Can the height-independent Pottel eGFR equation be used as a screening tool for chronic kidney disease in children?

Determination of plasma creatinine (Pcr) should be associated to an estimation of glomerular filtration rate (eGFR). Pottel et al. established a height-independent equation, eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr (Pottel-Belgium). The aims were to 1) determine a local height-independent equation (Pottel-Lyon), 2) evaluate the performance of these equations compared to the Schwartz 2009 and Schwartz-Lyon equations, and 3) evaluate the height-independent equations in laboratory routine. Therefore, 1) all first pediatric Pcr determination (December 2009-June 2011) were collected, and median of Pcr was determined for each 1-year age interval (Q-Lyon), 2) GFR was measured (mGFR) in 359 children (438 measures) and compared to eGFR, and 3) all first Pcr determination (January 2012-June 2013) were used to calculate eGFR with the Pottel-Lyon and the Pottel-Belgium equations. Pcr was determined by an IDMS-standardized enzymatic assay. In the population with a mGFR, the Pottel-Lyon and the Schwartz-Lyon showed the best performance (bias, P10 and P30). However, the performance in identifying patients with a mGFR < 75 mL/min/1.73 m(2) was similar for all the studied equations. CONCLUSION: The performance of the height-independent and dependent equations to identify mild renal dysfunction is similar. The height-independent Pottel equation could be proposed as an excellent screening tool for kidney disease when height information is not available. " WHAT IS KNOWN: " • Determination of plasma creatinine in children is rarely associated to an estimation of glomerular filtration rate due to the lack of height information. • Pottel et al. developed a height-independent equation (eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr for each age class. " WHAT IS NEW: " • The performance of the height-independent (Pottel) or height-dependent (Schwartz) equations is similar to identify renal dysfunction (GFR < 75 mL/min/1.73 m (2) ) in children. • The height-independent Pottel equation could be an excellent screening tool for kidney disease in a general pediatric laboratory when height information is not available.

Accuracy of different equations in estimating GFR in pediatric kidney transplant recipients.

BACKGROUND AND OBJECTIVE: The knowledge of renal function is crucial for the management of pediatric kidney transplant recipients. In this population, the most commonly used plasma creatinine (PCr)-based or cystatin C (CystC)-based GFR-predicting formulas may underperform (e.g., corticosteroids and trimethoprim may affect PCr concentration, whereas prednisone and calcineurin inhibitors may affect CystC concentration). This study evaluated the performance of six formulas in pediatric kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study used PCr-based formulas (bedside Schwartz, Schwartz-Lyon), CystC-based formulas (Hoek, Filler), and combined PCr-CystC-based formulas (CKD in Children [CKiD] 2012 and Zappitelli). The performance of these formulas was compared using inulin clearance as reference and assessed according to CKD stages in a historical cohort that included 73 pediatric kidney transplant recipients (199 measurements). The ability of the formulas to identify GFRs<60, <75, and <90 ml/min per 1.73 m(2) was assessed. RESULTS: At measured GFR (mGFR) ≥90 ml/min per 1.73 m(2) (nine patients; 23 measurements), the Zappitelli formula had the highest 30% accuracy (P30) (95% [95% confidence interval (95% CI), 87% to 100%]) and the bedside Schwartz had the highest 10% accuracy (P10) (56% [95% CI, 32% to 72%]). At mGFR≥60 and <90 ml/min per 1.73 m(2) (22 patients; 91 measurements), all formulas had P30 values >80%. However, only the CKiD 2012 formula had a P10 value >50%. At mGFR<60 ml/min per 1.73 m(2) (42 patients; 85 measurements), the CKiD 2012 and Schwartz-Lyon formulas had the highest P10 (45% [95% CI, 34% to 55%] and 43% [95% CI, 33% to 54%]) and P30 (90% [95% CI, 84% to 97%] and 91% [95% CI, 86% to 98%]). All studied equations except Hoek and Filler had areas under the receiver-operating characteristic curves significantly >90% in discriminating patients with renal dysfunction at various CKD stages (GFR<60, <75, and <90 ml/min per 1.73 m(2)). CONCLUSIONS: In pediatric kidney transplant recipients, the CKiD 2012 formula had the best performance at mGFRs<90 ml/min per 1.73 m(2). CystC-based formulas were not superior to PCr-based formulas.

In chronic kidney disease, serum α-Klotho is related to serum bicarbonate and proteinuria.

