M. Miltényi

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.

24 hour blood pressure monitoring in healthy and hypertensive children.

24 Hour ambulatory blood pressure monitoring (ABPM) was performed to provide data on the normal daily blood pressure of healthy schoolchildren and on patients with hypertension. The subjects studied were 123 healthy schoolchildren with a mean (SD) age of 12.5 (1.6) years (range 9.5-14.5 years), 24 children with borderline or mild hypertension, 17 with renal hypertension and normal renal function, 10 with chronic renal failure, and six with a renal allograft. In eight children with definite renal disease a second measurement was performed after treatment modification. The monitor used for ABPM was validated with a mercury column manometer. The mean (SD) of the signed differences of the blood pressure measured by the two methods was -0.19 (1.75) mmHg for the systolic and -0.21 (2.11) mmHg for the diastolic blood pressure (n = 60). Normal values for daytime and night time blood pressure were determined for those aged 10-14 years. The mean (SD) blood pressure of the 123 children was 109 (7)/66 (8) mmHg (systolic/diastolic) for the daytime and 96 (8)/52 (7) mmHg at night time. Of the 24 children with borderline or mild hypertension 14 had a raised blood pressure on ABPM. The circadian rhythm was disturbed in three children of this group. Even children with normal daytime blood pressure had significantly higher systolic blood pressure in the night when compared with the controls. The incidence of disturbed circadian rhythm was higher in the groups with renal hypertension (4/17 in the subgroup with normal renal function, 5/16 in the group with renal failure and/or transplantation). All children undergoing a second ABPM measurement had a lower average blood pressure after treatment adjustment. ABPM measurements were reproducible and accurate. The method provided new data on the physiological circadian variation of blood pressure in healthy children. It proved to be a helpful tool in the diagnosis of hypertension, particularly in the detection of cases of disturbance of the circadian rhythm of blood pressure pattern and individual adjustment of treatment.

Tubular dysfunction in type I diabetes mellitus.

Tubular function was investigated in patients with diabetic ketoacidosis and those with poorly controlled type I diabetes. Urinary excretion of beta 2 microglobulin and that of certain enzymes: gamma glutamyltransferase, leucine aminopeptidase, and N-acetyl-beta-D-glucosaminidase activities were significantly raised during ketoacidosis in 11 patients compared with healthy controls. In 13 poorly controlled diabetics, tubular electrolyte transport was studied and a significant reduction in tubular phosphate and sodium reabsorption was found. Tubular dysfunction occurring during diabetic ketoacidosis and in poorly controlled diabetics may contribute to the development of diabetic nephropathy.

Changes in plasma and urinary amino acid levels during diabetic ketoacidosis in children

Plasma and urinary concentrations of different amino acids were investigated during diabetic ketoacidosis (DKA) and 12, 24, 72 hours after initiation of therapy. In DKA, plasma concentration of glutamic acid, aspartic acid, valine, leucine and isoleucine significantly increased while that of asparagine and glutamine decreased compared to levels in well-controlled diabetic patients. The urinary excretion of branched-chain amino acids, histidine, serine and threonine was elevated while those of glutamic acid, glutamine, glycine and taurine were reduced. Among the different amino acids, histidine excretion had the highest variability. A strong correlation was found between the urinary excretion of several amino acids and that of the beta-2-microglobulin characterizing tubular dysfunction. Changes in the excretion of different amino acids reflect the altered metabolic state and renal function due to DKA.

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.

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.

Sympathetic-Adrenergic Activity and Acid-Base Regulation under Acute Physical Stress in Type I (Insulin-Dependent) Diabetic Children

To evaluate the efficacy of the acute-physical-stress response, plasma catecholamine and lactate levels, serum electrolytes, fructosamine, blood glucose and acid-base status were measured in insulin-dependent diabetes mellitus (IDDM) children and the data compared to those of healthy controls. Four groups were studied: group 1, healthy controls; group 2, newly diagnosed diabetic patients with an IDDM duration of 2-4 weeks; group 3, with an IDDM duration of 5-7 years; group 4, with an IDDM duration of 10-13 years. According to their fructosamine levels, IDDM children were in a well-controlled metabolic state. The physical stress was induced by 1.5-1.7 W/kg/10 min bicycle ergometer determined by a target pulse rate of 170/min. IDDM children exhibited pronounced lactic acidosis under stress (pH: group 2, 7.27 +/- 0.07; group 3, 7.28 +/- 0.05; group 4, 7.20 +/- 0.04, vs. group 1; 7.34 +/- 0.03). Baseline plasma norepinephrine and epinephrine levels showed a significant decrease parallel to the duration of IDDM. Stress induced an increase in the concentration of norepinephrine in each group, but the elevation was significantly higher in the IDDM children versus the controls. A significant negative correlation was found between pH and maximal plasma norepinephrine levels (y = 7.3-0.006x, r = -0.46, p < 0.02). Stress resulted in blood glucose elevation in 13 patients regardless of their pre-exercise blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary prostaglandins in hyperglycaemic ketoacidosis of type I diabetes mellitus

Urinary excretion of various renal prostaglandins was measured by radioimmunoassay and gas chromatography-mass spectrometry in children who had different degrees of metabolic control. Excretion in PGE2 in diabetic children was twice control values irrespective of the presence or absence of diabetic ketoacidosis (DKA). The urinary excretion of PGF2α was significantly increased in diabetic children with ketoacidosis, but not when diabetes was well controlled. The excretion of 13, 14 dihydro-15-keto PGE2, the major metabolite of circulating PGE2, was increased in all diabetic children, and was most elevated in ketoacidosis when it averaged 10 times basal excretion. Urinary excretion of PGI2α and of 6-keto-PGF1α, the metabolite of PGI2, was approximately doubled in DKA compared with values from healthy subjects. Excretion of PGE2 was twice control values in children with stable diatetes, whereas the equivalent value for TXB2, the metabolite of the active vasoconstrictor TXA2, was reduced by approximately 50%. We suggest that the increased excretion of prostacyclin metabolite may result from a protective biological action on the kidney opposing other vasoconstrictor hormone activity. PGE2 appears not to be involved in this process. The highly elevated excretion of PGE2 metabolite may represent an activation of systemic PGE metabolism during DKA.

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

Analysis of various vasoactive hormones during diabetic ketoacidosis (DKA)

ConclusionExtremely low plasma ANP levels in DKA associated with severe volume depletion suggest a negative feedback regulation of the hormone. In DKA the plasma volume and sodium regulating hormonal systems are markedly altered by the volume depletion. Plasma concentrations of vasoconstrictor and sodium and water retaining hormones like AVP, renin, aldosterone and noradrenaline are increased, whereas that of ANP, with potent vasodilator and natriuretic properties, is suppressed. Following volume repletion, most of the alterations are reversible.