Giuseppina Marra

Persistent tubular resistance to aldosterone in infants with congenital hydronephrosis corrected neonatally

Renal function of 18 infants who had undergone surgery in the neonatal period because of severe congenital hydronephrosis was followed up for 5 to 36 months (mean +/- SD 21 +/- 10 months). In all cases the diagnosis was made prenatally by sonography and confirmed at birth by intravenous urography. Creatinine clearance developed normally in all the children. Eight had a reduction in maximal urinary concentrating ability after intranasal DDAVP; this defect was transient and resolved after 4 to 5 months in all but one child, in whom it persisted. However, other tubular abnormalities were present. Throughout the observation period, patient serum potassium concentrations were significantly higher than normal, paralleled by a significant increase in plasma aldosterone concentration but with normal excretion fraction of sodium and potassium. There were no disturbances of acid-base balance. These findings may be accounted for by a persistent partial reduced sensitivity of the distal tubule to the action of aldosterone despite normal renal function. This alteration is usually mild, but may constitute a persistent metabolic risk despite successful surgical intervention.

Treatment data during pediatric home peritoneal teledialysis

Peritoneal teledialysis (telePD) is a modem-based communication link between the patients cyclers and a computer in the dialysis unit that allows the transmission and storage of a series of automated peritoneal dialysis (APD) treatment data. In order to evaluate the usefulness of telePD in quantifying the problems that may occur during pediatric APD, we retrospectively studied four patients with a median age of 14.1±1.8xa0years during their initial months of telePD. The selection criteria were potential non-compliance in two cases (patients 1 and 2) and catheter malposition or fibrin occlusion in two (patients 3 and 4). The patients were treated using a Fresenius PD Night Cycler with teledialysis software. Thirty consecutive treatments per patient in the 1st and 4th months were examined, and a series of treatment parameters was calculated. The percentage of treatments with alarms and the number of alarms per treatment were high in both the 1st and the 4th month, particularly in patients 3 and 4. The main causes of the alarms were tube kinking, catheter malfunction, fibrin occlusion, and failure of electrical power. The number of shortened treatments significantly decreased in the 4th month of telePD. One non-compliant family was identified during the 1st month of PD, but psychosocial support helped to decrease the number of shortened treatments due to non-compliance in the 4th month. During the 4th month of telePD, the dwell time/total treatment time ratio (which represents the time of contact between the peritoneum and dialysis fluid) increased as a result of technical interventions aimed at reducing the infusion plus drain time. In conclusion, telePD proved to be useful in detecting and solving the clinical and technical problems of APD.

Increased sodium requirement following early postnatal surgical correction of congenital uropathies in infants

Serum electrolyte equilibrium and plasma aldosterone concentrations were monitored in 19 infants who had severe obstructive uropathy or grade 5 vesico-ureteral reflux and were undergoing surgical correction in the first 2 months of life. Before surgery high plasma aldosterone levels were observed in 8 patients, but serum sodium and potassium concentrations were normal. Plasma concentrations of aldosterone were elevated in all patients during the week following surgery and 7 patients developed severe hyponatraemia, hyperkalaemia and weight loss despite very high plasma aldosterone concentrations. As a consequence 5 infants were infused with sodium chloride (4 mEq/kg per day) before and for 36h after surgery; this prevented metabolic imbalance. We conclude that infants undergoing surgical correction of uropathies may require a high sodium intake to maintain electrolyte balance and adequate growth.

Phosphate-induced PTH stimulation and calcitriol treatment in children with early chronic renal insufficiency

