Serum cystatin C as an endogenous marker of renal function in patients with mild to moderate impairment of kidney function.

BACKGROUND: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C was proposed as a new endogenous marker of GFR and in our study its diagnostic accuracy was compared with that of other markers of GFR. METHODS: In this study, 164 patients with CKD stages 2-3 (GFR 30-89 ml/min/1.73 m2), who had performed 51Cr-labelled ethylenediaminetetra-acetic acid clearance, were enrolled. In each patient, serum creatinine and serum cystatin C were determined. Creatinine clearance was calculated using the Cockcroft-Gault (C&G) and the modification of diet in renal disease (MDRD) formulas. RESULTS: The mean 51CrEDTA clearance was 57 ml/min/1.73 m2, the mean serum creatinine 149 micromol/l and the mean serum cystatin C 1.74 mg/l. We found significant correlation between 51CrEDTA clearance and serum creatinine (R = -0.666), serum cystatin C (R = -0.792), reciprocal of serum creatinine (R = 0.628), reciprocal of serum cystatin C (R = 0.753) and calculated creatinine clearance from the formulas C&G (R = 0.515) and MDRD formulas (R = 0.716). The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that serum cystatin C had a significantly higher diagnostic accuracy than serum creatinine (P = 0.04) and calculated creatinine clearance from the C&G formula (P < 0.0001), though only in female patients. No difference in diagnostic accuracy was found between serum cystatin C and creatinine clearance calculated from the MDRD formula. CONCLUSIONS: Our results indicate that serum cystatin C is a reliable marker of GFR in patients with mildly to moderately impaired kidney function and has a higher diagnostic accuracy than serum creatinine and calculated creatinine clearance from the C&G formula in female patients.     

Cystatin C as a marker of early changes of renal function in Fabry nephropathy

BACKGROUND: A sensitive, feasible and reproducible marker for renal function is necessary to evaluate the clinical efficacy of enzyme replacement therapy (ERT) in Fabry nephropathy. Serum creatinine has some limitations and cystatin C has been proposed, in other nephropathies, as a useful marker of renal function. The use of cystatin C as a marker of glomerular filtration rate (GFR) was investigated in Fabry patients receiving ERT. METHODS: Renal function was evaluated with serum creatinine, serum cystatin C and estimated GFR (through Modification of Diet in Renal Disease [MDRD], Cockcroft-Gault [C&G] and Hoek formulae) in 21 Fabry patients receiving ERT with agalsidase alfa for 3 years and in 13 Fabry patients receiving agalsidase alfa for 4 years. RESULTS: During years of ERT while serum creatinine remained stable, cystatin C values showed a significant, increasing trend right from the first year of ERT. CONCLUSIONS: In Fabry disease, cystatin C is a sensitive and reliable marker of renal function, and it should be taken into account when evaluating GFR trends during ERT.     

125Iodine-iothalamate clearance in children. A simple method to measure glomerular filtration

Glomerular filtration rate (GFR) is the most widely used test to evaluate renal function. Several clearance markers have been used to measure GFR in adults. In children, however, a simple and reliable method to measure GFR is not available. Renal¹²⁵iodine (I)-iothalamate clearance, after a single subcutaneous injection, is a simple and accurate test to measure GFR in adults. The validity of unlabelled iothalamate, as a marker for measurement of GFR in children, was reported recently. Unfortunately, the unlabelled iothalamate assay is arduous. We report our experience with a single subcutaneous injection of¹²⁵I-iothalamate to measure GFR in normal children and those with renal disease. A weight-adjusted dosing regimen was adopted. This regimen resulted in sufficient above-background radioactivity in both blood and urine for reproducible measurement of GFR. Intra-test variability for GFR was not affected by the degree of renal insufficiency. The test was well tolerated with only 2 patients developing mild headache during the procedure. Our study showed that renal clearance of¹²⁵I-iothalamate is reproducible, simple, and practical in healthy children and those with mild and advanced renal disease.     

