Renal Disease
6.1 Chronic Kidney Disease
Jeanna Blitz
DEFINITION AND STAGING
Chronic kidney disease (CKD) is defined as the presence of a marker of kidney damage, such as proteinuria on spot urine testing or a decreased glomerular filtration rate (GFR) to <60 mL/min/1.73 m2 for ≥3 months (1). A reduction in GFR to <60 mL/min/1.73 m2 represents loss of half or more of the adult level of normal kidney function. In adults, the estimated GFR (eGFR) is calculated using either the modified diet in renal disease or Cockcroft-Gault equations and is commonly included in the results report of a basic metabolic panel.
CKD is divided into stages to indicate the severity of renal impairment (Table 6.1). Note that stage 3 is further divided into stages 3a (GFR of 45 to 59 mL/min/1.73 m2) and 3b (GFR of 30 to 44 mL/min/1.73 m2) in order to reflect the sharp increase in morbidity and mortality that occurs between these GFR ranges (1). The presence and degree of albuminuria on a spot urine sample is now included in the staging scheme to provide more precise classification and more accurate prognostic information (Table 6.1). Estimated GFR and albuminuria should be reassessed at least annually in patients with CKD; however slight fluctuations in GFR are common and are not necessarily indicative of disease progression.
INCIDENCE AND PREVALENCE OF CKD
The incidence of CKD in the United States is rising; the Center for Disease Control projects that more than half of the adults in the United States will develop CKD in their lifetime (2). The incidence is increasing most rapidly in patients ≥65 years of age. This is likely due to an increase in the incidence of diseases responsible for CKD, such as hypertension and diabetes. Approximately 23 million adults in the United States have CKD, with millions more at risk. Individuals with CKD are up to 40 times more likely to die of CKD-related comorbidities than to reach end-stage renal disease (ESRD).
TABLE 6.1 Prognosis of Chronic Kidney Disease by Glomerular Filtration Rate and Albuminuria Categories | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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IMPACT ON PERIOPERATIVE MORBIDITY AND MORTALITY
CKD has long been recognized as an independent predictor of major adverse cardiac events (3) and is incorporated into many perioperative risk calculators (4,5,6). There is a graded relationship between preoperative eGFR and postoperative morbidity and mortality. Even early stages of CKD are independently associated with an increased 30-day mortality and morbidity after surgery, including a two- to fivefold greater risk of death and cardiac complications after elective, noncardiac surgery compared to patients with normal renal function. There is an established association between CKD and noncardiac adverse perioperative events, including AKI, cerebrovascular events, and increased hospital length of stay (7,8). All-cause perioperative mortality rates in patients with CKD range from 1% to
4%. In patients who undergo cardiac surgery, the estimated mortality rates are 10% to 20%. Increased levels of inflammatory markers in CKD and a strong association with other significant comorbidities, such as hypertension, hyperlipidemia, diabetes mellitus, and cardiovascular disease, may explain why CKD acts as a “risk multiplier” for morbidity, mortality, and cost in the perioperative period (Table 6.2).
4%. In patients who undergo cardiac surgery, the estimated mortality rates are 10% to 20%. Increased levels of inflammatory markers in CKD and a strong association with other significant comorbidities, such as hypertension, hyperlipidemia, diabetes mellitus, and cardiovascular disease, may explain why CKD acts as a “risk multiplier” for morbidity, mortality, and cost in the perioperative period (Table 6.2).
TABLE 6.2 Common Causes of Perioperative Mortality and Morbidity in Patients With CKD | ||||||||||||||
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DIAGNOSIS
While the incidence of CKD is rising, many patients who meet the criteria for CKD have not been formally diagnosed (9). Evidence suggests that CKD is underrecognized by patients and clinicians alike. Awareness of CKD in the US population is particularly low among certain subsets. Patients with hypertension, individuals who identify as non-Hispanic black, and men were reported to be less likely to be aware of their kidney disease (10).
A formal diagnosis of CKD requires confirmation that a reduction in GFR has been present for ≥3 months. Despite the prevalence of CKD and its impact on perioperative morbidity, making a diagnosis of CKD in the preoperative setting may be challenging due to lack of a long-term relationship with the patient or lack of access to longitudinal data. Furthermore, the development of CKD is often asymptomatic. Early stages of CKD may be identified by taking a careful medical history to
screen for risk factors, measuring the patient’s blood pressure, and obtaining routine laboratory studies (Table 6.3).
screen for risk factors, measuring the patient’s blood pressure, and obtaining routine laboratory studies (Table 6.3).
