The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in patients with cancer

Objective: Cisplatin is a potent antineoplastic agent used and its major limiting side effect is nephrotoxicity. The aims of the study are early detection of acute kidney injury (AKI) with biomarkers and investigation of the potential nephron-protective effects of theophylline. Methods: Glomerular filtration rates (GFR), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C were measured at 5th day of treatment in all of the patients. In addition, these parameters were measured repeatedly after the administration of cisplatin, at 2nd hour, 5th and 20th days. Patients: Sixty patients who are planned to receive cisplatin for the first time were included in the study. Patients were divided into two groups as Group 1 (n?=?30) (standard treatment arm) and Group II (n?=?30) (theophylline arm). Results: In both groups after the administration of cisplatin, GFR showed a significant decrease within time (p?=?0.006). Urine NGAL levels were significantly high after 2?h of cisplatin administration (p?p?=?0.025). After 5 days of cisplatin administration, urine protein levels were significantly higher in both groups (p?Conclusion: Results showed that urine NGAL level is a superior biomarker compared to serum creatinine and serum cystatin C in the detection of early AKI. Theophylline was found not to bring a complete protection for the kidneys, but less nephrotoxicity was developed when compared to the group not receiving theophylline.     

Renal functional reserve and renal hemodynamics in hypertensive patients

The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is a measure of functional and anatomic integrity of nephrons. It is not known what relation between RFR and kidney Doppler parameters. We aimed to study the relation between the RFR and renal hemodynamic parameters in hypertensive patients with and without nephropathy who had normal kidney function. Twenty-four hypertensive subjects with nephropathy (HTN-n, n?=?10) and hypertension without nephropathy (HTN, n?=?14) were included in the study. Control group included 11 healthy subjects. Baseline GFR (GFR1) and GFR after intake of egg protein 1?mg/kg of body weight were determined (GFR2). RFR was calculated by the following formula: (GFR2-GFR1)/GFR1?×?100%. Doppler ultrasonography was performed. Arterial blood pressure (BP), body mass index (BMI), and estimated GFR were also recorded. HTN and HTN-n groups had impaired levels of RFR compared with controls (p?<?0.05), significantly decreased value of flow velocity parameters (Vmax, Vmin), and increased RRI compared with controls. There was significant negative correlation of RFR with blood pressure levels (sBP, r?=??0.435, p?=?0.009; dBP, r?=??0.504, p?=?0.002), RRI (r?=??0.456, p?=?0.008), micro albuminuria (MAU, r?=??0.366, p?=?0.031) and positive correlation with Vmax and Vmin (r?=?0.556, p?=?0.001 and r?=?0.643, respectively, p?<?0.001). Linear regression showed that RRI and MAU were independent predictors of decreased RFR. RFR is lower in hypertensive patients despite near-normal level of kidney function and is related to particular level of BP. RRI and MAU were independent predictors of decreased RFR.     

Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

Purpose

To evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection.

Methods

The study included proteinuric (n?=?30) and non-proteinuric (n?=?30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n?=?20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days.

Results

The median (interquartile range) uKIM-1 level at the time of presentation was 246 (141–347) pg/mL in the proteinuric group, 83 (29–217) pg/mL in the non-proteinuric group, and 55 (21–123) pg/mL in the control group and significantly high in the proteinuric group than the others (p?<?0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p?<?0.05). In the multivariate regression analysis, non-albumin proteinuria (p?=?0.048) and BUN (p?=?0.034) were identified as independent factors predicting a high uKIM-1 level. After 21?±?4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased.

Conclusions

Our findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.

     

Formulas Estimating Glomerular Filtration Rate in the Evaluation of Living Kidney Donor Candidates: Comparison of Different Formulas With Scintigraphy-Measured Glomerular Filtration Rate