Serum cystatin C-immunoglobulin high-molecular-weight complexes in kidney and liver transplant patients

BACKGROUND: It has been suggested recently that the glomerular filtration rate (GFR) in renal transplant patients is underestimated by serum cystatin C due to an impaired filtration of complexed cystatin C with immunoglobulins. Consequently, serum cystatin C may not be a reliable marker of GFR in these patients. Our study was designed to determine whether this supposition is correct. METHODS: In 87 serum samples from patients with various kidney diseases, 182 samples from renal transplant patients, and 72 samples from liver transplant patients, the concentrations of cystatin C and creatinine were determined, as well as the residual concentration of cystatin C after precipitation of macromolecules with polyethylene glycol (PEG; 6000 molecular weight). RESULTS: The residual concentration of serum cystatin C after precipitation with PEG in all cases was much higher (70 to 100%) than that expected in the case of the existence of cystatin C-immunoglobulin complexes. In the kidney and liver transplant patients, there was no significant correlation between the residual concentration of cystatin C and the postoperative time (r = -0.098). CONCLUSIONS: The results suggest that in renal or liver transplant patients there is no formation of high molecular weight serum cystatin C-immunoglobulin complexes, regardless of the post-transplant period.     

Serum cystatin C--a superior marker of rapidly reduced glomerular filtration after uninephrectomy in kidney donors compared to creatinine

AIMS: Acute renal failure (ARF), defined by a rapid decrease of glomerular filtration rate (GFR), is associated with high mortality. Early and accurate detection of decreasing GFR is critical to prevent the progression of ARF and to potentially improve its outcome. Serum creatinine, the conventional GFR marker, has major limitations. We prospectively evaluated whether serum cystatin C detected a rapid GFR decrease earlier and more accurately than serum creatinine. METHODS: In ten patients undergoing nephrectomy for living related kidney transplantation, serum creatinine and cystatin C were determined daily. The decrease of GFR was quantitated preoperatively by creatinine clearance and MAG3 scintigraphy. The GFR decrease was defined by a 50-100% increase of cystatin C or creatinine from preoperative values. Ten patients without renal impairment served as controls. RESULTS: Initially, patients had a creatinine clearance of 105 +/- 14 ml/min/1.73 m2. Due to nephrectomy, patients lost 45 +/- 3% of their renal function. Serum cystatin C significantly increased already one, serum creatinine two days after nephrectomy. Cystatin C demonstrated an increase by 50-100% 1.4 +/- 0.9 days earlier than creatinine (p = 0.009). Serum cystatin C performed well detecting the GFR decrease with higher diagnostic values compared to creatinine. This was indicated by a sensitivity of 50, 70 and 80% of cystatin C to detect the GFR decrease on the three days following nephrectomy. CONCLUSIONS: Serum cystatin C detects rapid GFR decreases one to two days earlier than creatinine. Cystatin C is an early and accurate marker to detect rapid GFR decreases as in ARF.     

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.     

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     

Cystatin C: efficacy as screening test for reduced glomerular filtration rate

Serum cystatin C, a cysteine proteinase inhibitor, has been proposed as a marker of glomerular filtration rate (GFR). Serum cystatin C, serum creatinine and creatinine clearance were measured in 226 patients with various nephropathies, covering the entire range of renal function, to evaluate the efficacy of cystatin C as a screening test to detect reduced creatinine clearance in comparison to creatinine. Subgroups of 53 patients with glomerular and 26 patients with tubular impairment were compared to assess whether cystatin C performed differently in either glomerular or tubular impairment. Cystatin C detected reduced creatinine clearance with higher sensitivity (97 vs. 83%), and higher negative predictive value (96 vs. 87%) compared to creatinine. In parallel, 95% sensitivity of cystatin C as derived from receiver-operating characteristic plot was significantly higher (p < 0.05). In the subgroups with glomerular or tubular impairment, cystatin C and creatinine did not significantly differ with regard to efficacy. Serum cystatin C is as efficacious as serum creatinine to detect reduced GFR as measured by creatinine clearance. The efficacy of cystatin C as a screening test may even be superior compared to creatinine. In addition, the efficacy of cystatin C is independent of either glomerular or tubular impairment.     

