Median mGFR Research Articles

Estimating glomerular filtration rate in children: evaluation of creatinine- and cystatin C-based equations.

Glomerular filtration rate (GFR) estimated by creatinine- and/or cystatin C-based equations (eGFR) is widely used in daily practice. The purpose of our study was to compare new and old eGFR equations with measured GFR (mGFR) by iohexol clearance in a cohort of children with chronic kidney disease (CKD). We examined 96 children (median age 9.2years (range 0.25-17.5)) with CKD stages 1-5. A 7-point iohexol clearance (GFR7p) was defined as the reference method (median mGFR 66mL/min/1.73m2, range 6-153). Ten different eGFR equations, with or without body height, were evaluated: Schwartzbedside, SchwartzCKiD, SchwartzcysC, CAPA, LMREV, (LMREV + CAPA) / 2, FAScrea, FAScysC, FAScombi, FASheight. The accuracy was evaluated with percentage within 10 and 30% of GFR7p (P10 and P30). In the group with mGFR below 60mL/min/1.73m2, the SchwartzcysC equation had the lowest median bias (interquartile range; IQR) 3.27 (4.80) mL/min/1.73m2 and the highest accuracy with P10 of 44% and P30 of 85%. In the group with mGFR above 60mL/min/1.73m2, the SchwartzCKiD presented with the lowest bias 3.41 (13.1) mL/min/1.73m2 and P10 of 62% and P30 of 98%. Overall, the SchwartzcysC had the lowest bias - 1.49 (13.5) mL/min/1.73m2 and both SchwartzcysC and SchwartzCKiD showed P30 of 90%. P10 was 44 and 48%, respectively. The SchwartzcysC and the combined SchwartzCKiD present with lower bias and higher accuracy as compared to the other equations. The SchwartzcysC equation is a good height-independent alternative to the SchwartzCKiD equation in children and can be reported directly by the laboratory information system. ClinicalTrials.gov , Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Renal cortical volume: High correlation with pre- and post-operative renal function in living kidney donors

BackgroundCT volumetry has previously been proposed as an alternative to scintigraphy for the evaluation of pre-donation split renal function and the prediction of post-donation renal function in living kidney donors. The aim of our study was to retrospectively assess the relevance of three CT volumetry techniques for estimating pre-donation kidney function and predicting the risk for chronic kidney disease (CKD) at 1-year post-nephrectomy in a French cohort of living donors using isotopic measures of kidney function. MethodsKidney volume was quantified pre-donation for 105 donors using three methods total parenchymal three-dimensional renal volume (3DRV), total parenchymal renal volume contouring (RVCt), and renal cortical volume (RCoV). Subjects also had a 51Cr-EDTA scintigraphy to measure glomerular filtration rate (mGFR) pre-donation and 1-year after donation. For each volume, we tested for association with mGFR using univariate regression models, and computed receiver operating characteristics analyses to assess their predictive potential of post-donation CKD. ResultsOur population was composed of healthy subjects, who were predominantly female (69%) with a median age at donation of 51yo. Median mGFR was 102 mL/min/1.73 m2 at pre-donation and 66 mL/min/1.73 m2 1-year after nephrectomy. The pre-donation median volume of the preserved kidney was 156 cm3, 163 cm3 and 99 cm3 for the 3DRV, RVCt and RCoV methods respectively, with a high correlation observed between each technique (R > 0.84). For all methods, total kidney volume was significantly associated with pre-donation mGFR (P < 0.001). Preserved kidney volume was also strongly correlated with post-donation mGFR (P < 0.0001), with the strongest correlation observed for RCoV (R = 0.60 vs. R = 0.39 and R = 0.51 for 3DRV and RVCt, respectively). Finally, the RCoV method yielded the best predictive value of 1-year post-donation CKD (AUC = 0.80 vs. AUC = 0.76 and 0.70 for RVCt and 3DRV, respectively). ConclusionsIn our cohort of healthy donors with measured kidney function, cortical volumetry (RCoV) appears as the best volumetric technique to use as a surrogate to scintigraphy for estimating pre-donation split renal function and predicting post-donation renal outcomes.

