An Overview of Chronic Kidney Disease and Useful Strategies for Clinical Management

Introduction

The kidneys, located in the retroperitoneal space in the abdomen, are vital for patient health. They process several hundred liters of fluid a day and remove around two liters of waste products from the bloodstream. The volume of fluid that passes though the kidneys each minute is closely linked to cardiac output, and kidney function is a major issue for cath lab practitioners. The kidneys maintain the body’s balance of water and concentration of minerals such as sodium, potassium, and phosphorus in blood and remove waste by-products from the blood after digestion, muscle activity and exposure to chemicals or medications.¹ They also produce renin which helps regulate blood pressure, produce erythropoietin which stimulates red blood cell production, and produce an active form of vitamin D, needed for bone health.¹

Therefore, when working in the cardiac cath lab, it is essential to perform proper pre-procedural workups and assess patients for risk factors that may be associated with kidney disease. A crucial aspect of patient care is protecting the kidneys from contrast-induced nephropathy and acute renal failure that may be irreversible. While the probability of this occurring is usually very low, there are patients who are at a significantly increased risk of renal impairment after having a cardiac catheterization. Most of these patents have a disease process known as chronic kidney disease (CKD). 

In the United States, chronic kidney disease (CKD) is a national health crisis, and is commonly found in patients with diabetes, hypertension, coronary artery disease, or combinations of these factors. More than 20 million Americans over 20 years old have CKD and another 547,982 U.S. residents are currently under treatment for end-stage renal disease.² CKD is a serious condition associated with premature mortality, decreased quality of life, and increased health-care expenditures. Untreated CKD can result in end-stage renal disease, and necessitate dialysis or kidney transplantation. Since the risk factors for CKD include cardiovascular disease, diabetes, hypertension, and obesity³, CKD patients profile for coronary artery disease and are frequently seen in the cath lab. The number of patients with CKD is also rising as more American adults are obese and sedentary, and are developing Type II diabetes, cardiovascular disease and hypertension. Therefore, it is important to have as much knowledge as possible when working with these patients.

In contrast-based radiology, like computed tomography and cardiac catheterization, the number of patients who develop contrast-induced nephropathy after procedures is significantly larger in populations that have CKD and diabetes or hypertension. This requires staff awareness in obtaining pre-procedural lab work-ups, understanding patient co-morbidities, and promoting aggressive and effective strategies to prevent or minimize serious complications. CKD complicates cardiac catheterization and increases the likelihood of post-procedural events. While vascular access-related issues are the primary source of post-procedural complications, contrast-induced nephropathy is one of the more common major adverse events following a cardiac cath, and needs to be closely monitored and understood. Contrast-induced nephropathy onset can also be delayed by hours or days, making patient follow-up an important issue for CKD patients.

Evaluating kidney function

CKD slowly gets worse over time and is routinely recognized in five stages. In the early stages, CKD is usually asymptomatic, and develops over many years. It can progress so slowly that symptoms do not appear until kidney function is less than one-tenth of normal.⁴ The end result of CKD progression is end-stage renal disease, and either dialysis or kidney transplant. Because of the slow developing, asymptomatic nature of CKD, patients need to have their renal function assessed pre-cath, especially if they have diabetes, hypertension, known cardiovascular disease, and/or other risk factors for CKD.

CKD is defined according to the presence or absence of kidney damage and level of kidney function — irrespective of the type of kidney disease (diagnosis). Among individuals with CKD, the stages are defined according to kidney function.5 According to renal societies and government health agencies like the National Kidney Foundation and the National Institutes of Health, there are five stages of CKD:

• Stage 1: Kidney damage with normal or increased glomerular filtration rate (GFR)  (> 90 mL/min/1.73m²)
• Stage 2: Mild reduction in GFR (60-89 mL/min/1.73m²)
• Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73m²)
• Stage 4: Severe reduction in GFR (15-29 mL/min/1.73m²)
• Stage 5: Kidney failure  (GFR < 15 mL/min/1.73m² or dialysis)^5,6

Since CKD in stages 1-3 is often asymptomatic, patients may have already suffered kidney damage as a result of the advancement of disease. The best way to prevent and treat CKD is through regular physical exams, management of co-morbidities, regular blood pressure and blood glucose tests, renal function tests, and other clinical evaluations, as necessary. It is also important to understand that there is no cure for CKD. Once it is identified, the best treatment for CKD is routine care and medical management.