Functional effects of renal artery stent placement on treated and contralateral kidneys

BACKGROUND: This study examined the effects of stent placement for renal artery stenosis on the function of treated and contralateral kidneys. METHODS: Eighteen patients who underwent stent placement for unilateral renal artery stenosis presenting with hypertension and/or renal failure were studied before angiography and stent placement and at their one-year follow-up. Renal vein blood samples were taken at both sides, at each side simultaneously with a sample from the aorta, to measure the plasma renin concentration and the concentrations of 131I-hippuran and 125I-thalamate during constant systemic infusion of these radiochemicals. This allowed an assessment of the single-kidney contributions to the total renin secretion, effective renal plasma flow (131I-hippuran clearance) and glomerular filtration rate (125I-thalamate clearance). RESULTS: At the one-year follow-up, the vein-to-artery renin ratio at the treated side had decreased to normal, from 1.65 +/- 0.131 to 1.23 +/- 0.076 (mean +/- SEM; P = 0.011), indicating an improved renal blood flow. Contralaterally it rose from 1.09 +/- 0.042 to 1.17 +/- 0.029 (P = 0.055) at follow-up. The extraction ratio of 131I-hippuran improved at the treated side (0.48 +/- 0.049 to 0.62 +/- 0.034; P = 0.003) and contralaterally (0.67 +/- 0.033 to 0.73 +/- 0.026; P = 0.043). The extraction ratio of 125I-thalamate, which equals filtration fraction, improved at both sides (0.12 +/- 0.014 to 0.17 +/- 0.012 at the treated side, P = 0.001; 0.18 +/- 0.013 to 0.22 +/- 0.011 contralaterally, P = 0.002). Two-kidney effective renal blood flow and glomerular filtration rate remained unchanged. CONCLUSION: Renal artery stenting was capable of causing improvement of glomerular filtration rate of the treated kidney, although the overall glomerular filtration rate did not change.     

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C.

BACKGROUND: Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. METHODS: Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, beta2-microglobulin (beta2M), and [125I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. RESULTS: Cystatin C correlated best with GFR (r=0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and beta2M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and beta2M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For beta2M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 micromol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. CONCLUSION: Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and beta2M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.     

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.     

Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula?

It is common practice to estimate glomerular filtration rate (GFR) from the Schwartz formula (a height creatinine/ratio), although it has its limitations. Cystatin C was found to be a superior marker of GFR. No formula has been validated to estimate GFR from cystatin C in children. Children (aged 1.0–18 years, n=536) with various renal pathologies undergoing nuclear medicine GFR clearance studies (^99mTc-DTPA single-injection technique) were tested. Cystatin C was measured with a nephelometric assay. The Schwartz GFR was calculated using enzymatically determined serum creatinine in micromoles per liter using the constant 48 for adolescent males and 38 otherwise. Using multiple stepwise regression analysis on log/log-transformed data, we derived the following relationship between the cystatin C concentration and GFR: log(GFR)=1.962+[1.123*log(1/Cystatin C)]. Using the Bland and Altman analysis to test agreement between the Schwartz formula and gold standard GFR showed considerable bias, with a mean difference of +10.8% and a trend towards overestimation of the GFR by the Schwartz formula with lower GFRs. In contrast, the Bland and Altman analysis applied on the GFR estimate derived from cystatin C showed the mean difference to be negligible at +0.3% and no trend towards overestimation of the GFR with lower GFRs. In the regression analysis of the estimate and the GFR, the Schwartz estimate showed significant deviation from linearity, whereas the cystatin C estimate did not. In conclusion, the data suggest that this novel cystatin C-based GFR estimate shows significantly less bias and serves as a better estimate for GFR in children.This study was supported by a research grant from Dade Behring GmbH, Germany. There is no conflict of interest.     

Serum cystatin C as an index of renal function in kidney transplant patients

Management of renal transplant patients requires periodic measurement of renal function, which is usually assessed by measuring the glomerular filtration rate (GFR). The most commonly used marker for GFR is serum creatinine, although muscle wasting and tubular secretion may lead to overestimation of the actual GFR. Serum concentrations of the low-molecular-weight proteins, cystatin C and beta(2)-microglobulin (B(2)M), may afford useful markers to determine a reduced GFR. We investigated whether these molecules provide reliable indicators of renal function in 75 renal transplant patients. Cystatin C and B(2)M correlated significantly with creatinine (r =.648, P <.05 and r =.578, P <.05, respectively). Inverse serum creatinine was superior to inverse cystatin C and inverse B(2)M when renal function equations were used (r =.95, P <.05, according to MDRD; r =.87, P <.05, according to Cockroft-Gault). Receiver operating characteristic (ROC) analysis was performed to quantitate the accuracy of the different markers to detect reduced GFR using a cutoff value of 70 mL/min. No significant difference between the areas under the ROC curves comparing cystatin C and B(2)M was observed; however, serum creatinine demonstrated a significantly greater value than cystatin C (.981 vs.724, P =.001). We conclude that serum creatinine is a more efficacious marker than serum cystatin C to assess renal function.     