Effect of Calcineurin Inhibitor-Free, Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate After Heart Transplantation.

Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or CNI-free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. We tested if measured glomerular filtration rate (mGFR, by chrome-ethylenediaminetetraacetic acid clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitor Avoidance trial, where de novo HTx patients (n = 115) were randomized to EVR with complete CNI elimination 7 to 11 weeks post-HTx or standard CNI immunosuppression. In 66 patients, UACR measures were available at 1 year. In 7 patients in the EVR group, a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (P = 0.0004 and P = 0.03, respectively). Median UACR at 1 year was significantly higher in the EVR group (P = 0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r = -0.01, P = 0.9 and r = 0.15, P = 0.26, respectively) and in the EVR group between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r = 0.27, P = 0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function seem dissociated; hence, the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.

Association of plasma potassium with mortality and end-stage kidney disease in patients with chronic kidney disease under nephrologist care - The NephroTest study

BackgroundLow and high blood potassium levels are common and were both associated with poor outcomes in patients with chronic kidney disease (CKD). Whether such relationships may be altered in CKD patients receiving optimized nephrologist care is unknown.MethodsNephroTest is a hospital-based prospective cohort study that enrolled 2078 nondialysis patients (mean age: 59 ± 15 years, 66% men) in CKD stages 1 to 5 who underwent repeated extensive renal tests including plasma potassium (PK) and glomerular filtration rate (GFR) measured (mGFR) by 51Cr-EDTA renal clearance. Test reports included a reminder of recommended targets for each abnormal value to guide treatment adjustment. Main outcomes were cardiovascular (CV) and all-cause mortality before end-stage kidney disease (ESKD), and ESKD.ResultsAt baseline, median mGFR was 38.4 mL/min/1.73m2; prevalence of low PK (<4 mmol/L) was 26.5%, and of high PK (>5 mmol/L) 6.4%; 74.4% of patients used angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). After excluding 137 patients with baseline GFR < 10 mL/min/1.73m2 or lost to follow-up, 459 ESKD events and 236 deaths before ESKD (83 CV deaths) occurred during a median follow-up of 5 years. Compared to patients with PK within [4, 5] mmol/L at baseline, those with low PK had hazard ratios (HRs) [95% CI] for all-cause and CV mortality before ESKD, and for ESKD of 0.82 [0.58–1.16], 1.01 [0.52–1.95], and 1.14 [0.89–1.47], respectively, with corresponding figures for those with high PK of 0.79 [0.48–1.32], 1.5 [0.69–3.3], and 0.92 [0.70–1.21]. Considering time-varying PK did not materially change these findings, except for the HR of ESKD associated with high PK, 1.39 [1.09–1.78]. Among 1190 patients with at least two visits, PK had normalized at the second visit in 39.9 and 54.1% respectively of those with baseline low and high PK. Among those with low PK that normalized, ARB or ACEi use increased between the visits (68.3% vs 81.8%, P < .0001), and among those with high PK that normalized, potassium-binding resin and bicarbonate use increased (13.0% vs 37.0%, P < .001, and 4.4% vs 17.4%, P = 0.01, respectively) without decreased ACEi or ARB use.ConclusionIn these patients under nephrology care, neither low nor high PK was associated with excess mortality.