Seven children with early chronic renal insufficiency and without any evidence of abnormal bone metabolism, received an iv infusion of phosphate over 30 min. Serum concentrations of P, Ca, INS-PTH and 1,25(OH)2D3 were determined before and after the infusion for 3.5 hours. The patients underwent the same infusion test after a 3-month course with oral calcitriol. Before treatment, baseline calcium and phosphorus were within normal limits, INS-PTH level was slightly above the normal range while, although within normal limits, 1,25(OH)2D3 was significantly (p<0.05) lower than in normal controls. The same baseline biochemical findings were observed after treatment with calcitriol, except for a significant (p<0.05) increase in 1,25(OH)2D3 whose plasma concentrations had returned to the level of normal controls. The time course of phosphorus and calcium was similar both before and after calcitriol treatment. However, the INS-PTH response to phosphate load was significantly less pronounced after treatment, with peak levels of 41.9±9.4 pg/ml versus 35.7±7.6 respectively before and after treatment. During the infusion of phosphate, a significant drop in 1,25(OH)2D3 was also observed, but the decrease itself was significantly more important before than after calcitriol.This study demonstrates that, in children with early chronic renal insufficiency, a 12-week course with low dose calcitriol significantly reduces phosphate-induced PTH secretion. This is more likely to be a direct effect of calcitriol on the parathyroid glands than an effect mediated by calcium. This suggests the possible usefulness of low dose calcitriol treatment in preventing the development of overt secondary hyperparathyroidism.

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection.

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the babys urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear: NS may represent another manifestation of CMV disease.

Early Childhood Hyperkalemia: Variety of Pseudohypoaldosteronism

ABSTRACT. Fractional excretion of electrolytes, renal acidification capacity and the renin‐aldosterone system have been studied in 5 non‐azotemic children, 19‐25 months old, with mineralo‐corticoid resistant hyperkalemia, discovered in the first month of life. Although fractional potassium excretion was similar in patients and in a group of control healthy children (13.8± 5.2% vs. 8.7±6.4%) it was inappropriately low in the patients for their higher potassium concentration. Fractional sodium excretion was significantly increased in the patients (1.6±0.3% vs. 0.67±u.4, p<0.02). Normal net acid and ammonium excretion and intact ability to lower urinary pH during acid loading were observed in all patients. Mean values for plasma aldosterone (37.0±9.1 vs. 13.9±11.2 ng/dl), plasma renin activity (12.5±3.9 vs. 8±2.8 ng/ml/h) and plasma aldosterone/plasma potassium ratio (7.11±1.5 vs. 3.08 ±1.7) were higher in the patients than in the control subjects (all p<0.001). These data support the hypothesis that a partial lack of response of the renal tubule to endogenous mineralocorticoids was present in the patients. This type of pseudohypoaldosteronism is less severe than that described for the classic form and for early childhood renal acidosis.

Relevance of a database for monitoring a cooperative paediatric nephrology project in Nicaragua

Sirs, Many leading international scientific societies [European Society of Paediatric Nephrology (ESPN), International Society of Nephrology (ISN), International Pediatric Nephrology Association (IPNA), Latin American Pediatric Nephrology Association (ALANEPE) and others] and a significant number of pediatric nephrologists have contributed to the growth of our knowledge in the field of pediatric nephrology in developing countries over recent years [1–4]. Since 2000, we have been participating in a cooperative project in Nicaragua [5] with the aims of developing a tertiary pediatric nephrology centre in Managua (renal biopsies, dialysis and living donor transplantations) and a web network that links this centre and six Departmental hospitals in order to share diagnostic and treatment protocols and improve the early diagnosis and treatment of children with kidney and urinary tract diseases (KUTDs). The project includes the regular recording of the clinical data of all inand outpatients aged <19 years, for which an ad hoc computerised database was established in 2002 to contain basic demographic data, the diagnosis, the clinical course (cured, on or lost to follow-up, deceased), and annual creatinine clearance values or the type of renal replacement therapy (RRT) of patients with chronic renal failure (CRF; CrCl <75 ml/min/1.73 m). The data are regularly sent to the coordinating centre in Milan and discussed by e-mail or during meetings held twice a year in Nicaragua. As of December 2008, the data of 3376 children had been entered in the database, including 193 with CRF (Fig. 1). Analysis of the 56 deceased patients revealed that 95% had died during stage IV or V CKD according to the National Kidney Foundation (NKF) classification: 43% before RRT program was started in Managua (up to 2004), 22% while on RRT and 32% without starting RRT (for social problem). Although the project had undoubtedly improved the treatment of children with CRF by providing previously unavailable diagnostic and therapeutic resources, such as RRT, this was still a high rate of CRF-related mortality. The large number of children lost to follow-up or not entering the RRT programme was clearly not only due to limited medical facilities, but also to factors that could only be partially addressed by a simple cooperative project: logistics (distance from hospitals and the lack of transportation infrastructures), social problems (health education) and the families’ economic priorities [6]. An epidemiological analysis of the Departments fully covered by the project (61% of the country’s pediatric population) also indicated a lower incidence and prevalence of CRF than those reported in the ITALKID Italian Registry of CRF [7] (9.29 vs. 12.1 patients/year per million of the age-related population, and 40.3 vs. 74.7 patients per million of the age-related population, respectively), which was used for comparative purposes because of its similar patient selection and inclusion criteria. These data suggested that many G. Marra (*) :A. Edefonti Pediatric Nephrology and Dialysis Unit, Clinica Pediatrica G. e D. De Marchi, Fondazione O.M. Policlinico Mangiagalli e Regina Elena, Via Commenda 9, 20122 Milan, Italy e-mail: gimarra@hotmail.com