Cystatin C,creatinine, estimated glomerular filtration,and long-term mortality in stroke patients

Renal dysfunction is associated with mortality in patients after ischemic stroke. Cystatin C is a potentially superior marker of renal function compared to creatinine and estimated glomerular filtration rate (GFR). In our observational cohort study, 390 Caucasian patients suffered from acute ischemic stroke (mean age 70.9 years; 183 women and 207 men) were included and prospectively followed up to maximal 56 months. Serum creatinine and cystatin C were measured at admission to the hospital; GFR was estimated according to CKD-EPI creatinine and CKD-EPI creatinine/cystatin equations. According to values of serum creatinine, estimated GFR and serum cystatin C patients were divided into quintiles. In the follow-up period, 191 (49%) patients died. For serum cystatin C and estimated GFR based on creatinine and cystatin C, the mortality and the hazard ratios for long-term mortality increased from the first to the fifth quintile nearly linearly. The associations of serum creatinine and estimated GFR categories based on creatinine with long-term mortality were J-shaped. As compared with lowest quintile of serum cystatin C, the fifth quintile was associated with long-term mortality significantly also after multivariate adjustment (age, gender, initial stroke severity, known risk factors for stroke mortality). In contrast, in adjusted analysis serum creatinine and estimated GFR (CKD-EPI creatinine and CKD-EPI creatinine/cystatin) were not associated with long-term mortality. In summary, serum cystatin C was independently and better associated with the risk of long-term mortality in patients suffering from ischemic stroke than were creatinine and estimated GFR using both CKD-EPI equations.     

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     

Time course of serial cystatin C levels in comparison with serum creatinine after application of radiocontrast media

BACKGROUND: The delayed increase of creatinine after radiocontrast application is a potential reason for overlooking radiocontrast nephrotoxicity. Cystatin C may be more useful to rapidly assess a decrease in glomerular filtration rate (GFR). We compared cystatin C and creatinine to examine their kinetics after application of radiocontrast media. PATIENTS AND METHODS: Forty-one patients (60.8 +/- 8.8 years, 68% males) with normal to subnormal GFR scheduled for coronary angiography (27% with angioplasty), were studied for serum cystatin C and creatinine levels before, 5 h, 24 h and 48 h after angiography. Furthermore, alpha1-microglobulin was checked for evidence of tubular damage. RESULTS: At 5 hours after angiography, there was no significant change compared to baseline in either serum creatinine nor cystatin C. In comparison with the value immediately before coronary angiography, the increase of cystatin C achieved a maximum at 24 h after the application of the contrast agent (+7.2%). Within 48 h, cystatin C decreased to the level before angiography. Serum creatinine increased at 24 h (+7.7%) and continued to increase at 48 h (+11.3%). CONCLUSION: Cystatin C increases earlier after radiocontrast application compared with creatinine. Therefore, cystatin C needs to be investigated as a potential early marker for nephrotoxicity, especially in the upcoming setting of short-time hospitalizations for coronary angiographies and interventions. Thus, further studies in patients with renal failure undergoing radiocontrast application are warranted to assess the usefulness of cystatin C in respect of an earlier detection of radiocontrast nephrotoxicity.     

Glomerular and tubular functions in children with different forms of beta thalassemia

Abstract

Background: Although there are many available data about renal involvement in patients with beta thalassemia major (TM), the changes in renal functions of other types, such as thalassemia intermedia (TI) and thalassemia minor (TMin), were reported less. Therefore, we aimed to evaluate renal tubular and glomerular functions in patients with three types of beta thalassemia. Methods: This prospective case–control study was conducted on 118 beta-thalassemia patients (49 in TM, 18 in TI and 51 TMin) and 51 healthy controls. Glomerular functions [estimated glomerular filtration rate (GFR), serum cystatin C and urinary protein creatinine ratio] and tubular functions [fractioned sodium excretion (FENa), tubular reabsorption of phosphorus, urinary excretion of uric acid, levels of retinol-binding protein, alpha-1 macroglobulin (alpha-1M), and beta-2 microglobulin, calcium creatinine ratio] were assessed in all patients and controls. Results: The mean ages of the groups and controls at presentation were similar. Although GFR was similar in all patients and control groups, serum levels of cystatin C in patients with TM and TI were significantly higher compared to TMin and controls. Alpha-1M, FENa, urinary excretion of uric acid, and urine protein/creatinine ratio in TM and TI groups were significantly higher than the others. Mean cystatin C level was also higher in patients with TMin compared the controls. However, there were no significant differences according to all tubular and other glomerular functions between TMin and control groups. Conclusions: Although all types of beta thalassemia patients should be closely monitored to prevent further decrease in renal functions, the patients with TI should be considered to have a higher risk of glomerular and tubular deterioration as well as TM.     

Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation.

Renal dysfunction of variable severity is being increasingly recognized as a major complication of calcineurin inhibitors (CI), in some patients even necessitating renal transplantation. Close and effective monitoring of the renal function is indicated. Current methods for this monitoring are calculation of the glomerular filtration rate (GFR) based on creatinine or exogenous substances like 51Cr-EDTA. The first method is unreliable in children and the second is expensive and cumbersome. Cystatin C has been shown to be an accurate marker of glomerular filtration but has not been evaluated in a large cohort of pediatric patients before and after liver transplantation (LT). We evaluated the accuracy of cystatin C in 62 children (30 male) with LT, who had their 51Cr-EDTA measured on 40 occasions prior to LT and on 47 occasions after LT. The reciprocal of cystatin C correlated better with 51Cr-EDTA GFR (r = .78) than the reciprocal of creatinine (r = .40). Diagnostic accuracy in the identification of reduced GFR was assessed by ROC analysis. Cystatin C yielded the highest area under the ROC curve (AUC) in all groups assessed. From these data a cutoff level of cystatin C predicting 51Cr-EDTA GFR < 80 ml/min/1.73 m2 was calculated. A level of 1.06 mg/L was found to have a sensitivity of 91% and a specificity of 81%. Applying this cutoff level in our patient group would have avoided 51Cr-EDTA GFR estimation in 43 of the 87 estimations. In conclusion, the use of this simple test could be recommended as screening of renal dysfunction in children with liver disease and after LT.     

Serum cystatin C as an endogenous marker of renal function in patients with chronic kidney disease

The estimation of the glomerular filtration rate (GFR) is an essential part of the evaluation of patients with chronic kidney disease (CKD). Recently, serum cystatin C has been proposed as a new endogenous marker of GFR. Authors compared serum creatinine, creatinine clearance calculated from Cockcroft and Gault formula and serum cystatin C against (51)CrEDTA clearance in 252 patients with CKD and GFR <90 mL/min/1.73 m(2). Analysis of correlations and diagnostic accuracy (receiver operating characteristic curves) of different GFR markers indicate that serum cystatin C is a more reliable marker of GFR in patients with CKD than serum creatinine.     

Renal vascular changes in renal disease independent of hypertension.

INTRODUCTION: Cardiovascular disease is common in patients with renal disease, but little is known about the effect of renal disease and loss of renal function on vascular morphology. Intima proliferation of small renal arteries, which correlates with atherosclerosis in the aorta, is sometimes present in renal disease and has been shown to increase with age and hypertension. We studied the effect of chronic renal disease and renal function, independent of hypertension, on intima proliferation. METHODS: We retrospectively selected renal biopsies of subjects in whom a glomerular filtration rate (GFR) measurement with [(125)I] iothalamate had been performed. To separate the effects of renal disease and renal function, we selected biopsies from (A) normotensive controls undergoing nephrectomy because of renal carcinomas; (B) normotensive patients with renal disease and GFR > 90 ml/min; (C) normotensive patients with GFR 30-90 ml/min, and (D) hypertensive patients with a GFR < 90 ml/min. The area of the arteriolar lumen, intima, and media were measured. RESULTS: No significant changes from control subjects were observed in group B. Intima proliferation was observed when renal function declined (intima/total vessel surface ratio was 0.262 +/- 0.071 in group C, 0.192 +/- 0.032 in group A, and 0.205 +/- 0.035 in group B, P < 0.05). The intima proliferation was aggravated in patients with renal insufficiency and hypertension (0.333 +/- 0.121, P < 0.05). Media surface area was not different between groups. CONCLUSION: Renal disease with preserved GFR does not cause significant intima proliferation of small renal arteries. Loss of renal function is accompanied by intima proliferation, even in the absence of systemic hypertension.