Relationships of Measured Iohexol GFR and Estimated GFR With CKD-Related Biomarkers in Children and Adolescents

2 valid and reliable estimated glomerular filtration rate (GFR) equations for the pediatric population have been developed from directly measured GFR data in the Chronic Kidney Disease in Children (CKiD) cohort: the full CKiD and bedside CKiD equations. Although adult GFR estimating equations replicate relationships of measured GFR with biomarkers, it is unclear whether similar patterns exist among children and adolescents with chronic kidney disease (CKD). Prospective cohort study in children and adolescents. 730 participants contributed 1,539 study visits. Measured GFR by plasma iohexol disappearance (mGFR), estimated GFR by the full CKiD equation (eGFRCKiDfull; based on serum creatinine, cystatin C, serum urea nitrogen, height, and sex), and estimated GFR by the bedside CKiD equation (eGFRCKiDbed; calculated as 41.3× height [m]/serum creatinine [mg/dL]) were predictors of CKD-related biomarkers. Deviations of mGFR from eGFRCKiDfull and deviations of eGFRCKiDfull from eGFRCKiDbed from linear regressions (ie, residuals) were included in bivariate analyses. CKD-related biomarkers included values for urine protein-creatinine ratio, blood hemoglobin, serum phosphate, bicarbonate, potassium, systolic and diastolic blood pressure zscores, and height z scores. The median age of 730 participants with CKD was 12.5 years, with median mGFR, eGFRCKiDfull, and eGFRCKiDbed of 51.8, 54.0, and 53.2mL/min/1.73m2, respectively. eGFRCKiDfull demonstrated as strong or stronger associations with CKD-related biomarkers than mGFR; eGFRCKiDbed associations were significantly attenuated (ie, closer to the null). Residual information in mGFR did not substantially increase explained variability. eGFRCKiDbed estimated faster GFR decline relative to mGFR and eGFRCKiDfull. Simple linear summaries of biomarkers may not capture nonlinear associations. eGFRCKiDfull closely approximated mGFR to describe relationships with CKD-severity indicators and progression in this pediatric CKD population. eGFRCKiDbed offered similar inferences, but associations were attenuated and rate of progression was overestimated. The eGFRCKiDfull equation from 2012 is preferred for pediatric research purposes.

Comprehensive renal function evaluation in patients treated for synchronous bilateral Wilms tumor

ObjectivesThe purpose of this study was to perform a comprehensive assessment of long-term renal function in patients treated at our institution for synchronous bilateral Wilms tumor (BWT) and to determine the optimal method for estimating glomerular filtration rate (eGFR). MethodsSurgical approach, adjuvant therapy, and pathology reports were reviewed for patients with at least six months follow-up from definitive surgery. eGFRs, as assessed by the Schwartz and Chronic Kidney Disease in Children (CKiD) formulas, were compared to measured GFR (mGFR) determined by 99mTc-DTPA scanning. Urine studies, including microalbumin, β-microglobulin, and FENa were also reviewed. ResultsForty-two patients were identified. Of 36 living patients, 28 (77.8%) had greater than 6months follow-up, with a median overall follow-up of 5.2years (range: 1.4–13.4). The median mGFR was 97mL/min/1.73m2, while the median eGFRSchwartz and eGFRCKiD were 103.3mL/min/1.73m2 and 79.7mL/min/1.73m2, respectively, (p=0.13 and p=0.75, compared to mGFR). Eleven (39.3%) patients had at least one abnormal urine study (microalbumin >30μg/g creatinine, n=3; β-2 microglobulin >133μg/g creatinine, n=9; FENa>1%, n=4). ConclusionsIn our series, few patients had an abnormally low GFR. Neither method for estimating GFR gave a significantly different result from measured GFR, suggesting that the Schwartz equation is adequate, although specific urine tests may be more sensitive for detecting subtle renal dysfunction. Level of evidenceLevel IV — retrospective case series with no comparison group.

Urinary ammonia and long-term outcomes in chronic kidney disease

Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1-4. All patients had measured glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m(2). Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06-3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98-3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.

Estimated glomerular filtration rates cannot replace measured GFR in type 1 diabetes patients with hyperfiltration.