IntroductionEstimation of kidney function is crucial in the evaluation of living kidney donor candidates. Despite the multitude of glomerular filtration rate (GFR) formulas, no equation is universal, and none were validated in the population of kidney donors. Novel biomarkers, including beta trace protein (BTP) and cystatin C, are studied to help estimate GFR and improve the safe qualification of living kidney donors.AimThis study compares the accuracy of different formulas that estimate GFR with reference scintigraphy-measured GFR in the population of living kidney donor candidates.Material and MethodsThis study enrolled 30 healthy living kidney donor candidates. GFR was measured using the following 11 different formulas. For reference, GFR was assessed using 99m-Technetium-diethylenetriaminepentaacetic acid.ResultsThe accuracy of estimation was generally low in all formulas. The strongest correlation between measured GFR (mGFR) and estimated GFR (eGFR) was achieved by the Nankivell formula (R = 0.47, P = .009); however, in the group of patients with a body mass index of >25 kg/m², only the equations based on BTP had a statistically significant correlation with mGFR: White (R = 0.59; P = .016) and Poge (R = 0.53; P = .035). Bland-Altman plots revealed wide limits of agreement between eGFRs and mGFR in all groups of patients.ConclusionIn living kidney donor candidates, GFR estimation formulas should be chosen individually. White formula, which is based on BTP, may be a promising tool in estimating GFR in overweight potential living kidney donor candidates. More than 1 formula and personalized choice of GFR estimation method regarding the given patient should be performed in qualification of kidney donors.     

Evaluation of cystatin C with iohexol clearance in cardiac surgery

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery. Methods: Twenty‐one patients scheduled for elective coronary artery bypass grafting were prospectively enrolled in the study. Before surgery and on the second post‐operative day, an iohexol clearance was performed. Plasma cystatin C, plasma creatinine and plasma C‐reactive protein were determined before surgery and on the first, second, third and fifth post‐operative day. Estimated creatinine and cystatin C clearances were determined. Results: Post‐operative cystatin C and 1/cystatin C correlated strongly to iohexol clearance (r=?0.90 and 0.86) and so did creatinine and 1/creatinine (r=?0.83 and 0.78). Estimated creatinine clearance differed from iohexol clearance (P<0.01), whereas estimated cystatin C clearance did not differ from iohexol clearance (P=0.81). No correlation was found between C‐reactive protein and cystatin C. Conclusion: This study indicates that clearance estimations based on cystatin C are more accurate compared with estimations based on creatinine in determining GFR in cardiac surgery. Cystatin C has, in this study population, a stronger correlation to iohexol clearance than creatinine.     

To what extent estimated or measured GFR could predict subclinical graft fibrosis: a comparative prospective study with protocol biopsies

Monitoring of allograft function entails methods more accurate than serum creatinine and creatinine‐based GFR equations (eGFR). This prospective trial aimed at investigating the diagnostic accuracy of creatinine‐ and cystatin C‐based eGFR with measured GFR (mGFR) and compared them with graft fibrosis detected by protocol biopsies (PBx). Forty‐four kidney transplant recipients were enrolled. PBx were obtained postengraftment and at 6th and 12th months. GFR was measured by Tc‐99m DTPA at 3th, 6th, and 12th months after transplantation. Significant correlation existed between eGFR and mGFR at 3, 6, and 12 months (P < 0.0001). Cystatin C‐based Hoek and Larsson equations had the lowest bias and highest accuracy. The sum of interstitial fibrosis and tubular atrophy score increased from implantation to 6th and 12th months (0.52 ± 0.79, 0.84 ± 0.88, 1.50 ± 1.35). This was accompanied by reduction of mGFR from 54.1 ± 15.2 to 49.9 ± 15.2 and 46.8 ± 16.5 ml/min/1.73 m², while serum creatinine, cystatin C, and eGFR remained stable. Neither creatinine‐ nor cystatin C‐based GFR equations are reliable for detecting insidious graft fibrosis. In the first year after transplantation, mGFR, with its best proximity to histopathology, can be used to monitor allograft function and insidious graft fibrosis.     

The evaluation of renal hemodynamics changes in Familial Mediterranean fever with color Doppler sonography

Background: Renal resistive index (RRI) scanned through renal Doppler is a practical marker employed in measuring blood flow in renal and intrarenal arteries and in noninvasive evaluation of renal vascular resistance. We aimed to investigate the renal hemodynamic variations in patients with Familial Mediterranean Fever (FMF).

Material and methods: Seventy-nine FMF patients and 51 healthy subjects suitable for age and sex were included. Patients were divided into two groups according to their urinary albumin excretion. Fifty-two patients with 0–29?mg/day albuminuria were included in the normoalbuminuric group while 27 patients with 30–299?mg/day albuminuria were included in the microalbuminuric group.

Results: RRI values were higher in patients with FMF compared to the healthy subjects (p?p?=?0.002, p?p?=?0.013.

Conclusion: RRI may be a marker that may be used in assessing resistance to renal blood flow, early renal damage, and progression of renal damage in FMF patients.     

Is the urinary biomarkers assessment a non-invasive approach to tubular lesions of the solitary kidney?

Abstract

Introduction: The solitary kidney (SK) is currently debated in the literature, as living kidney donation is extensively used and the diagnosis of congenital SK is frequent. Tubulointerstitial lesions associated with adaptive phenomena may occur early within the SK. Aims: Analysis of the significance of urinary biomarkers in the assessment of tubulointerstitial lesions of the SK. Methods: A cross-sectional study of 37 patients with SK included 18 patients—acquired SK (mean age 56.44?±?12.20 years, interval from nephrectomy 10.94?±?9.37 years), 19 patients—congenital SK (mean age 41.52?±?10.54 years). Urinary NAG, urinary alpha-1-microglobulin, albuminuria, eGFR (CKD-EPI equation) were measured. Results: In acquired SK, NAG increased in 60.66%, urinary alpha 1-microglobulin in 16.66%, albuminuria in 55.55% of patients. Inverse correlation with eGFR presented NAG (R^2?=?0.537, p?=?0.022), urinary alpha 1-microglobulin (R^2?=?0.702, p?=?0.001), albuminuria (R^2?=?0.655, p?=?0.003). In congenital SK, NAG increased in 52.63%, urinary alpha 1-microglobulin in 5.26%, albuminuria in 47.36% of patients. In this group, urinary biomarkers correlated inversely with eGFR: NAG (R^2?=?0.743, p?<?0.001), urinary alpha 1-microglobulin (R^2?=?0.701, p?=?0.001), albuminuria (R^2?=?0.821, p?<?0.001). Significant correlations were found between the urinary biomarkers in both groups. Conclusions: Urinary biomarkers allow a non-invasive, sensitive, early assessment of the tubular lesions of the SK. Urinary biomarkers of PT injury parallel renal function decline, thus complementing the estimation of GFR. Monitoring of PT dysfunction is mandatory in patients with SK.     

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m² based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m², suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web‐based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.     

Cystatin C–Based Equation for Predicting the Glomerular Filtration Rate in Kidney Transplant Recipients

Background

Precise monitoring of the glomerular filtration rate (GFR) is needed to estimate the allograft function in kidney transplant recipients (KTRs). The GFR is widely estimated with the use of formulas based on serum cystatin C (SCys) and serum creatinine (SCr) levels. We compared the efficacy of SCys-based equations with that of SCr-based equations to predict the allograft function.

Clinical assessment of serum cystatin C as a marker of glomerular filtration rate in patients with various renal diseases

Background. Recent reports have raised questions about the validity of estimating glomerular function and changes in glomerular function from measurements of serum creatinine. To evaluate the clinical usefulness of serum creatinine levels in terms of estimation of glomerular filtration rate (GFR), we determined serum cystatin C levels in 152 patients with various renal diseases and compared them with serum creatinine levels. Methods. Serum cystatin C levels were measured by particle-enhanced immunonephelometry. Two-h creatinine clearance (Ccr) was used as an indicator of GFR. Results. There was a significant positive correlation between serum cystatin C and creatinine levels (r = 0.941) in patients with various renal diseases. Serum cystatin C and creatinine were inversely correlated to Ccr. The overall correlation between serum cystatin C and Ccr was slightly stronger than that between serum creatinine and Ccr. In the patient group with a critical Ccr level (Ccr, 60–80 ml/min per 1.48 m²), the correlation between the reciprocal serum cystatin C levels and Ccr (r = 0.441) was significantly stronger (P < 0.01) than that between the reciprocal serum creatinine levels and Ccr (r = 0.212). A mild reduction of Ccr was detected more easily by serum cystatin C than by serum creatinine, as the clinical sensitivity and specificity of serum cystatin C were superior to that of serum creatinine. Conclusions. The cystatin C assay by particle-enhanced immunonephelometry was found to be a sensitive, fully automated, and rapid method. Serum cystatin C appears to be a promising marker of GFR in patients with impaired renal function. Its diagnostic potential was slightly superior to that of serum creatinine in adults with various renal diseases. Received: October 7, 1998 / Accepted: November 4, 1999     

Performance of the Japanese Glomerular Filtration Rate Equation Based on Standardized Serum Cystatin C in Potential Kidney Donors

Background

It was reported that the glomerula filtration rate (GFR) equation based on serum creatinine underestimated the GFR in potential kidney donors. Recently, the Japanese GFR equation based on standardized serum cystatin C was reported. Therefore, we assessed the performance of the equation in potential kidney donors.

Methods

Forty-five potential kidney donors from 2 hospitals were included. GFR was measured (mGFR) using inulin renal clearance. Serum creatinine was measured using the enzymatic method. Serum cystatin C was measured using a nephelometric immunoassay (Siemens) and calibrated to the standardized value traceable to ERM-DA471/IFCC using an equation reported previously. The estimated GFR (eGFR) was calculated using the Japanese GFR equation based on serum creatinine (eGFRcreat) and the Japanese GFR equation based on serum cystatin C (eGFRcys). Bias (mGFR - eGFR) and accuracy (P30) of the equations were evaluated.

Results

Inulin clearance, eGFRcreat, and eGFRcys were 91.0 ± 18.2, 78.5 ± 18.8, and 93.3 ± 16.3 mL/min/1.73 m², respectively. Bias of eGFRcreat was 12.4 ± 15.8 mL/min/1.73 m² and significantly different from zero, indicating underestimation of GFR. Bias of eGFRcys was −2.3 ± 16.3 mL/min/1.73 m² and was not significantly different from zero, suggesting better performance. But, the precision (standard deviation [SD] of bias) and accuracy (P30: Percentage of participants with eGFR within 30% of mGFR) of eGFRcys were not better compared with eGFRcreat. Accuracies (P30) of eGFRcreat and eGFRcys were 87% (95% confidence interval [CI], 74–94) and 82% (95% CI, 69–91), respectively.

Conclusion

Bias of eGFRcys was better compared with eGFRcreat. But, the precision (SD of bias) and accuracy of eGFRcys were not superior compared with eGFRcreat in potential kidney donors.     

Comparison of serum cystatin C and creatinine levels in determining glomerular filtration rate in children with stage I to III chronic renal disease

Abstract

Background: Pediatric studies are relatively scarce on the superiority of cystatin C over creatinine in estimation of glomerular filtration rate (GFR). This study measured cystatin C and serum creatinine levels, and compared GFR estimated from these two parameters in patients with chronic renal disease. Methods: This prospective, observational, controlled study included 166 patients aged 1–18 years diagnosed with stage I to III chronic renal disease, and 29 age- and sex-matched control subjects. In all patients, GFR was estimated via creatinine clearance, Schwartz formula, Zappitelli 1 and Zappitelli 2 formula and the results were compared using Bland–Altman analysis. Results: Patients and controls did not differ with regard to height, body weight, BMI, serum creatinine and serum cystatin levels, and Schwartz formula-based GFR (p?>?0.05). There was a significant relationship between creatinine and cystatin C levels. However, although creatinine levels showed a significant association with age, height, and BMI, cystatin C levels showed no such association. ROC analysis showed that cystatin C performed better than creatinine in detecting low GFR. Conclusion: Cystatin C is a more sensitive and feasible indicator than creatinine for the diagnosis of stage I to III chronic renal disease.     

Estimated Glomerular Filtration Rate from Serum Cystatin C: Significant Differences among Several Equations Results

Objectives: Several equations for the estimation of glomerular filtration rate (GFR) from serum cystatin C have been reported. We compared the results obtained using these equations to test the homogeneity of their results as well as their usefulness in clinical practice. Design and methods: Seven hundred and twenty-seven outpatients were studied. Of these, 439 were male and 288 were female, and their mean age was 60.8 ± 24.1 years. GFR was estimated from serum creatinine using the abbreviated Modification of Diet in Renal Disease (MDRD-4) equation. GFR was estimated from serum cystatin C levels using five different equations. Results: The simplest (100/cystatin C) formula rendered the highest estimated GFR and the Hoek’s equation rendered the lowest GFR, even significantly lower than the MDRD-4 equation (p < 0.001, Student’s t-test). From the simplest formula to the Hoek equation the mean difference calculated was 25.1 ± 8.7 mL/min (p < 0.001, Student’s t-test). No differences by gender were found among the results of different equations. All cystatin C-derived equations reduced the number of patients diagnosed of chronic renal failure when compared with MDRD-4 formula. No patient with normal renal function was shifted to the renal disease group. Conclusions: A higher value could be expected when GFR is estimated from cystatin C. Nevertheless, vast differences were found in the results when tested using several equations. Physicians should be aware of this problem to avoid a wrong clinical diagnosis of renal function.     

Predictive performance of eGFR equations in South Africans of African and Indian ancestry compared with 99mTc-DTPA imaging

Background

South African guidelines for early detection and management of chronic kidney disease (CKD) recommend using the Cockcroft?CGault (CG) or Modification of Diet in Renal Disease (MDRD) equations for calculating estimated glomerular filtration rate (eGFR) with the correction factor, 1.212, included for MDRD-eGFR in black patients. We compared eGFR against technetium-99m-diethylenetriaminepentaacetic acid (^99mTc-DTPA) imaging.

Methods

Using clinical records, we retrospectively recorded demographic, clinical, and laboratory data as well as ^99mTc-DTPA-measured GFR (mGFR) results obtained from routine visits. Data from 148 patients of African (n?=?91) and Indian (n?=?57) ancestry were analyzed.

Results

Median (IQR) mGFR was 38.5 (44) ml/min/1.73?m², with no statistical difference between African and Indian patients (P?=?0. 573). In African patients with stage 3 CKD, MDRD-eGFR (unadjusted for black ethnicity) overestimated mGFR by 5.3% [2.0 (16.0) ml/min/1.73?m²] compared to CG-eGFR and MDRD-eGFR (corrected for black ethnicity) that overestimated mGFR by 17.7% [6.0 (15.0) ml/min/1.73?m²] and 17.1% [6.0 (17.5) ml/min/1.73?m²], respectively. In stage 1?C2, CKD eGFR overestimated mGFR by 52.5, 38.0, and 19.3% for CG, MDRD (ethnicity-corrected), and MDRD (without correction), respectively. In Indian stage 3 CKD patients, MDRD-eGFR underestimated mGFR by 35.6% [?21.0 (6.5) ml/min/1.73?m²] and CG-eGFR by 4.4% [?2.0 (27.0) ml/min/1.73?m²], while in stage 1?C2 CKD, CG-eGFR and MDRD-eGFR overestimated mGFR by 13.8 and 6.3%, respectively.

Conclusion

MDRD-eGFR calculated without the African-American correction factor improved GFR prediction in African CKD patients and using the MDRD correction factor of 1.0 in Indian patients as in Caucasians may be inappropriate.     

Estimated GFR associates with cardiovascular risk factors independently of measured GFR

Estimation of the GFR (eGFR) using creatinine- or cystatin C-based equations is imperfect, especially when the true GFR is normal or near-normal. Modest reductions in eGFR from the normal range variably predict cardiovascular morbidity. If eGFR associates not only with measured GFR (mGFR) but also with cardiovascular risk factors, the effects of these non-GFR-related factors might bias the association between eGFR and outcome. To investigate these potential non-GFR-related associations between eGFR and cardiovascular risk factors, we measured GFR by iohexol clearance in a sample from the general population (age 50 to 62 years) without known cardiovascular disease, diabetes, or kidney disease. Even after adjustment for mGFR, eGFR associated with traditional cardiovascular risk factors in multiple regression analyses. More risk factors influenced cystatin C-based eGFR than creatinine-based eGFR, adjusted for mGFR, and some of the risk factors exhibited nonlinear effects in generalized additive models (P<0.05). These results suggest that eGFR, calculated using standard creatinine- or cystatin C-based equations, partially depends on factors other than the true GFR. Thus, estimates of cardiovascular risk associated with small changes in eGFR must be interpreted with caution.     

Clinical usefulness of serum cystatin C and the pertinent estimation of glomerular filtration rate based on cystatin C

Aim: Although cystatin C has been developed as an alternative marker for estimating glomerular filtration rate (GFR), its clinical use is as yet limited. The significance of cystatin C for differentiating chronic kidney disease (CKD) stages and established cystatin C‐based equations estimating GFR were evaluated. Methods: The fresh frozen serum samples from CKD (n = 119) and healthy volunteers (n = 22) were evaluated. Serum creatinine (sCr) was measured by the kinetic Jaffé method, and recalibrated to the isotope dilution mass spectrometry (IDMS). Cystatin C was measured using a particle‐enhanced nephelometric assay. Results: CKD stages were more sensitively differentiated by cystatin C compared to sCr, especially in moderate and severe kidney dysfunction. Sex and body mass index did not affect cystatin C level. Pearson's correlation coefficients of reciprocal of cystatin C, measured and recalibrated sCr compared to systemic inulin clearance (Cl_in) were 0.757, 0.734 and 0.709, respectively. We derived novel pertinent equations based on cystatin C (model 1: 1.404 × cystatin C^?0.895 × age^0.006 × weight^1.074 × height^?1.562 × (0.865; if female); model 2: 43.287 × cystatin C^?0.906 × age^0.101 × (0.762; if female)]. Models 1 and 2 showed superior performance in representing systemic Cl_in than the IDMS Modification of Diet in Renal Disease (MDRD) study equations did (adjusted r² = 0.76 and 0.72 for models 1 and 2, and 0.64 and 0.65 for 4 and 6 variable IDMS MDRD equations, respectively). Conclusion: Cystatin C reflects kidney dysfunction sensitively, and thus cystatin C‐based estimation of GFR could provide a reliable support for clinical practice.     

