Giancarlo Lavoratti

Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity

A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined.

Neonatal Anuria by ACE Inhibitors during Pregnancy

Giancarlo Lavoratti, MD, Department of Pediatrics, Unit of Nephrology, Osp. A Meyer, V.L. Giordano 13, I-50135 Firenze (Italy) Dear Sir, Angiotensin-converting enzyme inhibitors (ACE-I) are effective hypotensive drugs and extensively used for the treatment of hypertension [1]. They affect both the angiotensin/aldosterone and bradykinin/prosta-glandin systems inhibiting the conversion of angiotensin I to angiotensin II, increasing circulating bradykinin levels and directly stimulating prostaglandin synthesis. These drugs are able to cross the human placenta [2, 3] and their use during pregnancy has been associated with fetal injury [4-7]. We report a case of neonatal anuria in an infant of a woman treated with ACE-I in the third trimester of pregnancy for hypertensive gestosis. This was a 36-week, 2,000 g male infant born of a 33-year-old second gravida, by cesarean section for severe oligo-hydramnios. Apgar score was 5 and 7 at 1 and 5 min respectively. The infant had growth restriction (-2 SD), hypocalvaria, profound hypotension and renal failure with no urine output. The kidneys were of normal size on renal ultrasound and the infant had no renal vasoconstriction on duplex Doppler scanning, no abnormalities of the urinary tract on the voiding cystourethrogram, no retroperitone-al/intra-abdominal masses on the abdominal computed tomography, and no cardiac dysfunctions on Doppler echocardiography. There was no history of maternal infections, but the mother had been treated for hypertensive gestosis from the 7th month of pregnancy with ACE-I (enalapril 20 mg/day) to the time of delivery. On day 3 of life, the infant was started on peritoneal dialysis. ACE activity and enalaprilat level were measured in the serum of the infant. Before dialysis, the ACE level was 7.4 μm/ml (normal 20/30). After peritoneal dialysis was started the ACE level in the serum rose to 20.5 μmol/ml. The enalaprilat level in the serum was 6.92 μg/ml, while that in the dialysate was 3.3 μg/ml. After 4 days of peritoneal dialysis the blood pressure returned to within normal limits for age. The urine output appeared on day 7 of life initially limited to 0.2 ml/kg/h, but gradually increased to 2.5 ml/kg/h. The peritoneal dialysis was interrupted on day 20 of life; a chronic renal failure remained.

Magnetic resonance imaging of renal osteodystrophy in children

Background. Improved life expectancy of children with chronic renal failure (CRF) has increased the number of patients with renal osteodystrophy and has brought to light novel and severe forms of the disease. These factors have contributed to the need to evaluate new, noninvasive imaging modalities for the detection of bone involvement. Objectives. To evaluate the potential of MRI in the detection of the bone changes of renal osteodystrophy as compared to conventional X-rays. Materials and methods. Fourteen children with CRF were examined with a 0.5-T MR unit using TI-weighted and STIR sequences and conventional radiographs. The following features were reviewed in a nonblinded study: skeletal deformities, thickening of cortical bone, trabecular pattern, intraosseous soft-tissue masses, osteonecrosis, extraskeletal calcifications and bone marrow signal changes. Results. MRI adequately demonstrated skeletal deformities, cortical thickening and irregular trabecular pattern. It showed osteonecrosis and intraosseous soft-tissue masses more conspicuously than X-ray. In addition, it revealed diffuse nonspecific signal changes in the bone marrow. Conclusion. MRI is a potentially useful tool for evaluating the bone changes of renal osteodystrophy.

Hemolytic uremic syndrome: epidemiological and clinical features of a pediatric population in Tuscany.

We retrospectively analyzed etiological, pathological and clinical features of the patients with hemolytic uremic syndrome (HUS) observed in the Pediatric Nephrology Unit at AOU Meyer of Florence. From January 1997 to December 2008, 22 cases were identified, with an annual incidence of 0.05 cases per 100,000 inhabitants, and 0.34 cases per 100,000 children <15 years old. 60% of the patients were D+ and 40% were D–, with an age distribution from 12 days to 13 years. Twenty patients (90%) had oligoanuria, lasting 6.4 ± 4 days for D+ patients versus 11.8 ± 4 days for D– patients. The development of chronic kidney disease positively correlates with the initial blood pressure value, the length of oligoanuria, and hospitalization. Microbiological investigations showed an association of D+HUS with different strains of Shiga toxin-producing Escherichia coli in 54% of the cases. D–HUS was associated with complement factor H deficiency in one patient. In the other cases, the triggering factors were pertussis, urinary tract infections and upper airway infections. While clinical and prognostic features correspond with literature data, in Tuscany the annual incidence is lower, and the percentage of D–HUS patients is higher than that observed in other studies.