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Background Combining estimated glomerular filtration rate (eGFR) equations based on creatinine and cystatin C has been shown to improve the accuracy of GFR estimation. This study aims to optimize this strategy for height-independent GFR estimation in children. Methods Retrospective study of 408 inulin clearance tests with simultaneous International Federation of Clinical Chemistry-calibrated measurements of creatinine, cystatin C, and urea in children (mean age 12.5 years, GFR 91.2 ml/min/1.73m.sup.2) comparing the arithmetic (mean.sub.arith) and geometric means (mean.sub.geom) of a height-independent creatinine-based (full age spectrum, based on age (FASage)) and a cystatin C-based equation (FAScys), with the complex height-dependent CKiD3 equation incorporating gender, height, cystatin C, creatinine, and urea. Results Mean.sub.geom had a P.sub.30 accuracy of 89.2% compared to mean.sub.arith 87.7% (p = 0.030) as well as lower bias and %precision error and performed almost as well as CKiD3 (P.sub.30 accuracy 90.9%). Modifying the weight of FASage and FAScys when calculating the means showed that an equal contribution was most accurate in most patients. In spina bifida patients, FAScys alone outperformed any combination. Malignancy or nephritis patients had slightly higher accuracy with weighted means favoring cystatin C or creatinine, respectively. Disagreement between FAScys and FASage was inversely correlated with the accuracy of mean.sub.geom. When disagreement exceeded 40%, application of weighted means based on diagnosis improved the performance of eGFR. Conclusions In the absence of height data, the optimal strategy for estimating GFR in children is by using the geometric mean of FASage and FAScys. When there is large disagreement between the two, weighted means based on diagnosis improve accuracy., Author(s): Emil den Bakker [sup.1] , Reinoud Gemke [sup.1] , Joanna A. E. van Wijk [sup.1] [sup.2] , Isabelle Hubeek [sup.3] , Birgit Stoffel-Wagner [sup.4] , Arend Bökenkamp [sup.1] [sup.2] [...]

The link between cystatin C and mortality independent of glomerular filtration rate (GFR) in adults has prompted the "Shrunken Pore Syndrome" (SPS) hypothesis, where high serum cystatin C with normal creatinine is explained by smaller glomerular pores, through which creatinine can pass freely, while the larger cystatin C, beta-trace protein (BTP) and pro-inflammatory molecules are retained. This study set out to apply the definition of SPS to children. In 294 children who underwent inulin clearance (Cin) test, serum creatinine, cystatin C and BTP were measured. For all three markers eGFRx was calculated using the full age spectrum equations. The ratio eGFRcys/eGFRcrea was plotted against the error of eGFRBTP(%) (i.e. eGFRBTP-Cin)/Cin*100%). Patients with and without SPS according to different cut-off points of eGFRcys/eGFRcrea and eGFRcys/Cin (i.e. ≤0.6,0.7,0.8) were compared in terms of eGFRx, Cin, error of eGFRx(%) and eGFRBTP/eGFRcrea-ratio. The ratio eGFRcys/eGFRcrea and error of eGFRBTP(%) were positively correlated. The prevalence of SPS by eGFRcys/eGFRcrea with a cut-off of 0.6 was 4.8%. Patients with SPS had a more negative error of eGFRcys(%) and eGFRBTP(%) and higher Cin regardless of the definition. Overestimation of eGFRcrea in patients with SPS was only present when using the eGFRcys/eGFRcrea rather than the eGFRcys/Cin definition. Cystatin C and BTP are related independent of creatinine, suggesting glomerular pore size as a common denominator. The prevalence of SPS in children is comparable to adults. For research in SPS, a definition based on eGFRcys/exogenous clearance study may be useful to study the effect of SPS on creatinine metabolism. [ABSTRACT FROM AUTHOR]

Sulfate is an important anion as sulfonation is essential in modulation of several compounds, such as exogens, polysaccharide chains of proteoglycans, cholesterol or cholesterol derivatives and tyrosine residues of several proteins. Sulfonation requires the presence of both the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and a sulfotransferase. Genetic disorders affecting sulfonation, associated with skeletal abnormalities, impaired neurological development and endocrinopathies, demonstrate the importance of sulfate. Yet sulfate is not measured in clinical practice. This review addresses sulfate metabolism and consequences of sulfonation defects, how to measure sulfate and why we should measure sulfate more often., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFR cystatin C ) and a creatinine-based (eGFR creatinine ) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFR cystatin C and eGFR creatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFR cystatin C compared to eGFR creatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFR cystatin C and a eGFR creatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFR cystatin and eGFR creatinine may help identify pediatric patients with Shrunken Pore Syndrome.