Cystatin C as a marker for glomerular filtration rate in pediatric patients

Cystatin C is a non-glycated 13-kilodalton basic protein produced by all nucleated cells. The low molecular mass and the basic nature of cystatin C, in combination with its stable production rate, suggest that the glomerular filtration rate (GFR) is the major determinant of cystatin C concentration in the peripheral circulation. Recently published studies have shown that cystatin C correlates more strongly than creatinine with GFR measured using the ⁵¹Cr-EDTA clearance. The aim of this study was to evaluate serum cystatin C as a marker for GFR in children. GFR was determined on medical indications using the ⁵¹Cr-EDTA technique in pediatric patients (2–16 years) in our renal unit. Simultaneously their cystatin C and creatinine concentrations were also measured. Of our 52 patients, 19 had a reduced renal function (<GFR 89 ml/min per 1.73 m²) based on the ⁵¹Cr-EDTA clearance. The correlation of cystatin C with the isotopic measurement of GFR tended to be stronger (r=0.89, P=0.073) than that of creatinine (r=0.80). Receiver operating characteristic analysis showed that the diagnostic accuracy of cystatin C was better (P=0.037) than that of creatinine in discriminating between subjects with normal renal function and those with reduced GFR. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine. Hence, cystatin C seems to be an attractive alternative for the estimation of GFR in children. Received: 13 May 1998 / Revised: 22 September 1998 / Accepted: 22 October 1998     

Modification of the Schwartz equations for children increases their accuracy at eGFR > 60 mL/min/1.73 m2

Aim: Estimation of eGFR in children with normal kidney function using the Schwartz equations results in underestimating real GFR. Materials and methods: We propose modification of three Schwartz equations – two based on creatinine concentration (eGFRScrBS bedside) and (eGFRScr) and one 3-marker based on creatinine, urea and cystatin C concentrations (eGFRS3M). The iohexol test (reference method) was performed 417 times in 353 children >2 years with mean GFR: 98?±?31.6?ml/min/1.73m². The assessment included also the Filler and Zappitelli equations. The modification was performed using methods: (1) based on equation, eGFR_cor?=?a [eGFR ? T] + T, where T?=?50, if eGFR?>?T, and a equals for: eGFRScrBS 1.4043, for eGFRScr 2.0048, for eGFRS3M 1.2951, and (2) based on correction of all coefficients of the original equation. Results: For comparison of all the results and for children with GFR?135?ml/min/1.73m² the correlation coefficient, relative error (RE) and root mean square relative error (RMSRE) was employed and revealed improvement of RE from 25.9 to 6.8 and 3.9% (depending on the correction method) for eGFRScr; from 19 to 8.1 and 3.9% for eGFRScrBS and: from 11.6% to 2.0 and 2.3% for eGFRS3M (respectively). The RMSRE values changed from 30 to 21.3 and 19.8% for eGFRScr, from 25.1 to 21.6 and 19.8% for eGFRScrBS and from 19.1 to 15.8 and 15.3 % for eGFRS3M. Conclusions: Modifications of Schwartz equations at GFR?>?60?ml/min/1.73m² significantly improves the accuracy of calculating eGFR. The 3-markers equation is more accurate and should be employed frequently.     

Preoperative serum cystatin C combined with dipstick proteinuria predicts acute kidney injury after cardiac surgery

Background: Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery. Methods: We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥?0.3?mg/dL or ≥?50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2?+?to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves. Results: The final cohort consisted of 616 patients aged 60.7?±?13.2 years, and baseline SCr was 75.8?±?26.4?μmol/L, estimated glomerular filtration rate (eGFR) 96.3?±?29.0?mL/min/1.73?m² and cystatin C 1.05?±?0.33?mg/L. Patients in higher cystatin C quartiles were older (p?p?=?0.021), hyperuricemia (p?p?p?=?0.002). Those with heavy proteinuria were more often to have diabetes mellitus (p?=?0.010), hyperuricemia (p?=?0.043), worse cardiac function (p?p?p?p?p?p?p?p?Conclusion: These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients undergoing cardiac surgery.