This study of children and young adults with type 1 diabetes with normal to high glomerular filtration rates (GFR) compared estimated GFR (eGFR) with measured GFR (mGFR). GFR was measured by inulin clearance, and we carried out simultaneous analyses of standardised creatinine and cystatin C. eGFR was calculated using different formulas. We enrolled 106 patients, including 56 males, aged 21.9 (standard deviation 9.2) years with 13.7 (9.1) years' duration of diabetes and a mean haemoglobin A1c (HbA1c ) of 7.7% (61 mmol/mol). The median mGFR was 128 (111-143) mL/min/1.73 m(2) . Most of the eGFR estimations failed to detect a significant proportion of hyperfiltration based on inulin clearance. The best accuracy (P30) between eGFR and mGFR was seen with eGFRCKD - EPI (92%), eGFRcys C Berg (86%), eGFRcys C CAPA (78%) and eGFRcys C Inker (84%) where eGFRCKD - EPI and eGFR cys C Berg showed the lowest bias. Most eGFRcys C measurements showed greater accuracy when combined with eGFRcr (P30 92-94%). The best accuracy (P30) and lowest bias were found with eGFRCKD - EPI and eGFR Berg. in this cohort. However, eGFR cannot accurately replace mGFR to detect hyperfiltration and follow GFR over time in young patients with type 1 diabetes.

G.P.172: Renal function in children and adolescents with Duchenne muscular dystrophy: a prospective study

Objectives: Improved life expectancy and the need for robust tools to monitor renal safety of emerging new therapies have fueled the interest in renal function in patients with Duchenne muscular dystrophy (DMD). We aimed to establish methodology for studying renal function in patients with DMD and using this methodology, to describe their renal function in detail. Methods: Twenty participants (5–22years old) were selected for a prospective cross-sectional study. Medical history was obtained and all patients underwent a physical examination, 24-h ambulatory blood pressure monitoring, ultrasound of the kidneys, 51 Cr-EDTA for GFR measurement (mGFR), blood and urine analysis. Results: Between February 2013 and July 2013, twenty patients were included. The median age was 15.5years. Twelve patients were treated with corticosteroids. Total protein/creatinine was increased in 17/18 patients, whereas 24-h urine protein was normal in 18/18 subjects. We detected nine patients with 51 Cr-EDTA GFR >P90 (135ml/min/m 2 ) and one patient with 51 Cr-EDTA GFR 2 . Median mGFR was 128ml/min/1.73m 2 . Nephromegaly (1 or 2 kidneys with a length >2SD) was found in 6/20 subjects. Hypertension (systolic and/or diastolic blood pressure >P95) was found in 9/20 subjects and a non-dipping profile was found in 13/20 subjects. Conclusions: This small prospective study demonstrates that urinary protein excretion expressed in mg creatinine is not reliable in DMD patients because of low urinary creatinine. We report a high prevalence of hyperfiltration, nephromegaly and hypertension corrected for body size. Our current findings on renal function and outcome in DMD patients require further studies to investigate the pathogenesis, the confounding issue of chronic steroid treatment and long-term prognosis.

G.P.173: Are current formulas for estimated glomerular filtration rate reliable in children and adolescents with Duchenne muscular dystrophy?

