinary tract and with antenatally diagnosed isolated pelvic dilatation. Urine IL-8 was measured in 159 infants aged 1 month to 1 year with acute UTI (group A, n = 26), resolved UTI (group B, n = 16), VUR without recent UTI (group C, n = 44), non-VUR congenital urinary anomalies without recent UTI (group D, n = 30), isolated antenatal pelvic dilatation (group E, n = 14) and in infants without known urinary tract condition (control group F, n = 29). Median values of urine IL-8/creatinine levels were 61.5, 4.64, 15.5, 14.3, 1.06 and 4.19 pg/µmol in groups A, B, C, D, E and F respectively. Compared with the control group, urine IL-8 was elevated in infants with acute UTI, VUR without acute UTI and congenital anomalies without acute UTI (p < 0.0001; p < 0.005; and p = 0.027 respectively), but not in infants with resolved UTI or with antenatal pelvic dilatation. Urine IL-8 levels are elevated in a variety of infectious and non-infectious urinary tract conditions, and hence may serve as a sensitive but not specific screening biomarker of urinary tract diseases.

Acute mastoiditis complicated by cerebral venous sinus thrombosis in children.

AIM: Diagnosis and management of complicated mastoiditis in childhood are still controversial. We investigated the clinical manifestations, evaluation and management of children with mastoiditis complicated with cerebral venous sinus thrombosis. METHODS: Retrospective cohort study that included all children admitted for acute mastoiditis over the last 5 years. Children were divided in two groups based on the presence or not of venous sinus thrombosis. Clinical, laboratory, imaging and management data were retrieved and compared. RESULTS: Overall, 20 children with acute mastoiditis were included, of whom 5 had magnetic resonance imaging-confirmed cerebral venous sinus thrombosis and elevated intracranial pressure (ICP). In all complicated cases, neurological signs rather than mastoiditis signs, prevailed. The more prominent neurologic signs observed were lethargy (60%), nuchal rigidity (60%), abducens nerve palsy (60%) and ataxic gait (20%). Treatment consisted of intravenous antibiotics combined with anticoagulation. Surgery was performed in four children (4/5). Complicated cases had prolonged symptoms prior to admission (p 0.002), presented with neurologic signs and symptoms (p < 0.001), underwent more often lumbar puncture (p < 0.001) and brain imaging (p < 0.001), and were treated with prolonged courses of antibiotics and surgery (<0.001), compared to children with uncomplicated mastoiditis. CONCLUSION: Neurological signs and symptoms and elevated ICP dominate in children with mastoiditis complicated with thrombosis. Brain imaging is essential for early diagnosis of cerebral venous sinus complications and appropriate management.

Case Report: Α Case of Endocarditis and Embolic Stroke in a Child, Suggestive of Acute Q Fever Infection.

Acute Q fever is usually asymptomatic or is associated with a mild self-limited course and a favorable outcome. The occurrence of endocarditis during acute infection by Coxiella burnetii is an emerging clinical entity observed in adults that has been attributed to an autoimmune complication of early infection. Herein, we report the first case of a previously healthy 2-year-old child with endocarditis complicated by septic embolic stroke, in which the identified microbiological evidence was suggestive of acute rather than chronic C. burnetii infection. The development of endocarditis in this case occurred in the absence of any autoimmune reaction, but in the context of a very mild form of congenital heart disease, a small ventricular septal defect, which might serve as a predisposing factor for endocarditis. This case suggests that acute Q fever endocarditis may affect children as well and can be attributed not only to autoimmune mechanisms but also to a potential effect of the infectious agent per se on the cardiac endothelium in patients with underlying heart defects, regardless of their severity.

Resistance against broad-spectrum beta-lactams among uropathogens in children.

The aim of this study was to investigate the prevalence trends and risk factors for urinary tract infection (UTI) caused by Enterobacteriaceae resistant to broad-spectrum beta-lactams in children. All Enterobacteriaceae uropathogens from children <15 years during the 11-year period 1997-2007 were included, and risk factors were evaluated. Of 523 Enterobacteriaceae isolated from 473 children, 30 (5.73%) were phenotypically resistant to broad-spectrum beta-lactams (18 Escherichia coli, ten Klebsiella spp, one Enterobacter spp, and one Citrobacter spp). The prevalence of resistance increased during the study period (p = 0.031). Resistance to cefoxitin was common (26/30), pointing to AmpC enzyme expression, and 2/30 isolates were resistant to carbapenems. Resistant Enterobacteriaceae were often community acquired (22/30, 73.3%) and related to male gender (p < 0.05), urinary tract abnormalities (p < 0.05), prophylactic antibiotics (p < 0.0001), longer hospitalization (p < 0.001), and UTI recurrences (p < 0.001). Co-resistance was more likely for cotrimoxazole, gentamicin, and ciprofloxacin (p < 0.0001). In conclusion, our study points to increasing prevalence of Enterobacteriaceae uropathogens resistant to broad-spectrum beta-lactams in the community setting, which limits the utility of first-line antibiotics and questions the validity of using prophylaxis after a first UTI episode.

