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The ABCs of chronic kidney disease

Zuber, Kim, PA-C; Davis, Jane, DNP

Journal of the American Academy of PAs: October 2018 - Volume 31 - Issue 10 - p 17–25
doi: 10.1097/01.JAA.0000545065.71225.f5
CME: Nephrology

ABSTRACT Management of patients with chronic kidney disease has evolved since the last Kidney Disease Improving Global Outcomes clinical practice guideline was published in 2012. This article reviews the most recent guidelines, common management issues in primary care, kidney risk and outcome calculators, and over-the-counter medications that may cause community-acquired acute kidney injury.

Kim Zuber is executive director of the American Academy of Nephrology PAs. Jane Davis practices in the Department of Nephrology at the University of Alabama at Birmingham. The authors have disclosed no potential conflicts of interest, financial or otherwise.

Earn Category I CME Credit by reading both CME articles in this issue, reviewing the post-test, then taking the online test at http://cme.aapa.org. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of October 2018.

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CASE

Figure

Figure

Box 1

Box 1

A 63-year-old black woman new to the area presented to the office to establish care. Her past medical history includes type 2 diabetes, hypertension, obesity, and hyperlipidemia. She takes lisinopril, atorvastatin, metformin, and adult low-dose aspirin.

A physical examination revealed a BP of 148/92 mm Hg, body mass index (BMI) of 39, no edema, and regular cardiac rate and rhythm without bruits. An orthopedic examination was normal. A complete metabolic panel was within normal limits except for a serum creatinine of 1.2 mg/dL (glomerular filtration rate [GFR] of 56 mL/min/1.73 m2), A1C of 8.3% (from history), cholesterol of 211 mg/dL, high-density lipoprotein level of 51 mg/dL, low-density lipoprotein level of 152 mg/dL, and triglycerides of 176 mg/dL.

Box 2

Box 2

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DISCUSSION

Kidney disease is a worldwide epidemic. Researchers estimate that more than 850 million people are affected—twice the number of people with diabetes and 20 times the number of people with cancer or HIV.1 More than 30 million Americans, or about 15% of the population, have chronic kidney disease (CKD) and most do not know they have it.2 CKD is responsible for more deaths annually than breast cancer or prostate cancer.3 In 2016, the cost to Medicare for patients with CKD exceeded 20% of the entire Medicare budget.4 CKD is more common in adults over age 60 years and in women. Diabetes is the most common comorbid condition.4

In 2012, Kidney Disease Improving Global Outcomes (KDIGO) published CKD international guidelines that laid out the staging of CKD with regard to GFR and albuminuria (Figure 1).5 For the first time, guidelines directed clinicians to monitor patients' albuminuria to predict CKD progression. The introduction of ICD-10 coding further allowed clinicians to code CKD stages using the patients' urine albumin level. Often, the electronic health record in hospitals and medical systems will flag a CKD diagnosis, remind clinicians to check patients' urine, and suggest that clinicians consider aspirin therapy and/or add an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) if appropriate. Studies have shown that following these interventions, CKD is more often listed as a current procedural terminology code but after the diagnosis is made, many clinicians are unsure of the next steps.6

FIGURE 1

FIGURE 1

Urine albumin-to-creatinine ratio (UACR) is considered the gold standard for monitoring and following patients with CKD. The spot UACR has been shown to be more accurate for measuring and monitoring albuminuria than a 24-hour specimen.5 Multiple studies have shown that albuminuria occurs before a rise in serum creatinine and is predictive of CKD progression.4,5 Clinicians who do not practice nephrology may be confused about which urine study to order. For this reason, the National Kidney Foundation (NKF) has joined with laboratories around the country to initiate standardized laboratory monitoring for early CKD via a kidney profile. This includes a serum creatinine and UACR to stage kidney disease. Nephrologists believe that letting clinicians simply check a kidney profile box will simplify and increase screening and aid in patient management.7

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HYPERTENSION

What is the goal BP for patients with CKD? Nephrology professionals and clinicians have done themselves no favors by having multiple answers.

