Mariann Dobos

Urinary calcium and oxalate excretion in children

We have established normal values for calcium/creatinine (Ca/Cr) and oxalate/creatinine (Ox/Cr) ratios in 25 infants (aged 1–7 days) and 391 children (aged 1 month to 14.5 years) and compared these with values obtained in 137 children with post-glomerular haematuria and 27 with nephrolithiasis. Oxalate was measured by ion chromatography. Nomograms of Marshall and Robertson were used to calculate urine saturation to calcium oxalate. The Ca/Cr ratio was normally distributed whereas the Ox/Cr ratio had a log-normal distribution. The molar ratio of Ca/Cr was the lowest in the first days of life and the highest between 7 month and 1.5 years (mean±SD=0.39±0.28 mmol/mmol). Following a slight decrease it stabilised by the age of 6 years (0.34±0.19 mmol/mmol). The highest Ox/Cr values were measured during the 1st month of life [geometric mean 133 (range 61–280) μmol/mmol], followed by a gradual decrease until 11 years of age [mean 24 (range 6–82) μmol/mmol]. Thirty-six haematuric children had hypercalciuria (26%), 23 had absorptive hypercalciuria, 13 renal type. Children with absorptive hypercalciuria on a calcium-restricted diet had significantly higher oxalate excretion than those with renal hypercalciuria and the control group [38 (range 28–49) vs. 22 (range 16–29) and 23 (range 22–27) μmol/mol respectively,P<0.01]. Calcium oxalate urine saturation of stone patients was higher than that of patients with haematuria and the normal population (1.18±0.05 vs. 1.06±0.03,P<0.03 and 0.84±0.03,P<0.001 respectively). The measurement of Ca/Cr and Ox/Cr in first-morning urine samples is suitable for screening for hypercalciuria and hyperoxaluria. Interpretation of the values requires age-specific reference values. Both calcium and oxalate determinations should be part of the evaluation of patients with haematuria, hypercalciuria or nephrolithiasis.

Normal kidney function and elevated natriuresis in young men born with low birth weight

Abstract The aim of our study was to characterize renal function and its relationship to blood pressure in healthy young Caucasian men born with a birth weight under 2,500 g (LBW). Urinary protein patterns, N-acetylglucosamine and γ-glutamyltransferase activities, fractional sodium and potassium excretions, glomerular filtration rate, blood pressure, and erythrocyte Na+/K+-ATPase activities were determined in 65 subjects, of whom 49 were born with LBW. Signs of glomerular or tubular damage were not detected in the LBW population. However, the blood pressure and the renal sodium excretion were inversely correlated to the subjects’ birth weight and were higher in LBW subjects than in controls. In contrast, the erythrocyte Na+/K+-ATPase activities were lower in LBW subjects. An inverse correlation was detected between the subjects’ Na+/K+-ATPase activities and the renal sodium excretion or blood pressure. In summary, our results suggest that: (1) in young LBW Caucasian males signs of early glomerular and tubular impairment are not present; (2) the elevated renal sodium excretion may be a result of higher blood pressure; (3) the alteration of Na+/K+-ATPase activity might play a role either in the elevation of blood pressure and/or in the enhanced natriuresis of LBW subjects.

Sodium transport and bone mineral density in hypercalciuria with thiazide treatment.

Abstract.Erythrocyte sodium-potassium (Na+/K+) -ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6–16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean±SEM 2,156±110 μmol P/l erythrocyte per hour vs. 3,165±175, P<0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90±0.07 mmol/mmol versus 0.51±0.06 respectively, P<0.01. The corresponding iPTH levels were 5.9±0.6 pmol/l and 5.1±0.7, P<0.05. The Na+/K+-ATPase activity increased significantly (2,769±169 μmol P/l erythrocyte per hour vs. 2,156±110 in the control period, P<0.01) and the Na+/Li+ countertransport decreased (268±28 μmol Li/l erythrocyte per hour vs. 328+26 in the control period, P<0.03). The bone mineral density Z score rose from –1.3±0.26 to –0.8±0.22 (P<0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.