The question of futility and Roger C. Bone.

Medical futility, one of the most debated end-of-life issues in medical ethics, has been discussed among physicians and scholars for years but remained an unresolved question. Roger C. Bone (1941-1997), an outstanding pulmonologist and critical care specialist, devoted his last years to ethical issues of terminal care, while facing himself metastatic renal cancer. Criticising the abuse of technology in terminal care and the administrative and financial interference on medical decisions, he bequeathed important points on futility, bringing also patients' views into attention. He stressed the importance of physician-patient relationship and prompted physicians to remain honest with their patients and stand with them till their very last moments. Roger Bone's insight of futility, terminal care and physician-patient relationship remains an important legacy for health care professionals and for families and patients facing end-of-life issues.

When to Think of Rickettsia.

Rickettsiae are globally encountered pathogens with foci of endemicity and epidemic exacerbations under circumstances of crowding and decline of sanitation. Diagnosis is often missed due to misconceptions about epidemiology, confusing terminology and nonspecific clinical presentation. Rickettsioses should be considered in children with febrile illnesses exceeding the usual duration of a viral infection, in particular in children with rash, lymphadenopathy and nearly normal first-line laboratory tests, who reside in or return from endemic areas, recall a compatible contact history, have a constellation of symptoms starting after an arthropod bite, live under troubled social circumstances, or are part of a cluster of similar cases.

A Novel CLCN5 Splice Site Mutation in a Boy with Incomplete Phenotype of Dent Disease.

Dent disease is a rare X-linked renal proximal tubulopathy presenting with low-molecular-weight proteinuria (LMWP), hypercalciuria, and nephrocalcinosis, other signs of incomplete renal Fanconi syndrome, and renal failure. Early identification of patients who harbor disease-associated mutations is important for effective medical care and avoidance of unnecessary interventions. We report the case of an asymptomatic 9-year-old boy who presented with proteinuria in routine examination. Further investigation revealed the presence of nephrotic range proteinuria, mostly LMWP and mild hypercalciuria without nephrocalcinosis, or other features of tubular dysfunction. Renal function, growth, and bone mineral density were within regular limits. The male gender and the presence of LMWP and hypercalciuria even in the absence of other findings prompted us to genetic investigation for Dent disease. A novel splice site mutation (c.416-2A > G) of the chloride voltage-gated channel 5 ( CLCN5 ) gene, responsible for Dent disease type 1 was identified. In silico analysis revealed that this mutation interferes with the mating of exons 4 and 5. Due to early molecular diagnosis, our patient did not undergo a renal biopsy, neither required aggressive pharmacological interventions. This case underscores the diversity and complexity of CLCN5 mutations and highlights the importance of early molecular testing in male patients with incomplete phenotype of Dent disease.

Siesta and sleep patterns in a sample of adolescents in Greece.

BACKGROUND: Sleep behaviors and disturbances in adolescence are being increasingly investigated. The aim of the present study was to investigate the sleep habits of adolescents living in provincial Greece. METHODS: Responses to pre-constructed questionnaires on sleep habits and disturbances from 471 high-school students (259 boys; 212 girls), aged 14-18 years, attending four high schools of rural and semi-urban areas in north-western Greece, were analyzed. RESULTS: The median nocturnal and total sleep duration was 7.5 h (range, 2.5-11 h) and 8.5 h (range, 2.5-14 h), respectively, and the average bedtime was 23.55 hours. Male students, older adolescents and residents of towns went to bed later than female students, younger adolescents and residents of villages (P = 0.039, P = 0.0003 and P = 0.056, respectively). Siesta on a regular basis was reported by 43% and on an occasional basis by 46% of the students. Siesta median duration was 1.5 h (range 0.5-4.5 h). Daytime sleepiness, difficulties in morning awakening and in falling asleep, and night awakenings were reported by 26.3%, 17.4%, 17.2% and 11.2%, respectively. Students who had siestas reported less daytime sleepiness (P < 0.0001). Significant differences were observed between boys and girls regarding sleep disturbances. CONCLUSION: Adolescents in provincial Greece present with a different sleep pattern as compared to their northern European peers, characterized by late bedtime and midday siesta. Similarly to their peers in other countries, considerable rates of sleep disturbances were reported.