Publication of seemingly contradictory studies specific to patients with CKD continue to crowd clinicians' inboxes. The last series of KDIGO hypertension guidelines in use are more than 6 years old.8 The goals were between 130-140/80-90 mm Hg depending on patient comorbidities. Since those guidelines were published, multiple guidelines have been published with conflicting goals.9-11 Thus, many nephrologists will accept a BP of less than 140/90 mm Hg as a treatment goal but still push to obtain a BP less than 130/80 mm Hg, particularly for patients with diabetes.12 The American Diabetes Association (ADA) has recommended a goal of less than 140/90 mm Hg for patients with diabetes.13 Individual clinicians and practices often will use one guideline to eliminate confusion and standardize care across the practice.

In actuality, the story is a bit more nuanced. A 2013 Veterans Administration (VA) study showed that a diastolic BP below 80 mm Hg actually increased the risk of acute kidney injury (AKI) because the kidney needs perfusion.14 The Systolic Blood Pressure Intervention Trial (SPRINT) was a BP study that included CKD patients and monitored for increasing loss of GFR as a secondary endpoint.15 However, one of the exclusion criteria for SPRINT was diabetes, which is prevalent in patients with CKD and thus this limits our ability to state that a patient with CKD and diabetes should be at a lower BP.15,16 We simply do not know if the lower goals (less than 120 mm Hg systolic) of SPRINT would help or harm patients with CKD and diabetes.17 We do know that the incidence of AKI was increased in the strict control arm (those with the goal of systolic BP less than 120 mm Hg).15 Overall, patients in the strict control arm had reductions in death both from cardiovascular disease (CVD) and all-cause mortality, which argues for the 120 mm Hg goal, accepting the lack of peer-reviewed data in patients with diabetes.

Clinicians must be cautious in pushing toward lower BPs in older patients with CKD and multiple comorbidities. Orthostatic hypotension is associated with increased incidence of falls. Patients with lower GFRs have more fragile bones and an increased risk of hip fractures. These complications often result in patient loss of independence and increased admission to long-term care facilities.18

Lowering dietary sodium intake is an often-missed yet vitally important intervention for managing hypertension. Most adults in the United States consume more than 3,500 mg of sodium daily; the recommended goal for patients with CKD is 1,500 mg/day.19 Interventions to lower sodium intake can be more effective in black patients with hypertension who are highly sodium-sensitive.20 Reducing sodium often can be as effective as adding a second hypertensive medication in all patients.21

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Case patient

The addition of a second hypertensive medication is warranted due to her BP of 148/92 mm Hg, no matter which guideline you use. Recent observational studies have shown that a calcium channel blocker is the safest selection for this patient.22 A discussion of limiting dietary sodium is vital.

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CARDIOVASCULAR DISEASE

The combination of CKD and diabetes significantly raises the risk of CVD and death.23,24 This includes coronary heart disease, stroke, peripheral vascular disease, heart failure, and dysrhythmias. For women with diabetes, the risk is even higher; diabetes raises the risk of heart attacks by four times (versus two times in men) and outcomes are poorer.25 The addition of statins will reduce the risk of CVD in patients with stages 2 through 4 CKD.26,27 For patients in stage 5 or 5D (on dialysis) CKD, the benefit of statin medications is less clear-cut and statin therapy does not appear to reduce death rates.26

CKD increases the incidence of death due to cardiac dysrhythmias.28 The risks of sudden cardiac death are well documented; other common abnormalities include atrial fibrillation (AF)/atrial flutter, supraventricular tachycardia, and ventricular dysrhythmias.28 For patients with a creatinine clearance between 30 and 50 mL/min and AF, warfarin or one of the new direct oral anticoagulants (DOACs) can be used.28 DOACs have been shown to be noninferior compared with warfarin, although a recent publication stated exactly the opposite: increased bleeding with DOACs in comparison with warfarin.28,29 The safety profile of the DOACs appears to be better than warfarin.30 For patients with stage 4, 5, or 5D CKD, only observational data exist, not research data, and data are insufficient at this time to recommend any type of anticoagulation for these patients.28

A recent publication confirmed what many clinicians in nephrology have suspected for many years: treating older adults with CKD with anticoagulants significantly increases adverse reactions and may actually worsen their clinical condition.31 A study in England and Wales looked at nearly 5,000 patients with AF, all over age 65 years, and found those taking anticoagulants were 2.6 times more likely to experience a stroke and 2.4 times more likely to experience hemorrhage during a 2-year follow-up.31 Although many cardiologists treat patients with AF and more advanced CKD (GFR of less than 25 mm/min) with anticoagulants, keep in mind that patients with reduced kidney function (that is, lower GFR) are more likely to have complications, be fragile (more likely to fall), and have comorbidities.23,31 Consider not placing these patients on anticoagulants.

