Alfredo Vallo

Hypomagnesaemia of hereditary renal origin.

Cases of hypomagnesaemia of hereditary renal origin represent at least three different congenital disorders of tubular reabsorption of magnesium (Mg).Isolated familial hypomagnesaemia has been reported in a heterogeneous group of patients and an autosomal dominant pattern of inheritance has often been found to be present.Familial hypokalaemia-hypomagnesaemia, inherited as an autosomal recessive trait, has been reported in 17 patients and we now describe 3 additional cases. Hypomagnesaemia is accompanied by hypokalaemia, metabolic alkalosis, hypocalciuria and moderate sodium chloride wasting. Titration of renal Mg reabsorption indicates the presence of a low threshold but a normal Tm. The inherited defect is probably situated at the level of the distal convoluted tubule and mimics the therapeutic effect of thiazides. This condition is frequently confused with Bartters syndrome.Familial hypomagnesaemia-hypercalciuria, also inherited as an autosomal resessive trait, has been reported in at least 15 patients and we now add 3 new cases. Hypomagnesaemia is always accompanied by hypercalciuria and nephrocalcinosis. Ocular abnormalities such as myopia and horizontal nystagmus are often present. Hypermagnesiuria is of a greater degree than that observed in the previous entity and reflects a low Tm of Mg reabsorption. The defect must be situated at the level of the ascending limb of the loop of Henle and affects the transport of both calcium and Mg but not of sodium and chloride. This condition has not been clearly separated from hereditary distal renal tubular acidosis in the literature.

Transient pseudohypoaldosteronism secondary to obstructive uropathy in infancy

A syndrome of renal tubular resistance to aldosterone has been identified in infants with obstructive uropathy and urinary tract infection. Six infants (ages 9 days to 7 months) were seen with fever, vomiting, polyuria, dehydration, or failure to thrive. Urine cultures were positive for Escherichia coli. Radiologic studies demonstrated bilateral ureterohydronephrosis (four patients), left ureteral duplication with upper pole hydronephrosis (one), and left vesicoureteral reflux (one). The infants had hyponatremia, hyperkalemia, and metabolic acidosis. Plasma aldosterone concentration was markedly elevated, and plasma renin activity was similar to or higher than that reported in normal infants of comparable age. Fractional excretion of potassium was not significantly different from control values, both in absolute terms or when related to glomerular filtration rate, but fractional sodium excretion was significantly increased. The UK/UNa ratio was significantly lower in the patients. After medical or surgical therapy (when appropriate), all blood and urine determinations returned to normal, except for UK/UNa values, which although higher, remained significantly diminished. Our data indicate that a hyperkalemic salt-losing state can arise in infants with obstructive uropathy and urinary tract infection as a consequence of tubular unresponsiveness to aldosterone, and that the clinician should rule out such cause before establishing the diagnosis of primary pseudohypoaldosteronism.

Transtubular potassium concentration gradient: a useful test to estimate renal aldosterone bio-activity in infants and children

AbstractThe present investigation was designed to validate the usefulness of transtubular potassium (K) concentration gradient (TTKG) as an indicator of aldosterone bio-activity in infants and children. TTKG was calculated by the formula:

Natural history of primary distal renal tubular acidosis treated since infancy

\frac{{[K]urine: (urine/plasma)osmolality}}{{[K]venous blood.}}

A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain

We compared this index with fractional K excretion (FEK) and urine K concentration to urine sodium (Na) concentration ratio (UK/UNa) in 473 normal children aged 1 month–15 years. Values of TTKG followed a non-gaussian distribution (median, 6.3; 3rd centile, 4.1; 97th centile, 13.4). TTKG in infants (n=108; median, 7.8) was significantly higher than in children (n=365; median, 6.0). TTKG correlated directly with FEK and UK/UNa. Indices of K excretion were also assessed in 13 patients with hypo- and pseudohypoaldosteronism. TTKG values varied between 1.6 and 4.1 and were all below the 3rd percentile established for the age of the subject. We conclude that calculation of TTKG is an easy and sensitive method for the evaluation of mineralocorticoid action in distal and collecting tubules.