OBJECTIVES: Klotho is an "aging-suppressor" gene and encodes a single-pass transmembrane protein predominantly expressed in renal tubules. Whether chronic kidney disease (CKD) affects serum Klotho is poorly documented. We aimed to measure the relationship of serum α-Klotho with renal function, acid-base status, bone biomarkers, and proteinuria in CKD patients. DESIGN SETTING, PARTICIPANTS, AND MEASUREMENTS: We measured serum α-Klotho, serum FGF23, and glomerular filtration rate by inulin clearance in 60 CKD patients between January and July 2011. We also measured serum creatinine, bicarbonate, calcium, phosphorus, parathyroid hormone, C-reactive protein, and 25-OH vitamin D. Proteinuria was obtained from a 24-h urine collection. RESULTS: The median serum α-Klotho was 478 (348-658) pg/mL. We found an inverse relationship between serum α-Klotho and serum creatinine (r = -0.36, P = .007), proteinuria (r = -0.36, P = .013), and a positive relationship with serum bicarbonate (r = 0.33, P = .011). There was no further significant relation between serum α-Klotho and inulin clearance or serum FGF23. Multiple regression analysis including serum bicarbonate, serum creatinine, and proteinuria indicated that only serum bicarbonate was associated with serum α-Klotho (P = .003). CONCLUSIONS: This study shows that in CKD, serum α-Klotho is related to serum bicarbonate and proteinuria and not to renal function. Further research is required to determine whether correcting these 2 amenable conditions would improve serum α-Klotho.

The relationship between renal function and plasma concentration of the cachectic factor zinc-alpha2-glycoprotein (ZAG) in adult patients with chronic kidney disease.

Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the relationship between plasma ZAG concentration and renal function in patients with a large range of glomerular filtration rate (GFR). Plasma ZAG concentration and its relationship to GFR were investigated in 71 patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD and PD patients compared to non-CKD controls (P<0.01). The hemodialysis session further increased plasma ZAG concentration (+39%, P<0.01). An inverse relationship was found between ZAG levels and plasma protein (rs = -0.284; P<0.01), albumin (rs = -0.282, P<0.05), hemoglobin (rs = -0.267, P<0.05) and HDL-cholesterol (rs = -0.264, P<0.05) and a positive correlation were seen with plasma urea (rs = 0.283; P<0.01). In multiple regression analyses, plasma urea and HDL-cholesterol were the only variables associated with plasma ZAG (r2 = 0.406, P<0.001). In CKD-5 patients, plasma accumulation of ZAG was not correlated with protein energy wasting. Further prospective studies are however needed to better elucidate the potential role of ZAG in end-stage renal disease.

Accuracy of GFR estimation in obese patients.

BACKGROUND AND OBJECTIVES: Adequate estimation of renal function in obese patients is essential for the classification of patients in CKD category as well as the dose adjustment of drugs. However, the body size descriptor for GFR indexation is still debatable, and formulas are not validated in patients with extreme variations of weight. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 209 stages 1-5 CKD obese patients referred to the Department of Renal Function Study at the University Hospital in Lyon between 2010 and 2013 because of suspected renal dysfunction. GFR was estimated with the Chronic Kidney Disease and Epidemiology equation (CKD-EPI) and measured with a gold standard method (inulin or iohexol) not indexed (mGFR) or indexed to body surface area determined by the Dubois and Dubois formula with either real (mGFRr) or ideal (mGFRi) body weight. Mean bias (eGFR-mGFR), precision, and accuracy of mGFR were compared with the results obtained for nonobese participants (body mass index between 18.5 and 24.9) who had a GFR measurement during the same period of time. RESULTS: Mean mGFRr (51.6 ± 24.2 ml/min per 1.73 m(2)) was significantly lower than mGFR, mGFRi, and eGFRCKD-EPI. eGFRCKD-EPI had less bias with mGFR (0.29; -1.7 to 2.3) and mGFRi (-1.62; -3.1 to 0.45) compared with mGFRr (8.7; 7 to 10). This result was confirmed with better accuracy for the whole cohort (78% for mGFR, 84% for mGFRi, and 72% for mGFRr) and participants with CKD stages 3-5. Moreover, the Bland Altman plot showed better agreement between mGFR and eGFRCKD-EPI. The bias between eGFRCKD-EPI and mGFRr was greater in obese than nonobese participants (8.7 versus 0.58, P<0.001). CONCLUSIONS: This study shows that, in obese CKD patients, the performance of eGFRCKD-EPI is good for GFR ≤ 60 ml/min per 1.73 m(2). Indexation of mGFR with body surface area using ideal body weight gives less bias than mGFR scaled with body surface area using real body weight.