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Case patient

She does not have a rhythm abnormality but a cardiac consult is warranted because of her higher risk of CVD.

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DIABETES

Although lifestyle changes are always the first consideration, patients often also need medication management.32 Multiple new medications have been introduced for treating diabetes, raising questions about how to use them in patients with CKD. About one-third of patients with diabetes will progress to diabetic nephropathy.4,33 Diabetes continues to be the leading cause of end-stage renal disease (ESRD).4 Many clinicians know to test for albuminuria and add an ACE inhibitor or ARB to reduce the rate of CKD progression in patients with diabetes. Guidelines state that the patients with diabetes and albuminuria but without hypertension should be treated with an ACE inhibitor or ARB. Now, newer studies have shown that mortality is increased in the patients with diabetes who do not have albuminuria.34 Although treatment can reduce albuminuria and slow progression to ESRD in patients with diabetes and albuminuria, survival rates have not increased for patients with CKD and diabetes without albuminuria. How to manage these patients has yet to be determined.

The dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide (GLP), and sodium/glucose cotransporter 2 (SGLT2) inhibitors may improve survival in patients with diabetes and CKD by lowering A1C.35,36 SGLT2 inhibitors and GLP-1 receptor agonists have been shown to reduce the risk of CVD and promote weight loss in patients with CKD (Table 1).35,36 As studies are published, these recommendations will continue to evolve.

TABLE 1

TABLE 1

SGLT2 inhibitors appear to be very promising for patients with CKD.37 In those with stage 3a or 3b CKD, although A1C was not improved, the decline in GFR was slowed along with a decrease in urinary albumin.38 Multiple studies have shown that SGLT2 inhibitors have renoprotective qualities, although these are secondary analyses of cardiovascular studies.36,39 The CREDENCE study was stopped early (in July 2018) and the data should be released at any time. Clinicians in nephrology hope that this will answer the questions about using SGLT2 inhibitors in patients with CKD.40 The speculation is that sodium excretion, rather than A1C reduction, is responsible for the renoprotective qualities of SGLT2 inhibitors.41

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Case patient

She does not have a UACR result although her A1C is high (8.3%) and she is overweight (BMI 39). An SGLT2 inhibitor would be an excellent selection and might negate the need to add a second antihypertensive. Due to the diuretic properties of SGLT2 inhibitors, her BP likely would decrease. Adverse reactions such as an increase in mycotic infections can be mitigated by encouraging the patient to wash the perineum with water or use a moist towelette after urination.

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OBESITY

Obesity is linked to diabetes and CKD.42 Communication occurs between the gut and the kidney, and CKD contributes to alterations in the microbiome. In addition, changes in the gut have been shown to contribute to uremic symptoms of inflammation, insulin resistance, malnutrition, and CKD progression.43

Recent studies have shown that bariatric surgery slows CKD progression.42,44-46 In a long-term (18-year) control-matched study conducted in Sweden, the incidence of ESRD was half in obese patients (those with a BMI above 35) who had had gastric bypass surgery compared with those who did not have the surgery.42 Clinicians should emphasize weight loss and consider referring patients for bariatric surgery evaluation as appropriate.

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Case patient

Her BMI (39) and comorbidities (hypertension, diabetes, CKD) are prime indications for weight loss management.

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THE CONTINUUM OF AKI AND CKD

In the last 10 years, AKI and CKD have been recognized as being on a continuum rather than discrete entities.47 From 2000 to 2014, AKI diagnoses have increased 139% as there has been a greater spotlight on the issue.48 The international 0by25 and Think Kidneys campaigns, which aim to reduce the incidence of AKI by 2025, seem to be hitting a wall as the incidence of AKI increases.49-51