In the cardiac cath lab, since many patients may be outpatients, secondary referrals, transfers or emergencies, the pre-cath consent and evaluation may be the first contact that the cath lab staff has with the patient. Routine lab assessments, including blood urea nitrogen (BUN) and creatinine, should be considered for these patients, especially for those who have risk factors for CKD. They provide vital, inexpensive screening information. However, to fully assess renal function and understand the progression of CKD, these results need to be augmented with an estimated glomerular filtration rate (eGFR). This is because eGFR takes important variables into consideration that may include race, sex, age, creatinine and weight. This is important, because a person with a serum creatinine of 1.2 who is 40 years old may have an eGFR >60, while a fragile octogenarian may have the same creatinine and an eGFR of <40.

An eGFR should be the gold standard in the clinical lab and the cath lab for measuring renal function and defining the stage of kidney disease. Because eGFR is defined by comprehensive criteria, it is a more reliable predictor of renal function. It is important to note that serum creatinine alone should NOT be used as a measure of kidney function, especially for patients who are high risk, elderly, or in need of large contrast doses and anti-coagulation. All clinical laboratories should report an estimate of GFR alongside a measurement of serum creatinine. In clinical laboratories without the ability to automatically incorporate race into the Modification of Diet in Renal Disease study (MDRD) calculation, adjusted values for race should be determined (multiply by 1.21 for African-Americans)⁷ and cath lab personnel should know how to hand-calculate an eGFR.

In order to determine eGFR, there are numerous formulas and guidelines available. The most commonly used ones in cath lab practice are the MDRD and Cockcroft-Gault formulas. The MDRD study equation has many advantages, because it is more accurate and precise than the Cockcroft-Gault equation for persons with a GFR < approximately 90 mL/min per 1.73m², predicts GFR as measured by using an accepted method (urinary clearance of I-iothalamate), was developed on a large (n > 1,000) database containing persons with various kidney diseases, and was tested on a validation database containing more than 500 additional patients.⁸ However, the Cockcroft-Gault formula is frequently used in the cath lab, is acceptable for evaluating renal function, and is used to calculate dosing of anti-coagulation therapies such as anti-thrombin or glycoprotein IIb/IIIa drugs during cardiac cath if an MDRD GFR is not available. The two most common eGFR formulas are:

• MDRD GFR: GFR (mL/min/1.73 m²) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American) (conventional units)⁹
• The Cockcroft-Gault eGFR formula: Cockcroft-Gault GFR = (140-age) x (Wt in kg) x (0.85 if female) / (72 x Cr)¹⁰

Recently, at our own facility, the value of assessing a patient’s renal function via eGFR was clearly demonstrated when performing a catheterization and intervention on a patient. The patient was 82 years old and had a history of coronary artery disease and renal artery stenosis. Serum creatinine was 1.67, but the Cockcroft-Gault eGFR revealed an eGFR of 18 mL/min/1.73m². This patient, in stage 4 CKD, was well managed with hydration of 0.9 normal saline at 75cc/hr upon arrival to the hospital. It was continued through the procedure and 6 hours post-cath. The patient had ventricular function assessed at the beginning of the cath to ensure that the left ventricular end diastolic pressure (LVEDP) could tolerate this fluid challenge. The patient had continuous urine output, which was monitored throughout the admission period. In the first 24 hours post cath, the patient had a urine output of > 2000ccs. The patient also received the renal dosing for bivalirudin, further aiding in patient management and in obtaining hemostasis post cath. Serum creatinine actually declined to 1.5 the day after the procedure and the patient was discharged without complications.

What is contrast-induced nephropathy and acute renal failure?

For clinical and research purposes, contrast-induced nephropathy is defined as:

• An acute decline in renal function;
• An increase in the serum creatinine value (≥ 0.5 mg/dL, ≥ 25%, or both);
• Or a diminution of renal function, identified by a decrease in creatinine clearance or the GFR 2-3 days after contrast medium exposure.

Serum creatinine levels peak in 3-5 days, and renal function returns to baseline in 7-21 days.^11,12 The incidence of contrast-induced acute kidney injury/contrast-induced nephropathy is low (2%) in the general population, but it is higher in certain groups. Patients who have both CKD and diabetes mellitus, for instance, are at highest risk and the incidence of contrast-induced acute kidney injury/contrast-induced nephropathy is as high as 50% for patients with multiple risk factors.¹³ While contrast-induced nephropathy usually resolves, it can become permanent and cause a patient to develop end stage renal disease. This requires dialysis or renal transplant, and can also reduce patient life expectancy, cause significant and dangerous electrolyte imbalances, leave residual damage to the kidneys after resolution of contrast-induced nephropathy, and cause other major medical issues.

