Vitamin D deficiency during late pregnancy mediates placenta-associated complications.

During pregnancy, maternal vitamin D insufficiency could increase the risk of preeclampsia. Aim of the study was to evaluate the relationship between vitamin D status and the occurrence of placenta-mediated complications (PMCs) in a population at high risk. A prospective multicenter cohort study of 200 pregnant patients was conducted. The vitamin D level of patients with placenta-mediated complications was lower at 32 weeks compared to uncomplicated pregnancies (P = 0.001). At 32 weeks, the risk of occurrence of PMCs was five times higher in patients with vitamin D deficiency (RR: 5.14 95% CI (1.50-17.55)) compared to patients with normal vitamin D levels. There was a strong, inverse relationship between serum 25(OH)D levels at 32 weeks and the subsequent risk of PMCs (P = 0.001). At 32 weeks, the vitamin D level of patients with late-onset PMCs was lower than the one of patients with early-onset PMCs and of patients without PMCs (P < 0.0001). These results suggest a role of vitamin D in the maintenance of placental performance and therefore in the prevention of the onset of late PMC.

UMOD polymorphism rs12917707 is not associated with severe or stable IgA nephropathy in a large Caucasian cohort.

BACKGROUND: Genetic factors are suspected in the pathogenesis of IgA nephropathy, as well as in the course of IgA nephropathy progression towards end stage renal failure. UMOD polymorphism rs12917707 is known to associate with end stage renal failure of mixed aetiologies. METHODS: We tested a large cohort of Caucasian patients for association of rs12917707 with IgA nephropathy showing a benign, stable course and with IgA nephropathy that progressed toward end stage renal failure. RESULTS: No association was observed between either groups, and a non-significant trend was observed for more severe IgA nephropathy with the allele reported to protect against end stage renal failure of mixed aetiologies. CONCLUSION: We conclude that UMOD is unlikely to play a role in IgA nephropathy pathogenesis nor progression to end stage renal failure, and suggest that UMOD effects are restricted to some causes of renal disease, e.g. diabetes or hypertension.

The podocin mutation R229Q and early recurrence (within the first year) of glomerular disease after renal transplantation.

BACKGROUND: Podocin is a key protein involved in the pathogenesis of steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis (FSGS) and is characterized by a high rate of early recurrence after renal transplantation (RTx) in children and adults. MATERIAL AND METHODS: We studied 206 RTx adult recipients: 187 with a diagnosis of glomerular nephropathy, GN (biopsy-proven in 149, clinical in 38), plus 19 with unknown diagnosis as original kidney disease (OKD), the NPHS2 gene polymorphism, G755A, and correlated with the presence of early recurrence of OKD within the first year (proteinuria over 1 g/day and graft-biopsy proven). RESULTS: The A allele podocin gene mutation frequency was 3.4% (14/412) overall - 7.1% (4/56) in FSGS as expected, but surprisingly 5.7% (6/106) in IgA nephropathy. Fifty recipients (24.3%) developed proteinuria >1 g/d, with 12 recipients demonstrating early clinico-pathological recurrence by 1 year (5.8%) with 5/28 in FSGS, 2/53 in IgAN, 2/14 in membranoproliferative GN (with 1 graft loss within the first year), 1/19 in crescentic GN, 1/19 in unknown disease, and 1/38 in clinical GN. Only 2 recurrent patients (both with FSGS) had the R229Q podocin mutation (16.7%). CONCLUSIONS: The podocin mutation R229Q may play a role in the pathogenesis of FSGS and in early recurrence after transplantation, but does not allow accurate prediction of recurrence or the associated potential for prevention.

MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients.

BACKGROUND: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed. METHODS: We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of Cr-EDTA (n=337). RESULTS: Mean measured GFR (mGFR) was 50±19 mL/min/1.73 m. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR <60 mL/min/1.73 m and between 60 and 90 mL/min/1.73 m. For mGFR >90 mL/min/1.73 m, there were no significant differences between the two equations in terms of performance. CONCLUSIONS: The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages.

GFR estimation using standardized cystatin C in kidney transplant recipients.