AKI can be classified as community-acquired or hospital-acquired. The incidence of community-acquired AKI is increasing and the mortality and morbidity of this disorder has surpassed that of hospital-acquired AKI.52 Many patients inadvertently increase their risk for community-acquired AKI by using frequent nonsteroidal anti-inflammatory drugs (NSAIDs) for minor aches and pains, dehydration associated with beverages containing high levels of sodium (sports drinks), patients who supplement with creatine powder and/or steroids all increase incidence of community-acquired AKI.53 The incidence is also increased in patients with diabetes or hypertension who continue to take their oral medications when sick (see the details as to what is defined as sick below), not eating, and/or vomiting/diarrhea. In Europe and Canada, sick-day rules are given to patients by pharmacists.54 These tell patients to hold their oral diabetic and hypertensive medications if they are running a fever or experiencing gastrointestinal (GI) symptoms such as vomiting or diarrhea.55 The belief is that this will reduce iatrogenic AKI.

Hospital-acquired AKI has multiple causes, including IV contrast, dehydration from NPO status or reduced ambulation, sepsis, medications, and simply being in the hospital.

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Case patient

Remind her not to take metformin if she is not eating due to sickness. She also should be advised to avoid using NSAIDs except for short periods and to consider acetaminophen for pain first.

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COGNITIVE FUNCTION

A recent publication showed that children and adolescents with CKD have decreased cognitive function corresponding to their stage of CKD; lower neurocognitive function is associated with a lower GFR.56 In adult brains, changes in white matter and small cerebral vessel disease herald what is commonly referred to as uremic brain.57 The acute loss of kidney function in AKI causes more cognitive changes than CKD as the brain does not have time to adapt. For black patients over age 65 years, reducing hypertension also appears to reduce the incidence of dementia.58

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Case patient

Cognitive testing may be appropriate in the future. Her BP needs to be lowered.

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POLLUTION

A recent observational study linking EPA and NASA data with more than 2 million VA patient medical records showed that patients who lived in areas of the country with higher pollution (more small particular matter) had a significant decline in GFR.59 For many patients, moving is not an option but clinicians who are educated about local pollution levels can identify patients at risk of CKD.

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Case patient

She has moved from a higher pollution area to a lower pollution area, reducing her CKD risk.

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GENETICS

Since the 2013 New England Journal of Medicine publication reporting the link between the APOL1 gene and hypertension in the sub-Saharan African population, the question of why those patients had the highest rate of CKD and ESRD in the United States is partially answered.60,61 Carrying one copy of the APOL1 gene increases the risk of hypertension and progression of CKD to ESRD; carrying two copies further increases the risk.62 However, carrying one copy of the gene is protective against the bite of the African tsetse fly, which carries African sleeping sickness.

One of the most commonly missed diagnoses in patients with CKD is autosomal dominant polycystic kidney disease (ADPKD).63 Although this is a genetic disease, presentation (age, rate of loss of function, symptoms) is variable within families. Hypertension is usually the first presenting symptom. A discussion of family history for a patient newly diagnosed with hypertension, along with a high rate of suspicion, can help to diagnose ADPKD earlier in the disease, thus slowing progression to ESRD.

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Case patient

She is at risk; however, APOL1 testing is used for screening kidney donors rather than community-wide. Because of her family history of hypertension, her previous clinician ordered a renal ultrasound, which did not show ADPKD.

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OTC MEDICATIONS

Many over-the-counter (OTC) medications can cause AKI in stable patients with CKD (Tables 2 and 3). Many practices have developed patient education materials outlining which OTC medications patients with CKD need to take with caution.64

TABLE 2

TABLE 2

TABLE 3

TABLE 3

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Case patient

Provide her with a yellow caution list of OTC medications.

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CAFFEINE

A recent study with data collected from NHANES data showed that patients with CKD who consumed higher amounts of caffeine were 24% less likely to die of all causes, even when accounting for age, sex, race, BP, smoking, BMI, and other confounders.65 Even a small increase in the amount of caffeine consumption appeared to improve survival for patients with CKD. This is an observational study and researchers cannot state that increasing caffeine intake will reduce mortality for patients with CKD. However, the data are interesting.

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Case patient

She drinks coffee.

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DENTAL AND EYE

Patient with CKD and periodontal disease have a higher mortality than those with CKD and healthy gums.66 In the NHANES III study, the death rate for patients with CKD is increased if they also have gum disease.67 If simple interventions with dental health can affect patient survival, clinicians should intervene. Regular eye and dental examinations are recommended for patients with diabetes and those with CKD.68

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Case patient

The patient and her family are new to the area. Encourage them to find a dentist and ophthalmologist and schedule checkups.

