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Biomedical subjects

A Drukker

Publications and source records attributed to A Drukker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Why do newborn infants have a high plasma creatinine?

BACKGROUND: Plasma creatinine (Pcr) levels at birth are greatly elevated in relation to the size (and the muscle mass) of the newborn infant and remain so for 1 to 2 weeks. Particularly intriguing is the fact that Pcr levels are higher in preterm than in term infants and for a longer postnatal period. The smaller the birth weight, the higher the Pcr. This cannot be explained by maternal transfer of Pcr or by the absolute and relative (to adult body surface area) reduced glomerular filtration rate of the newborn. Perhaps the renal handling of creatinine is involved. DESIGN: In 522 pairs of mothers and fetuses, maternal and fetal Pcr were compared from 16 weeks of gestation until term. Pcr was measured in 66 newborns of various birth weights and followed for 1 month. Creatinine clearance (Ccr) and inulin clearance (Cin) were measured simultaneously in adult (n = 8) and newborn (n = 20) New Zealand White rabbits. In the latter, nephrogenesis continues after birth and they are therefore a good animal model for the study of the renal function in premature infants. PATIENT: A case of a premature male infant is presented (gestation: 29 weeks; birth weight: 1410 g) suspected of having sepsis because of premature rupture of membranes and postpartum maternal fever. This suspicion was not confirmed. Blood chemistry evaluation showed a high Pcr at birth (0.85 mg/dL, 75 micromol/L), even higher than that of the mother (0.77 mg/dL, 68 micromol/L). The Pcr started to decrease after approximately 1 week but remained elevated throughout 1 month of follow-up. RESULTS: From the maternal-fetal Pcr measurements it was quite evident that during the second half of gestation the small molecular weight creatinine (113 dalton, 0.3 nm radius) of the mother and fetus equilibrates at all maternal Pcr levels. The newborn Pcr levels were not only high at the time of birth but remained so for more than 3 weeks. It was also shown that the smaller the infant the higher the Pcr levels. The results of the animal experimental data showed that adult rabbits had the normal physiologic pattern in which Ccr overestimates Cin (Ccr/Cin ratio >1.0). In contrast, the results in the newborn rabbits showed an unexpected underestimation of the Ccr vis-à-vis Cin (Ccr/Cin ratio <1.0). This means, as is explained at length in the "Discussion" of this article, that the preterm newborn infant reabsorbs creatinine along the renal tubule. CONCLUSION: The riddle of the high Pcr levels in term and particularly in preterm newborns seems to be solved. Once the umbilical cord is severed, the perfect intrauterine maternal-fetal biochemical balance is disturbed. Thereafter, the already transferred exogenous, adult-level creatinine will rapidly disappear in the first urine specimens passed by the now autonomous newborn infant. A new steady state is achieved in due time, based on independent neonatal factors. One of these factors is the unusual occurrence of tubular creatinine reabsorption. We hypothesize that this latter temporary phenomenon is attributable to back-flow of creatinine across leaky immature tubular and vascular structures. With time, maturational renal changes will impose a barrier to creatinine. From that point onwards, total body muscle mass, glomerular filtration rate, and tubular secretion will in health determine the Pcr level of the individual. plasma creatinine, tubular handling of creatinine, newborn, premature infants.

Absorption↗
PubMed1999

Primary hyperoxaluria type I: a model for multiple mutations in a monogenic disease within a distinct ethnic group.

Primary hyperoxaluria type 1 is an autosomal recessive inherited metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of phenotypes ranging from renal failure in infancy to mere renal stones in late adulthood. Mutations in the AGXT gene, encoding the liver-specific enzyme alanine:glyoxylate aminotransferase, are responsible for the disease. Seven mutations were detected in eight families in Israel. Four of these mutations are novel and three occur in children living in single-clan villages. The mutations are scattered along various exons (1, 4, 5, 7, 9, 10), and on different alleles comprising at least five different haplotypes. All but one of the mutations are in a homozygous pattern, reflecting the high rate of consanguinity in our patient population. Two affected brothers are homozygous for two different mutations expressed on the same allele. The patients comprise a distinct ethnic group (Israeli Arabs) residing in a confined geographic area. These results, which are supported by previous data, suggest for the first time that the phenomenon of multiple mutations in a relatively closed isolate is common and almost exclusive to the Israeli-Arab population. Potential mechanisms including selective advantage to heterozygotes, digenic inheritance, and the recent emergence of multiple mutations are discussed.

Arabs↗
PubMed1998

Pitfalls in measuring inulin and para-amino-hippuric acid clearances.

Various carbohydrates and a variety of widely used medicines interfere with the generally used laboratory methods for determining inulin and para-aminohippuric acid (PAH). When these pitfalls are not recognized, false measurements of inulin and PAH clearances, which represent glomerular filtration rate and renal plasma flow respectively, are obtained. When performing these tests a careful history of dietary habits and oral drug therapy must be taken.

Ammonium Chloride↗
PubMed1998

Long-term followup of renal functional reserve capacity after unilateral nephrectomy in childhood.

PURPOSE: We establish renal function and renal reserve capacity in the long-term followup of unilateral nephrectomy in childhood. MATERIALS AND METHODS: We recalled 37 subjects who underwent unilateral nephrectomy during childhood (age less than 16 years) to determine glomerular filtration rate, renal plasma flow and functional renal reserve capacity after oral protein loading. Interval since nephrectomy was 0.5 to 10 years in 10 cases, 11 to 20 in 13 and more than 20 years in 14, during which regular repeated renal function tests were done at our hospital. None of the patients had hypertension or significant proteinuria and all developed normally into adults. A group of 7 healthy normal subjects with 2 kidneys served as controls. RESULTS: Creatinine clearance increased 34% immediately after surgery from a mean plus or minus standard error value of 78.6 +/- 6 to 105.4 +/- 7.2 ml. per minute per 1.73 m.2, peaked 2 to 6 months postoperatively and then plateaued (approximately 125 ml. per minute per 1.73 m.2). This level of renal function was sustained for more than 20 years. At the present testing glomerular filtration rate and renal plasma flow were not different from those of the controls. Renal reserve capacity was normal (stable) only during the first decade after unilateral nephrectomy (approximately 6% decrease), and it decreased by 50% at 10 to 20 and 66% at 20 to 30 years later. CONCLUSIONS: This long-term followup study demonstrates that a single remnant human kidney continues to function normally for more than 20 years. The prolonged increased workload does not interfere with normal development and maturation. The renal reserve capacity decreased significantly during the years may, however, indicate a vulnerability of the single kidney and raises the possibility of renal functional impairment with much longer followup.

Adolescent↗
PubMed1998

Excessive dietary protein and suboptimal caloric intake have a negative effect on the growth of children with chronic renal disease before and during growth hormone therapy.

Although diet and nutrition are an integral part of the management of individuals with chronic renal failure (CRF), little has been written on the effect of nutrition on the growth response to growth hormone (GH) in CRF. We studied the GH axis and nutritional status of 31 prepubertal children aged 8.7 +/- 0.5 years with a height standard deviation score (SDS) of -3.2 +/- 0.2 (mean +/- SEM) with CRF. Sixteen CRF patients on hemodialysis and 15 on peritoneal dialysis were studied. Forty-four age-matched normal short children without GH deficiency served as controls. Spontaneous 12-hour GH and stimulated GH values were significantly higher and GH binding protein (GHBP) was significantly lower in the CRF patients than in the normal short children. Both before the initiation of GH therapy and after the first year of treatment, the growth velocity (SDS) was inversely correlated with dietary protein intake and positively correlated with caloric intake. GH was administered at a dosage of 28 and 21 IU/m2/wk to the CRF group and the normal short children, respectively, divided into seven daily doses. The growth response of the normal short children was significantly greater than that of the CRF patients. GH therapy induced a smaller increment in GHBP and IGF-I in the CRF patients versus the normal short children (8.8 +/- 2.2 and 10.2 +/- 2.7 v 24.8 +/- 1.3 and 27.6 +/- 2.5 nmol/L, respectively, P < .01). The 1-year growth velocity of the CRF children was most closely correlated with dietary protein and caloric intake. The nutritional status of CRF patients is concluded to be a major factor in growth both before and during GH therapy.

Alkaline Phosphatase↗
PubMed1998

Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. METHODS: Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). RESULTS: Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. CONCLUSIONS: Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.

Adolescent↗
PubMed1998

Variability in management of symptomless microhaematuria in schoolchildren.

The evaluation of incidentally detected symptomless microhaematuria in schoolchildren is controversial. Some authors advocate varying numbers of immediate tests, while others recommend investigations only in cases who develop systemic symptoms or signs, or a decline in renal function. The objective of this study was to estimate the extent to which this uncertainty affects the declared habits of practising physicians. A sample of 16 family physicians, 42 primary care paediatricians and 26 full-time hospital-based paediatric nephrologists in Israel were asked to complete a survey using a written case of a hypothetical eight-year-old boy with incidentally detected symptomless microhaematuria. Responses were received from 16 (100%), 18 (43%) and 18 (69%), respectively. The mean number of requested tests, other than follow-up examination of the urine, were 1.5 (range 0-5) for family physicians, 2.5 (1-5) for primary care paediatricians and 5.3 (2-12) for paediatric nephrologists, at an average cost of NIS 408 (US$ 136), NIS 454 (US$ 151) and NIS 860 (US$ 286), respectively. There was also a marked variability within subspecialty groups, so that some family physicians recommended more tests at a higher cost than some of the paediatric nephrologists. There was a marked and unexplained variability within and among the three groups of respondents regarding the extent of the evaluation. The main reason for this variability is probably the uncertainty about the scientifically appropriate way to approach this condition in a symptomless child.

Child↗
PubMed1998

Effect of magnesium sulfate on kidney function in the newborn rabbit.

The aim of this study was to investigate the acute, short-term effects of the intravenous (i.v.) administration of magnesium (Mg) sulfate on renal function in the newborn rabbit. Eight anesthetized and mechanically ventilated, normoxemic, newborn New Zealand white rabbits were studied. We measured mean arterial blood pressure (MAP), urine volume (V), glomerular filtration rate (GFR), renal plasma flow (RPF) and calculated renal blood flow, filtration fraction (FF) and renal vascular resistance (RVR) under control conditions and in two experimental periods after the i.v. Mg sulfate load. Mg sulfate administration in a dose 100 mg/kg followed by 50 mg/kg/h caused a significant fall (p < 0.001) in MAP, GFR and RPF, whereas the RVR increased (p < 0.01). FF did not change significantly (p: NS/0.05) and V remained constant. These results show that the acute i.v. administration of Mg sulfate to newborn rabbits causes systemic vasodilatation with a fall in MAP. The increase in RVR, without consistent change in FF, suggests that the renal vasculature of the 'immature' neonatal rabbit reacts to these changes by preferential afferent arteriolar vasoconstriction.

Animals↗
PubMed1998

Creatinine reabsorption by the newborn rabbit kidney.

Plasma creatinine levels are elevated in the first postnatal days, and the highest plasma creatinine values are observed in the most premature infants. These high plasma creatinine levels remain "elevated" beyond the period in which the high plasma creatinine levels can be explained by maternal transfer of creatinine. To better define the renal handling of creatinine by the immature kidney, creatinine and inulin clearances were simultaneously measured in two groups of neonatal and one group of adult anesthetized, ventilated rabbits. In the adult animals the ratio of the creatinine and inulin clearance was as expected more than one (1.21), indicating an overestimation of the true GFR due to tubular secretion of creatinine. The creatinine and inulin clearance ratio in the first group of newborn animals, who received an exogenous creatinine infusion to achieve plasma creatinine levels comparable to those in the adult animals (84.1 +/- 1.0 mumol/L; 0.95 +/- 0.01 mg/dL), was 0.84. When in the second group of neonatal animals the plasma creatinine level was artificially doubled to 155.0 +/- 3.9 mumol/L (1.33 +/- 0.17 mg/dL), no significant difference between both clearance values was found (ratio: 0.96). These data show that in the newborn rabbit creatinine is reabsorbed along the tubule, an observation that can best be explained by the back-leak of creatinine across leaky immature tubules.

Absorption↗
PubMed1998

Failure of antioxidant therapy to attenuate interstitial disease in rats with reversible nephrotic syndrome.