Acute kidney injury associated with administration of iodinated contrast media is the third most-common cause of renal failure in hospitalized patients. The number of patients at risk for contrast-induced nephropathy has been increasing, due to an increased incidence of CKD, increasing numbers of diabetics, and those with predisposition for kidney disease in an expanding elderly population.14 In addition, as more contrast-based medical imaging and intervention is performed, including cardiac catheterizations and computed tomography scans, contrast-induced nephropathy and acute renal failure incidents in the hospital setting are increasing. Since acute renal failure after coronary intervention is associated with a 36% in-hospital mortality rate and a 19% two-year survival rate15, proper screening and precautions can have a major impact on patient outcomes.

Clinical trials and research data

In the past several years, important research has helped clarify treatment strategies for patients that have CKD. The purpose of these strategies is to prevent or minimize CKD, and to make imaging studies as safe as possible. Key research has studied the use of different contrast media, N-acetylcysteine, sodium bicarbonate, saline, and the use of fluid replacement and contrast assist devices. Findings offer options to improve outcomes, but the ability to fully prevent contrast-induced nephropathy has not yet been uncovered.

The PREDICT study, a key trial looking at contrast media, suggested that there is no difference between iopamidol 370 and iodixanol 320, two contrast media, in preventing the incidence of contrast-induced nephropathy in patients with diabetes and CKD.¹² PREDICT supports the results of earlier published studies such as IMPACT^12a and CARE^12b, and suggests that all non-ionic contrast agents are essentially the same as far as contrast-induced nephropathy incidents post contrast-based imaging.  

However, a recent study of a large trial group in China suggests that contrast-induced nephropathy can be significantly reduced in elderly populations by using iodixanol (Visipaque, GE Medical). Results from the largest comparative, randomized clinical trial to date of patients at risk for contrast-induced nephropathy demonstrated that iodixanol was associated with an eight times lower rate of contrast-induced nephropathy in high-risk elderly patients when compared with low-osmolar iopromide, another commonly used contrast medium. Since elderly patients have diminished baseline eGFR, this may be a significant finding.¹⁶ 

Another important trial, ACT, indicated that N-acetylcysteine does not reduce the risk of contrast-induced nephropathy or other clinically relevant outcomes in patients undergoing coronary and vascular angiography, based on trial data presented at the 2010 American Heart Association (AHA) Scientific Sessions.¹⁷ Specifically, ACT findings do not support routine prophylactic administration of oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy in chronic renal insufficiency patients undergoing coronary angiography.¹⁸ This is an important finding, as N-acetylcysteine had been considered as an important adjunct therapy for prevention of contrast-induced nephropathy.

Sodium bicarbonate-based hydration is another pharmacologic therapy that is used in cath labs, but with conflicting data about its effectiveness. For instance, sodium bicarbonate-based hydration was found to be superior to normal saline in prevention of contrast-induced nephropathy in one updated meta-analysis. Contrast-induced nephropathy occurred in a total of 109 patients in the 1,327 patients of the sodium bicarbonate arms (range 1.4% to 31.0%) compared with 175 such events in the 1,306 subjects treated with normal saline (range 2.7% to 34.5%).¹⁹ Yet other trials contradict these findings. The MEENA trial looked at two methods of hydration prior to coronary angiography. According to MEENA, 0.9% saline hydration was similar to sodium bicarbonate for the prevention of contrast-induced nephropathy. However, in the REMEDIAL trial, sodium bicarbonate was superior to normal saline alone in preventing contrast-induced nephropathy.²⁰ The ACT II trial has been designed to clarify this issue and results are pending. Findings will have an important impact on the care of CKD patients.

Another trial suggests that the RenalGuard system (PLC Medical Systems) for fluid replacement may have clinical significance for contrast-induced nephropathy patients. The RenalGuard System for IV fluid administration, which matches hydration to urine output, roughly halved the occurrence of contrast-induced acute kidney injury compared with conventional hydration in REMEDIAL II trial.²¹ This data is encouraging, and it raises the question of whether RenalGuard should be used in the management of CKD patients and the prevention of contrast-induced nephropathy.