A new equation to estimate the glomerular filtration rate in children, adolescents and young adults.

BACKGROUND: A new estimated glomerular filtration rate (eGFR) equation, designed for isotope dilution mass spectrometry-standardized serum creatinine (Scr), is presented for use in children, adolescent boys and girls and young adults. METHODS: The new equation, eGFR = 107.3/(Scr/Q), is based on the concept of normalized Scr: Q is the normalization value and is considered as the Scr concentration for the average healthy child, adolescent or young adult of a specific height (L) and is modeled as a height-dependent polynomial of the fourth degree. RESULTS: The well-known Schwartz equation [eGFR = kL/Scr, k = 0.413 (Schwartz) or k = 0.373 (Schwartz-Lyon)] for children between 1 and 14 years can be seen as a special case of the new equation for which the Q-polynomial is simplified to a linear equation: Q = 0.0035 × L (cm). The new eGFR equation has been validated in a data set of n = 750 children, adolescents and young adults aged 10-25, against the true GFR (inulin method), and outperforms the selected (but most used) creatinine-based eGFR equations for children, mainly in the healthy GFR region. CONCLUSIONS: The new Q(height)-eGFR equation serves as an excellent screening tool for kidney disease in 1-25-year-old children, adolescents and young adults.

Creatinine- versus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis.

UNLABELLED: Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or >15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/min/1.73 m(2)). CONCLUSION: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging.

Performance of creatinine-based equations compared in older patients.

BACKGROUND: The current equations for estimating glomerular filtration rate (GFR) have limited precision in older people. The Berlin Initiative Study (BIS-1) equation has recently been developed to improve the precision and accuracy of GFR estimation in older people, over the previous simplified Modification of Diet in Renal Disease (MDRD) Study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. METHODS: The study included 224 white patients aged >70 years who had simultaneous measurements of plasma creatinine and renal clearance of inulin. Creatinine assays used an enzymatic method with calibrators defined by isotope dilution mass spectrometry. The performance of BIS-1, MDRD and CKD-EPI equations in estimating GFR were compared. RESULTS: BIS-1 was the most accurate: the percentage of GFR estimates that fell within the range of measured GFR ± 30% (P30) was 75.56% vs. 70.67% with MDRD and 72% with CKD-EPI. BIS-1 had the lowest median bias: (interquartile range) (4.1 (11.4) vs 5.8 (12.7) and 5.4 (12.8) respectively) the highest precision (the SD of the estimated GFR minus measured GFR differences was 9.21 vs 12.78 and 10.83 mL/min/1.73 m² respectively) and the highest concordance correlation coefficient (CCC) (0.82 vs. 0.74 and 0.79 respectively, p<0.05). However, in chronic kidney disease (CKD) stages 4 and 5, the CKD-EPI equation had the highest P30, the lowest median bias and the highest CCC: it was more accurate than the BIS-1 equation. CONCLUSION: Among the 3 creatinine-based equations compared, BIS-1 was the most reliable for assessing renal function in older white patients, especially in those with CKD stages 1 to 3.

The relation between renal function and serum sclerostin in adult patients with CKD.

BACKGROUND AND OBJECTIVES: Sclerostin, a bone antianabolic peptide involved in osteoporosis, is elevated in patients undergoing maintenance dialysis. However, there are no data for patients with early CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between January and July 2010, serum sclerostin and GFR (calculated by inulin clearance) were measured in 90 patients with CKD. Fasting blood samples were also drawn for determination of calcium, phosphorus, parathyroid hormone, bone alkaline phosphatase, and 25-OH vitamin D. RESULTS: Median GFR was 66.5 (interquartile range, 40.0-88.3) ml/min per 1.73 m(2). Median sclerostin level was 53.5 (interquartile range, 37.5-77.2) pmol/L, was higher in patients with a GFR <60 ml/min per 1.73 m(2), and was highest in those with ESRD. Sclerostin levels were significantly more elevated in men than women (P<0.05). An inverse relationship was found between sclerostin and GFR (r=-0.58; P<0.001), and a positive correlation was seen with age (r=0.34; P<0.01) and serum phosphate (r=0.26; P=0.02). In multiple regression analyses, GFR, sex, and serum phosphate were the only variables associated with serum sclerostin (P<0.001). Age lost its relationship with sclerostin level. CONCLUSIONS: This is the first study reporting higher serum sclerostin levels starting at CKD stage III. GFR, sex, and serum phosphate were the only measures associated with sclerostin level, suggesting that the effect of age reported in the literature might instead be attributable to the altered renal function in the elderly. Correcting the serum phosphorus level may be associated with lower sclerostin levels.