The present two studies were designed to determine whether oxidized LDL contributes to the tubulointerstitial changes seen in rats during the acute phase of acute puromycin aminonucleoside nephrosis (PAN). In the single-dose study, rats were given one injection of puromycin aminonucleoside (PA; 15 mg/100 g body wt) and killed 1, 2, or 3 wk thereafter. The four animal groups were saline controls, PAN controls, PAN plus probucol, and PAN plus lovastatin. This study showed that the addition of probucol significantly reduced the mean levels of serum cholesterol and renal lipid-peroxidation products, an effect not seen with lovastatin therapy. Compared with saline controls, PAN controls had a significant increase in total kidney collagen (7.9 +/- 1.2 versus 5.9 +/- 0.6 mg/kidney at 3 wk). Neither probucol nor lovastatin therapy attenuated the interstitial inflammation or fibrosis. In the multidose study, rats were given the same initial PA dose and were uninephrectomized on day 12. They were killed on day 35 after two smaller PA doses were given on days 16 and 23. Animal groups were saline controls, PAN controls, PAN plus probucol, and PAN plus vitamin E. Hepatic lipid-peroxidation products were significantly lower in the probucol-treated, but not in the vitamin E-treated, PAN groups when compared with the PAN controls. Neither probucol nor vitamin E prevented the increase in total kidney collagen that was observed in the PAN control group (7.4 +/- 0.7, 10.1 +/- 2.6, and 9.3 +/- 1.8 mg of collagen/kidney, respectively, versus 5.4 +/- 0.5 mg/kidney for the saline controls). Renal cortical mRNA levels for matrix-encoding genes and protease inhibitors were similar in the three nephrotic groups. Transforming growth factor-beta1 mRNA levels were highly variable within each group and not significantly different at day 35, but showed a significant positive correlation with the degree of albuminuria (r = 0.70). The present results demonstrate that the treatment of acutely nephrotic rats with antioxidant therapy did not attenuate interstitial inflammation or fibrosis. We speculate that other factors, possibly a consequence of proteinuria itself, are the predominant pathogenetic mediators of the tubulointerstitial damage in acute nephrotic syndrome.

Animals↗
PubMed1998

Living unrelated (commercial) renal transplantation in children.

Long waiting times for cadaveric renal transplantation has led the frustrated parents of Arab children with end-stage renal disease treated in our center to seek commercial renal transplantation (CRT) outside Israel. During the past 3 yr, 18 children, aged 13 +/- 1 yr, underwent CRT in one center in Iraq. Post-CRT follow-up was 20.2 +/- 2.5 mo. Immediate complications (abroad) included: death on the day of surgery (n = 1) and vascular thrombotic events requiring removal of a previously functioning graft (n = 2). There was a high incidence of urologic problems, mainly as a result of inadequate uretero-vesical anastomosis. Calculated creatinine clearance at 6, 12, 18, 24, and 30 mo was 84.7 +/- 6.4, 91.0 +/- 6.8, 90.8 +/- 6.2, 82.5 +/- 9.5, and 77.7 +/- 8.2 ml/min per 1.73 m2 respectively, representing excellent graft function in 13 patients and slightly compromised function in two children. One- and two-year patient survival was 94.4%, with a graft survival of 83.3%. CRT in these Arab children had a favorable outcome despite severe early postoperative complications. Graft function at follow-up was comparable to cadaveric renal transplantation in Israel. This may reflect a propensity for healthy young adult donors. Despite these results, the authors oppose and discourage the practice of CRT on legal and ethical grounds. Not to provide follow-up care in this specific group of patients would not have been in their best interest.

Adolescent↗
PubMed1997

The progression of chronic renal disease: immunological, nutritional and intrinsic renal mechanisms.