Improved life expectancy and the need to monitor renal safety of new therapies have fueled interest in renal function in patients with Duchenne muscular dystrophy (DMD). We assessed the usefulness of estimated glomerular filtration rate (eGFR) formulas based on serum creatinine (sCr) and/or cystatin C (CysC) in children and adolescents with DMD. DMD patients have low sCr values since they have less muscle mass. SCr-based formulas may therefore have limitations. CysC, being independent of muscle mass, may serve as a valuable alternative for eGFR in DMD. In a prospective cross-sectional study, 18 patients (5–22 years) underwent 51 Cr-EDTA for GFR measurement (mGFR), blood and urine analysis. Values for renal clearance obtained with sCr-based, CysC-based and sCr/CysC-based eGFR formulas were compared to mGFR. Median mGFR was 128 ml/min/1.73 m 2 . Nine patients had a mGFR >P90 (135 ml/min/m 2 ). Because of very low sCr values (mean ± SD: 0.16 ± 0.07 mg/dL), sCr-based and sCr/CysC-based formulas overestimate GFR. Mean eGFR ± SD was 464.0 ± 264.1 ml/min/1.73 m 2 for Schwartz, 464.2 ± 269.4 ml/min/1.73 m 2 for Flanders Metadata, 178.7 ± 61.1 ml/min/1.73 m 2 for height-independent and 479.9 ± 327.0 ml/min/1.73 m 2 for the Q (height) equation. CysC values (0.78 ± 0.13 mg/L) are within normal adult reference ranges. However, sCr/CysC-based formulas result in mean eGFR ± SD of 154.2 ± 34.7 ml/min/1.73 m 2 for Zappitelli and 169.2 ± 43.7 ml/min/1.73 m 2 for Bouvet. Concerning CysC-based equations the mean eGFR ± SD was 153.8 ± 60.3 ml/min/1.73 m 2 for Larsson, 125.4 ± 21.9 ml/min/1.73 m 2 for Filler and 105.4 ± 19.1 ml/min/1.73 m 2 for Zappitelli. This study demonstrates that sCr-based and sCr/CysC-based formulas should not be used for eGFR in DMD. However, even though mGFR and CysC-based equations showed a better agreement, more research is needed to confirm the preliminary findings that CysC-based equations are suitable for eGFR in DMD patients.

HIV Viremia and T-Cell Activation Differentially Affect the Performance of Glomerular Filtration Rate Equations Based on Creatinine and Cystatin C

BackgroundSerum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established.MethodsWe assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry.ResultsThe median mGFR was >100 ml/min/1.73 m2 in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C.ConclusionsThe performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.

Renal Function Can Improve at Any Stage of Chronic Kidney Disease

IntroductionEven though renal function decline is considered relentless in chronic kidney disease (CKD), improvement has been shown in patients with hypertensive nephropathy. Whether this can occur in any type of nephropathy and at any stage is unknown as are the features of patients who improve.MethodsWe identified 406 patients in the NephroTest cohort with glomerular filtration rates (mGFR) measured by 51Cr-EDTA clearance at least 3 times during at least 2 years of follow-up. Individual examination of mGFR trajectories by 4 independent nephrologists classified patients as improvers, defined as those showing a sustained mGFR increase, or nonimprovers. Twelve patients with erratic trajectories were excluded. Baseline data were compared between improvers and nonimprovers, as was the number of recommended therapeutic targets achieved over time (specifically, for systolic and diastolic blood pressure, proteinuria, and use of renin angiotensin system blockers).ResultsMeasured GFR improved over time in 62 patients (15.3%). Their median mGFR slope was +1.88[IQR 1.38, 3.55] ml/min/year; it was −2.23[−3.9, −0.91] for the 332 nonimprovers. Improvers had various nephropathies, but not diabetic glomerulopathy or polycystic kidney disease. They did not differ from nonimprovers for age, sex, cardiovascular history, or CKD stage, but their urinary albumin excretion rate was lower. Improvers achieved significantly more recommended therapeutic targets (2.74±0.87) than nonimprovers (2.44±0.80, p<0.01). They also had fewer CKD-related metabolic complications and a lower prevalence of 25OH-vitamin-D deficiency.ConclusionGFR improvement is possible in CKD patients at any CKD stage through stage 4–5. It is noteworthy that this GFR improvement is associated with a decrease in the number of metabolic complications over time.

Relation Between Circulating Levels of 25(OH) Vitamin D and Parathyroid Hormone in Chronic Kidney Disease: Quest for a Threshold

Vitamin D deficiency is common in patients with chronic kidney disease (CKD). Current guidelines recommend treatment strategies in these patients similar to those for the general population, but the vitamin D nutritional status sufficient to prevent PTH levels from increasing in CKD is unknown. OBJECTIVE, MAIN OUTCOME MEASURE: Our aim was to study the relation between circulating PTH and 25(OH)D levels and to search for a 25(OH)D threshold associated with a significant PTH increase. In the hospital-referred NephroTest cohort study, we measured 25(OH)D, PTH, and glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance in 929 adult patients with nondialysis CKD stages 1 to 5 and no vitamin D supplementation. Patients' mean age was 60.1 ± 14.7 years; 71% were men, and 9% were black. Their median mGFR was 37.8 mL/min/1.73 m². We found a 25(OH)D threshold of 8 ng/mL with an upper limit of 20 ng/mL (95% confidence interval) by linear piecewise regression modeling of log-PTH for 25(OH)D adjusted for mGFR, age, race, and ionized calcium level. The smoothed curve confirmed that PTH concentration rose steeply when circulating 25(OH)D levels fell to less than 20 ng/mL. Spontaneous 25(OH)D levels greater than 20 ng/mL seem sufficient to control serum PTH in CKD patients. This result reinforces guidelines to supplement vitamin D only if less than 30 ng/mL.

Can Plasma NGAL Predict Renal Response to Conversion from Calcineurin Inhbitor- to Everolimus Based Immunosuppression after Cardiac Transplantation?

Purpose Useful predictors of renal recovery following conversion from calcineurin inhibitor (CNI) to proliferation signal inhibitor based therapy are lacking. We hypothesized that plasma-neutrophil gelatinase-associated lipocalin (P-NGAL) - a new marker of kidney damage - in long term cardiac transplant recipients could predict improvement in glomerular filtration rate one year after conversion to an everolimus based regimen. Methods and Materials P-NGAL was measured at baseline in 88 cardiac transplant patients (median age 62 years, median 5 years post transplant) with mild to moderate renal dysfunction randomized to continuation of conventional immunosuppression (CNI, antiproliferative agent, steroid) or treatment with low dose everolimus, low dose CNI, an antiproliferative agent and steroid. Glomerular filtration rate was measured at baseline and after 1 year using crEDTA clearance (mGFR). Results Median P-NGAL was 109 (97-144) pg/L. Patients with NGAl above median were heavier and had higher white blood cell count and higher hsC-reactive protein levels at baseline. Median mGFR at baseline was 53 ml/min/1.73 m 2 . P-NGAL correlated with mGFR (R 2 =0.21, P 2 =0.32, P 2 ), P=0.006). Baseline P-NGAL predicted mGFR after one year (R 2 =0.18, P Conclusions P-NGAL and GFR correlate in long-term heart transplant recipients with renal dysfunction. P-NGAL did not predict improvement of renal function after conversion to everolimus based immunosuppression.

Relationship of Copeptin, a Surrogate Marker for Arginine Vasopressin, With Change in Total Kidney Volume and GFR Decline in Autosomal Dominant Polycystic Kidney Disease: Results From the CRISP Cohort

Experimental studies indicate that arginine vasopressin (AVP) may have deleterious effects in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, the significance of AVP in human ADPKD is unclear. Longitudinal observational study with 8.5 (IQR, 7.7-9.0) years' follow-up (CRISP [Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease]). 241 patients with ADPKD with creatinine clearance >70 mL/min. Plasma copeptin concentration, a surrogate marker for AVP. Change in measured glomerular filtration rate (mGFR, assessed by iothalamate clearance) and total kidney volume (measured by magnetic resonance imaging). Baseline copeptin level, plasma and urinary osmolality, and measurements of total kidney volume and mGFR during follow-up. In these patients (median age, 34 [IQR, 25-40] years; 38% men; median mGFR, 94 [IQR, 79-145] mL/min/1.73 m(2); median total kidney volume, 859 [IQR, 577-1,299] mL), median copeptin level was 2.9 (IQR, 1.8-5.1) pmol/L. Copeptin was not associated with plasma osmolality (P = 0.3), the physiologic stimulus for AVP release, but was associated significantly with change in total kidney volume during follow-up (P < 0.001). This association remained significant after adjusting for sex, age, cardiovascular risk factors, and diuretic use (P = 0.03). Copeptin level was associated borderline significantly with change in mGFR after adjusting for these variables (P = 0.09). No standardization of hydration status at time of copeptin measurement. These data show that in ADPKD, copeptin level, as a marker for AVP, is not correlated with plasma osmolality. Most importantly, high copeptin levels are associated independently with disease progression in early ADPKD. This is in line with experimental studies that indicate a disease-promoting role for AVP.