BACKGROUND: The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients. STUDY DESIGN: Study of diagnostic test accuracy. SETTING & PARTICIPANTS: 670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012. INDEX TEST: Estimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysC-based CKD-EPI equations (eGFR(cys) and eGFR(cr-cys), respectively) and the 2009 SCr-based CKD-EPI equation (eGFR(cr)), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011. REFERENCE TEST: Measured GFR (mGFR) using urinary clearance of inulin. RESULTS: Bias (the difference between mGFR and eGFR) was significantly smaller for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (-2.82 and -0.54 vs +4.4 mL/min/1.73 m(2), respectively; P < 0.001). Precision (standard deviation of the mean bias) also was better for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (12 and 11 vs 13 mL/min/1.73 m(2) [P < 0.001 for both comparisons]). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (81% and 86% vs 75%, respectively [P = 0.004 and P < 0.001]). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m(2) for eGFR(cr-cys) and eGFR(cys) versus eGFR(cr) was 18.8% [95% CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%]. LIMITATIONS: Patients were exclusively of European descent; association with transplant outcome was not evaluated. CONCLUSIONS: Our data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009).

Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy.

Mesangial and circulating IgA1 with aberrantly glycosylated hinge region O-glycans characterize IgA nephropathy (IgAN). Unlike healthy individuals, some IgA1 is galactose deficient in patients with IgAN, leaving terminal N-acetylgalactosamine residues in the hinge region exposed. Circulating autoantibodies that recognize such galactose-deficient IgA1 as an autoantigen, or the levels of the autoantigen itself, may allow prediction of disease progression. Here, we analyzed serum samples obtained at diagnosis for autoantigen and autoantibodies from 97 patients with IgAN selected from our prospective cohort according to their absolute renal risk for progression to dialysis or death (0, very low; 1, low; 2, high; 3, very high). We also analyzed samples from controls comprising 30 healthy volunteers and 30 patients with non-IgAN disease. The mean follow-up was 13.8 years. We found that mean serum levels of total autoantigen, normalized IgG autoantibody, and total IgA autoantibody were significantly higher in patients than in the combined controls (all P≤0.01). Furthermore, increasing levels correlated with worse clinical outcomes. In Cox regression and Kaplan-Meier analyses, IgG autoantibody levels ≥1.33 predicted dialysis or death (both P≤0.01). In conclusion, these data suggest that serum levels of IgG and IgA autoantibodies strongly associate with the progression of IgAN nephropathy.

Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis.

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²-3×10⁻¹°), with heterogeneity detected only at the PSMB9/TAP1 locus (I²â€Š= 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻4). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²8). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

Single nucleotidic polymorphism 844 A->G of FCAR is not associated with IgA nephropathy in Caucasians.

BACKGROUND: IgA nephropathy is characterized by a high heterogeneity of clinical expression with 10-30% of patients progressing to end-stage renal failure. The gene of the FcαRI or CD89 presents a single-nucleotide polymorphism responsible for a proinflammatory phenotype of neutrophils in vitro and ex vivo. The aim of our study was to assess whether this CD89 polymorphism 844 A->G is (i) a marker of disease susceptibility and/or (ii) associated with a more severe prognosis. METHODS: All patients diagnosed with IgA nephropathy and for whom DNA frozen sample was available were included in this European monocentric retrospective analysis and compared to a cohort of healthy volunteers. Allelic discrimination was performed by real-time quantitative polymerase chain reaction (Applied Biosystems™). We first compared the distribution of A and G alleles between patients and volunteers and then studied the relationships between alleles and renal survival, histological score, proteinuria and renal function at diagnosis. RESULTS: Seven hundred and twenty-six patients were analyzed for the study of susceptibility and 425 in the association study. The presence of the G allele was not associated with the occurrence of IgA nephropathy (χ(2) test 0.57, ns). Likewise, renal survival and the criteria for disease activity at time of diagnosis were not affected by the presence of the G allele. CONCLUSIONS: No significant association between 844 A->G CD89 polymorphism and the expression of the IgA nephropathy in Caucasians exists. This result does, however, not preclude the implication of other CD89 polymorphisms neither the possibility for a role of CD89 in the pathogenesis of IgA nephropathy.

