Impaired Glomerular Filtration Rate Research Articles

Early parasympathetic neuropathy associated with elevated fasting plasma C‐peptide concentrations and late parasympathetic neuropathy with hyperglycaemia and other microvascular complications

To examine the relationship between parasympathetic neuropathy, hyperinsulinaemia, glycaemic control (HbA(1c)), and future diabetic complications. We assessed parasympathetic nerve function [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic control (HbA(1c)), fasting plasma (f-p-) C-peptide in 82 Type 2 diabetic patients (age 61 +/- 1 years) 5 and 12-15 years after diagnosis. Diabetic retinopathy was assessed 15 years after diagnosis. High HbA(1c) values in the first study were associated with retinopathy (with 8.6 +/- 2.0 vs. without retinopathy 6.2 +/- 1.9%; P < 0.0001) and disturbed parasympathetic nerve function (low E/I ratio; r(s) = -0.41; P = 0.0061) in the second study, as well as with deteriorations in GFR between the first and second study (r(s) = 0.62; P < 0.0001). Patients with parasympathetic neuropathy in the first study had significantly higher f-p-C-peptide concentrations than those without 3 years (1.20 +/- 0.43 vs. 0.86 +/- 0.40 nmol/l; P = 0.0015) and 5 years (1.20 +/- 0.44 vs. 0.82 +/- 0.33 nmol/l; P < 0.0001), but not 15 years after diagnosis. High HbA(1c) values 5 years after diagnosis of Type 2 diabetes were associated with retinopathy, disturbed parasympathetic nerve function, and deterioration in GFR 7-10 years later. Parasympathetic neuropathy 5 years after diagnosis was associated with high C-peptide concentrations. Parasympathetic nerve function has to be considered when beta-cell function is evaluated. Hyperglycaemia is an important factor for the development of complications in Type 2 diabetes.

An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population

We questioned which factors determine the risk for developing renal function impairment. To that purpose, we studied the incidence of newly diagnosed impaired renal function (GFR <60 mL/min/1.73m2) in the PREVEND cohort (N=8592), which is enriched for the presence of albuminuria, and which was first studied in 1997-1998. Of this cohort, 6894 subjects were studied again four years later. Subjects with known renal disease, GFR <60 mL/min, missing GFR values, or sediment abnormalities at the first screening were excluded from the present analysis (N=872). We examined whether albuminuria is associated with the de novo development of an impaired renal function. GFR was 90.3 (SD 16.3) mL/min/1.73m2 at baseline, and 11.6% of the subjects had an albuminuria of more than 30 mg/day. After a follow-up of four years, 253 subjects (4.2%) were found to have a GFR <60 mL/min/1.73m2. The subjects with newly diagnosed impaired GFR were older, had a higher blood pressure, serum cholesterol, plasma glucose, and urinary albumin excretion at the first examination, and had a lower GFR to start with than those with a GFR >60 at the second evaluation. Subjects with de novo impaired GFR had a comparable BMI and smoked less frequently compared with subjects with GFR >60. In multivariate analysis, urinary albumin excretion was independently predictive for the risk of developing an impaired GFR (P=0.001). Also in the general population, measurement of urinary albumin excretion may prove to be a valuable tool to detect subjects at risk for later development of renal failure, independent of the presence of other cardiovascular risk factors.

Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13307 patients in five TIMI trials

To determine the association of glomerular filtration rate (GFR) with clinical outcomes in the setting of non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Data were pooled from five NSTE-ACS TIMI trials (TIMI 11A and B, TIMI 12, OPUS-TIMI 16 and TACTICS-TIMI 18) and were available in 13 307 patients. GFR was assessed as a continuous and a categorical variable (normal: > or = 90 mL/min/1.73 m2, n=4952; mildly decreased: 60-89 mL/min/1.73 m2, n=6262; and moderately to severely decreased GFR: <60 mL/min/1.73 m2, n=2093). There was an independent association between decreasing GFR and mortality at 30 days (OR 1.19, 95% CI 1.12-1.27, p<0.001) and at 6 months (OR 1.16, 95% CI 1.11-1.22, p<0.001). The combination of TIMI risk score (TRS) and decreasing GFR provided further mortality risk stratification with highest 30-day and 6-month mortality rates among patients with the lowest GFR who also had a TRS > or = 5 (9.1% and 15.4%, respectively). Decreasing GFR was also independently associated with stroke and recurrent ischaemia at 30-days as well as with major bleeding (p<0.001). In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS.

