Accuracy and Limitations of Equations for Predicting the Glomerular Filtration Rate during Follow-up of Patients with Non-diabetic Nephropathies

Guy Rostoker; Pierre Andrivet; Isabelle Pham; Mireille Griuncelli; Serge Adnot

Disclosures

BMC Nephrology 

In This Article

Methods

Study Population

We recently reported a cross-sectional investigation in which we prospectively studied 269 European adults with chronic renal disease (260 with non diabetic nephropathies and 9 with diabetes mellitus).[4] We also conducted a longitudinally study of 126 patients of this cohort. These patients had non-diabetic nephropahies (mainly glomerular diseases) and had repeated measures of their GFR by inulin clearance during long-term follow-up. A total of 452 inulin clearance assays were carried out in these patients. All the patients gave their informed consent to the study, which was approved by the local ethics committee.

Basing on inulin clearance, the patients were divided into two subgroups: patients whose renal function deteriorated during follow-up (n = 65) and patients whose renal function improved (n = 61).

The subgroup of patients whose renal function deteriorated during follow-up comprised 51 men and 14 with a median age of 37 years (range 20–65 y). Twenty-four patients had primary IgA nephropathy, 13 had idiopathic membranous nephropathy, 7 had an idiopathic nephrotic syndrome, 3 had mesangioproliferative glomerulonephritis, 9 had systemic diseases (Henoch-Schönlein purpura: 4; lupus erythematosus: 2; primary sicca syndrome: 2; ANCA vasculitis:1), 5 had hereditary nephritis (1 polycystic renal disease, 1 Alport syndrome; 1 sickle cell anemia, 2 miscellaneous) and 4 had inherited or acquired urologic abnormalities of the kidneys, with no repercussions on bladder voiding.

The subgroup of patients whose renal function improved during follow-up comprised 39 men and 22 women with a median age of 43 years (range 17–69 y). Nineteen patients had primary IgA nephropathy, 9 had idiopathic membranous nephropathy, 11 had an idiopathic nephrotic syndrome, 2 had mesangioproliferative glomerulonephritis, 2 had crescentic glomerulonephritis, 7 had systemic diseases (lupus erythematosus: 4; Behçet disease: 1; systemic sclerosis: 1, Atkinson-Clarkson syndrome 1), 2 had hypertensive nephritis (nephroangiosclerosis), 3 had hereditary nephritis (1 polycystic renal disease, 1 thin glomerular membrane disease, 1 Fabry disease) and 6 had inherited or acquired urologic abnormalities of the kidneys with no repercussions on bladder voiding.

GFR Measurements

GFR was measured in each patient by using the reference inulin method (GFR-inulin) at the Physiology Department of Henri Mondor University Hospital as previously reported.[5] Briefly, an intravenous catheter was inserted into an arm and used to draw blood samples for inulin clearance measurement. The height and body weight of the patient were recorded prior to an oral water load (8 ml/kg body weight). The patient was then placed in the supine position. A priming dose of inulin (Inutest: Fresenius Pharma, Linz, Austria), 0.12 mL/kg body weight of a 25% solution diluted in 130 mL of isotonic mannitol solution, was infused intravenously (10 mL/min) into the other arm. Then a continuous infusion of Inutest 25% (0.32 mL/kg body weight) diluted in 250 mL of isotonic mannitol solution was given at a rate of 0.9 mL/min. After a 90-minute equilibration period, the bladder was emptied and urine was collected for two 30-minute periods. For inulin measurement, urine was deproteinized, the polymer was hydrolyzed with hydrochloric acid, and a colorimetric assay based on the Galli and Jeanmaire technique was performed. The first blood sample, taken before the infusions, was used as a blank. GFR was calculated as the arithmetic mean of the GFR values obtained during the two periods of urine collection. GFR-inulin data were corrected for a standard body surface area of 1.73 m2.

Creatinine was measured in the first blood sample, taken before the inulin infusions, using a modified Jaffe method (Randox reagent; Bayer, Montpellier, France).

In each patient the GFR was also estimated from the serum creatinine concentration by using the Cockcroft and Gault equation, as follows:

With the results multiplied by 0.85 for females; where age is in years, weight in kg and serum creatinine in micromol/L.[2,3]

GFR was also estimated with a modified Cockcroft and Gault formula taking body surface area (BSA) into account, as follows:[4]

The body surface area was calculated with the Dubois and Dubois equation[13]

The following abbreviated MDRD equation was used [5]

Mayo clinic Quadratic equation [6] =

serum creatinine is expressed in mg/dl; if SCr < 0.8 mg/dl, use 0.8 for SCr

Statistical Analyses

As inulin clearance and GFR estimates were normally distributedin the overall population, we used repeated-measures analysis of variance with the Dunnet multiple comparisons test as post-test (Instat 3, GraphPad, San Diego USA). Correlations among the five GFR methods were studied by using the Pearson linear coefficient of correlation and coefficient of determination (Instat 3, GraphPad, San Diego USA). Paired comparisons of inulin clearance were performed with the paired t test, whereas paired comparison of creatinine used the Wilcoxon test (Instat 3, GraphPad, San Diego USA). The accuracy of the GFR estimates in the whole group was assessed in terms of the proportion of predicted values falling within 10%, 30% and 50% of the true GFR measured by inulin clearance.

In each of the two study subgroups (patients whose renal function deteriorated and those whose renal function improved), the annual slope of GFR (change in GFR in ml/min/1.73 m2/year) was used, as advocated by Fontseré and coworkers,[11] to assess the variability of the prediction equations compared with the inulin method during follow-up. The annual GFR slope was determined for each GFR-inulin and with each prediction equation as the loss or gain in the glomerular filtration rate during the study period, with respect to baseline values at the start of follow-up, and standardized for 12 months.[11]

As the values did not have a Gaussian distribution in the Kolmogorov and Smirnov test;[14] (Instat 3, GraphPad, San Diego USA), we used the non parametric repeated-measure analysis of variance (Friedman Test) with the Dunn's multiple comparisons test as post-test to compare the five GFR methods for determining the annual slope[14] (Instat 3, GraphPad, San Diego USA). P values < 0.05 were considered significant.[14] Correlations among the four GFR methods for determining the slope were studied with Spearman's rank-order correlation coefficient.[14] We then performed a concordance study as described by Bland and Altman, in which the differences between the methods are plotted against their mean values[15] (Prism 4, GraphPad, San Diego USA). The ability of a creatinine-based equation to properly categorize the trend in GFR was defined as the proportion of patients defined by the inulin clearance as having either improved or deteriorated renal function and who were correctly identified as such by the GFR estimate. The proportions of correctly categorized patients were compared by using the X2 test[14] (Instat 3, GraphPad, San Diego USA). The characteristics of the patients were analyzed using either analysis of variance (parametric or non parametric according to the Gaussian distribution), a t test or the X2 test. Finally, we used receiver-operator characteristic (ROC) curves to examine the ability of the estimates to discriminate progressors from improvers (Prism 4 software, Graphpad, San Diego, USA). Values in the text and tables are means ± SD or medians and ranges, depending on the normality of the distribution.

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