Hydrochlorothiazide treatment of children with hypercalciuria: effects and side effects.

Urinary excretion of calcium and the changes in serum cholesterol fractions were investigated in 15 children with renal hypercalciuria, following 3-month hydrochlorothiazide (HCT) treatment (daily dose 1 mg/kg). Urinary calcium excretion (expressed as the ratio of calcium to creatinine) reached its lowest value after 2 weeks. It was still below the initial value at the end of the 3rd month of treatment (0.84±0.06, 0.29±0.03 and 0.6±0.09 mmol/mmol, respectively). A significant rise in the total serum cholesterol level (4.64±0.23 vs. 4.25±0.18 mmol/l before treatment,P<0.01) and the lowdensity lipoprotein (LDL)-cholesterol fraction (2.6±0.24 vs. 2.31±0.31 before treatment,P<0.01) was observed at the end of the 3rd month, while high-density lipoprotein (HDL)-cholesterol was slightly decreased. A significant elevation of the LDL/HDL ratio was also observed (from 1.76±0.17 to 2.2±0.17,P<0.001), indicating an increase in the atherogenic cholesterol fractions. The risks and benefits of the thiazide therapy should be considered before starting long-term treatment of children with hypercalciuria and haematuria or renal stone disease.

Monitoring cardiovascular changes during hemodialysis in children

Abstract Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7±3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r=–0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r=0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P<0.05 and P<0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r=0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.

Developmental changes in erythrocyte Na+,K+-ATPase subunit abundance and enzyme activity in neonates

AIM To study the relation between erythrocyte Na+,K+-ATPase subunit isoform composition, Na+,K+-ATPase activity, and cation pump function in preterm and term neonates. DESIGN Erythrocyte Na+,K+-ATPase subunit isoform abundance, Na+,K+-ATPase activity, and cation pump function were studied in blood samples obtained from 56 preterm neonates of 28–32 weeks gestation (group 1), 58 preterm neonates of 33–36 weeks gestation (group 2), and 122 term neonates (group 3) during the first two postnatal days. RESULTS α1isoform abundance was higher and β2 isoform abundance was lower in group 1 than in group 3 (p = 0.0002). α2 and β1 isoform abundance did not change with maturation and there was no evidence for the presence of the α3 isoform. Gestational age was inversely related to Na+,K+-ATPase activity (p = 0.0001) and directly related to intracellular Na+ concentration (p = 0.0025). CONCLUSIONS Expression of the α1 and β2Na+,K+-ATPase subunit isoforms is developmentally regulated. The increased abundance of α1isoforms of immature neonates translates to increased ATPase activity. The lower intracellular Na+ concentration of immature neonates suggests that their erythrocyte Na+,K+-ATPase cation pump function may also be increased.

Alterations of Urinary Carbon Dioxide Tension, Electrolyte Handling and Low Molecular Weight Protein Excretion in Acute Pyelonephritis

ABSTRACT. Renal tubular function tests were performed in 45 children suffering from upper and lower urinary tract infections. Determinations were made of the urinary carbon dioxide tension in maximally alkaline urine as an index of distal tubular H+ ‐ion secretion, of urinary protein excretion, and of urinary sodium and phosphate handling. Urinary Pco2 was low (2.7±13.9 mmHg) in acute pyelonephritis compared to values in healthy children (52 ±32 mmHg) or those with cystitis (48±34 mmHg). At the onset of pyelonephritis an elevated fractional excretion of sodium (1.38±0.38 vs. 0.50±0.20%) and decreased phosphate reabsorption (69.2±7.1 vs. 90.4±4.9%) were also observed. Significantly elevated urinary low molecular weight protein excretion was also found in pyelonephritis. These data indicate the existence of proximal and distal tubular dysfunction at the onset of acute bacterial pyelonephritis.