Increased urinary excretion of alpha1-microglobulin at 6 months after transplantation is associated with urinary excretion of transforming growth factor-beta1 and indicates poor long-term renal outcome.

Albumin and alpha1-microglobulin (alpha1M) are absorbed by two specific receptors in tubular epithelial cells. Any cell injury will disturb the reabsorption of these proteins, The increased urinary excretions of albumin or alpha1M could thus serve as a marker of subclinical graft lesions and as an early indicator of chronic allograft dysfunction. We measured 24-hour urinary excretions of albumin, alpha1M, and transforming growth factor (TGF)-beta1 at 6 months after transplantation in 79 renal-graft recipients and recorded the changes in 24-hour creatinine clearance an average 51 (range 14-72) posttransplant follow-up months. At 6 months from transplantation, 46 of 79 (58%) patients were normoalbuminuric, 25 (32%) microalbuminuric, and 8 (10%) macroalbuminuric. In normoalbuminuric patients, urinary alpha1M/creatinine ratio was 10 times, and TGF-beta1/creatinine ratio approximately 5 times, higher than in the healthy subjects but lower than in albuminuric patients. In all patients, urinary alpha1M correlated with urinary TGF-beta1 (r=0.508, P<0.001), with albumin (r=0.220, P<0.05), and with the annual changes in 24-hour creatinine clearance (r=-0.273, P<0.05). During follow-up, renal function deteriorated in 20 of 33 (60%) patients with alpha1M/creatinine ratio greater than 5 mg/mmol, but only in 1 of 46 (2%) patients whose ratio was less than 5 mg/mmol (P<0.01), giving the ratio 5 mg/mmol or greater a 95% sensitivity to detect patients with poor long-term outcome. We show proximal tubular injury, measured by increased urinary alpha1M, to be present even in normoalbuminuric patients and to be associated with increased excretion of TGF-beta1 and with the annual deterioration of glomerular filtration rate. These findings show increased alpha1M/creatinine ratio to be an early and sensitive indicator of poor long-term outcome in renal-transplant patients.

Clinically important renal impairment in various groups of old persons

Objective – To assess renal function in various groups of elderly persons, and to determine the proportion of patients with clinically important renal impairment. Design – Cross-sectional study. Participants – Three geriatric populations aged 70 years and over, representing increasing levels of care/treatment: community-dwelling elderly referred to a geriatric outpatient department, inpatients on a geriatric ward, and nursing home patients. Main outcome measures – Cockroft and Gault's formula was applied to calculate glomerular filtration rate (GFR). Differences in GFR between age groups and between care levels were explored. Results – Altogether 288 elderly persons were included in the study. We observed a general age-related decline of renal function. Only 2% of the participants had normal renal function (GFR >90 ml/min), 13% had light (GFR 60–89 ml/min), 68% moderate (GFR 30–59 ml/min), and 17% severe (GFR 15–29 ml/min) impairment in GFR. Moderate or severely decreased GFR was observed in 75% of the outpatients, 78% of the patients from the geriatric ward, and 91% of the nursing home patients. Altogether 99% of patients aged 85+ had renal impairment necessitating dosing adjustment for drugs that are mainly eliminated through renal excretion. Conclusion – Clinically important renal impairment is common in old age, especially in the frailest elderly living in nursing homes. This finding underlines the necessity for close supervision of drug treatment based on renal function in old age.

Renal actions of the cancion® Cardiac Recovery System in severe experimental heart failure