Slow progression of renal failure in a child with infantile cystinosis.

Cystinosis is a rare autosomal recessive lysosomal transport disorder, characterized by the accumulation of the aminoacid cystine and progressive dysfunction of several organs. Kidneys are severely affected, and the most frequent form, infantile nephropathic cystinosis, presents with growth failure in infancy, renal Fanconi syndrome and end-stage renal disease by the first decade of life. We report of a girl with infantile nephropathic cystinosis that has reached adolescence without the need of renal replacement therapy and without extrarenal manifestations despite her delayed diagnosis and treatment initiation. The girl with this intermediate phenotype was found to have compound heterozygosity of one known (1015G > A) and one novel (587_588insA) mutation in CTNS gene. Our case points to the wide clinical presentation of infantile nephropathic cystinosis and suggest that long-term outcome is not always ominous as generally thought.

Invasive non-typhoidal salmonellosis in immunocompetent infants and children.

OBJECTIVE: To investigate the extraintestinal manifestations of non-typhoidal Salmonellae (NTS) infection in immunocompetent infants and children. METHOD: The study took place at the University General Hospital at Heraklion, Crete. Over a 10-year period from 1993-2002 we studied 1087 patients, of whom 443 were children less than 14 years old, with a culture-proven diagnosis of NTS infection. Stool and blood cultures were routinely obtained in patients presenting with fever and diarrhea. The cases of invasive infection in otherwise well children, including bacteremia and/or extraintestinal focal infections were further analyzed. RESULTS: Invasive cases were less common in children than adults (4.06% vs. 8.7%; relative risk 0.467; 95% confidence intervals (CI) 0.279-0.784; p=0.0033). Furthermore, invasive cases were much less common in the otherwise well than in immunocompromised children (3.5% vs. 21.4%; relative risk 0.163; 95% CI 0.053-0.500; p=0.0008). The 15 otherwise well children with invasive NTS infection were aged from 3 weeks to 7.5 years, and nine were aged less than 12 months. Among them, 11 presented with bacteremia, and four with focal extraintestinal infections (rectal abscess, deep neck abscess, urinary tract infection, elbow arthritis). Salmonella enterica subsp. enterica serovars Enteritidis and Virchow were the most common invasive serotypes. All invasive strains were susceptible to beta-lactams including ampicillin, and to cotrimoxazole. All patients made a complete recovery with intravenous antibiotics and did not present with relapses or major infections during long-term follow-up. CONCLUSION: Invasive non-typhoidal salmonellosis in immunocompetent children is less frequent than in both immunocompromised children and in adulthood. However, invasive cases may well occur in otherwise healthy children, especially during infancy. In these patients, prompt appropriate treatment leads to favorable outcomes.

Serum and urine interleukin-6 and transforming growth factor-beta1 in young infants with pyelonephritis.

BACKGROUND: Cytokines are involved both in the acute response during pyelonephritis and in the progression to renal scarring. The aim of the present study was to assess the pro-inflammatory interleukin-6 (IL-6) and the anti-inflammatory pro-fibrotic transforming growth factor-beta1 (TGF-beta) in very young infants with pyelonephritis. METHODS: Serum and urine concentrations of IL-6 and TGF-beta1 were determined by enzyme immunoassay in infants with acute pyelonephritis before antibiotic treatment and in infants with non-renal fever. IL-6 was studied in 12 infants with pyelonephritis and in eight with non-renal fever (median ages, 2 months for both groups). TGF-beta1 was studied in 11 infants with pyelonephritis and in nine with non-renal fever (median ages, 2 and 4 months, respectively). RESULTS: No significant differences were documented in serum concentrations of IL-6 and TGF-beta1 between patients and controls. Urine IL-6 levels were significantly higher in infants with pyelonephritis than in controls (medians, 147 and 21.4 pg/ml, respectively; P = 0.0106). The urine levels of TGF-beta1 were lower in infants with pyelonephritis than in controls, although not significantly (medians, 6.12 and 11.0 ng/ml, respectively; P = 0.0705). CONCLUSIONS: Our findings confirm the implication of IL-6 but not of TGF-beta1 in the pathogenesis of the early stages of pyelonephritis in young infants. Tauhe role of the pro-fibrotic TGF-beta1 in the development of renal scarring deserves further investigation.