Uromodulin and Vesico-Ureteral Reflux: A Genetic Study.

Vesicoureteral reflux (VUR) is associated with urinary tract infections (UTI) and renal scars. The kidney damage is correlated with the grade of reflux and the number of UTI, but other factors may also play a role. Uromodulin (UMOD) is a protein produced by kidney tubular cells, forming a matrix in the lumen. We evaluated whether the common variant rs4293393 in the UMOD gene was associated with febrile UTI (FUTI) and/or scars in a group of children with VUR. A total of 31 patients with primary VUR were enrolled. Renal scars were detected in 16 children; no scar was detected in 15 children. Genotype rs4293393 TC (TC) was present in 8 patients, 7 (88%) had scars; genotype rs4293393 TT (TT) was found in 23 patients, and 9 (39%) had scars. Among children with scars, those with TC compared with those with TT were younger (mean age 77 vs. 101 months), their reflux grade was comparable (3.7 vs. 3.9), and the number of FUTI was lower (2.9 vs. 3.7 per patient). Children with VUR carrying UMOD genotype rs4293393 TC seem more prone to developing renal scars, independent of FUTI.

[Survey on the Prevalence of Rare Kidney Diseases in Sicily].

Renal Diseases represent almost 6% of all Rare Diseases but are often misdiagnosed. In a survey made in Sicily in 2016, based on cases reported from all public hospitals according to a list of rare kidney diseases, we were able to collect 337 cases (199 males and 138 females). The highest prevalence was detected in children: 13.9 cases in 100.000 children; the mean age was 10, and the median 5 years, at the time of the diagnosis. Comparing our data with those available in the Sicilian Register of Rare Diseases we found that only 141 cases (54%) were present in the register. Promoting regional registries of rare kidney diseases in Italy may be useful for epidemiologic studies.

[Nephrocalcinosis in children].

Nephrocalcinosis (NC) is a renal disease characterized by deposition of calcium salts into the renal medulla. There are several causes, organic, iatrogenic, hereditary and sometimes related to extrarenal diseases. We studied 34 children affected by NC, 21 M and 13 F (average age at diagnosis 7.8 months), with the aim of analyzing the associated diseases, clinical manifestations, metabolic abnormalities, growth and renal function at onset and after follow-up. At onset 70% of patients were asymptomatic and diagnosis was occasional. Renal function was normal in 33 patients. The most frequent clinical symptoms were failure to thrive (9%), abdominal pain (6%), proteinuria/hematuria (7%). The associated diseases were: tubulopathies (8 pcs - tubular acidosis, Dent, Bartter and Lowe Syndromes), medullary sponge kidney, policalicosis (3 pcs ), Short bowel Syndrome (3 pcs), hyperparathyroidism, hypothyroidism (2 pcs), thalassemia (1pc), tyrosinemia (1 pc.). We recognized two forms of hypervitaminosis D. In a pc NC would be correlated with prematurity, another one with lipid necrosis. Among the metabolic abnormalities, observed in 25% of pcs, hyperoxaluria is the most frequent (47%), hypercalciuria (20%), hypercalcemia (15%). In some cases we found endocrine non pathogenic alterations: hypovitaminosis D (2 pcs) and hypoparathyroidism (6 pcs). During follow-up the growth was normal in 87% of cases and glomerular function was stable in 90% of pcs; IRC developed in 3 cases. From our analysis, it appears that the treatment of the underlying condition of NC is associated with catch-up growth and stabilization of renal function in most patients, but not with the reduction of the degree of the NC.

[Atypical Hemolytic Uremic Syndrome: experience of a pediatric center].

In the last two years we admitted in our Hospital 38 children with acute renal failure (ARF). Six of them were affected by hemolytic uremic syndrome (HUS) atypical. The aHUS is diagnosed in the presence of thrombotic microangiopathy (MAT), renal insufficiency (GFR 5%). The clinical presentation of our children has been varied and so also its evolution. Patients observed were all male, aged 2 to 12 years, and no one had a family history of kidney disease. In four patients we documented alterations of complement factors (MCP deficiency and factor H and presence of anti factor H). Repeated blood transfusions were required in 4 patients and in 3 patients the platelet count was slightly reduced. In 5 patients we did plasmapheresis and in 3 patients dialysis (hemodialysis and peritoneal dialysis). In three patients in whom the diagnosis was not clear, renal biopsy was performed to confirm the diagnosis. Eculizumab was administered in 3 patients resistant to plasma exchange. We obtain a rapid response on MAT with normalization of platelet count. The effect on renal function was variable (complete remission in a patient, partial improvement in another, and unresponsiveness in the last). The last had on Kidney biopsy signs of severe impairment and we documented the presence of antibodies to eculizumab. HUS is a rare condition, but probably much more common than reported. In children with ARF and microangiopathic anemia is necessary evaluated complement factors as early to obtain an improved clinical response to treatment with eculizumab.

Early origin of adult renal disease.

Observational studies in humans and experimental studies in animals have clearly shown that renal failure may start early in life. 'Fetal programming' is regulated by adaptations occurring in uterus including maternal nutrition, placental blood supply, and epigenetic changes. Low birth weight predisposes to hypertension and renal insufficiency. Congenital abnormalities of the kidney and urinary tract, adverse postnatal events, wrong nutritional habits may produce renal damage that will become clinically relevant in adulthood. Prevention should start early in children at risk of renal disease.