Management of the congenital solitary kidney: consensus recommendations of the Italian Society of Pediatric Nephrology.

BACKGROUND: In recent years, several studies have been published on the prognosis of children with congenital solitary kidney (CSK), with controversial results, and a worldwide consensus on management and follow-up is lacking. In this consensus statement, the Italian Society of Pediatric Nephrology summarizes the current knowledge on CSK and presents recommendations for its management, including diagnostic approach, nutritional and lifestyle habits, and follow-up. We recommend that any antenatal suspicion/diagnosis of CSK be confirmed by neonatal ultrasound (US), avoiding the routine use of further imaging if no other anomalies of kidney/urinary tract are detected. A CSK without additional abnormalities is expected to undergo compensatory enlargement, which should be assessed by US. We recommend that urinalysis, but not blood tests or genetic analysis, be routinely performed at diagnosis in infants and children showing compensatory enlargement of the CSK. Extrarenal malformations should be searched for, particularly genital tract malformations in females. An excessive protein and salt intake should be avoided, while sport participation should not be restricted. We recommend a lifelong follow-up, which should be tailored on risk stratification, as follows: low risk: CSK with compensatory enlargement, medium risk: CSK without compensatory enlargement and/or additional CAKUT, and high risk: decreased GFR and/or proteinuria, and/or hypertension. We recommend that in children at low-risk periodic US, urinalysis and BP measurement be performed; in those at medium risk, we recommend that serum creatinine also be measured; in high-risk children, the schedule has to be tailored according to kidney function and clinical data.

Pediatric Minimal Change Disease and AKI following the Pfizer-BioNTech COVID-19 Vaccine: causal or incidental correlation?

The global coronavirus 2019 (COVID-19) pandemic required vaccination even in children to reduce infection. We report on the development of acute kidney injury (AKI) and minimal change disease (MCD) nephrotic syndrome (NS), shortly after the first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). A 12-year-old previously healthy boy was referred to our hospital with complaints of peripheral edema and nephrotic range proteinuria. Nine days earlier he had received his first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). Seven days after injection, he developed leg edema, which rapidly progressed to anasarca with significant weight gain. On admission, serum creatinine was 1.3 mg/dL and 24-hour urinary protein excretion was 4 grams with fluid overload. As kidney function continued to decline over the next days, empirical steroid treatment and renal replacement therapy with ultrafiltration were started and kidney biopsy was performed. Seven days after steroid therapy, kidney function began to improve, gradually returning to normal. The association of MCD, nephrotic syndrome and AKI hasn't been previously described following the Pfizer-BioNTech COVID-19 vaccine in pediatric population, but this triad has been reported in adults. We need further similar case reports to establish the real incidence of this possible vaccine side effect.

T-lymphocyte populations and cytokines in childhood nephrotic syndrome.

We investigated lymphocyte subpopulations and the production of cytokines by T helper cell subtype 1 (Th1), Th2, and monocytes/macrophages (tumor necrosis factor-alpha [TNF-alpha]) in peripheral-blood mononuclear cells of 18 children with steroid-sensitive (SS) nephrotic syndrome (NS) and 10 children with steroid-resistant (SR) NS. Mean age was 10.9 +/- 5.7 years, with a mean follow-up before the study of 6 +/- 5 years. To evaluate the possible relationship between cytokine levels and response to treatment, patients with SS and SR NS were assessed during relapse/marked proteinuria (group A), total/partial remission (group B), and off treatment (group C). In children with SS and SR NS, we found no significant difference in CD3 counts compared with controls. The proportion of CD4 cells decreased significantly in relapse and off therapy compared with controls in children with SS NS, whereas in those with SR NS, there was a concomitant reduction in all groups. B-Lymphocyte counts were significantly increased in either group versus controls. In SR NS, CD8 and natural killer cell levels increased during relapse versus controls. The CD4+/CD8+ ratio was reduced to the same degree in those with SS and SR NS. In patients with SR NS, we observed increased levels of soluble interleukin-2 (IL-2) receptor (sIL-2R) from corresponding control values (P < 0.01). A significant increase in TNF-alpha levels was found in patients with SS and SR NS versus controls. High levels of IL-2, sIL-2R, and interferon-gamma during relapse in patients with SS NS give further evidence for a Th1 pattern that might be involved in the pathogenesis of NS, and monitoring the Th1/Th2 balance would be useful in evaluating the response to therapy.