Background: Congestive heart failure (CHF) is a complex disease in which cardiorenal dysfunction reflects clinical status and prognosis. Evidence suggests mechanical unloading of the heart leads to molecular and functional myocardial recovery. The Cancion® Cardiac Recovery System (CRS), a novel percutaneously inserted extracorporeal mechanical device, superimposes continuous aortic flow on existing pulsatile flow. Previous studies in experimental CHF report decreased left ventricular filling pressures with CRS. Early studies in human CHF report decreased pulmonary capillary wedge pressure (PCWP) and plasma creatinine after employment of the CRS. The mechanisms for cardiorenal improvement remain unclear. To further characterize renal resonses to CRS we evaluated renal excretory and hemodynamic function before and after 4 hrs. of CRS therapy in an established model of severe CHF. Methods: Adult male dogs (n = 4) were paced at 240 bpm for 10 days consistent with an established model of CHF characterized by neurohumoral activation, systemic vasoconstriction, impaired cardiac pump function, increased filling pressures, sodium retention and impaired glomerular filtration rate (GFR) and renal blood flow (RBF). Dogs were then anaesthetized and the CRS device inserted percutaneously via the femoral artery into the descending aorta. A baseline clearance for urinary sodium excretion (UNaV) and inulin clearance to measure GFR was obtained. Cardiac filling pressures were measured via a Swan-Ganz catheter, mean arterial pressure (MAP) monitored, and RBF measured with a flow probe. The CRS was activated for 4 hrs., then deactivated and another clearance obtained. Resuts: UNaV (μEq/min) increased (440%±134%, p<0.05 vs baseline) after 4 hours of CRS therapy. GFR (15±5 vs 24±6mL/mim, NS) and RBF (130±12 vs 145±34 mL/min, NS) were maintained and tended to increase despite decreases in MAP (114±10 vs 83±6 mmHg, p<0.05). Consistent with previous studies PCWP decreased (23±2 vs 15±1 mmHg, p<0.05). Conclusion: We report that CRS device activation promotes natriuresis in severe experimental CHF despite decreased MAP. GFR, an important prognostic predictor in CHF is maintained. Consistent with previous studies employment of the CRS results in decreased PCWP in experimental CHF. The time course of these cardiorenal findings suggests neurohumorally mediated mechanisms. Further studies are warranted to elucidate these mechanisms.

Suprarenal fixation of endograft in abdominal aortic aneurysm treatment: focus on renal function.

The objective of this work was to evaluate any variation of renal function detected by renal scintigraphy after the suprarenal fixation of endografts for abdominal aortic aneurysm (AAA) repair. In the few articles that have considered this problem, renal function was evaluated only by biochemical tests, which are inadequate in demonstrating small changes in renal function and in appreciating the worsening of a single kidney's function. Between April 1999 and May 2002, 47 patients with an inappropriate infrarenal proximal neck had a suprarenal fixation for AAA. To assess renal function, a technetium-99m diethylene triamine penta-acetic acid (TC-DTPA) perfusion scintigraphy was performed preoperatively on the third postoperative day and at 6, 12 months, and then yearly thereafter. Worsening of renal function was defined as a decrease of glomerular filtration rate (GFR) > or =20% (detected with Gates method). Serum creatinine level was tested preoperatively and at the first and third postoperative day. Endograft deployment was technically successful in 44 patients (93.6%); clinical perioperative success was obtained in 46 patients (97.8%). In 12 patients (25.5%), a permanent reduction of the GFR was observed using postoperative TC-DTPA perfusion scintigraphy. By 99m TC-DTPA perfusion scintigraphy, a permanent reduction of GFR was observed postoperatively in 12 patients. A slight GFR reduction (<20%) was present in 7 (14.9%) patients, due to the planned occlusion of accessory renal arteries. A more significant GFR reduction (>20%) was present unexpectedly in 5 (10.6%) patients, in 3 of these a single kidney was involved, in 5 both with an increase of the serum creatinine level >20%. Suprarenal fixation of endografts in AAA treatment is a safe procedure with good early and midterm procedural results and a risk of GFR impairment (>20%) of 10.6%.

NEW MARKER FOR THE EARLY DIAGNOSIS OF NEPHROPATHY ASSOCIATED WITH TYPE II DIABETES MELLITUS

In this study the relationship between values of serum cystatin C or serum creatinine and prognostic stages of type II diabetic nephropathy was determined. Blood samples from 87 patients with type II diabetes were obtained from Nephrology Department, Zagazig University Hospitals, Zagazig, Egypt. Patients were categorized into five stages as follows: stage I, stage II, stage IIIa, stage IIIb, and stage IV according to the concentration of albumin in their 24 hours urines. The values of both serum cystatin C and creatinine were measured. It was found that, the mean levels of serum cystatin C in stage IIIb, were significantly higher than those in stages I or II (p < 0.00001/ p < 0.0005 respectively). The mean values of serum cystatin C in stages III, and IV were also significantly higher than those in stage I (p < 0.00001). However, the mean values of serum creatinine in stage IIIa, were not significantly higher than those in stages I or II. The values of serum creatinine in stages III, and IV were significantly higher than those in stage I (p < 0.00001). The Receiver Operating Characteristic (ROC) plot indicated that, serum cystatin C may be superior to serum creatinine for detecting impaired glomerular filtration rate (GFR). It appears that the values of serum cystatin C may be of value in predicting prognostic stages of patients with type II diabetic nephropathy.

Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2-16 years) with normal GFR (range 85-169 ml/min per 1.73 m(2)) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1+/-3.6), while the average concentrations of parathyroid hormone (36+/-13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22+/-14 ng/ml), and 1,25(OH)(2)D (59+/-22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS ( r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy ( r=-0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from -1.6 to 3.2, resulting in a height SDS range of -1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid ( r=-0.71, P<0.05) and with the duration of the disease ( r=-0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.

Increased levels of N(epsilon)-(carboxymethyl)lysine and N(epsilon)-(carboxyethyl)lysine in type 1 diabetic patients with impaired renal function: correlation with markers of endothelial dysfunction.

Diabetic and non-diabetic patients with renal failure have an increased risk for cardiovascular disease, which may be the result of uraemic toxins, including advanced glycation end-products (AGEs). The aim of the study was to investigate the levels of well-characterized AGEs, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) in relation to kidney function and to study the relationship of these AGEs to endothelial function and inflammation in type 1 diabetic patients. Plasma levels of CML and CEL were measured in 60 type 1 diabetic patients categorized as having normal glomerular filtration rate (GFR) (>80 ml/min, n = 31) or decreased GFR (<80 ml/min, n = 29) as estimated by the Cockcroft-Gault formula. To assess the relationship of these AGEs to endothelial function and inflammation, markers of endothelial function von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), tissue type-specific plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP), a marker of inflammatory activity, were determined by enzyme-linked immunosorbent assays. Plasma levels of CML and CEL were increased in diabetic patients with decreased GFR as compared with patients with normal GFR [CML 4.9 (2-12.6) vs 2.9 (1.7-4.4) micromol/l, P<0.000; and CEL 1.7 (0.9-3.3) vs 1.2 (1.7-4.4) micromol/l, P = 0.004, respectively). Independently of the GFR, the plasma levels of CML and CEL were significantly associated with sVCAM-1, vWf and sTM. Plasma levels of CML and CEL rise with deterioration of GFR. Furthermore, CML and CEL levels are associated with markers of endothelial activation independently of renal function. This suggests an involvement of these AGEs in the acceleration of cardiovascular complications in patients with renal impairment.

Serum cystatin C assay for the detection of early renal impairment in diabetic patients.

The ability to assess renal function in diabetes patients rapidly and early is of major importance. This study was designed to determine whether cystatin C can replace serum creatinine as the screening marker for reduced glomerular filtration rate (GFR) in type 2 diabetes patients. The study was performed on 51 type 2 diabetic patients. GFR was estimated by the plasma clearance of (99m)Tc-DTPA. The correlation between (99m)Tc-DTPA clearance and levels of serum cystatin C, serum creatinine, and creatinine clearance was determined. Sensitivity and specificity for the diagnosis of renal impairment (defined as GFR<68 ml/min) were calculated by a receiver operating characteristic (ROC) curve for serum cystatin C, serum creatinine, and creatinine clearance. The correlation coefficients with (99m)Tc-DTPA clearance were -0.744 for serum cystatin C, -0.658 for serum creatinine, and +0.625 for creatinine clearance (P<0.001). With a cutoff value of 68 mL/min, the area under the ROC curve (AUC) was 0.891 for cystatin C, 0.77 for creatinine, and 0.753 for creatinine clearance. The AUC was statistically different between serum cystatin C and creatinine clearance (P<0.05). The ROC plot indicates that cystatin C is superior to serum creatinine and creatinine clearance for detecting impaired GFR. Serum cystatin C appropriately reflects GFR in diabetes, and is more efficacious than serum creatinine and creatinine clearance in detecting reduced GFR in type 2 diabetes patients.

Pregnancy after lower urinary tract reconstruction for congenital abnormalities.