Early renal abnormalities in children with postnatally diagnosed autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) in children is often regarded as a benign condition. However, previous studies pointed out renal-related anomalies which may benefit from early appropriate treatments. This study was conducted to evaluate the prevalence and severity of early renal dysfunction in ADPKD children. METHODS: An extensive renal evaluation was performed in 52 consecutive ADPKD patients diagnosed either from prenatal screening or post-natal ultrasound (US) examination (54 % males, mean age 10 ± 4 years [1-17]). RESULTS: Three patients had both systolic (SBP) and diastolic (DBP) blood pressure above the 95th percentile, one patient had a "high normal" DBP, and one child was treated with an angiotensin-converting enzyme inhibitor (ACEI). The mean ± SD glomerular filtration rate (GFR ml/min per 1.73 m(2), inulin clearance) was 115 ± 26 [47-168] but six children (12 %) had a GFR < 90 and 11 (21 %) experienced hyperfiltration (GFR > 135). Microalbuminuria (2 < Ualb/Ucr ≤ 20 mg/mmol) was found in 25 patients and five had macroalbuminuria (>20 mg/mmol). CONCLUSIONS: Early renal manifestations are frequent in ADPKD children, including hypertension in 6 %, albuminuria in 58 %, and decreased GFR in 12 %. In conclusion, renal function in children with ADPKD should be regularly assessed in order to manage early renal dysfunction and even consider further therapeutic intervention.

GFR estimation in adolescents and young adults.

The performance of creatinine-based equations to obtain the estimated GFR in adolescents and young adults is poorly understood. We assessed creatinine-based GFR estimating equations in a cross-section of 751 adolescents and young adults (1054 measurements), using inulin clearance (measured GFR [mGFR]) as the reference method. We evaluated the following: Cockcroft-Gault, four-variable Modified Diet in Renal Disease, and the Chronic Kidney Disease Epidemiology Collaboration equations for adult participants, as well as the Schwartz 2009 and Schwartz-Lyon equations for pediatric age groups. Participants ranged in age from 10 to 26 years (mean 16.8 years); we divided the population into four groups according to age (10-12 years, 13-17 years, 18-21 years, and 21-25 years). Evaluation of the agreement between these formulas and mGFR (e.g., correlation, Bland-Altman plots, bias, and accuracy) showed that there was a good correlation between mGFR and both pediatric formulas in all age groups, whereas the adult formulas substantially overestimated mGFR. In conclusion, we recommend the use of pediatric equations to estimate GFR from childhood to early adulthood.

Deferasirox-induced renal impairment in children: an increasing concern for pediatricians.

BACKGROUND: Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy in transfusion-related iron overload. Whereas emerging long-term data confirm the safety of the drug, with transient moderate elevation of serum creatinine level, several authors have reported renal tubular dysfunction. The aim of this study was to evaluate tubular and glomerular function before and after the initiation of DFX therapy in a pediatric patient population. METHODS: Ten children (4 girls, mean age 12.4 ± 3.9 years) enrolled in a routine blood transfusion program were treated with 24.8 ± 9.6 mg/kg per day of DFX, and renal function was assessed before and 17.2 ± 8.9 months after the initiation of DFX therapy. RESULTS: Prior to treatment with DFX, all patients had a normal glomerular function rate (GFR) (125 ± 15 ml/min per 1.73 m(2)) and normal tubular function. Following the initiation of DFX therapy, the GFR decreased by approximately 20 % with one patient with a GFR of <80 mL/min per 1.73 m(2) and seven patients with a GFR of <100 mL/min per 1.73 m(2). Two patients experienced a generalized proximal tubular dysfunction whereas nine patients presented at least one sign of proximal tubular dysfunction. CONCLUSIONS: Renal toxicity is a frequent adverse event of DFX treatment, presenting as both glomerular and proximal dysfunction. A routine renal assessment is therefore required to prevent chronic kidney disease that may result from prolonged tubular injury.

Schwartz formula: is one k-coefficient adequate for all children?

BACKGROUND/OBJECTIVE: Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population. PATIENTS/METHODS: We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort. RESULTS: In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient. CONCLUSIONS: The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance.

[An asymptomatic chronic hypokalaemia]. / Une hypokaliémie chronique asymptomatique.