Postasphyxial Reoxygenation Reduces the Activity of Na+/K+-ATPase in the Erythrocytes of Newborn Piglets

The aim of our study was to determine whether the impairment of Na⁺/K⁺ pump is detectable in erythrocytes during hypoxia and reoxygenation. Acute asphyxia was induced in 10 newborn piglets for 1 h by bilateral pneumothorax. The Na⁺/K⁺-ATPase activity, Na⁺, K⁺ and ATP content of RBCs were determined in baseline condition (p_aO₂: 60.4 ± 9.3 mm Hg), at the end of the hypoxic period (1 h) (p_aO₂: 30.2 ± 10.3 mm Hg), then hourly during the reoxygenation phase (2, 3, 4 h) (p_aO₂: 54.8 ± 9.0, 56.1 ± 8.7, 57.2 ± 9.6 mm Hg). The Na⁺/K⁺-ATPase activity was constant during the first 3 h. However, it decreased at 4 h (676 ± 168 versus baseline 833 ± 141 U, p < 0.05). The highest ATP content was measured also at this point (4.32 ± 0.57 versus baseline 3.27 ± 0.45 mmol/l RBC, p < 0.01). The Na⁺ content was lower at 1 and 2 h (14.0 ± 1.8; 13.8 ± 1.2 versus baseline 15.7 ± 1.2 mmol/100 g Hb, p < 0.05), but later it became normal. Plasma monovalent cationic levels and intracellular K⁺ content did not alter during the experiment. Our results indicate that the deterioration of enzyme activity occurs within the same time-frame that previously described morphological alterations in brain tissue develop, so the RBC Na⁺/K⁺-ATPase activity might reflect the progress of posthypoxial brain damage.

Reduced Glomerular Filtration and Elevated Urinary Protein Excretion in Diabetic Ketoacidosis

ABSTRACT. Glomerular filtration rate (GFR) was measured by two methods in 9 children with diabetic ketoacidosis (DKA), directly by true creatinine clearance and indirectly by means of serum beta‐2‐microglobulin levels. We found significantly reduced GFR in the first hours of DKA. The rapid improvement in GFR after fluid and electrolyte replacement indicates that volume depletion is the major cause of low filtration rate. In spite of the reduced GFR we observed pronounced albuminuria and low molecular weight (LMW) proteinuria. We conclude that the pathological albuminuria and microalbuminuria in DKA are caused not by glomerular hyperfiltration but by tubular dysfunction

Sodium-lithium countertransport in children with nephrotic syndrome.

Abstract The mechanisms of sodium retention in edema-forming minimal change nephrotic syndrome (MCNS) have not been completely evaluated. The aim of this study was to characterize the transmembrane sodium transport in nephrotic syndrome by measuring the erythrocyte sodium-lithium countertransport (SLC) in vitro. Eighteen children with MCNS were studied in the edema-forming state, and subsequently at the beginning of remission. Nephrotic children with edema retained sodium (10±12 μmol/day) and had a higher SLC [426±118 vs. 281±60 µmol/l red blood cells (RBC) per hour, P=0.003). The intracellular sodium concentration of nephrotics was 6.1±2.1 mmol/l RBC, which did not differ from that of controls (6.42±2.24, n=13). In remission sodium balance became negative (–30 ±21 mmol/day), and the SLC decreased but still differed significantly from control values (P=0.009). The intracellular sodium content decreased to 4.4±0.9 mmol/l RBC (P=0.002). There was a negative correlation between erythrocyte SLC and plasma albumin concentration (r=0.48, P=0.003), and urinary sodium excretion rate (r=0.66, P=0.001). In conclusion, erythrocyte SLC is high in the edema-forming state of childhood nephrotic syndrome and decreases with the onset of remission. A role for the SLC in the altered sodium homeostasis of nephrotic syndrome is suggested.