Normokalaemic pseudohypoaldosteronism is present in children with acute pyelonephritis

Although the acute renal toxicity of cisplatin has been well documented, long-term follow-up studies in cisplatin-treated children are scanty. We have evaluated the incidence and characteristics of both acute and chronic nephrotoxicity in 22 children (median age 8 years) treated with cisplatin as part of different chemotherapeutic protocols. All patients exhibited a significant and progressive decrease in plasma magnesium (Mg) values soon after cisplatin administration. Magnesiuria also increased immediately after therapy. Hypomagnesemia (plasma Mg < 1.4 mg/dl) occurred in 10 patients and it was dose-dependent. Minimal and mean cumulated doses inducing hypomagnesemia were 300 and 500 mg/m2, respectively. In 18 children we followed renal function prospectively for a mean time of 2.3 years after arrest of cisplatin therapy. Chronic hypomagnesemia and moderate elevation of plasma creatinine were observed in 6 children, hypocalciuria in 5 children, and hypokalemia in 1 child. Presence of hypomagnesemia was unrelated to the total dose received or the time elapsed since cisplatin therapy. Renal function studies, performed in the 6 children with chronic hypomagnesemia, revealed different degrees of impairment in Mg reabsorption. The functional characteristics of chronic cisplatin nephrotoxicity found in the present series-contrary to prior reports-are not comparable to those present in the inherited Gitelmans syndrome.

Biochemical features of dietary chloride deficiency syndrome: A comparative study of 30 cases

Clinical and pathophysiologic studies were performed in five unrelated children with primary distal renal tubular acidosis who were diagnosed during infancy and followed for 3 to 9 1/2 years. All patients had permanent defects in hydrogen ion secretion, sodium reabsorption, and concentrating capacity. A transient, age-related, proximal tubular defect in sodium and bicarbonate reabsorption was also present. Renal bicarbonate wasting was mainly observed during the first years of life and progressively decreased with advancing age. Glomerular filtration rate remained within normal limits. Following sustained therapy with sodium and potassium bicarbonate, the patients had optimal growth, arrest of progression of nephrocalcinosis, and lack of other characteristic features of the disease with the exception of polyuria. Dosage of alkali was mainly determined by the magnitude of the renal bicarbonate loss and decreased progressively from a maximum of 3.9 to 10.0 mEq/kg/day during the first year of life to about 3 mEq/kg/day at or beyond 6 years of age. The total dosage of alkali required could be derived by the sum of the urinary excretion of bicarbonate plus 2 mEq/kg/day, which represents mean endogenous acid production. Although calciuria was normal when metabolic acidosis was corrected, patients with higher urinary sodium excretion had higher urinary excretion of calcium and thus were at greater risk of developing nephrocalcinosis if therapy was not carefully controlled.

Renal tubular hyperkalaemia in childhood

Summary: A study using fractional clearances during orally induced water diuresis was designed to delineate the mechanism underlying defective tubular reabsorption of sodium in very low-birth-weight neonates. The use of clearance methodology during maximal water diuresis may give an indirect estimate of distal sodium delivery [urine volume (V), CH2O + CNa+K], sodium reabsorption at the diluting segments (CH2O), and proportion of the distal load reabsorbed distally (CH2O/CH2O + CNa+K), when all values are corrected to 100 ml glomerular filtration rate.The study was carried out in 28 healthy newborn infants who were grouped according to conceptual age (CA): 13 infants with mean birth weight of 1370 ± 330 g and mean CA of 31.8 wk (range, 28-34 wk), and 15 infants with mean birth weight of 2330 2 550 g and mean CA of 37.9 wk (range, 35-41 wk). All studies were performed at 6-7 days of age. It was demonstrated that higher urinary osmolality (67.5 ± 23.2 versus 52.9 ± 9.4 mOsm/kg, P < 0.0025) and higher fractional sodium excretion (2.3 ± 1.8 versus 0.9 2 0.5 ml/dl glomerular filtration, P < 0.01) observed in the group of very preterm infants resulted from significantly decreased proximal (V: 18.7 2 6.0 versus 13.3 ± 3.6 ml/dl glomerular filtration, P < 0.005; CH2O + CNa+K: 17.1 ± 5.2 versus 11.9 ± 3.3 ml/dl glomerular filtration, P < 0.005) and distal (CH2O/CH2O + CNa+K × 100: 81.9 ± 8.2 versus 88.2 ± 4.5%, P < 0.01) tubular sodium reabsorption. Distal sodium delivery correlated significantly and inversely with CA when all subjects were considered, but when correlations were assessed separately in each group, only in the group of very preterm infants were significant correlations present between CA and urinary osmolality, sodium and chloride clearances, and percentage of distal sodium reabsorption.These results suggest that the urinary sodium loss observed in very preterm infants depends on the incapacity of the distal tubule to cope with the arrival of an increased fractional load of sodium. A modest defect in urinary dilution is observed as an obligatory consequence.