TABLE 6.3 Risk Factors for Susceptibility to CKD | |||||||||||||||||||||||
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PREOPERATIVE EVALUATION AND OPTIMIZATION
Due to the lack of perioperative-specific evidence-based guidelines for optimal management of CKD patients, current guidelines for long-term management of CKD are often extended to the preoperative period (Table 6.4).
TABLE 6.4 Preoperative Assessment and Optimization of Patients at Increased Risk of CKD | |||||||||||||
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SPECIFIC COMORBIDITIES
Hypertension may be the cause or the result of CKD. Poorly controlled hypertension increases the risk of perioperative complications, including major cardiac events. The pathophysiology of hypertension in CKD is complex and multifactorial, including alterations in the regulation of the renin-angiotensin system, aldosterone and sodium, disruption of the sympathetic nervous system, and vascular disease related to atherosclerosis and vascular calcification (11). In advanced CKD, volume overload may contribute to hypertension. Although the SPRINT trial demonstrated significant benefits with lowering systolic blood pressure (BP) to <120 mm Hg, the results are limited to patients with baseline proteinuria of <1 g/day, eGFR >20 mL/min/1.73 m2, nondiabetics, and an ejection fraction >35% (12). Altered vascular physiology in CKD may increase the risk of adverse events, such as AKI or ischemia, if BP is lowered too rapidly or falls below the threshold where autoregulation fails to maintain adequate blood flow. By contrast, the Joint National Commission 8 guidelines recommend a BP target of <140/90 mm Hg for patients with CKD who are <60 years of age versus a target of <150/90 for patients >age 60 (13). ACEIs or ARBs are often initiated as first-line therapy for hypertension in patients with CKD, due to their renal-protective effects. It is important to weigh the benefit of adequate preoperative BP control with the risk
of prolonged intraoperative hypotension due to continuation of these agents in the preoperative period.
of prolonged intraoperative hypotension due to continuation of these agents in the preoperative period.
CAD in patients with CKD is extremely common. Screen for the presence of preoperative cardiac risk factors including: smoking, diabetes mellitus, obesity, other vascular disease, and dyslipidemia, as well as symptoms such as angina or dyspnea on exertion. The Duke activity status index has been validated for the assessment of exercise capacity in patients with CKD (14). See Chapter 3.1.
Hypercholesterolemia is a common diagnosis in patients with CKD, and cardiovascular disease is the leading cause of death in this patient population; adult patients with CKD who are not on dialysis should be taking a statin. Statins are continued in the perioperative period.
Results of the SPRINT trials have led to the recommendation of a target hemoglobin A1c (HbA1c) of <7% to prevent or delay progression of the microvascular complications of diabetes, including diabetic CKD. A target HbA1c >7% may be more appropriate in individuals with other comorbidities, risk of hypoglycemia, or limited life expectancy.
Anemia in CKD may be due to iron or erythropoietin deficiency or erythropoietin hyporesponsiveness. Transfusion of red blood cells, erythropoiesisstimulating agents, and intravenous iron therapy can treat anemia associated with CKD. Although no specific preoperative standard exists defining safe preoperative hematocrit levels with CKD (15), the National Kidney Foundation (NKF) Dialysis Outcomes Quality Initiative (DOQI) guidelines recommend a target of 11 to 12 g/dL in patients with CKD, but not to exceed 13 g/dL. See Chapter 9.1 for management of anemia. The potential benefit of a blood transfusion to mitigate complications from surgery must be weighed against the risk of developing transfusion-induced antibodies. HLA sensitization prolongs the waiting time for transplantation and reduces graft survival. Women are at greater risk of HLA sensitization than men.
All patients with CKD are at an increased risk of AKI perioperatively. See Chapters 6.1, 6.3 and 6.5 for strategies to mitigate postoperative AKI. Obtaining a serum creatinine to estimate the GFR and screening for albuminuria are important tests that are necessary for staging CKD and predicting clinical outcomes such as AKI and all-cause mortality. Albuminuria is an important indicator of increased glomerular permeability to macromolecules and widespread endothelial dysfunction including cardiovascular disease, which may occur as a result of CKD and associated conditions such as hypertension, diabetes, hypercholesterolemia, smoking, and obesity. Results of a urinary albumin-creatinine ratio (uACR) and eGFR should be reviewed or obtained preoperatively for patients at risk for or with CKD (11). Results within the last 6 months to a year are typically acceptable as long as no changes are expected.