The value of estimated GFR in comparison to measured GFR for the assessment of renal function in adult patients with Fabry disease

Renal disease is one of the major complications in Fabry disease, an X-linked lysosomal storage disease due to deficiency of the enzyme alpha-galactosidase A. The aim of our study was to determine the value of creatinine-, cystatin C- and beta-trace-based formulas for the estimation of glomerular filtration rate (eGFR) in Fabry patients. For comparison, the gold standard method (125)I-labelled iothalamate/(131)I-labelled hippuran [measured GFR (mGFR)] was used. GFR was estimated by using 11 different formulas based on creatinine, cystatin C and beta-trace protein. Accuracy and precision, detection of early decline of renal function and follow-up of renal function by eGFR was compared to mGFR. One hundred and thirty-six GFR measurements and plasma samples were available from 36 (20 male) Fabry patients, treated with agalsidase alpha or beta with a median follow-up of 3.1 (range 1.5-5.2) years. Median mGFR was 97.3 (15.5-148.6) ml/min/1.73 m(2) in males and 84.4 (23.0-131.0) ml/min/1.73 m(2) in females at the start of follow-up. Although none of the investigated endogenous markers proved to be an equivalent substitute for mGFR in Fabry patients, the Stevens equation, a creatinine- and cystatin C-based formula, most closely approximated the mGFR. When a creatinine-based formula is preferred, considering that there is no standardized method available for cystatin C, the abbreviated Modification of Diet in Renal Disease (aMDRD) and the recently developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas had the best performance. In male Fabry patients, the aMDRD may overestimate GFR, especially in the higher ranges. In these cases, CKD-EPI may perform better.

Sleep and Fatigue Symptoms in Children and Adolescents With CKD: A Cross-sectional Analysis From the Chronic Kidney Disease in Children (CKiD) Study

Although symptoms of sleepiness and fatigue are common in adults with chronic kidney disease (CKD), little is known about the prevalence of these symptoms in children with CKD. Cross-sectional analysis within a cohort study. We describe the frequency and severity of sleep problems and fatigue and assess the extent of their association with measured glomerular filtration rate (mGFR) and health-related quality of life (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort. Sleep and fatigue-related items from the Pediatric Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List were used. Median mGFR was 42.0 mL/min/1.73 m(2) (25th-75th percentiles, 31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2). Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m(2) had 2.07 (95% CI, 1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of having more severe parent reports of low energy than children with mGFR > or = 50 mL/min/1.73 m(2). Compared with participants with mGFR > or = 50 mL/min/1.73 m(2), those with mGFR < 30 mL/min/1.73 m(2) had 3.92 (95% CI, 1.37-11.17) higher odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73 m(2) had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day. Low energy, trouble sleeping, and weakness were associated with lower HRQOL scores. Symptoms of sleep and fatigue represent the child's or parent's perception of symptom severity, whereas individual items can lead to imprecise measurements of sleep and fatigue. Lower mGFR was associated with increased weakness, low energy, and daytime sleepiness. Furthermore, a strong association between trouble sleeping, low energy, and weakness with decreases in overall HRQOL was observed. Detection and treatment of poor sleep and fatigue may improve the development and HRQOL of children and adolescents with CKD.