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PRIMARY CARE ISSUES

The usual vaccinations and preventive issues are vitally important in patients with CKD. As patients lose kidney function, their immune response decreases.69 Thus, vaccinations early in the course of the disease are more effective. All patients, regardless of risk factors, should be tested for HIV at least once during their lifetime.70 Hepatitis C testing is encouraged for patients born between 1945 and 1965.71 Hepatitis C is more prevalent among patients with CKD than the general population.72 Due to this higher incidence, patients also should be evaluated for hepatitis B antibodies; if these are low, administer hepatitis B vaccines. Tdap also is recommended for patients with CKD, especially those who are around young children.69

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Case patient

Although she was tested for HIV, she had not been tested for hepatitis C. She is due for her shingles, Tdap, and pneumonia vaccines but had already received her influenza vaccine for this year.

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PREDICTIONS

In 2011, a kidney risk calculator (http://kidneyfailurerisk.com) was developed to help clinicians predict which patients would be more likely to progress to ESRD.73 This tool has since been validated nationally and internationally, and accurately predicts 1- and 5-year progression of CKD to ESRD.73 The patient's age, region (North America or not), sex, GFR, and UACR are needed to use the calculator.

One of the other issues that arises when caring for patients with CKD is What is too much treatment? Everyone loses kidney function with age and older adults with multiple comorbidities may be better with medical management instead of dialysis with its multiple interventions.74 The surprise question (Would you be surprised if this patient dies within the next 6 months?) has been shown to be predictive of survival in patients with CKD and ESRD.75 Dialysis does not increase survival for patients older than age 75 years with more than two comorbid conditions.74 However, these patients have increased use of critical care medicine and increased risk of dying in the hospital or ICU. An entire subgroup of nephrology has been developed to care for these patients and to medically manage their symptoms of kidney disease.76

End-of-life discussions and goals of care should begin early in the provider-patient relationship. Patients and their loved ones need to define for themselves how they wish to live and what interventions they consider acceptable. Dialysis is not always the best choice for a patient; often for an older adult or a patient with multiple comorbidities, symptom management may improve quality of life with little sacrifice of quantity. The KDIGO calculator for CKD stages 4 and 5 (www.kdigo.org/equation) can help guide clinicians in these discussions. This calculator lets clinicians make informed decisions about patient management and can be used by primary care providers for end-of-life discussions.

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Case patient

We need her UACR before we can use the kidney risk calculator.

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CONCLUSION

Primary care visits often do not allow enough time to include all the nuances needed to care for patients with CKD. This means that a prioritized plan for CKD management is important. The initial visit should include a complete history and physical, social/family history along with laboratory orders (complete metabolic panel, UACR, hepatitis C, and HIV screens). Often, the initial visit is too short for the clinician and patient to discuss lifestyle changes in detail, although the National Kidney Disease Education Program (NKDEP) and the NKF offer multiple free patient education materials. Subsequent visits can focus on medication adjustments, including medications for hypertension and diabetes; discussing and administering vaccines; referrals to specialists or for tests; and monitoring for disease progression. Patient education is essential at every visit—many patients with CKD feel fine and do not fully understand that their kidneys are problematic until they are told this multiple times.

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Case patient

Laboratory tests were ordered, family and historical data collected, and a return visit scheduled. Physical examination upon return showed a still-elevated BP of 144/94 mm Hg without obvious edema and an unchanged BMI. Her new A1C was 8%, and serum creatinine was 1.3 mg/dL (GFR, 51 mL/min). Her UACR showed 30 mg/dL of albumin, putting her at risk of CKD progression. She had made an appointment with cardiology.

We decided to try to cover as many of the issues with as few medications as possible. We added an SGLT2 inhibitor to lower weight, BP, and A1C while also looking for both renal and cardiac protection. We gave the usual precautions of AKI, OTC medications, and asked her to repeat a complete metabolic panel in 4 weeks. She is scheduled to return in 3 months, at which time we will discuss vaccinations and the follow-up from cardiology.

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            Keywords:

            chronic kidney disease; CKD; acute kidney injury (AKI); diabetes; hypertension; KDIGO

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