Atopy in childhood idiopathic nephrotic syndrome.

AIM: Aim of the study was to evaluate the immunoallergic pattern and their modulating serum cytokines in children with primary manifestation of nephrotic syndrome, in order to analyse the correlation with disease activity and the outcome of childhood NS. MATERIALS AND METHODS: We have evaluated 72 children: 58 steroid-sensitive and 14 steroid-resistant; 42 subjects were the healthy controls. In all were measured serum: T cell-subset, cytokines by Th-1, Th-2, total IgE levels and specific IgE antibodies. RESULTS: Of the 72 children investigated, 35 (48.6%) had either a history of atopy and/or elevated serum IgE; 14 of these children (40%) had clinical sign of an atopic disease (asthma, rhinitis, dermatitis) and 21 (60%) had elevated sIgE. The atopy was more frequent among SS than SRNS patients (52% versus 36%, p<0.05). The CD19 were significantly increased in nephrotic patients compared with controls. IL-4 levels were not different from those in normal control both in SS and SRNS patients, either in relapse than in remission. There was no correlation between the sIgE and IL-4 levels. Therefore, IL-5 and Il-13 levels were significantly higher in SSNS compared to controls, in both pre than posttreatment, and higher in atopic patients. Interestingly, IL-6 and IL-10 levels were significantly increased in SRNS pretreatment compared to posttreatment and controls and, only for IL-10, significantly higher in atopic patients. CONCLUSION: In our study, only 40% of atopic children had a positive allergic history and 51.4% of the nephrotic children had normal sIgE levels, both pre and posttreatment, indicating different aetiologies, as immune mechanisms, in the pathogenesis of NS. Therefore, specific IgE antibodies were not related to disease activity, suggesting that IgE production might be co-incident in childhood NS. However, the increased production of IL-5 and IL-13 in atopic SSNS may indicate that these cytokines are involved in the enhanced production of sIgE while IL-4 have a role as controlling cytokine.

Pelviureteral junction obstruction: correlation of renal cell apoptosis and differential renal function.

PURPOSE: We evaluated the relationship between renal biopsy changes and preoperative and postoperative renal scans in 29 male and 14 female infants with prenatal severe hydronephrosis and unilateral ureteropelvic junction obstruction. We also verified on immunohistochemical studies glomerular changes, degeneration of the epithelium of the proximal tubules, interstitial fibrosis and inflammation and apoptotic nuclei. MATERIALS AND METHODS: In the children, all with prenatal diagnosis of hydronephrosis, ureteropelvic junction obstruction was diagnosed with 99mtechnetium mercaptoacetyltriglycine renal scan performed in all patients at ages 4 to 6 weeks to establish baseline differential renal function. All patients underwent renal biopsies at the time of pyeloplasty. The biopsy samples were examined with histological and immunohistochemical methods for antigens associated with apoptosis, such as clusterin, CD95, TDAG51 and bcl-2. Renograms were performed 3 months after surgical repair. RESULTS: The male-to-female ratio was 2.1:1. There was no difference between males and females in regard to baseline differential renal function of the affected kidney. All biopsy samples confirmed degeneration of the epithelium of the proximal tubules, interstitial focal fibrosis was found in 4 samples, mild chronic inflammation with lymphoid aggregates in 4 and focal Bowman's space dilatation in 1. No specimen demonstrated apoptotic nuclei as confirmed by immunohistochemical study which showed the presence of bcl-2 and absence of CD95, TDAG51 and clusterin, probably because there was no dysplasia in the samples examined. CONCLUSIONS: These results indicate absence of apoptosis in the kidney with preoperative uptake less than 40% and minimal histological changes.