Comparison of acid and enzymatic methods for inulin dosage: analytical performances and impact on glomerular filtration rate evaluation.

Among issues susceptible to hamper a reliable measurement of inulin clearance, those regarding the dosage of inulin are largely neglected. We have compared the analytical performances of 2 commonly used methods of inulin dosage (one "acid" and one "enzymatic" method) and studied their potential impact on the glomerular filtration rate (GFR) value given by inulin clearance. Repeatability, uncertainty and the beta-expectation limits were evaluated from pre-determined serum and urine pools of inulin. Agreement between the two methods was analyzed from 99 inulin clearances performed in renal transplant patients. Impact of the method of dosage on GFR evaluation was simulated according to the respective beta-expectations limits of each method. Overall, intra-assay coefficient of variability and relative bias were inferior to 5% and 10% for both methods. Contrary to the acid method, analytical performance of the enzymatic method was not influenced by the presence of glucose. The relative difference in GFR values obtained with the two methods in transplant patients was -0.4 ± 10%. Simulations suggested that changes in inulin concentration attributable to analytical error could modify the value of GFR from -12% to +28%. In conclusion, while analytical performances are globally acceptable for both methods, they are not strictly equivalent. The impact on the determination of GFR, albeit limited, is not negligible and adds to other sources of inaccuracy. International standardization for the dosage of inulin is necessary.

[Measurement of inulin: development]. / Le dosage de l'inuline : mise au point.

Inulin clearance is still considered as the gold standard method to measure glomerular filtration rate. This method has been proposed in thirties by Smith and Shannon but the inulin measurement method still remains complex. Interferences, notably with the glucose, must also be considered. Two main methods have been proposed to measure inulin both in urine and plasma: "acid" or enzymatic methods. "Acid" methods are colorimetric. Fructose is actually measured after inulin hydrolysis in acid milieu. Different methods have been described to measure fructose. Among these methods, the measurement using anthrone is the most popular. Several enzymatic methods have also been published. These have more precision and the interference with glucose is probably less even if relatively few studies are available. HPLC methods for inulin measurement have also been described. This method is specific and accurate. While inulin is an unquestioned reference method for glomerular filtration rate, its measurement in urine and plasma remains tricky and at risk of interferences. Additional trials seem necessary to analytically validate and compare all the methods available on the market.

Predicting the risk for dialysis or death in IgA nephropathy.

For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8). Overall, the ARR score allowed significant risk stratification (P < 0.0001). The cumulative incidence of death or dialysis at 10 and 20 years was 2 and 4%, respectively, for ARR=0; 2 and 9% for ARR=1; 7 and 18% for ARR=2; and 29 and 64% for ARR=3, in adequately treated patients. When achieved, control of hypertension and reduction of proteinuria reduced the risk for death or dialysis. In conclusion, the absolute renal risk score, determined at diagnosis, associates with risk for dialysis or death.

Creatinine-based GFR predicting equations in renal transplantation: reassessing the tubular secretion effect.

BACKGROUND: The real utility of blocking the tubular secretion of creatinine with cimetidine in order to ameliorate the prediction of renal graft function is questionable, particularly in the context of an increasing diffusion of the Modification of Diet in Renal Disease (MDRD) study equation. We have compared the impact of cimetidine on the performances of the Cockcroft-Gault (C-G) and MDRD equations in 56 renal transplant patients with an estimated glomerular filter rate (GFR) >30 mL/min/1.73 m(2) for whom true GFR was directly measured by inulin clearance. METHODS: Serum creatinine concentration (SCr) was measured [isotope dilution mass spectrometry (IDMS) traceable enzymatic assay] at the beginning of the inulin clearance procedure and 2 days later, after three oral cimetidine doses of 800 mg every 12 h. Predictive and diagnostic performances of the re-expressed MDRD and C-G formulas were compared before and after cimetidine intake. RESULTS: Mean SCr (+/-SD) increased from 120 micromol/L (+/-34) before to 154 micromol/L (+/-47) after cimetidine. The beneficial effect of cimetidine was significant only on the accuracy of the C-G formula (accuracy 30% post-cimetidine of 93 and 79% for the C-G and MDRD equations, respectively). Likewise, while a higher proportion of patients were correctly staged using the chronic kidney disease classification after cimetidine with the C-G equation (59% before and 68% after), no improvement was seen with the MDRD formula (59 vs 57%). For both equations, receiver operating characteristic curves analysis showed only a marginal gain in GFR prediction. CONCLUSION: Our data do not support the use of a cimetidine-based strategy for the evaluation of renal graft function in the clinic, particularly when the GFR is estimated by the MDRD equation.