The majority of patients with any initial renal insult show progression of renal damage over time. The histological end-result is often the same, whatever the initial lesion, and consists of an increase in extracellular matrix (ECM) and ultimately glomerulosclerosis. The clinical rate of progression correlates mainly with the degree of interstitial, rather than with that of glomerular damage. The main culprits for the ultimate interstitial damage and the rate of progression of renal disease, are the type and degree of the initial (e.g. immunological) insult and the magnitude of the proteinuria. Hypertension (intraglomerular) is an independent risk factor. Control of hypertension with angiotension converting enzyme (ACE) inhibitors or angiotensin II (AII) receptor blockers, reduction of protein and fat intake, anti-oxidative therapy and a variety of experimental measures reduce the progression of renal damage in animal experiments. Some of these interventions have also been shown to be beneficial in a number of controlled clinical studies, in well-defined renal disease entities in humans. These new data provide insight into the pathogenesis of chronic renal damage and raise the hope that in the not too far future, effective strategies can be devised to attenuate the progression of acquired renal disease.

Diet↗
PubMed1996

Symptomless microhaematuria in schoolchildren: causes for variable management strategies.

We reviewed published data on the frequency of underlying disorders in schoolchildren with microscopic or gross isolated haematuria (IH), and evaluated management strategies. We found five reports of microscopic IH in screened asymptomatic schoolchildren, three reports of microscopic IH detected by case-finding, and five surveys of kidney biopsies in referred children with microscopic and gross IH. We listed the reported underlying disorders, and estimated the benefit from their early detection and treatment. Most children with microscopic IH, whether detected by screening or case-finding, had no significant underlying disease. Some had disorders that may benefit from early treatment (membranoproliferative glomerulonephritis, obstructive uropathy, urolithiasis), or counselling (hereditary nephropathy, renal cystic disease). The combined prevalence of these five diseases was 0-7.2% in children with microscopic IH detected by screening, and 3.3%-13.6% in those with microscopic IH detected by case-finding. The combined prevalence of membranoproliferative glomerulonephritis and hereditary nephropathy among kidney biopsies was 11.6%-31.6% in children with microscopic IH, and 3.6%-42.1% in children with gross IH. Variable management strategies for schoolchildren with IH result from uncertainty about the frequency of underlying disorders and the efficacy of their early treatment. With no evidence that detecting IH leads to prevention of renal function impairment, screening for IH in symptomless schoolchildren is not warranted. Once detected, however, IH justifies further investigation.

Child↗
PubMed1995

Acquired glomerulocystic kidney disease following haemolytic-uraemic syndrome.

Glomerulocystic kidney disease is a rare condition, usually seen in infants and young children, characterised by cystic dilatation of the glomeruli. It may be sporadic or represent the congenital expression of dominant polycystic kidney disease. Glomerular cysts may also be seen in association with various syndromes and as a component of dysplastic kidneys. Only two cases of acquired glomerulocystic kidneys have been described, both in adults. The cystic change followed haemolytic-uraemic syndrome in one patient and systemic sclerosis in the other. These two conditions are closely related and may be indistinguishable pathologically. We report a case of acquired glomerulocystic kidney in a child which followed the haemolytic-uraemic syndrome. The factors leading to glomerulocystic kidney following haemolytic-uraemic syndrome are unknown and need further evaluation.

Adolescent↗
PubMed1995

Oxalosis of bone: report of four cases and a new radiological staging.

Oxalosis of bone is caused by a combination of crystalline calcium oxalate deposition in bone and renal osteodystrophy in patients with chronic renal failure. The present paper presents the radiographic findings of oxalosis of bone in four patients who have been followed over a period of from 4 to 16 years. Four successive characteristic stages can be recognized in the development of the skeletal changes.

Adolescent↗
PubMed1994

Changes in body composition of children with chronic renal failure during growth hormone treatment.

Growth hormone (GH) has different known metabolic effects, among which are lipolysis and anabolic action. We have studied the changes in body composition of children with chronic renal failure (CRF) after 1 year of daily treatment with GH. Body fat percentage and fat body mass (FBM) were derived from four site skinfold measurements; lean body mass (LBM) from total body potassium (TBK) and mid-arm muscle circumference (MAMC); bone mineral density (BMD) was measured by dual photon absorptiometry. GH treatment had a positive effect on weight, height and MAMC, but no effect on LBM (as reflected by TBK), FBM and BMD. Z-scores were derived in order to compare subjects with a normal population. While no significant change in z-score was noticed for weight, height, MAMC, FBM and BMD, TBK decreased during treatment. We conclude that GH therapy does not ultimately increase LBM in CRF patients compared with other GH-treated groups.

Body Composition↗