We report the case of an asymptomatic patient presenting a severe chronic renal hypokalaemia. Once being sure of no diuretics use, two hypothesis can be mentioned for a normotensive patient presenting an hypokalaemia associated with a metabolic alcalosis: Bartter syndrome or Gitelman syndrome. The highlighting of low magnesaemia and hypocalciuria strongly concentrates the diagnosis on Gitelman syndrome. First, this has been strengthened by the results of renal function tests and later it has confirmed by molecular diagnosis with the identification of a known homozygous mutation on SLC12A3 gene. In the patient family, the same chromosomal abnormality has been found in the young sister. For these two patients the treatment ordered is an antikaliuretic diuretic, magnesium and potassium supplements. This case shows the difficulty to diagnose Gitelman syndrome: it is frequently mistaken for Bartter syndrome. The main differences between these two syndromes are magnesaemia and calciuria. Furthemore , patients with Gitelman syndrome are often asymptomatic, this explains why prevalence of this illness is probably underestimated.

Performance of the chronic kidney disease epidemiology collaboration equation to estimate glomerular filtration rate in diabetic patients.

OBJECTIVE: The best method to estimate glomerular filtration rate (GFR) in diabetic patients is still largely debated. We compared the performance of creatinine-based formulas in a European diabetic population. RESEARCH DESIGN AND METHODS: We compared the performance of Cockcroft and Gault, simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equations in 246 diabetic patients by calculating the mean bias and the interquartile range (IQR) of the bias, 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance. RESULTS: For the whole population, the IQR was slightly lower for CKD-EPI, but the mean bias was lower and P10 and P30 were higher for MDRD. Similar results were observed in specific subgroups, including patients with mild renal insufficiency, obese patients, or type 2 diabetic patients. CONCLUSIONS: In our population, the CKD-EPI formula does not exhibit better performance than the simplified MDRD formula for estimating GFR.

The best way to detect elevated albuminuria.

BACKGROUND: It has been reported that first morning specimens are more reliable than random spot specimens to assess 24-hour urinary albumin excretion rate (UAER), especially if albuminuria is expressed as albuminuria to creatininuria ratio. We aimed to investigate the influence of (a) posture and activity and (b) the units to best estimate 24-hour albuminuria. METHODS: In this retrospective study, 24-hour UAER was compared to 60 min 'supine' and 90 min 'activity' albuminuria in 124 patients tested for resistant hypertension. The ability to adjust urinary albumin concentration (UAC) to creatininuria (ACR) or to collection duration (tAER) values in order to increase the reliability of albuminuria values was also analyzed. RESULTS: Compared to 24-hour UAER, UAC (mg/l), tAER (µg/min) and ACR (mg/mmol) during the supine period had a similar concordance rate in normo-, micro- and macroalbuminuric patients. The UAC in the supine period was well related to 24-hour UAER. However, UAC almost doubled during activity. Adjustment to creatininuria improved the correlation between albuminuria during both periods and 24-hour UAER, but mainly during the activity period. CONCLUSIONS: Our results confirm that UAC is dependent on physical activity. Correction of UAC by creatininuria (ACR) provides a satisfactory estimation of 24-hour UAER. Thus, for practical reasons, it is advisable to use ACR, where no differences appear to exist, whether a supine urine sample or an activity urine sample is obtained.

Which creatinine and cystatin C equations can be reliably used in children?

BACKGROUND AND OBJECTIVES: Estimation of GFR in children is challenging; reference methods are cumbersome, and formulas have limitations. The aims of this study were to evaluate (1) the new creatinine-based formula recently proposed by Schwartz using a kinetic colorimetric compensated Jaffe technique; (2) some cystatin C-derived formulas (Hoek, Le Bricon, Larsson, Rule, Filler, and Zappitelli) using a nephelemetric technique; and (3) combined formulas using both cystatin and creatinine (Zappitelli and Bouvet). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: These formulas were evaluated in a cross-sectional cohort of 252 children with moderate CKD or normal GFR, in comparison with the reference standard (inulin clearance, iGFR). Mean age, body weight, height, creatinine, and cystatin C were 10.7 ± 4.0 years, 35 ± 15 kg, 137 ± 20 cm, 55 ± 30 µmol/L, and 0.91 ± 0.35 mg/L, respectively. RESULTS: Mean ± SD iGFR was 101 ± 32 ml/min per 1.73 m². When evaluating agreement between these formulas and iGFR (e.g. correlation, Bland Altman plots, bias, and accuracies), there was a good correlation between iGFR and all Le Bricon, Larsson, Rule, and Zappitelli (both) and locally adapted Schwartz and 2009 Schwartz formulas; by contrast, Filler and original 1976 Schwartz formulas overestimated iGFR, whereas Hoek and Bouvet formulas underestimated iGFR. CONCLUSION: Different cystatin C-derived formulas (at least Larsson and Le Bricon) for estimating GFR as well as the Zappitelli combined formula are accurate in addition to the new Schwartz bedside formula in a general pediatric population.

