Ulf Nyman

Contrast-Medium-Induced Nephropathy Correlated to the Ratio Between Dose in Gram Iodine and Estimated GFR in ml/min

Purpose: To suggest a more precise tool when assessing the risk of contrast-medium-induced nephropathy (CIN), i.e. the ratio between contrast medium (CM) dose expressed in grams of iodine (g-I) and estimated glomerular filtration rate in ml/min (eGFR; based on equations using serum-creatinine (s-Cr), weight, height, age, and/or sex), here named I-dose/GFR ratio. Material and Methods: A Medline search of published CIN investigations reporting mean eGFR and mean dose of low-osmolality CM (LOCM) identified 10 randomized controlled prophylactic and 2 cohort coronary investigations, and 3 randomized and 1 cohort computed tomographic (CT) investigation. From the randomized trials, data were collected only from the placebo or control arms, unless there was no significant difference between the control and test groups. The mean I-dose/GFR ratio of each study was correlated with the mean frequency of CIN-1 (s-Cr rise⩾44.2 µmol/l or ⩾20–25%) and CIN-2 (oliguria or requiring dialysis). A maximum dose according to an I-dose/GFR ratio = 1 in patients with s-Cr ranging from 100 to 300 µmol/l was compared with that of Cigarroas formula and with a “European consensus” threshold published by the European Society of Urogenital Radiology, both using s-Cr alone to predict renal function. McCulloughs formula was used to assess the risk of CIN requiring dialysis at an I-dose/GFR ratio = 1 with LOCM. Results: The coronary investigations revealed a linear correlation with a correlation coefficient between the I-dose/GFR ratio and the frequency of CIN-1 and CIN-2 of 0.91 (P<0.001) and 0.84 (P = 0.001), respectively. At a mean I-dose/GFR ratio = 1, the regression line indicated a 10% risk of CIN-1 and a 1% risk of CIN-2. At a mean I-dose/GFR ratio = 3, the risk of CIN-1 and CIN-2 increased to about 50% and 15%, respectively. Pooled weighted data from the CT investigations revealed a 12% risk of CIN-1 at a mean I-dose/GFR ratio = 1.1 and no cases of CIN-2. The maximum CM dose according to an I-dose/GFR ratio = 1 was about 30–50% of that of both Cigarroas formula and the “European consensus” in elderly low-weight individuals, while it was similar for middle-aged individuals weighing about 90 kg. McCulloughs formula suggests that there will be an exponentially increasing risk of CIN requiring dialysis, but at an I-dose/GFR ratio = 1 and using LOCM it will not exceed 1% until GFR decreases below 30 ml/min in diabetics and below 20 ml/min in non-diabetics. Conclusion: Using the I-dose/GFR ratio may be a more expedient way of improving risk assessment of CIN than todays common practice of estimating CM dose from volume alone and renal function from s-Cr alone. Prospective studies based on individual patient data are encouraged to define the risk of CIN at various I-dose/GFR ratios and correlated to type of CM, examination, risk factors, etc.

Prediction of relative glomerular filtration rate in adults: New improved equations based on Swedish Caucasians and standardized plasma‐creatinine assays

Objective. To evaluate newly developed equations predicting relative glomerular filtration rate (GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease (MDRD) and Mayo Clinic equations using enzymatic and zero‐calibrated plasma creatinine assays. Material and methods. GFR was measured with iohexol clearance adjusted to 1.73 m2. One population sample (n = 436/Lund) was used to derive an equation based on plasma‐creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n = 414/Malmö). The coefficients of the equations were eventually fine‐tuned using all 850 patients and yielding Lund–Malmö equations without (LM) and with LBM‐term (LMLBM). Their performance was compared with the MDRDCC (conventional creatinine calibration), MDRDIDMS (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. Results. The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRDCC resulted in +19.0/+10.2 % median bias, while bias for the other equations was<10 %. LMLBM had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p<0.001) better than for MDRDIDMS (80 %). In men with BMI<20 kg/m2, MDRDIDMS/LM had +46 %/+19 % median bias. MDRDIDMS also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LMLBM equation had<10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR⩾90 mL/min/1.73 m2. Conclusion. The newly developed Lund–Malmö equations for GFR estimation performed better than the MDRDIDMS and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.

Revised equations for estimating glomerular filtration rate based on the Lund-Malmö Study cohort

Abstract Objective. To increase the accuracy of estimated GFR (eGFR) from creatinine overall and at measured GFR ≥90 mL/min per 1.73 m2 by revising the Lund-Malmö (LM) equations, to elaborate on more complex forms to improve the LM and CKD-EPI equations further, and to assess benefits of adding lean body mass (LBM). Material and methods. Swedish Caucasians (n = 850, 376 women; median 60, range 18–95 years) referred for GFR measurement (plasma iohexol-clearance: median 55, range 5–173 mL/min/1.73 m2) constituted the Lund-Malmö Study cohort. Bias, precision, accuracy, expressed as median absolute percentage difference and percentage of estimates ±10% (P10) and ±30% (P30) of measured GFR, and classification ability with respect to five GFR stages were compared with the original LM, CKD-EPI and MDRD equations. Results. LM Revised overall performed better than LM Original without LBM due to increased accuracy at measured GFR ≥90 mL/min/1.73 m2. Further extensions of the CKD-EPI or LM equations did not substantially improve overall performance. In particular, the performance of LM Revised at measured GFR ≥90 mL/min/1.73 m2 could not be improved further without decreasing accuracy and classification ability at lower GFR-levels. Adding LBM to the equations had no strong effect on accuracy. Conclusion. Comparisons with the CKD-EPI and MDRD equations suggest that the LM equations are superior for the present Swedish population, due to markedly higher accuracy of the LM equations at measured GFR <30 mL/min/1.73 m2. However, the LM equations cannot be recommended for use in general clinical practice until validated in other populations.

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

Objective. To determine ‘true’ glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. Material and methods. Twenty healthy volunteers (11 females) with a median age of 27 years (range 19–36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. Results. ‘True’ GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106–129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. Conclusions. Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Preserved Pelvic Circulation after Stent-Graft Treatment of Complex Aortoiliac Artery Aneurysms: A New Approach

Purpose: To describe an endovascular technique that allows stent-graft treatment of aortoiliac aneurysmal disease affecting both common iliac arteries (CIA), with maintenance of pelvic circulation on one side. Technique: For patients with aortoiliac aneurysms, both common femoral arteries (CFA) were surgically exposed. One internal iliac artery (IIA) was initially embolized with coils. A bifurcated stent-graft main body was deployed with the proximal end just below the renal arteries. On the ipsilateral side, the stent-graft limb was extended 3 cm beyond the orifice of the embolized IIA into the external iliac artery (EIA) using stent-graft limb extenders. On the contralateral side, the stent-graft limb was deployed so that the distal end was 10 to 15 mm proximal to the patent IIA orifice. Via a left brachial artery access, the IIA was catheterized, and stent-grafts were deployed from the distal end of the contralateral AAA stent-graft limb into the IIA. A femorofemoral crossover graft provided circulation to the leg ipsilateral to the IIA stent-graft, and the EIA on the same side was ligated. The technique can also be modified to treat isolated bilateral CIA aneurysms. Conclusions: By extending the distal aspect of the stent-graft into an IIA, bilateral CIA aneurysms can be excluded while preserving pelvic circulation on one side.

The CKD-EPI and MDRD equations to estimate GFR. Validation in the Swedish Lund-Malmo Study cohort

Abstract Objective. To compare the recently developed CKD-EPI equation to estimate GFR in adult Swedish-Caucasians with the MDRD equation. Material and methods. Swedish-Caucasians (N = 850, 376 females; median age 60, range 5–95 years) referred for plasma iohexol-clearance (median 55, range 5–223 mL/min/1.73 m2) constituted the Lund-Malmö Study cohort. Bias, precision (interquartile range, IQR, of the differences between estimated and measured GFR), accuracy expressed as percentage of estimates ±10% (P10) and ±30% (P30) of measured GFR, and classification ability for five GFR stages <15, 15–29, 30–59, 60–89 and ≥90 mL/min/1.73 m2 were compared. Results. Overall there were no important differences between the equations; CKD-EPI/MDRD median values of bias +5.4%/+3.4%, IQR both 14 mL/min/1.73 m2, P10 36%/34%, P30 both 80%, and correctly classified GFR stages 68%/67%. P30 for the CKD-EPI equation was substantially higher than for MDRD at GFR ≥90 mL/min/1.73 m2 (93% versus 79%). The MDRD equation performed better in the GFR interval 30–89 mL/min/1.73 m2, while accuracy was limited for both equations at GFR <30 mL/min/1.73 m2 (P30 <75% in both females and males). The CKD-EPI/MDRD equations caused a +22%/+14% bias in the 18–39 year interval and the MDRD equation a +18% bias ≥80 years. Both equations performed poorly in males with BMI <20 kg/m2 (CKD-EPI/MDRD median bias +36%/46%). Conclusion. Overall the recently developed CKD-EPI equation performed well but was not superior to the MDRD equation. The CKD-EPI equation may be preferred in screenings of general populations and in the elderly. None of the equations appeared reliable among patients with markedly decreased GFR, young adults and underweight males.

Different equations to combine creatinine and cystatin C to predict GFR. Arithmetic mean of existing equations performs as well as complex combinations

Abstract Purpose: To test various ways of combining creatinine and cystatin C in equations to predict glomerular filtration rate (GFR). Material and methods: Performance of the following expressions to predict GFR was compared with measured GFR (iohexol clearance, mL/min/1.73 m2) in 857 patients: (i) Lund-Malmö creatinine equation, (ii) Grubb cystatin C equation, (iii) arithmetic mean of (1) and (2), (iv) geometric mean of (1) and (2), (v) linear regression on (1) and (2), (vi) regression on (1) and cystatin C, and (vii) regression on creatinine, cystatin C, age and gender. Results: For the entire cohort median percent error (bias) was <5% for all expressions, though all expressions tended to underestimate (−8.3 to 15.8%) GFR at levels ≥90 mL/min/1.73 m2. The five expressions combining creatinine and cystatin C significantly improved correlation and accuracy (p<0.001) within 15 and 30% of measured GFR compared with the equations based on the separate analytes and with no significant difference between the five expressions. In a subgroup of patients with neurological disease and muscle atrophy the cystatin C equation performed better than the expressions combining creatinine and cystatin C. Conclusion: Simply calculating the arithmetic mean of predicted GFR based on separate creatinine and cystatin C equations performs equally well as more complex equations. Reporting GFR based on separate creatinine and cystatin C equations, and their arithmetic mean also has the definite advantage that the physician can choose the estimated GFR, most appropriate depending on the clinical setting and patient characteristics.

Standardization of p-creatinine assays and use of lean body mass allow improved prediction of calculated glomerular filtration rate in adults: A new equation

Objective. To evaluate the Cockcroft–Gault (CG) equation, using various body weight expressions, and the Sawyer equation in predicting glomerular filtration rate (GFR) using an enzymatic and zero‐calibrated Jaffe plasma‐creatinine assay, and to derive a new robust equation in adults. Material and methods. The CG weight measures included total, ideal and adjusted body weight (ABW; lowest of total and ideal) and two lean body mass (LBM) expressions, while the Sawyer equation is based primarily on LBM. Iohexol clearance was used to measure GFR. One derivation set (n = 436; enzymatic assay) was used to evaluate and bias‐adjust existing equations when indicated, and to derive a new equation based on plasma‐creatinine, age, gender and the body weight measure yielding the best adjusted R2. All equations were then validated in a separate set (n = 414; Jaffe assay). Results. The existing equations all performed similarly in both sets. Prediction errors of equations based on LBM showed no correlation with BMI. The CGABW and Sawyer equations performed best. The new equation with LBM yielded the highest adjusted R2. In the combined set (n = 850), its accuracy (86 %/98 % of estimates within 30 %/50 % of measured GFR) was significantly better than for the CGABW (79 %/95 %) and Sawyer equations (79 %/93 %) (p<0.001) for each 30 mL/min GFR subgroup within ±30 % and ±50 %, except within ±30 % >120 mL/min. Prediction error did not correlate with BMI, age or gender. Conclusion. A new creatinine‐based equation derived in a mainly Caucasian patient sample is a better predictor of GFR than CG‐type equations irrespective of the body weight measure used or, if bias‐adjusted, when using zero‐calibrated creatinine assays.

Nephrotoxicity after renal angiography using iodine and gadolinium contrast media in pigs with renal damage

Iodine contrast medium (I-CM) induced nephrotoxicity is recognized for many years and is especially frequent in patients with pre-existing renal insufficiency alone or combined with diabetes mellitus. The use of non-ionic low osmolar contrast media (LOCM) has reduced the risk of renal injury after X-ray arteriography in patients with renal impairment (1). The importance of nephrotoxicity may increase in the future, due to an anticipated higher number of examinations of elderly subjects, who often have impaired renal function. Furthermore, interventional radiology uses large doses of contrast media (CM). These risk factors make it necessary to adopt some strategies to overcome the problems with nephrotoxicity associated with CM administration in patients with renal damage, for instance the use of non-ionic LOCM (1) and adequate

Validation of a new plasma cystatin C-based formula and the Modification of Diet in Renal Disease creatinine-based formula for determination of glomerular filtration rate

Objective. New proposed definitions of chronic kidney disease necessitate the development and use of simple and accurate methods for estimating glomerular filtration rate (GFR). Plasma cystatin C has been shown to be a more reliable GFR marker than creatinine and formulae for estimating GFR have been reported. The purpose of this study was to validate a cystatin C-based GFR prediction equation in a different population from the derivation set but using the cystatin C assay of a single laboratory, and to compare the results with that of the creatinine-based Modification of Diet in Renal Disease (MDRD) Study equation. Material and methods. A newly presented formula based on plasma cystatin C and gender and the MDRD formula based on creatinine for estimation of GFR were validated in an unselective patient material. Single sample iohexol clearance was used as the GFR reference method in 406 consecutive patients with GFR varying from normal to poor renal function. The creatinine assay used was standardized to express true plasma creatinine. Results. Median bias (1.1%) and accuracy (79.1% of the estimates within ±30% of iohexol clearance) of the cystatin C formula were close to the derivation set. The accuracy was significantly higher than that of the original four-variable MDRD equation (73.2%; median bias 9.8%). However, the accuracy did not differ significantly from that of the re-expressed MDRD formula (79.6%; median bias 3.2%) based on true creatinine. Both formulae performed with a low bias and acceptable accuracy up to a GFR of 90 ml/min/1.73 m2. Conclusions. GFR estimation based on plasma cystatin C performed equally well in the validation as in the derivation set, and was as accurate as the re-expressed MDRD creatinine-based equation.