RESUMEN
The prevalence of nephrocalcinosis (NC) in preterm neonates in recent reports is 7-41%. The wide range in prevalence is a consequence of different study populations and ultrasound equipment and criteria, in addition to a moderate interobserver variation. NC in preterm neonates has a multifactorial aetiology, consisting of low gestational age and birth weight, often in combination with severe respiratory disease, and occurs as a result of an imbalance between stone-promoting and stone-inhibiting factors. A limited number of histological studies suggest that calcium oxalate crystals play an important role in NC in premature neonates. In 85% of children resolution of NC occurs in the first years of life. Prematurity, per se, is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. In addition, NC in preterm neonates can have long-term sequelae for glomerular and tubular function. Long-term follow-up of blood pressure and renal function of prematurely born children, especially with neonatal NC, is recommended. Prevention of NC with (low) oral doses of citrate has not resulted in a significant decrease in the prevalence of NC; a higher citrate dosage deserves further study. Future research pertaining to prevention of NC in preterm neonates is crucial.
Asunto(s)
Recien Nacido Prematuro , Nefrocalcinosis/diagnóstico , Animales , Oxalato de Calcio/análisis , Oxalato de Calcio/metabolismo , Ácido Cítrico/farmacología , Modelos Animales de Enfermedad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Riñón/diagnóstico por imagen , Riñón/patología , Masculino , Nefrocalcinosis/epidemiología , Nefrocalcinosis/etiología , Nefrocalcinosis/terapia , Prevalencia , Ratas , Tomografía Computarizada por Rayos X , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: The aim of our study was to examine long-term effects of nephrocalcinosis in prematurely born children. PATIENTS AND METHODS: Preterm neonates (gestational age <32 weeks) with (n = 42) and without (n = 32) nephrocalcinosis were prospectively studied at a mean age of 7.5 (+/-1.0) years. RESULTS: Blood pressure did not differ in ex-preterm infants with and without nephrocalcinosis but was significantly higher than expected for healthy children. In comparison to healthy children, more ex-preterm infants with neonatal nephrocalcinosis had (mild) chronic renal insufficiency (glomerular filtration rate: <85 mL/min per 1.73 m2; 6 of 40); this is in contrast to ex-preterm infants without neonatal nephrocalcinosis (2 of 32). Tubular phosphate reabsorption and plasma bicarbonate were significantly lower in children with nephrocalcinosis compared with children without nephrocalcinosis. In addition, more ex-preterm infants with and without nephrocalcinosis than expected had low values for plasma bicarbonate and early-morning urine osmolality compared with healthy children. Kidney length of ex-preterm infants with and without nephrocalcinosis was significantly smaller than expected in healthy children of the same height. Nephrocalcinosis persisted long-term in 4 of 42 children but was not related to blood pressure, kidney length, or renal function. CONCLUSIONS: Nephrocalcinosis in preterm neonates can have long-term sequelae for glomerular and tubular function. Furthermore, prematurity per se is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. Long-term follow-up of blood pressure and renal glomerular and tubular function of preterm neonates, especially with neonatal nephrocalcinosis, seems warranted.
Asunto(s)
Presión Sanguínea , Recien Nacido Prematuro , Nefrocalcinosis/fisiopatología , Calcio/orina , Niño , Desarrollo Infantil , Ácido Cítrico/orina , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Riñón/diagnóstico por imagen , Riñón/fisiología , Estudios Longitudinales , Masculino , Nefrocalcinosis/complicaciones , Tamaño de los Órganos , Estudios Prospectivos , Valores de Referencia , Insuficiencia Renal/etiología , Insuficiencia Renal/orina , UltrasonografíaRESUMEN
Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U-calcium/citrate is one of the contributing factors to the development of NC. In stone-forming children and adults citrate supplementation is a successful preventive therapy. In this randomized controlled trial the effect of citrate therapy was studied on the development of NC in preterm neonates with a gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age 29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36 preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight 1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography (US) was performed at term. U-citrate/creatinine and U-pH were significantly higher and U-calcium/citrate was significantly lower in the citrate group at day 14, 21 and 28 compared with the control group (P<0.05). Complications of citrate administration were not encountered, however the incidence of NC was not significantly different in the treated (34%) compared with the control group (44%), P=0.37. Preterm neonates treated with citrate in the first months of life have higher U-citrate/creatinine and lower U-calcium/citrate compared with controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does not prevent NC. Whether a higher dose or potassium citrate decreases the incidence of NC should be evaluated in further studies.
Asunto(s)
Ácido Cítrico/farmacología , Recien Nacido Prematuro/fisiología , Nefrocalcinosis/prevención & control , Humanos , Recién NacidoRESUMEN
The aim of the study was to evaluate the natural course of nephrocalcinosis (NC) in preterm neonates and the effect of NC on blood pressure and renal glomerular and tubular function. In a prospective observational study of 201 preterm neonates (gestational age <32 weeks) NC was present at term in 83 patients (41%), who were subsequently examined at 6, 12, and 24 months, and until August 2000 annually (with a maximum of 4 years) if NC persisted. Examination consisted of blood pressure measurement, renal ultrasonography, and glomerular and tubular function tests. The probability that NC, when present at term, would persist for 15 and 30 months was 34% [21-45, 95% confidence interval (CI)] and 15% (5-25, 95% CI) (Kaplan-Meier), respectively. Urinary tract infection did not occur more frequently in patients with NC (2.5%) than patients without NC at term (4.4%). Systolic and diastolic blood pressures above the 95th percentile were found in 39% and 48% of patients at 1 year and 30% and 34% at 2 years ( P<0.001). Mean glomerular filtration rate (GFR) (inulin clearance) at 1 and 2 years was 92 and 102 ml/min per 1.73 m(2), respectively. TP/GFR and excretion of alpha(1)-microglobulin were normal. The desmopressin test was impaired in 4 of 30 patients at 1 year and 2 of 25 at 2 years. It was concluded that while proximal tubular function is unaffected in children with neonatal NC, high blood pressure and impaired glomerular and distal tubular function might occur more frequently than in healthy children. Although no relationship can be proven between NC and hypertension or diminished renal function in this study, these results justify a large follow-up study with matched controlled study groups.