Renal Function in Cystic Fibrosis

The effect of saline extracellular volume expansion (4 ml/min/10 kg b.w. X 60 min) on renal function has been studied in patients with cystic fibrosis (CF) and in normal age-matched controls. Basal values for glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and chloride (Na, Cl) handling were similar in both groups. Saline expansion resulted in an increase in GFR and RPF in the CF patients: 127 +/- 18 ml/min/1.73 sqm BSA to 166 +/- 5; p less than 0.001, but not in the control group: 112 +/- 10 to 120 +/- 20. These hemodynamic changes were associated with increased proximal tubular reabsorption of NaCl in the CF patients whereas controls had reduced NaCl reabsorption. Renin and aldosterone levels suggested that increased NaCl reabsorption in CF patients was not secondary to chronic extracellular volume contraction or salt loss. These results support the hypothesis that the renal tubule is involved in the generalised electrolyte transport disorder exhibited in other epithelial structures. This study also indicated that the regulation of renal hemodynamics is altered in CF. The relationship between the disorder of proximal tubular salt handling and changes in renal hemodynamics is not known, but the observed changes imply a tubulo-glomerular feedback mechanism.

Renal tubular acidosis in a case of Shwachman's syndrome.

ABSTRACT. We describe metabolic acidosis in a 15‐month‐old girl with clinical features of Shwachmans syndrome. Renal function tests indicated that the patient had type 1 renal tubular acidosis. Based on our findings and other reports of renal tubular dysfunction in patients with Shwachmans syndrome, we conclude that it is important to look for a possible renal tubular defect in this syndrome.

RENAL FUNCTION IN INFANTS WITH CONGENITAL HYDRONEPHROSIS OPERATED IN THE FIRST MONTH OF LIFE

In utero diagnosis of hydronephrosis may allow early surgical intervention with possible beneficial effects on the long term renal function. We have prospectively followed 13 of such neonates with grade 3-4 hydronephrosis who had been operated in the first month of life. 10 stenosis of the pyelouretheral junction (5 monolateral), 2 vescicouretheral reflux (1 monolateral), 1 uretral valves. Serum creatinine, electrolytes, maximal urinary concentrating ability after DDAVP, urinary acidification and ammoniogenesis after oral NH4Cl, PRA and serum aldosterone concentration were measured at various intervals. The follow up ranges from 4 to 40 months. Creatinine clearance was normal in all infants at all ages, reduced concentrating ability (Osmu 700) was present in 11/13 infants 9 months but tended to disappear after 2 months. 10/13 infants had mild hyperkalemia (K+5.5-6.5 mEq/1) during the first months. This was accompanied by serum aldosterone concentrations exceeding the normal values for age and suggests a reduced tubular response to aldosterone. A deficient ammoniogenesis was present in 3/13 subjects but all could normally lower U pH below 5.5. UTIs were a minor problem (0.5 episodes/months/infant). These results indicate that mild tubular impairment is present in neonates with congenital hydronephrosis after neonatal surgical correction and tend to ameliorate gradually.