To evaluate the effect of pregnancy on renal function, and the effect of congenital urinary tract abnormality and reconstruction on pregnancy and delivery. The case notes were reviewed of 20 women (median age 32.5 years) who had had 29 live babies. Data collected included patient demographics, congenital urological abnormality, urological reconstructive procedure(s) and any subsequent urological complications. Pregnancy details, including urological and obstetric complications, presentation and mode of delivery, were obtained via a postal questionnaire from the relevant obstetrician. Seven patients had exstrophy-epispadias, seven spinal dysraphism, two sacral agenesis, and one each cerebral palsy, epispadias, imperforate anus and small bladder with vesico-ureteric reflux and congenital incontinence. They had had a mean (range) of 5.7 (1-12) urological reconstructive procedures each. Patients with exstrophy-epispadias had significantly more operations (mean 7.8) than those with spinal dysraphism (mean 4.14) or other diagnoses (mean 2.6) (P < 0.01). At the last follow-up 13 patients had an enterocystoplasty, six a neobladder and one an ileal conduit. Pregnancy-related urological complications were urinary tract infection in 15, upper tract obstruction requiring nephrostomy and stent in three, Mitrofanoff difficulties in two and pyelonephritis in one. There was no significant deterioration in glomerular filtration rate or serum creatinine after pregnancy. Only 10 of the births were normal or assisted vaginal deliveries. Seven patients had emergency and 12 had elective Caesarean sections for obstetric indications, including four breech births in the seven patients with vesical exstrophy. Pregnancy has no long-term effect on renal function and does not compromise reconstruction. Although there is a substantial complication rate and an increased need for Caesarean section, pregnancy in women with lower urinary tract reconstruction for congenital urological abnormalities is ultimately safe for both mother and baby. Interdisciplinary co-operation is desirable for a successful outcome.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

Aim. Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock‐Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock‐Schwartz formula, using Cin as the gold standard. Methods: Ninety‐nine children (51 m/48 f), with a median age of 8.3 y (1.0–17.9) were studied. Using a cut‐off for Cin of 100ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. Results: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock‐Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. Conclusion: GFR is better assessed by the Haycock‐Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

Serum Cystatin C Is a More Sensitive and More Accurate Marker of Glomerular Filtration Rate than Enzymatic Measurements of Creatinine in Renal Transplantation

Background/Aims: Serum creatinine has several drawbacks as marker of glomerular filtration rate (GFR), and therefore serum cystatin C has been proposed as a more optimal GFR marker. Previous reports have suggested benefits of serum cystatin C measurements in patients with renal transplants. The purpose of the present study was to evaluate the diagnostic accuracy of cystatin C measurements compared with enzymatic creatinine measurements as serum markers of GFR (established from plasma clearance of iohexol) in a large cohort of stable renal transplant recipients and in the early postoperative phase. Methods: Renal transplant patients (n = 125) with stable graft function were evaluated from reciprocals of serum creatinine and cystatin C compared with iohexol clearance. Fourteen patients were examined immediately after the onset of renal function. Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Results: In stable renal transplant recipients, serum cystatin C showed a significantly (p = 0.033) closer correlation (r = 0.89 or 79% co-variance) with iohexol clearance than did serum creatinine (r = 0.81 or 66% co-variance). Using the χ² test and a cut-off at 60 ml/min/1.73 m², serum cystatin C levels demonstrated significantly higher sensitivity for early GFR impairment (p = 0.0045) compared with serum creatinine measurements. On the first day after transplantation, serum cystatin C fell more rapidly than serum creatinine. Conclusion: Serum cystatin C levels correlate significantly closer to accurate measurements of GFR and are significantly more sensitive to detect early GFR impairment than enzymatic measurements of creatinine in serum.

Serum levels of beta-trace protein and glomerular filtration rate—preliminary results

The aim of this study was to evaluate the relationship between serum levels of beta-trace protein (BTP), a low molecular weight (MW) protein, and glomerular filtration rate (GFR). GFR and serum levels of BTP, and for comparison creatinine (Creat), cystatin C (Cys) and β2-microglobulin (β2M), were measured in 60 patients, with renal function ranging from normality to advanced renal failure. Serum levels of BTP progressively increased with the reduction of GFR. A good correlation was found between GFR and serum levels of BTP ( r=0.918), Creat ( r=0.932), Cys ( r=0.937), and β2M ( r=0.924). Furthermore, no statistically significant difference was found between BTP and Creat, Cys, β2M, as indicators of a moderate GFR impairment. These preliminary data indicate that BTP might be suitable as an indicator of GFR.