Hydration therapy, however, remains the cornerstone of contrast-induced nephropathy prevention, and all other treatments are compared against it for effectiveness. According to Renu Bansal, MD, renal perfusion is decreased for up to 20 hours following contrast administration. Intravascular volume expansion through the use of normal saline solution maintains renal blood flow, preserves nitric oxide production, prevents medullary hypoxemia, and enhances contrast elimination. Furthermore, the Contrast-Induced Nephropathy (CIN) Consensus Working Panel found that adequate intravenous volume expansion with isotonic crystalloids (1-1.5 mL/kg/h), 3-12 hours before the procedure and continued for 6-24 hours afterward, decreases the incidence of contrast-induced nephropathy in patients at risk.²² This is well supported in the literature, and also offers important considerations for patients with CKD who come to the cath lab as outpatients.

As increasing numbers of cath lab patients are seen electively as outpatients, care and management is also changing. For instance, 24-hour IV hydration with saline is highly effective in the prevention of contrast-induced nephropathy, but economic pressures have increased the number of cardiac catheterizations performed on the day of hospital admission. Therefore, an outpatient oral pre-catheterization volume supplementation strategy has enormous appeal.²³ As outpatients are highly unlikely to undergo emergency bypass surgery, judicious oral hydration strategies can be very effective for CKD management.²⁴ Being NPO (nothing by mouth) after midnight, for instance, doesn’t mean that fluid intake needs to be completely restricted.

One effective strategy for minimizing contrast usage in personal practice has been the use of the ACIST contrast injection system (ACIST Medical Systems). The ACIST device was studied to see if it has a significant impact on contrast-induced nephropathy, as well as reducing contrast usage. A retrospective, observational study was conducted involving 2,175 patients from April 2002 through November 2004 who underwent coronary catheterizations and percutaneous coronary intervention procedures at Wake Forest University Baptist Medical Center in North Carolina. Data were compared between patients undergoing traditional hand injection methods (n=1,798) and those who were treated using the ACIST variable-rate, automated contrast injection method (n= 377) to reduce contrast volumes, in conjunction with contemporary strategies of hydration and N-acetylcysteine use. It was found that the use of the ACIST device to reduce contrast volume in conjunction with strategies to minimize contrast-induced nephropathy resulted in a 28% reduction in contrast volume, a 31% lower incidence of contrast-induced nephropathy, and a 49% lower incidence of acute renal failure, when compared to traditional hand injection methods.²⁵

CKD and contrast-induced nephropathy treatments are being aggressively studied, as CKD is a serious issue, not only in the cath lab, but also in critical care areas and with surgical procedures. The objective of the cath lab is to use the best practices available, as dictated by solid research, and to use all of the assets of the lab and hospital to promote an integrated plan that involves the pre and post care areas. It also requires educating patients and optimizing the treatment of co-morbidities that contribute to CKD and contrast-induced nephropathy.

So, when working with CKD patients, what are specific treatments and strategies that work to prevent or minimize CIN?

1. Whenever possible, do non-contrast workups first. Non-invasive imaging and tests can help the physician isolate areas of interest and potential culprit lesions. They can either eliminate the need for catheterization, or promote better strategic and tactical approaches to the diagnostic and interventional phases of the procedure.
2. For diabetics, hypertensives, and other patients who are high risk for CKD, or who have known CKD or end-stage renal disease, assess BUN, creatinine, and eGFR pre-catheterization. Other labs, as determined by patient profile or patient care guidelines, may also provide important information regarding risks to the patient.
3. Hydration with intravenous normal saline has consistently been shown to prevent or ameliorate contrast-induced renal impairment in patients with and without existing renal dysfunction. Hydration prevents contrast-induced nephropathy by ameliorating the effect of contrast agents.²⁰ Hydration is highly effective, and should not be underestimated or underused as a front-line treatment for CKD/contrast-induced nephropathy.

While ACT II is currently assessing the use of sodium bi-carbonate solution to reduce contrast-induced nephropathy, hydration is the gold standard. For outpatients with CKD, oral hydration should be considered and encouraged the day before arrival. Intravenous hydration should be started on admission, and continued post cath, according to physician recommendations. When working with CKD patients, do not be shy about asking the physician to consider hydration, especially if lab values identify CKD before catheterization. 