The importance of smoking cessation must be emphasized in this population. Patients should be encouraged to exercise for 30 minutes five times weekly and to maintain a healthy weight.
Potentially nephrotoxic medications are to be avoided to reduce the risk of AKI. These medications include: nonsteroidal anti-inflammatory agents, intravenous contrast dye, metformin, lithium, and digoxin. Patients may benefit from holding ACEIs and ARBs preoperatively, due to the risk of profound intraoperative hypotension.
REFERENCES
1. Inker LA, Astor BC, Fox CH, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63:713-735.
2. Hoerger TJ, Simpson SA, Yarnoff BO, et al. The future burden of CKD in the United States: a simulation model for the CDC CKD Initiative. Am J Kidney Dis. 2015;65: 403-411.
3. Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130: 2215-2245.
4. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999;100:1043-1049.
5. Bilimoria KY, Liu Y, Paruch JL, et al. Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons. J Am Coll Surg. 2013;217:833-42.e1-3.
6. Gupta PK, Gupta H, Sundaram A, et al. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circulation. 2011;124:381-387.
7. Ackland GL, Laing CM. Chronic kidney disease: a gateway for perioperative medicine. Br J Anaesth. 2014;113:902-905.
8. Mases A, Sabate S, Guilera N, et al. Preoperative estimated glomerular filtration rate and the risk of major adverse cardiovascular and cerebrovascular events in non-cardiac surgery. Br J Anaesth. 2014;113:644-651.
9. McClellan WM, Newsome BB, McClure LA, et al. Chronic kidney disease is often unrecognized among patients with coronary heart disease: The REGARDS cohort study. Am J Nephrol. 2009;29:10-17.
10. Ackland P. Prevalence, detection, evaluation and management of chronic kidney disease. BMJ. 2014;348:f7688.
11. Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension. 2004;44:595-601.
12. Gosmanova EO, Kovesdy CP. Blood pressure targets in CKD: lessons learned from SPRINT and previous observational studies. Curr Cardiol Rep. 2016;18:88.
13. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
14. Ravani P, Kilb B, Bedi H, et al. The Duke activity status index in patients with chronic kidney disease: a reliability study. Clin J Am Soc Nephrol. 2012;7:573-580.
15. Apfelbaum JL, Connis RT, Nickinovich DG, et al. Practice advisory for preanesthesia evaluation: an updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology. 2012;116:522-538.
6.2 End Stage Renal Disease on Dialysis
Jeanna Blitz
End-stage renal disease (ESRD) may occur as the result of progression to stage 5 CKD (eGFR <15 mL/min), the sequelae of AKI, or status post nephrectomy. Patients with ESRD ultimately require either dialysis or a renal transplant.
INCIDENCE AND PREVALENCE OF ESRD
Currently, there are approximately 871,000 patients in the United States with ESRD. Compared to white patients, the prevalence in African Americans is 3.7 times greater, 1.5 times greater in Asians, and 1.4 times greater in Native Americans. The incidence of ESRD has stabilized in all races at approximately 350 cases per million and has remained level since 2001 (1). The median wait time for a transplant is 3.6 years (2).
PROGNOSIS
The benefit of dialysis on life expectancy is variable, depending on age, functional status, and the presence of comorbidities. Five independent factors predict the likelihood of patients dying within 6 months while on dialysis: serum albumin, answering no to the “surprise” question (i.e., would I be surprised if my patient died in the next 6 months?), age, presence of dementia, and peripheral arterial disease. This prediction model has been developed into an online tool to assist with prognostication in dialysis patients (http://touchcalc.com/calculators/sq). It is important to consider the patient’s goals of care when deciding whether or not to initiate dialysis.
Renal transplant patients have an 85.5% 5-year survival rate which is more than twice the 35.8% 5-year survival rate for dialysis patients (3). In patients on dialysis, a poor functional status (a score of <70 as measured on a modified Karnofsky activity scale) is associated with early mortality (Fig. 6.1, Tables 6.5 and 6.6) (4).