Familial nephrogenic syndrome of inappropriate antidiuresis: dissociation between aquaporin-2 and vasopressin excretion.

CONTEXT: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), the X-linked disease resulting from activating mutation of the vasopressin V2 receptor gene (AVPR2), is a recently described condition causative of episodes of hyponatremia in boys and male and female adults. OBJECTIVE: The objective of the study was the pathophysiological characterization of NSIAD. DESIGN: A family with NSIAD was identified and investigated for hyponatremic episodes and degrees of urine dilution defects. For the first time, the impact of the mutated V2R on aquaporin 2 (AQP2) excretion is reported. SETTING: The study was conducted at a referral center. PATIENTS: Five patients of seven carriers (two young brothers and their mother and her two sisters) were investigated together with age-matched controls. INTERVENTIONS: There were no interventions. RESULTS: In NSIAD patients, urinary AQP2 excretion occurred independently of concomitant vasopressin excretion and strongly correlated with urine osmolality, confirming direct AQP2 involvement in urine concentration. Water loading was followed by a very slow and incomplete elimination in the asymptomatic hemizygous boy with no suppression of AQP2 excretion and a delayed elimination in the heterozygous women because of an incomplete suppression of AQP2, and it induced hyponatremia in all NSIAD patients. Two hemizygous carriers presented with severe hyponatremia-induced seizures, and the repetition in one of them led to mental retardation. CONCLUSIONS: Hyponatremia was a constant and characteristic aspect of the abnormal response to even mild water-loading tests in an asymptomatic hemizygous child as well as heterozygous adults. We confirm the phenotypic variability of NSIAD, a disease that should be regarded in pediatric intensive care units in presence of severe and/or recurrent hyponatremia, and also in adults, because carriers are prone to hyponatremia.

Adaptation of an enzymatic polyfructosan assay to clinical practice.

Inulin or polyfructosan clearance is regarded as the most accurate method of assessing the glomerular filtration rate. We propose an enzymatic method of polyfructosan determination based on the hydrolysis of polyfructosan into fructose by inulinase and the elimination of the interfering quantity of glucose by glucose oxidase. This spectrophotometric microplate formatted assay, which demonstrated very good specificity and reproducibility (within-run precision <1% and between-run precision <3.5%), is cheap and simple to perform and can be used by all analytical laboratories and in all clinical conditions.

What is the best alternative to inulin clearance to estimate GFR in patients with decompensated alcoholic cirrhosis?

BACKGROUND: Accurate evaluation of the glomerular filtration rate (GFR) in patients awaiting liver transplantation is important because they have a greater risk of impaired renal function. A major percentage of these patients have alcoholic cirrhosis, and the accuracy of bedside used GFR estimates have not been specifically evaluated in this group. The aim of this study was to evaluate the validity of the simplified Modification of Diet in Renal Diseases (MDRD) and Cockcroft and Gault (CG) formulas in patients with decompensated alcoholic cirrhosis in comparison to inulin clearance as the reference method. METHODS: GFR estimated by the simplified MDRD and CG formulas were retrospectively compared to the true GFR measured by inulin clearance in a single-centre cohort of 148 patients with decompensated alcoholic cirrhosis. RESULTS: Mean ± standard deviation of age, body mass index, inulin clearance and MDRD and CG estimates were 54.4 ± 6.9 years, 26.5 ± 4.7 kg/m(2), 76.9 ± 28.0 mL/min per 1.73 m(2), 99.4 ± 34.0 mL/min per 1.73 m(2) and 98.7 ± 32.0 mL/min per 1.73 m(2), respectively; 70% of the patients had a GFR, measured by inulin clearance, below 90 mL/min per 1.73 m(2). The difference between estimated GFR and true GFR were 23 ± 23 mL/min per 1.73 m(2) for MDRD and 22 ± 20 mL/min per 1.73 m(2) for Cockcroft and Gault. CONCLUSIONS: The simplified MDRD and CG formulas largely overestimated GFR in patients with decompensated alcoholic cirrhosis. Results of such bedside formulas should be interpreted with caution in these patients.