4. For patients with known CKD, perform left ventricular and left ventricular (LV) end diastolic pressure measurements, pre-contrast injection. If the LV function is normal, then hydration can be used to promote a safer procedure.
5. Use technology to your advantage. Consider the use of a mechanical injection device like the ACIST, which has been proven in a large clinical trial to significantly reduce contrast loads and contrast-induced nephropathy. This is particularly true in interventions, where frequent “puffs” of contrast can turn into surprisingly high volumes. Bi-plane imaging can reduce contrast loads by 50% and aids in the process of conforming to the CIN panel recommendations on contrast usage. With bi-plane imaging, we have been able to perform dozens of cases on patients with serum creatinine >2.0 or reduced eGFR, and use less than 25 ccs of contrast to make a diagnosis. Other technology, such as last image hold and last fluoro save can also reduce contrast usage.
6. Consider staging the procedure if a CKD patient is stable or has complex, non-surgical disease. Numerous studies have shown that the volume of contrast is a risk factor for contrast-induced nephropathy. The mean contrast volume is higher in patients with contrast-induced nephropathy, and most multivariate analyses have shown that contrast volume is an independent predictor of contrast-induced acute kidney injury. As a general rule, the volume of contrast received should not exceed twice the baseline level of eGFR, so patients with significant CKD should receive < 30 mL of contrast for diagnosis, and less than100 mL for interventions.²⁶
7. For octogenarians, consider iodixanol. Octogenarians have much higher morbidity and mortality rates than the general population, especially after major complications like CIN. Since they are becoming a larger percentage of the cath lab population, they need to be treated with special care. 
8. Consider overnight admission, post cath, to aggressively hydrate patients with advanced CKD, as they may take 24 hours or more to manifest signs and symptoms of contrast-induced nephropathy.
9. Educate cath lab patients about their CKD, especially those in high-risk groups. Invest them in the process, and teach them about warning signs of contrast-induced nephropathy and severe renal disease.
10. Conduct regular internal and external quality assurance follow-ups to track CIN and other complication rates. Knowledge is a vital tool in promoting the best outcomes for patients. Be diligent with internal reporting, and regularly meet and debrief about complications when they occur. It is also useful to be part of a national registry like the American College of Cardiology’s National Cardiovascular Data Registry (ACC-NCDR). It is not only useful for reporting complications and broad-based patient care trends, but creates a culture that works to understand patient outcomes, improve them, and identify critical trends in institutional performance.
11. In patients having acute coronary syndrome (ACS)/ST-elevation myocardial infarction (STEMI),  pre-PCI hydration can reduce the risk of contrast-induced kidney damage, when compared with groups that received either subsequent or no hydration. Early hydration had a significant impact on preserving kidney function in a STEMI group of 450 patients that received early hydration versus groups who received no hydration or post-procedural hydration. There were half the number of creatinine elevations > 25%, and eGFR decreases of > 25% in the group who received early hydration as part of their STEMI care.²⁷ There was also evidence of better in-hospital survival rates in the group who received early hydration. While nothing should interfere with emergency revascularization, there still needs to be emphasis placed on total patient care. 
12. Don’t be complacent when working with end-stage renal disease patients on hemodialysis. The volumes of both oral fluids, maintenance IVs, procedural flushing, and contrast should be included in the fluid intake of dialysis patients. Therefore, while the kidneys can’t be injured in a chronic dialysis patient, fluid overload needs to be considered, especially when high volumes of contrast need to be used.

Conclusion

Chronic kidney disease is a major medical issue that requires high-caliber care and expert patient management in the pre-, peri- and post-cath lab settings. Complications of contrast-induced nephropathy include renal failure that may require dialysis, and it is suspected of increasing short- and long-term morbidity and mortality rates. This is especially true in patients with diabetes and hypertension. Therefore, patients with risk factors for CKD should be worked up thoroughly pre-cath, and managed with hydration and other appropriate medical strategies. Contrast should be avoided or minimized to make a diagnosis for this patient group, but they are likely to fit the classic profile for coronary artery disease. Thus, we can expect to frequently work with CKD patients in the cath lab, and need to be proactive and knowledgeable about this select patient population.

Acknowledgements. We wish to thank Christine Dalin, MT, ASCP, and Roseann Gualtieri, MT, ASCP, from Pennsylvania Hospital’s point of care testing department, for helping us find lab values and other valuable resources that made this paper possible.

The authors can be contacted at richardmerschen@verizon.net.

This article received double-blind peer review from members of the Cath Lab Digest editorial board.

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