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Biomedical subjects

A Drukker

Publications and source records attributed to A Drukker.

At least 19 recordsLinked to original sources

Prevalence of complications in children with chronic kidney disease according to KDOQI.

The Kidney Disease Outcome and Quality Initiative (KDOQI) Group recommended guidelines for the monitoring and treatment of chronic kidney disease (CKD) in 2002. These recommendations were based on the prevalence of known complications as seen in adults. In children, the exact prevalence of these complications is unknown. We therefore conducted a cross-sectional study of 366 patients with CKD in a single center to analyze the prevalence of these complications across all stages of kidney disease. Patients were categorized to their KDOQI stage of CKD according to their estimated renal function as determined from serum cystatin C. Fifty seven percent of patients had CKD stage 1, 29.0% stage 2, 10.4% stage 3 and 4.1% stages 4+5. Uropathies (31%) were the most prevalent causes of CKD. Glomerular disease accounted for 27%. The overall prevalence of complications was as follows: hypertension 70.2%, anemia 36.6%, proteinuria 11.5%, and metabolic bone disease 16.9%. Metabolic bone disease and anemia occurred frequently, even with a glomerular filtration rate >60 ml/min/1.73 m2. Growth failure (11.5%) was also common and is not a component of the KDOQI guidelines for CKD in children. The prevalence of all complications increased with worsening stage of kidney disease (all P-values significant). In summary, this study supports the KDOQI guidelines in defining and staging CKD in children. This study also highlights the differences in the causes and complications that occur in CKD between adults and pediatrics. We recommend modification of the KDOQI guidelines for children to reflect the differences described in this paper.

Acidosis↗

The renal hemodynamic effects of Aspirin in newborn and young adult rabbits.

A group of neonatal (n=10) and 12-week-old (n=12) anesthetized, ventilated New Zealand white rabbits received an acute i.v. dose (40 mg/kg body weight) of acetylsalicylic acid (ASA, Aspirin). In the neonatal animals, i.v. ASA caused within 20 min a significant (P<0.01) fall in renal blood flow and glomerular filtration rate (GFR), with an equally significant (P<0.01) increase in filtration fraction and renal vascular resistance. The latter indicates greatly augmented renal vasconstriction or more precisely reduction in intrarenal vasodilatation by inhibition of vasodilatory prostaglandin (PG) synthesis. Urine volume decreased. The 12-week-old young adult animals responded in a similar, but significantly attenuated fashion. These experiments demonstrate that inhibition of PG synthesis in neonatal animals causes very rapid, reversible vasoconstriction, with a reduction in GFR. In addition, this study confirms previous observations that the renal hemodynamic response to the inhibition of PG synthesis is far more pronounced in neonatal animals than in (young) adult rabbits.

Age Factors↗

Dipstick measurements of urine specific gravity are unreliable.

AIM: To evaluate the reliability of dipstick measurements of urine specific gravity (U-SG). METHODS: Fresh urine specimens were tested for urine pH and osmolality (U-pH, U-Osm) by a pH meter and an osmometer, and for U-SG by three different methods (refractometry, automatic readout of a dipstick (Clinitek-50), and (visual) change of colour of the dipstick). RESULTS: The correlations between the visual U-SG dipstick measurements and U-SG determined by a refractometer and the comparison of Clinitek((R))-50 dipstick U-SG measurements with U-Osm were less than optimal, showing very wide scatter of values. Only the U-SG refractometer values and U-Osm had a good linear correlation. The tested dipstick was unreliable for the bedside determination of U-SG, even after correction for U-pH, as recommended by the manufacturer. CONCLUSIONS: Among the bedside determinations, only refractometry gives reliable U-SG results. Dipstick U-SG measurements should be abandoned.

Humans↗

The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy.

The healthy term, and particularly the premature infant, is born with a very low glomerular filtration rate (GFR), controlled by a delicate balance of intrarenal vasoconstrictor and vasodilator forces. Vasoactive disturbances can easily further reduce the already low GFR. The newborn infant is thus prone to develop vasomotor nephropathy (VMNP) or acute renal failure (ARF). The main causes for ARF at this young age are prerenal mechanisms, and include hypotension, hypovolemia, hypoxemia perinatal asphyxia, and neonatal septicemia. Other causes include the administration of angiotensin converting enzyme inhibitors, indomethacin and tolazoline. The most-important factors governing the ultimate renal prognosis are the severity of the underlying disorder, the rapidity of an accurate diagnosis, prompt treatment, and avoidance of severe iatrogenic complications. The immediate treatment is of particular importance in VMNP, i.e., prerenal ischemic ARF, and consists of correcting abnormalities in fluid homeostasis and reduction of the complications of the acute azotemic state (uremia, hyperkalemia, acidosis, and hypertension). In severe and prolonged (established) ARF, temporary dialysis therapy may be indicated. Prerenal ARF with oliguria or anuria warrants immediate volume resuscitation. Special attention should be given to infants with congestive heart failure (CHF). The sick neonate with persistent oliguria and CHF should be treated with intravenous dopamine. Furosemide (FM) is the second line of therapy for babies with indomethacin-induced ARF. In most other conditions, the therapeutic effect of FM is limited to a transient increase in urine flow, without improving basic renal function. The special conditions of the maturing kidney have to be appreciated in order to protect babies from undue renal injury. With the increasing knowledge of the mechanisms governing the development of ARF, progress has been made in the development of new treatment modalities. For example theophylline, calcium antagonists, ATP-MgCl2, thyroxine, and a variety of cytokines may in the near future be used to prevent or ameliorate VMNP and/or recently established ARF. With a combination of time-honored and new therapeutic strategies, there may well be a brighter future for neonates with vasomotor, prerenal, ischemic ARF.

Humans↗

Torasemide is an effective diuretic in the newborn rabbit.

The effect of intravenous (i.v.) torasemide on diuresis and renal function was evaluated in three groups of normoxemic, 5- to 10-day-old, newborn New Zealand White rabbits. The animals of group 1 received 0.2 mg/kg of torasemide i.v., whereas in group 2 an i.v. dose of 1.0 mg/kg was given. The third group of animals received a bolus i.v. dose of 1.0 mg/kg torasemide with continuous i.v. replacement of estimated urinary fluid and electrolyte losses. Torasemide proved to be an effective, potassium-sparing diuretic, without significant effect on glomerular filtration rate (GFR). Renal blood flow (RBF) fell and the renal vascular resistance (RVR) rose in all three groups of animals, although the rise in RVR in group 3 was not significant. These changes in renal hemodynamics were most pronounced in the animals of group 2 and are probably secondary to torasemide-induced hypovolemia (2.8% loss of body weight) and accompanying humoral reactions, such as an increase in angiotensin II (not measured). When the latter is prevented by simultaneous re-infusion of an electrolyte solution (group 3), replacing urinary losses, GFR increases and the changes in RBF and RVR are blunted. We conclude that torasemide is an effective, potassium-sparing diuretic in newborn rabbits. No evidence was found for a vasodilatory action of the drug.

Animals↗

Hypothyroidism in primary hyperoxaluria type 1.

We describe 4 patients, aged 3 months to 23 years, with end-stage renal disease and severe, symptomatic hypothyroidism. All 4 had primary hyperoxaluria type 1 (PH1) with diffuse tissue (kidneys, skeleton, eyes, heart) calcium-oxalate deposition, a condition known as oxalosis. The hypothyroidism responded to thyroid hormone replacement therapy. Clinical hypothyroidism within the framework of PH1/oxalosis was probably caused by thyroid tissue damage from an abundance of calcium oxalate. We recommend that thyroid function be monitored in patients with PH1 and oxalosis.

Child, Preschool↗

Failure of the loop diuretic torasemide to improve renal function of hypoxemic vasomotor nephropathy in the newborn rabbit.

The use of diuretic therapy in vasomotor nephropathy is a controversial topic. It is generally agreed that diuretics in this situation enhance urinary output, reduce the degree of volume expansion, and improve cardiac and especially the compromised lung function. It is less clear whether diuretic therapy improves kidney function. The present study evaluates the effects of intravenous torasemide on renal function in 25 anesthetized ventilated hypoxemic newborn New Zealand White rabbits with vasomotor nephropathy. This well-established animal model mimics the renal physiology of the human newborn and, in particular, that of the premature infant. Three groups of hypoxemic rabbits were studied. The animals of group 1 (n = 8) received no diuretic therapy (hypoxemic control), and those of group 2 (n = 9) were given a single intravenous dose of torasemide (1 mg/kg) in a curative fashion 2 h after hypoxemia was induced. In the third group of animals (n = 8), torasemide was given preventively; a bolus intravenous dose of torasemide (0.2 mg/kg) was given before the induction of hypoxemia and sustained by the addition of 0.2 mg x kg(-1) x h(-1) of the drug to the continuous intravenous infusion given throughout the entire 3-h hypoxemic period. Hypoxemia alone (group 1) caused acute renal insufficiency with a significant fall in mean arterial blood pressure, GFR, and renal blood flow; the renal vascular resistance increased, and the filtration fraction was unchanged. The curative dose of torasemide (group 2) induced a significant diuresis and natriuresis with minimal augmentation of urinary potassium excretion, converting mildly oliguric to nonoliguric acute renal insufficiency. In this group of animals, torasemide did not improve the glomerular dysfunction. The preventive dose of torasemide (group 3) even somewhat worsened the already impaired renal functions without further increasing the diuretic effect of the drug. We conclude that in hypoxemic newborn animals with renal dysfunction, torasemide is an effective potassium-sparing diuretic that unfortunately does not improve renal blood flow and GFR. The failure of torasemide to attenuate the glomerular dysfunction of hypoxemic vasomotor nephropathy in the newborn rabbit is disturbing. These data certainly caution against the overzealous use of loop diuretics in hypoxemic oliguric neonates.