Renal function and outcome of PTRA and stenting for atherosclerotic renal artery stenosis

Prior studies of percutaneous transluminal renal artery angioplasty and stenting (PTRAS) for atherosclerotic renal artery stenosis (RAS) have shown that renal function is improved in about 25%, stabilizes in about 40%, but worsens in about 25% of patients. The factors predicting benefit remain controversial. We tested the hypothesis that the baseline glomerular filtration rate (GFR) predicts the changes in GFR and blood pressure (BP) after PTRAS. Treated hypertensive patients with positive renal color-coded duplex Doppler velocimetry and clinical criteria were screened by arteriography. Patients (N = 105) were included if they had an RAS >or=70%, a transluminal pressure gradient >or=30 mm Hg and, they had more than 100 days of follow-up. GFR was calculated from the serum creatinine concentration (SCr). Patients were divided by baseline GFR into subgroups with normal to mildly impaired (N = 52) or moderately to severely impaired (N = 53) initial GFR, according to a GFR >or=50 or <50 mL. min-1 respectively. All received PTRAS. For the entire group, after a mean follow-up period of 371 days, there were significant reductions in systolic and diastolic BP (before, 160 +/- 26/91 +/- 12 vs. after, 145 +/- 20/83 +/- 10 mm Hg, respectively; mean +/- SD; P < 0.0001), and a modest increase in the calculated GFR (before, 54 +/- 26 vs. after, 62 +/- 28 mL. min-1; mean +/- SD; P < 0.007). However, in the subgroup of patients with an initially lower GFR there was a significant increase in the calculated GFR (from 33.3 +/- 10 to 54 +/- 24 mL. min-1; mean +/- SD; P < 0.0001) despite no significant change in BP (161 +/- 27/90 +/- 12 vs. 151 +/- 21/86 +/- 12; P = NS). In contrast, in the subgroup with an initially higher GFR, there were significant (P < 0.0001) reductions in systolic BP (from 159 +/- 25 to 138 +/- 16 mm Hg) and diastolic BP (from 91 +/- 11 to 81 +/- 9 mm Hg), but no significant change in the calculated GFR (from 75 +/- 21 to 70.2 +/- 30 mL. min-1; P = NS). The significance of GFR variation in subgroups remained after correction of baseline data to exclude the influence of the expected regression to the mean. Patients with atherosclerotic RAS fulfilling strict criteria of severity may have significant improvements in BP one year after PTRAS but only modest in GFR. The initial GFR may anticipate whether the benefits in the outcome will be in renal function enhancement (those with an initially depressed GFR) or in hypertension control (those with an initially normal or mildly impaired GFR).

Renal Pathology in Fabry Disease

Fabry disease is an X-linked recessive lysosomal storage disease that is caused by deficient activity of the lysosomal enzyme α-galactosidase A (α-Gal A), an enzyme that cleaves terminal α-galactosyl residues. This deficiency results in progressive lysosomal accumulation of glycosphingolipid with

β-Trace Protein, Cystatin C, β2-Microglobulin, and Creatinine Compared for Detecting Impaired Glomerular Filtration Rates in Children

Because of the limitations of serum creatinine as a marker of glomerular filtration rate (GFR) in children, we assessed the diagnostic accuracy of the novel marker beta-trace protein (BTP) in comparison with cystatin C (Cys-C), beta(2)-microglobulin (beta(2)-MG), and creatinine as conventional indicators of reduced GFR. We obtained serum samples from 225 children (age range, 0.2-18 years) with various renal pathologies who were referred for nuclear medicine clearance investigations (technetium-diethylenetriamine pentaacetic acid or chromium-EDTA). We measured Cys-C, BTP (nephelometric tests; Dade Behring), beta(2)-MG (Tinaquant; Roche), and creatinine (enzymatic assay; Creatinine-PAP; Roche). Seventy-five children had reduced GFR (<90 mL x min(-1) x 1.73 m(-2)). One hundred fifty children (independent of gender and age) with values >90 mL x min(-1) x 1.73 m(-2) comprised the control group with gaussian distributions of BTP and Cys-C concentrations. The upper reference limits (97.5 percentile) were 1.01 mg/L for BTP and 1.20 mg/L for Cys-C. The correlations of nuclear medicine clearance with the reciprocals of BTP, Cys-C, and the Schwartz GFR estimate were significantly higher (r = 0.653, 0.765, and 0.706, respectively; P <0.05) than with the reciprocal of creatinine or beta(2)-MG (r = 0.500 and 0.557, respectively). ROC analysis showed a significantly higher diagnostic accuracy of BTP, Cys-C, and the GFR estimate for the detection of impaired GFR than serum creatinine (P <0.05). Compared to creatinine, BTP increased the diagnostic sensitivity by approximately 30%, but it was not more sensitive than Cys-C or the Schwartz GFR estimate. BTP is superior to serum creatinine and an alternative for Cys-C to detect mildly reduced GFR in children, but it is not better than the Schwartz GFR estimate.

Cystatin C: An Improved Estimator of Glomerular Filtration Rate?

Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.