Search

Background Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. Methods Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2-17 years. Validated equations included Schwartz-2009.sub.CR/2012.sub.CR/CYS/CR+CYS, FAS.sub.CR/CYS/CR+CYS, LMR.sub.CR, Schwartz-Lyon.sub.CR, Berg.sub.CYS, CAPA.sub.CYS, CKD-EPI.sub.CYS, Andersen.sub.CR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P.sub.10) and ± 30% (P.sub.30) of mGFR. Results Three of the cystatin C equations, Berg.sub.CYS, CAPA.sub.CYS and CKD-EPI.sub.CYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPI.sub.CYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-Lyon.sub.CR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m.sup.2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations. Conclusions The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations., Author(s): Jonas Björk [sup.1] [sup.2] , Ulf Nyman [sup.3] , Ulla Berg [sup.4] , Pierre Delanaye [sup.5] , Laurence Dubourg [sup.6] , Karolien Goffin [sup.7] , Anders Grubb [sup.8] , [...]

Byline: Mohamed. El-Gamasy, Redha. Alarabawy Background: It is not easy to suspect whether newly born infants diagnosed as hypoxic ischemic encephalopathy (HIE) will develop impairment of renal function, so there [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.01.010 Byline: T. Arndt Keywords: Creatinine; Cut-off; Drug screen; Gender; Urine Abstract: Background: Statistical data from a wide cohort of subjects should provide arguements for a more valid interpretation of urine-creatinine concentrations as laboratory marker of urine dilution. Methods: Unselected, consecutive urine-creatinine concentrations from 11,811 women and 13,009 men in a clinical chemistry laboratory (mainly from clinical trials and employment medicine departments) and from 7300 women and 12,456 men in a toxicological chemistry laboratory (mainly from drug screenings for re-issuing drivers licenses or from employment medicine departments) were evaluated by descriptive and comparative statistics. Results: Women (clinical chemistry lab, toxicological chemistry lab): mean 723mg/L, 921mg/L; median 568mg/L, 728mg/L; 2.5-97.5% percentile range 189-2198mg/L, 129-2690mg/L. Men (clinical chemistry lab, toxicological chemistry lab): mean 975mg/L, 1395mg/L; median 802mg/L, 1241mg/L; 2.5-97.5% percentile range 256-2660mg/L, 204-3520mg/L. The rate of urine-creatinine concentrations of >3000mg/L (up to 3-fold of the upper limit of the reference range) was higher for men in both laboratories and for both genders in the toxicological chemistry lab compared with the clinical chemistry lab (toxicological chemistry lab: 697 for men (5.6%) and 111 for women (1.5%), clinical chemistry lab: 200 for men (1.5%) and 93 for women (0.8%)). Conclusions: Utmost caution should be taken when interpreting urinary creatinine concentrations that fall below so-called cut-offs. Cut-offs greater than the gender-specific 2.5% percentiles bear a high risk of misinterpretation regarding urine adulteration. Such cut-offs are no longer acceptable. At present, the borderline range of >50mg/L to Author Affiliation: Bioscientia Institut fuer Medizinische Diagnostik GmbH, Konrad-Adenauer-StraAe 17, D - 55218 Ingelheim, Germany Article History: Received 12 August 2008; Revised 7 January 2009; Accepted 14 January 2009