 Figure 6.1 Patient survival rates by dialysis and transplant. |
TABLE 6.5 Comorbidities That Decrease Survival in ESRD | ||||||||
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CAUSES OF ESRD AND ASSOCIATED COMORBID CONDITIONS
Diabetes and high blood pressure are the leading causes of CKD and ESRD (Table 6.7). There is a graded relationship between the stage of CKD and the severity of the associated complications.
Patients with CKD are more likely to die from a myocardial infarction or cerebrovascular accident than from their kidney disease. Even small decreases in GFR increase the risk of developing vascular disease.
Anemia: Develops due to a decrease in erythropoietin, a hormone secreted by the kidneys that directs red blood cell production.
TABLE 6.6 Modified Karnofsky scale: (70-100 = better prognosis) versus (<30-69 = worse prognosis)
96-100
Normal function, no disability
91-95
Minor signs and symptoms, full activity
70-75
Independent, limited to home
65-69
Needs assistance with errands
50-54
Home attendant, not totally disabled
40-44
Nursing home for chronic care
35-39
Hospitalized, fair condition
30-34
Hospitalized, poor condition
<30
Hospitalized, progressive fatal process
Modified with permission from Ifudu O, Mayers J, Matthew J, et al. Dismal rehabilitation in geriatric inner-city hemodialysis patients. JAMA. 1994;271(1):29-33. ©1994 American Medical Association. All rights reserved.
TABLE 6.7 Common Causes of End-Stage Renal Disease
Diabetes mellitus
High blood pressure
Glomerulonephritis
Polycystic kidney disease
Severe anatomical problems of the urinary tract
Secondary hyperparathyroidism develops due to hyperphosphatemia, vitamin D deficiency and resistance.
Osteodystrophy is due to high levels of parathyroid hormone.
Chronic metabolic acidosis and hyperkalemia are both a consequence of, and a contributor to, the progression of CKD.
PREANESTHESIA EVALUATION AND OPTIMIZATION
Patients with ESRD require longer hospital stays and have increased complications compared to patients with normal renal function after surgery (5,6). Almost half of all dialysis patients having surgery have cardiovascular disease (7). Cardiac risk assessment before noncardiac surgery follows the American College of Cardiology/American Heart Association (ACC/AHA) guidelines (8,9). See Chapter 3.1.
Hypertension is a common diagnosis in the dialysis population. Volume overload may be a contributing factor, so optimization of preoperative fluid status with dialysis should be a first-line consideration. Discontinuing ACEIs and ARBs preoperatively to mitigate intraoperative hypotension and possible increased risk of AKI may be prudent. Patients continue all other antihypertensive medications preoperatively.
Pulmonary hypertension is found in a high proportion of dialysis patients with an arteriovenous fistula.
Cardiac autonomic neuropathy with elevated resting heart rate (>100 bpm) and lack of heart rate variability during exercise or deep breathing tests are common.
Systolic dysfunction due to myocardial fibrosis and calcium overload from secondary hyperparathyroidism occurs.
Heart failure with volume overload is due to impaired renal excretion of sodium and water, and low oncotic pressure can cause pulmonary edema.
Pericarditis may occur in the terminal stage of uremia.
Elevated serum cardiac troponin T levels may be chronically elevated due to concentration during dialysis. Diagnosing an ACS perioperatively may be affected.
Hyperkalemia is common and no recommendations exist for safe preoperative potassium values. Patients with ESRD may be more tolerant of chronic hyperkalemia. Patients with significantly elevated serum potassium concentration should have a 12-lead electrocardiogram (ECG).
Metabolic acidosis may decrease the efficacy of some local anesthetics.
Platelet dysfunction due to uremia may be attenuated by dialysis preoperatively. Caution is advised with the administration and/or continuation of antiplatelet agents or
other medications that may increase bleeding risk. Intraoperative hemorrhage related to uremic platelet dysfunction may be treated with desmopressin or cryoprecipitate.
Anemia is common and no preoperative-specific standard exists regarding safe hemoglobin (Hgb) levels in patients with ESRD. The NKF DOQI guidelines recommend an Hgb 11 to 12 g/dL, not to exceed 13 g/dL in all patients with CKD. Red cell transfusions, erythropoiesis-stimulating agents, and intravenous iron therapy can treat anemia associated with ESRD. The potential benefit of a perioperative blood transfusion to mitigate complications from perioperative bleeding is weighed against the risk of transfusion-induced antibody formation. HLA sensitization prolongs the waiting time for renal transplantation and reduces graft survival. Women are at greater risk of HLA sensitization than men.Related posts:
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