Cystatin C-based equations in renal transplantation: moving toward a better glomerular filtration rate prediction?

Creatinine-based glomerular filtration rate (GFR) estimators perform poorly in renal transplant recipients. Cystatin C might be a better alternative to serum creatinine in assessing renal graft function. We compared several cystatin C-based equations with the modification diet renal disease (MDRD) equation in 120 adult renal transplant recipients for whom the GFR was measured by the gold standard inulin clearance. Mean inulin-measured GFR was 52.6 mL/min/1.73 m (range, 13-119). The Hoek, Rule, Le Bricon, and Filler cystatin C-based formulas showed significantly better performances (accuracy 30% of 82%, 81%, 78%, and 71%), than the MDRD equation (58%, Mac Nemar test, P<0.01). Sensitivity to detect a GFR below 60 mL/min/1.73 m was significantly higher for the Hoek and the Rule equations (0.95, 95% CI 0.91-1) than for the MDRD equation (0.76, 95% CI 0.67-0.85). These data confirm that cystatin C as a GFR marker offers significant advantages over creatinine in renal transplantation.

Antithymocyte globulin (ATG) induction therapy and disease recurrence in renal transplant recipients with primary IgA nephropathy.

Recurrence of primary IgA nephropathy after renal transplantation is clearly a time-dependent event, justifying the use of Kaplan-Meier and Cox regression analyses to sort the significant risk factors. In this retrospective study, we focused on the potential role of induction immunosuppressive therapy. We studied 116 renal transplantation (84 males, 112 cadaveric donors, 95 first grafts, mean age at Tx=46.1 years) who received, as induction, antithymocyte globulin (ATG) in 29, anti-CD25 in 35, and none in 52, associated with different maintenance therapy overtime. The 10-year cumulative recurrence rate was overall 36%, but only 9% after ATG induction when compared with 41% without induction (P=0.001). Multivariate Cox regression confirmed that ATG was protective with a 80% reduction in relative risk (P=0.01). In conclusion, this important finding needs to be confirmed in a prospective trial and if so will have major implication.

IL5RA and TNFRSF6B gene variants are associated with sporadic IgA nephropathy.

Familial clustering and genome-wide linkage scans strongly support a genetic susceptibility to familial IgA nephropathy (IgAN), but genetic factors that predispose to sporadic IgAN are unknown. A high-throughput single nucleotide polymorphism (SNP) association study was conducted using a customized Illumina BeadChip in 732 white patients with biopsy-proven IgAN and 503 control subjects from Canada, France, and Finland. Approximately 93% of 1536 SNPs on the array were tag SNPs from Phase I+II of the HapMap with a minor allele frequency > or =5%, designed to capture the common variants of genes within the critical interval of IGAN1 on chromosome 6q22 and 69 biologic candidate genes for IgAN. SNPs of suggestive or significant association were identified by using logistic regression to adjust for age, gender, study site, and population stratification. Despite using a dense marker set that covered an average interval of 6.5 kb between SNPs, there was no strong and consistent association signal within the IGAN1 critical interval. Among the biologic candidate genes examined, two significant association signals were found at IL5RA and TNFRSF6B, the latter being particularly interesting because this gene encodes a decoy receptor for a TNF family ligand that causes IgAN in mice when overexpressed. Pending replication, these data suggest that variants of IL5RA and TNFRSF6B may predispose to sporadic IgAN.