Acute Kidney Injury↗

The renal hemodynamic effects of ibuprofen in the newborn rabbit.

In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.

Animals↗

The use of Luria's method for the neurobehavioral assessment of encephalopathy in an adolescent: application in a rehabilitation setting.

Standardized neuropsychological test batteries demonstrate their greatest reliability and validity in patients with focal, well-defined neurologic disease. In these patients, the test profiles typically highlight focal areas of strengths and weaknesses in the brain. However, the clinical utility of standard test batteries and their reliance on scaled score differences is limited when evaluating patients with severe or diffuse neurobehavioral disorders. In the present case study, we applied the qualitative approach of Alexander Luria to the neuropsychological evaluation of a severely impaired adolescent, unable to complete psychometric tests. Luria's investigative method was able to assist in the localization of the brain dysfunction and the neurologic diagnosis of a young patient with an unusual neurologic presentation secondary to serious multisystem disease. The initial neuropsychological diagnostic impressions were later confirmed by diagnostic testing. The test results were also used to provide recommendations for ongoing neurorehabilitation of the patient.

Clinical Conference↗

Spot urine samples for evaluating solute excretion in the first week of life.

AIM: To evaluate whether the urinary creatinine concentration is a reliable reference value to standardise urinary solute excretion in a spot urine sample during the first week of life. METHODS: Spontaneously voided urine specimens were obtained in 48 healthy, full term neonates, aged 1 to 6 days (median 2.4) and in 168 healthy older children with a median age of 1.5 years (range 1 month to 3 years). In 62% of the children two urine samples were available with an interval of 2 to 4 (neonates) and 7 days (older children). RESULTS: In neonates both the urinary creatinine concentration and the urinary creatinine:osmolality ratios were significantly higher than in the older children, and were spread over a wider range. During the first postnatal week of life the mean urinary creatinine and urinary creatinine: osmolality ratio values in the first urine samples were also significantly higher than in the second samples. In children aged between 1 month and 3 years of age, these data were remarkably stable without any significant changes between repeat urine samples. CONCLUSIONS: The urinary creatinine concentration during the first days of life is high and variable, even when corrected for urinary osmolality. This is the opposite of what is found in older children and adults. Urinary creatinine and the urinary creatinine:osmolality ratio, therefore, cannot be used to standardise the urinary excretion of solutes in the first week of life.

Biomarkers↗

The effects of dimethyl sulfoxide on renal function of the newborn rabbit.

The purpose of this study was to establish the effects of intravenous dimethyl sulfoxide (DMSO), a solvent used in a wide variety of products (medicines), on kidney function in the newborn rabbit. Three groups of anesthetized, ventilated, normoxemic 4- to 8-day-old New Zealand White rabbits received a 90-min intravenous infusion of DMSO at a dose of 1.11 (group 1), 16.5 (group 2) or 111 microgram/ kg/h (group 3). The only change observed in the animals of group 1 was a significant increase in filtration fraction (FF; p < 0. 001), whereas no change at all was observed in the renal functional parameters of the animals of group 2. The highest dose of DMSO (group 3), however, caused a very significant (p < 0.001) decrease in renal blood flow (RBF) and a rise in renal vascular resistance (RVR), FF and urine volume (UV). Glomerular filtration rate (GFR) and systemic parameters such as pH, mean arterial blood pressure and heart rate did not change. The rise in GFR, RVR, UV (group 3 vs. 2) and FF (groups 3 vs. 2 and 2 vs. 1) was dose-dependent. No significant dose-dependent decrease in RBF was found. To the best of our knowledge, there are no previous reports on the effect of DMSO on renal function in the solvent doses used in this study. We ascribe the reported effects to the 'immaturity' of the newborn rabbit kidney. Consequently, this agent should be used with great caution in developmental studies.

Animals↗

Renal function in cyanotic congenital heart disease.

We performed renal function tests in 18 young patients, 1.8-14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 +/- 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 +/- 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 +/- 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.

Acid-Base Equilibrium↗