Byline: Narendra Aladangady (1,6), Pietro G. Coen (2), Madeleine P. White (3), Margaret D. Rae (4), T. James Beattie (5) Keywords: Urinary calcium; Urinary phosphate; Urinary creatinine; Nephrocalcinosis; Percentile Abstract: The aims of this study were to determine reference ranges for the urinary calcium (UCa/Cr) and phosphate (UPO.sub.4/Cr) creatinine ratios and to study factors influencing these ratios in a representative population of preterm infants managed according to current nutritional guidelines. Spot urine samples were obtained from 186 preterm infants (gestation 24--34 weeks) for measurement of UCa/Cr and UPO.sub.4/Cr ratios as part of a routine metabolic bone screening program, once every 2--4 weeks from the 3rd to the 18th week of life. Data were also collected on gender, appropriate or small for gestational age (SGA), nutrition [total parenteral nutrition (TPN), preterm or term formula, and breast milk], plasma Ca, PO.sub.4, urea, and electrolytes and on the use of drugs (frusemide, dexamethasone, and theophylline). Data from infants treated with any of these three drugs were analysed separately and not included in establishing the reference ranges for UCa/Cr and UPO.sub.4/Cr. The mean gestational age of the study population was 28 weeks (range 24--34 weeks). The 95th percentile for UCa/Cr at 3 weeks of age was 3.8 mmol/mmol and decreased significantly with increasing postnatal age ( P &lt 0.001). The 95th percentile for UPO.sub.4/Cr was 26.69 mmol/mmol at 3 weeks of age, but this did not change significantly with increasing postnatal age ( P =0.296). On univariate analysis there was no significant association of UCa/Cr and UPO.sub.4/Cr with gender and type of enteral nutrition. The UCa/Cr was lower in infants who were SGA ( P =0.013) and with low plasma Ca ( P =0.008). Infants on TPN had significantly higher UCa/Cr ( P =0.019) and lower UPO.sub.4/Cr ratios ( P a$?0.001). Multivariate analysis confirmed the decrease in UCa/Cr ratio with increasing postnatal age, but the SGA effect was eliminated. The use of furosemide ( P &lt 0.001) and theophylline ( P =0.003) was associated with a significant increase in the UCa/Cr ratio. The use of dexamethasone was also associated with an increase in UCa/Cr ratio, but this did not achieve statistical significance ( P =0.339). The use of furosemide, theophylline, and dexamethasone had no effect on UPO.sub.4/Cr. We report a reference range for UCa/Cr and UPO.sub.4/Cr ratios and factors influencing these ratios in a representative population of preterm infants between 24 and 34 weeks gestation, managed according to current nutritional guidelines. Author Affiliation: (1) Department of Neonatology, The Queen Mother&apos;s Hospital, Glasgow, G3 8SJ, UK (2) Department of Medical Statistics, Queen Mary, University of London, Mile End, London, UK (3) Department of Neonatology, Southern General Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK (4) Department of Biochemistry, The Royal Hospital for Sick Children, Yorkhill, Glasgow, G3 8SJ, UK (5) Department of Nephrology, The Royal Hospital for Sick Children, Yorkhill, Glasgow, G3 8SJ, UK (6) Neonatal Unit, Homerton University Hospital/Barts and the London School of Medicine and Dentistry, Homerton Row, London, E9 6SR, UK Article History: Registration Date: 18/06/2004 Received Date: 03/02/2003 Accepted Date: 18/05/2004 Online Date: 03/09/2004 Article note: Editorial comment: this paper describing urinary excretion of calcium and phosphate in preterm infants elicited completely different reactions from the three referees selected to review the manuscript. It is important to establish reference ranges for urinary excretion of these minerals. Nevertheless, it is also important to understand the effect of dietary intake of both calcium and phosphate in defining normative data. It is essential that readers of this article also read the accompanying commentary by Professor Frank Pohlandt.

A planar microchip-based creatinine biosensor employing an oxidizing layer (e.g., a Pb[O.sub.2] film), where interfering redox-active substances are broken (i.e., oxidized) to redox-inactive products, was developed to facilitate the microfabrication of the sensor and to provide improved, reliable determination of creatinine in physiological samples. The feasibility of using hydrophilic polyurethanes in permselective barrier membranes for creatinine biosensors and the effect of adding a silanizing agent (adhesion promoter) on the sensor performance (e.g., sensitivity, stability, and lifetime) are described. The proposed creatinine microsensor with a three-layer configuration, i.e., enzyme, protecting, and oxidizing layers, exhibits good electrochemical performance in terms of response time ([t.sub.95%] = 98 s at 100 [right arrow] 200 [micro]M creatinine change), linearity (1-1000 [micro]M, r = 0.9997), detection limit (0.8 [micro]M), and lifetime (~35 days). The creatinine biosensor devised in a differential sensing arrangement that compensates the erroneous results from creatine is considered to be suitable for assay of serum specimens.

A new sensing motif for the detection and quantification of creatinine, which is an important small molecule marker of renal dysfunction, is developed. Motif is based on intelligent polymerized crystalline colloidal array (IPCCA) materials, in which a three-dimensional crystalline colloidal array(CCA) of monodisperse, highly charged polystyrene latex particles is polymerized within lightly cross-linked polyacrylamide hydrogels.

Okusa, Mark D., Joel Linden, Timothy Macdonald, and Liping Huang. Selective [A.sub.2A] adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney. Am. J. Physiol. 277 (Renal Physiol. 46): F404-F412, 1999.--[A.sub.2A] adenosine receptors ([A.sub.2A]-ARs) are known modulators of renal hemodynamics and potent inhibitors of inflammation. We sought to determine whether selective activation of [A.sub.2A]-Ars protects kidneys from ischemia-reperfusion injury. The ester derivative of DWH-146 (DWH-146e), a selective [A.sub.2A] agonist, was found to be more potent and selective for [A.sub.2A]-ARs than the prototype compound CGS-21680. Osmotic minipumps were implanted subcutaneously to infuse into rats either vehicle or DWH-146e (0.004 [Micro]g [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1]), during and after ischemia-reperfusion injury. Following 24 and 48 h of reperfusion, the rise in serum creatinine and blood urea nitrogen for vehicle-treated rats was substantially elevated compared with DWH-146e-treated rats. Histological examination revealed widespread tubular epithelial necrosis and vascular congestion in the outer medulla of vehicle-treated compared with DWH-146e-treated animals. ZM-241385, a selective [A.sub.2A] antagonist, blocked the protective effect of DWH-146e. Delaying administration of DWH-146e until the initiation of reperfusion also decreased serum creatinine. We conclude that 1) selective [A.sub.2A]-AR activation by DWH-146e reduces ischemia-reperfusion injury in rat kidneys, 2) the effect of DWH-146e is [A.sub.2A] receptor mediated, and 3) the protective effects are mediated by preventing injury during the reperfusion period. acute renal failure; ischemia; inflammation; DWH-146 ester; ZM-241385

Ling, Hong, Charles Edelstein, Patricia Gengaro, Xianhong Meng, Scott Lucia, Mladen Knotek, Adisorn Wangsiripaisan, Yeuxian Shi, and Robert Schrier. Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice. Am. J. Physiol. 277 (Renal Physiol. 46): F383-F390, 1999.--Renal ischemia-reperfusion (UR) injury was investigated in inducible nitric oxide synthase (iNOS) knockout mice. After a 26-min bilateral renal pedicle clamp, serum creatinine concentrations (in mg/dl) in wild-type mice after a 24-h reperfusion were 0.25 [+ or -] 0.03 in sham-operated controls and 2.3 [+ or -] 0.38 in ischemic mice (P [is less than] 0.01); after 48 h, concentrations (in mg/dl) were 0.25 [+ or -] 0.03 in controls and 2.0 [+ or -] 0.18 in ischemic mice (P [is less than] 0.01). iNOS knockout mice demonstrated an attenuation of serum creatinine concentration after renal UR injury. Serum creatinine concentrations (mg/dl) after a 24-h reperfusion were 2.3 [+ or -] 0.22 in wild-type ischemic and 1.21 [+ or -] 0.25 in iNOS knockout ischemic mice (P [+ or -] 0.05); after 48 h, concentrations were 2.0 [+ or -] 0.18 in wild-type ischemic and 0.96 [+ or -] 0.25 in iNOS knockout ischemic mice (P [is less than] 0.01). Histological scoring of acute tubular necrosis in iNOS knockout mice was decreased compared with that in wild-type controls (0.88 [+ or -] 0.2 vs. 3.3 [+ or -] 0.3, P [is less than] 0.05). iNOS protein in the renal cortex of wild-type mice subjected to renal I/R injury was undetectable up to 48 h. However, a strong upregulation of heat shock protein 72 expression was observed in renal cortex of iNOS knockout mice under basal conditions. In conclusion, kidneys of iNOS knockout mice were protected against ischemic acute renal failure. This protective effect may be related to a compensatory upregulation of heat shock protein 72. acute renal failure; heat shock protein; serum creatinine

The researchers studiend the frequency and pathogenesis of hyperuricemia and gout during cyclosporine therapy. The patients studied had all been renal transplant recipients. The use of cyclosporine was required in these patients in order to minimize the risk of post-implant rejection of the transplanted kidney. The use of cyclosporine is complicated by numerous potential nonimmunologic side effects. The data accumulated in this study strongly suggest that hyperuricemia occurs as a consequence of decreased urate.

Several studies have suggested that small amounts of albumin protein in the urine (microalbuminuria) of diabetic patients is a sign of degenerative kidney changes. This study tested the relation of albumin urine excretion to the microscopic appearance of kidney tissues in 48 patients with insulin-dependent (Type 1) diabetes, as evaluated with light and electron microscopes, which allow cells to be examined at very high magnification. The results were also correlated with other clinical and laboratory findings. The authors conclude that finding traces of albumin by itself is insufficient to predict accurately the level of anatomic kidney damage. However, when this condition is present with high blood pressure and

Malignant hypertension, or high blood pressure, can cause severe kidney dysfunction. Treatment with drugs has been shown to stop the progression of kidney damage or even improve kidney function. However, primary hypertension with other causes, such as poor sodium excretion, can also damage the kidney. Despite the successful use of drugs to control high blood pressure, their ability to prevent or improve kidney deterioration in these latter patients has not been so convincing. Factors influencing the deterioration of kidney function in patients with primary hypertension were examined in 94 patients. Of these patients, 15 percent had some degree of impaired kidney function. Out of 61 patients with controlled high blood pressure (diastolic pressure of less than 90 mm Hg), 16 percent had deteriorating kidney function. The remaining 33 patients, who had poor blood pressure control, had insufficient kidney function in 12 percent. Results indicate that black patients were almost two times more likely to have impaired kidney function than white patients. Older people, people missing office visits and workers who performed physical labor were more likely to have insufficient kidney function. Results suggest that with adequate management of blood pressure, 85 percent of people with primary hypertension can maintain good kidney function. For black people, however, hypertension is still a leading cause of death.