Predicting glomerular filtration rate in kidney transplantation: are the K/DOQI guidelines applicable?

The kidney disease outcomes quality initiative (K/DOQI) guidelines introduced a classification of chronic kidney disease (CKD) based on the level of kidney function. In order to predict the glomerular filtration rate (GFR), they specifically recommended the use of the modification of diet in renal disease (MDRD) study and Cockcroft-Gault (C-G) equations. Since the performance of these estimates has been questioned, we sought to determine whether these recommendations might be applicable in renal transplantation. Following the K/DOQI methodology, we compared the GFR estimated by the MDRD and C-G equations with 476 inulin clearances performed in 284 renal transplant recipients. Even though the MDRD equations provided a better prediction than C-G formula, none of them reached the level of accuracy required by the K/DOQI standards. At least, 25% of the calculated GFR gave a prediction beyond 30% of the corresponding inulin clearance value. In addition, when classified according to their predicted GFR, less than two-thirds of the transplant patients turned out to be assigned to the correct stage of CKD. We conclude that, in renal transplantation, the predictive performance of both C-G and MDRD study equations appears to be particularly impaired and may potentially compromise the validity of the K/DOQI guidelines if implemented in their current form.

G protein beta3 subunit C825T polymorphism in primary IgA nephropathy.

BACKGROUND: The T allele of the G protein beta3 subunit (GNB3) C825T polymorphism has been associated with increased signal transduction, increased activity of the kidney Na+/H+ exchanger, and also with late-onset essential hypertension. Hypertension is a strong independent risk factor for progression in IgA nephropathy (IgAN). METHODS: We have studied this polymorphism in a regularly followed cohort of 299 biopsy-proven incident cases of IgAN, collected from 1989 to 1999 [208 males (70%)] and compared the genotypes and alleles distributions to 303 local Caucasian controls matched for the male predominance (214 males). The technique used was a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with BseDI as restriction enzyme and specific primers, followed by gel electrophoresis. RESULTS: The TT, CT, and CC genotype frequencies were 13.7%, 45.8%, and 40.5% in IgAN, respectively, versus 7.6%, 47.2%, and 45.2% in controls, respectively (chi(2)= 6.16; P= 0.05). The excess of TT patients versus non-TT was significant in IgAN versus controls (chi(2)= 5.94; P= 0.015). The T allele frequency was 0.366 in IgAN versus 0.312 in controls (chi(2)= 3.97; P= 0.05). This data indicated that this polymorphism had a significant but mild influence on the occurrence/initiation of IgAN (RR = 1.81; 95% CI 1.07-3.07). In contrast, we could not demonstrate any significant and sustained difference in the clinical presentation and evolution of the homozygous TT patients compared to non-TT patients (CC + CT) despite a mean and median follow-up about 10 years. The progression to arterial hypertension or to chronic renal failure or to end-stage renal failure (ESRF) was not significantly different. In addition, multivariate Cox regression analysis excluded a significant independent role of C825T polymorphism on progression. CONCLUSION: The C825T GNB3 polymorphism had a mild influence on occurrence/initiation of IgAN, but played no significant role in the progression of the disease.

Assessing renal graft function in clinical trials: can tests predicting glomerular filtration rate substitute for a reference method?

BACKGROUND: In clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients. We aimed to compare the performances of six GFR tests with inulin clearance in this population. METHODS: Five hundred consecutive inulin clearances performed in 294 renal transplant recipients with stable renal function were retrospectively selected. For each of them, we computed six estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser, Jelliffe, Nankivell, and Levey formulas. Their respective performance was assessed by correlation (simple linear regression), accuracy (dispersion of true error), and agreement (Bland and Altman method). RESULTS: Each GFR test closely correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR tests did not show any significant difference in accuracy between the Levey, Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR tests displayed considerable lack of agreement with limits of agreement over 40 mL/min/1.73 m2 apart. The proportion of predicted GFR differing from inulin clearance by +/- 10 mL/min/1.73 m2, ranged from 34% for the Jelliffe formula to 53% for the Nankivell's one. CONCLUSION: None of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement.