November 2010, Volume 60, Issue 11

Original Article

Assessment of Renal insufficiency in patients with normal serum creatinine levels undergoing angiography

Syed Hasnain Mujtaba  ( Department of Cardiology, National Institute of Cardiovascular Diseases, Karachi. )
Tariq Ashraf  ( Department of Cardiology, National Institute of Cardiovascular Diseases, Karachi. )
Sumbal Nasir Mahmood  ( Department of Medicine, Dr. Ziauddin Medical University and Hospital, Karachi. )
Qudsia Anjum  ( Department of Family Medicine, Al-Ahli Hospital, Doha, Qatar. )

Abstract

Objective: To determine the frequency of patients with underlying renal insufficiency having normal serum creatinine level proceeding for coronary angiography.
Methods: A total of 693 patients from September 2009 to February 2010 undergoing diagnostic coronary angiography at the National Institute of Cardiovascular Diseases (NICVD) with normal serum creatinine < 1.5mg/dl were selected. Glomerular filtration rate (GFR) was calculated for each patient using the Cockcroft-Gault (C-G) equation and a GFR < 80ml/min was labeled as renal insufficiency.
Results: The mean age of males was 51.86±10.19 years and 51.52 ± 9.80 years for females. Almost one-third (n=236, 34.1%) of patients had GFR <80ml/min; comparison between male (n=168, 31.2%) and female (n=68, 43.9%) was significant (p-value 0.003). Age group breakdown showed majority of patients (n=196; 83.05%) with GFR <80 ml/min ranged between 40-69 years (p-value 0.001).
Conclusion: This study has shown that most of the patients with normal serum creatinine have abnormal GFR. Serum creatinine, which is considered to be an important screening test in patients with renal impairment, might remain in the normal range despite the renal function being significantly impaired. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range (JPMA 60:915; 2010).

Introduction

The high global burden of cardiovascular disease (CVD) has resulted in a large number of patients requiring cardiac catheterization and percutaneous coronary intervention (PCI). This is particularly relevant to South Asian countries Pakistan, which are in the midst of a CVD epidemic.1 CVD is strongly associated with co-morbid conditions like Diabetes mellitus (DM) and hypertension (HTN), which might affect renal function, leading to a large pool of patients with impaired renal function undergoing angiography or PCI, thereby increasing the risk of Contrast induced nephropathy (CIN).2 The ever expanding use of contrast media-based imaging techniques especially with an aging population and increasing procedural complexity, CIN remains a serious concern for interventional cardiologists.3 Studies have shown that renal insufficiency at baseline is the most important risk factor for CIN.1,4,5 Many physicians rely on serum creatinine (SCr) as a screening test for renal impairment, however SCr levels could remain within the normal range even when normal renal function is significantly impaired.6 In contrast, Glomerular filtration rate (GFR) has been traditionally considered the best overall index of kidney function in health and disease.7 A more accurate approximation of renal function can be obtained using formulae such as the Cockcroft-Gault equation8-11 to calculate GFR from SCr. In a study, it was found that 13.9% of patients with normal SCr levels had substantially abnormal calculated GFR with C-G values < 50ml/min.12 In addition, an estimated 29.9% adult population of urban Pakistan have been reported to have reduced GFR. It is evident that using GFR estimating equations for evaluation of reduced GFR in South Asians would be better.13
Since GFR decreases with increasing age inspite of normal SCr levels, screening patients undergoing coronary angiography with GFR estimating equation like the C-G equation will help identify underlying renal insufficiency and subsequently decrease the risk of CIN.
The objective of this study was to determine the frequency of patients with underlying renal insufficiency having normal serum creatinine level proceeding for coronary angiography.

Patients and Methods

Six hundred ninety three (693) patients with SCr < 1.5 mg/dl who underwent coronary angiography from September 2009 to February 2010 at the National Institute of Cardiovascular Diseases were included in the study.
The only exclusion criterion was not to enroll patients with SCr > 1.5mg/dl. An informed verbal consent was taken from all the patients enrolled. Venous blood sample from each patient was drawn and analyzed on Dimension RXL Max of Dad Behring using modified Jaffe Kinetic reaction method. Patient\'s age was noted and weight in kg was measured using a standard bathroom scale. The Cockcroft-Gault (C-G) equation: (140-age) x (weight in kg) / serum creatinine Cr (mg/dl) x 72 x (0.85 if female) was applied to calculate each patient\'s GFR in ml/min.
The data was entered and analyzed using SPSS version 10.0 (SPSS Inc, Chicago, US). Mean and standard deviation were calculated for continuous variables and frequencies were computed for categorical variables.
Patients having GFR <80ml/min were labeled as having underlying renal insufficiency. Statistical significance was considered at a p-value <0.05.

Results

A total of 693 patients undergoing coronary angiography with SCr < 1.5 mg/dl were included in this study and GFR was calculated for each patient using the C-G equation.
Gender wise distribution, mean and standard deviation for age and weight is shown in (Table-1).

Mean creatinine for males was 0.96±0.20 (mg/dl) and 0.82±0.20 (mg/dl) for females (p= 0.001). Mean GFR for males was 95.12±28.28 (ml/min) and 86.13±27.77 (ml/min) for females (p= 0.001). Overall, 236 (34.1%) patients had a GFR <80ml/min, out of which 168 (31.2%) were males and 68 (43.9%) females (p= 0.003). Age group breakdown showed majority of patients (196; 83.05%) with GFR <80 ranged between 40-69 years (p= 0.001) (Table-2).

As anticipated, correlation of GFR and age showed a decreasing GFR trend with increasing age (p <0.05) (Figure).

Discussion

Renal function is usually assessed by checking SCr because of its simplicity and being economical. However, SCr does not give accurate information about the GFR. In two different studies, a considerable number of patients ranging from 13.9-29.9% have shown to have low GFR with normal SCr.12,13 If SCr alone was to be considered as a marker of renal function, there is a likely chance of missing a significant number of patients who actually have underlying renal insufficiency, who would subsequently develop CIN. For measuring GFR, several formulae have been developed to estimate GFR from SCr considering the patient\'s age, sex and weight. The C-G and MDRD (Modification of Diet in Renal Disease) equations are the most widely used that give a close estimate of the GFR.11 These creatinine-based formulae being cost effective and easy to manage can be a useful tool for identifying patients with underlying renal insufficiency and thus preventing the subsequent development of CIN.
In the present era, where radiological procedures involving contrast agent are being commonly performed in diagnosing CVD, the incidence of CIN is expected to rise, with an existing prevalence of 3.3 to 16.5%.4,14 CIN is an important cause of acute renal failure associated with high morbidity, extended hospital stay and high mortality.4,15,16
The C-G formula has been shown to correlate well with [99mTc] -DTPA measured GFR over the GFR range of 14-100ml/min, with a correlation coefficient of 1.01, r=0.92.17 According to National Kidney Foundation (NKF) guidelines, a GFR of 60-89ml/min indicates renal damage.18 The <80ml/min cutoff was used in this study to label a patient as renal insufficient considering that GFR decreases with increasing age is in accordance with the Baltimore Longitudinal Study.19 Another study revealed that a normal patient with a GFR of 120ml/min at age 30 could still have a GFR of >80ml/min at age 80.20
In Pakistan, a study conducted in 2005 estimated the prevalence of reduced GFR at 29.9% in individuals aged 40 and above which is comparable to our results.13
The present study has some limitations. First, the estimation of abnormal GFR is based on a single measurement of SCr that may not be accurate which might lead to over or under estimating patients with abnormal GFR. Secondly, we used calculated GFR and not measured GFR to diagnose renal insufficiency which is not the gold standard.
This study highlighted the importance of measuring GFR in patients undergoing radiological procedures involving the use of contrast agent. Most cardiologists rely on SCr levels being in the normal range and do not calculate the GFR, thus exposing patients with underlying renal insufficiency to high risk of CIN. Whether this specific subgroup is at increased risk of developing CIN or should preventive protocols be applied to them still needs to be established. Nonetheless, it is recommended that calculated GFR instead of SCr be used especially in patients undergoing procedures involving use of radio-contrast agents like coronary angiography.

Acknowledgement

The authors are grateful to Mr Ejaz Alam who helped with the data analysis and Ms Farah Mujtaba for the assistance in entering data and typing the article.

References

1.Jafar TH, Jafary FH, Jessani S, Chaturvedi N. Heart disease epidemic in Pakistan: women and men at equal risk. Am Heart J 2005; 150: 221-6.
2.Uddin MA, Rabbani MA, Jafary FH, Bhatti MA, Islam M. Contrast nephropathy in high-risk patients undergoing coronary angiography and intervention. J Coll Physicians Surg Pak 2005; 15: 791-4.
3.Nikolsky E, Mehran R. Hydration protocols to reduce the incidence of contrast-induced nephropathy. J Invasive Cardiol 2008; 20: 527-38.
4.Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002; 105: 2259-64.
5.Barrett BJ, Parfrey PS, Vavasour HM, McDonald J, Kent G, Hefferton D, et al. Contrast nephropathy in patients with impaired renal function: high versus low osmolar media. Kidney Int 1992; 41: 1274-9.
6.Levey AS, Perrone RD, Madias NE. Serum creatinine and renal function. Annu Rev Med 1988; 39: 465-90.
7.Smith HW. Comparative physiology of the kidney. J Am Med Assoc 1953; 153: 1512-4.
8.Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
9.Campens D, Buntinx F. Selecting the best renal function tests. A meta-analysis of diagnostic studies. Int J Technol Assess Health Care 1997; 13: 343-56..
10.Walser M. Assessing renal function from creatinine measurements in adults with chronic renal failure. Am J Kidney Dis 1998; 32: 23-31.
11.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-70.
12.Duncan L, Heathcote J, Djurdjev O, Levin A. Screening for renal disease using serum creatinine: who are we missing? Nephrol Dial Transplant. 2001; 16: 1042-6.
13.Jafar TH, Schmid CH, Levey AS. Serum creatinine as marker of kidney function in South Asians: a study of reduced GFR in adults in Pakistan. J Am Soc Nephrol 2005; 16: 1413-9.
14.Iakovou I, Dangas G, Mehran R, Lansky AJ, Ashby DT, Fahy M, et al .Impact of gender on the incidence and outcome of contrast-induced nephropathy after percutaneous coronary intervention. J Invasive Cardiol 2003; 15: 18-22.
15.McCullough PA, Wolyn R, Rocher LL, Levin RN, O\'Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997; 103: 368-75.
16.Murphy SW, Barrett BJ, Parfrey PS. Contrast nephropathy. J Am Soc Nephrol 2000; 11: 177-82..
17.Cochran M, St John A. A comparison between estimates of GFR using [99mTc]DTPA clearance and the approximation of Cockcroft and Gault. Aust N Z J Med 1993; 23: 494-7.
18.Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: 137-47.
19.Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33: 278-85.
20.Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem. 1992; 38: 1933-53.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: