SOAP. – Chronic Kidney Disease – SỔ TAY LÂM SÀNG

Cheryl A. Glass

Definition

Chronic kidney disease (CKD) is defined as an abnormality of kidney structure or function that is present for greater than 3 months. CKD is specifically defined as follows:

A.The persistent and usually progressive reduction in glomerular filtration rate (GFR) less than 60 mL/min/1.73 m², and/or

B.Albuminuria: More than 30 mg of urinary albumin per gram of urinary creatinine.

C.CKD is a disorder that leads to progressive kidney damage from a variety of causes, including diabetes, hypertension (HTN) cardiovascular (CV) disease, urinary obstructions, prolonged use of nephrotoxic medications, and inherited diseases such as polycystic kidney disease. Associated comorbidities of CKD include renal osteodystrophy, anemia, metabolic acidosis, and malnutrition. Early recognition of CKD as well as treatment of complications can improve long-term outcomes.

The five stages of CKD are:

1.Stage 1: Kidney damage with normal kidney function (estimated glomerular filtration rate [eGFR] ≥90 mL/min/1.73 m²) and persistent (≥3 months) proteinuria.

2.Stage 2: Kidney damage with mild loss of kidney function (eGFR 60–89 mL/min/1.73 m²) and persistent (≥3 months) proteinuria.

3.Stage 3: Mild to severe loss of kidney function (eGFR 30–59 mL/min/1.73 m²).

4.Stage 4: Severe loss of kidney function (eGFR 15–29 mL/min/1.73 m²).

5.Stage 5: Kidney failure requiring dialysis or transplant for survival. Also known as end-stage renal disease (ESRD) (eGFR<15 mL/min/1.73 m²).

Incidence

A.Kidney disease kills more people than breast or prostate cancer. The overall prevalence of CKD in the general population is 14%.

B.By age group, CKD is more prevalent among older persons aged above 60 than among younger persons aged 40 to 59.

C.CVD contributes to more than half of all deaths among patients with ESRD.

D.African Americans are about 3.5 times more likely to develop ESRD than Whites. Hispanics are about 1.5 times more likely to develop ESRD than non-Hispanics.

Pathogenesis

Blood from the renal arteries and their subdivisions is delivered to the glomeruli. The glomeruli form an ultrafiltrate, nearly free of protein and blood elements, which subsequently flows into the renal tubules. The tubules reabsorb and secrete solute and/or water from the ultrafiltrate. The final tubular fluid, the urine, leaves the kidney, draining sequentially into the renal pelvis, ureter, and bladder, from which it is excreted through the urethra. The causes of CKD are traditionally classified by which portion of the renal anatomy is most affected by the disorder.

A.Vascular disease: Vascular disorders of the kidneys may involve partial or complete occlusion of large, medium, or small renal vessels. Examples of macrovascular or large renal vessel disease are renal artery stenosis and atherosclerotic disease. Benign HTN arteriolar nephrosclerosis results when chronic HTN damages small blood vessels, glomeruli, renal tubules, and interstitial tissues. Glomerulosclerosis is a severe microvascular or small vessel kidney disease caused by diabetes and uncontrolled HTN in which glomerular function of blood filtration is lost as fibrous scar tissue replaces the glomeruli. Loss of glomerular function leads to proteinuria, hematuria, HTN, and nephrosis, with variable progression to ESRD. Proteinuria occurs because of changes to capillary endothelial cells, the glomerular basement membrane (GBM), or podocytes, which normally filter serum protein selectively by size and charge.

B.Tubular and interstitial disease: As with vascular disease, chronic tubulointerstitial nephritis (CTIN) can be primary or secondary to glomerular damage and renovascular disease. CTIN arises when chronic tubular insults cause gradual interstitial infiltration and fibrosis, tubular atrophy and dysfunction, and a gradual deterioration of renal function, usually over years. Causes of CTIN are immune disorders, infections, reflux or obstructive nephropathy, and drugs. Analgesic abuse nephropathy (AAN) is a type of CTIN caused by cumulative lifetime use of large amounts of certain analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs).

Predisposing Factors

A.Diabetes.

B.HTN.

C.CV disease.

D.Chronic use of analgesics such as NSAIDs.

E.Autoimmune disorder.

F.Polycystic kidney disease.

G.Urinary tract obstructions such as BPH or kidney stones.

H.Recurrent urinary tract infections (UTIs).

I.Older than 60 years of age (age alone is not a reason for screening).

J.High-risk ethnic groups: African American, Native American, Pacific Islanders, Asian descent, or Hispanic smokers.

K.Exposure to toxins.

L.Family history of kidney disease.

Common Complaints

A.For CKD Stages 1 and 2 there are usually no presenting complaints; however, HTN is usually present. CKD is usually identified through routine screening of kidney function and urine tests for microalbumin.

Signs and Symptoms

A.In CKD Stage 3, the person will develop CKD complications but will still not usually have identifiable signs/symptoms:

1.HTN.

2.Decreased dietary calcium absorption.

3.Reduced renal phosphate excretion.

4.Elevation of parathyroid hormone.

5.Altered lipoprotein metabolism.

6.Reduced spontaneous protein intake.

7.Anemia.

8.Left ventricular hypertrophy.

9.Salt and water retention.

10.Decreased renal potassium excretion.

B.Signs/symptoms gradually worsen as the person moves to Stage 4 CKD. The person will begin to display signs and symptoms of complications:

1.Changes in bone density.

2.Fatigue and pallor related to anemia.

3.Edema.

4.Decreases in muscle mass.

C.As the CKD progresses to Stage 5, in addition to gradual worsening of the signs/symptoms noted in Stages 3 and 4, the person will experience symptoms indicating chronic uremia:

1.Impaired sleep.

2.Nocturia.

3.Fatigue.

4.Anorexia, nausea, vomiting, and weight change.

5.Decreased mental acuity.

6.Pruritus.

7.Edema.

8.Respiratory symptoms, including orthopnea and dyspnea.

9.Muscle cramps, twitching, and restless legs.

10.Peripheral neuropathy.

Subjective Data

A.Review the patient’s medical history to identify risk factors for CKD (previously noted in the section Predisposing Factors).

B.Elicit information about how well risk factors such as diabetes mellitus (DM) and HTN are controlled.

C.Review onset and duration of signs/symptoms of CKD complications and uremia.

D.Review all medications, including all over-the-counter (OTC) medications, especially NSAIDs, and supplements. Obtain specific information about dosing and length of time the drug was used.

E.Elicit smoking history.

Physical Exam

A.Observe general demeanor, attentiveness, and signs of fatigue.

B.Measure vital signs:

1.Vital signs, including orthostatic BP and pulse.

2.Height and weight to calculate body mass index (BMI). A BMI calculator is located at www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/english_bmi_calculator/bmi_calculator.html:

a.Record weight and BMI on each visit for comparison.

C.Inspect:

1.Skin for color, moisture, turgor, and signs of scratching caused by chronic pruritus.

2.Neck for jugular venous distension.

3.Abdomen for distension.

4.Extremities for edema, muscle mass, and signs of pain disorders such as arthritis.

D.Auscultate:

1.Lungs for rales.

2.Heart for cardiac heave, gallop, or rub.

3.Abdominal or femoral bruit.

E.Palpate:

1.Abdomen for masses, distension.

2.Bladder or flank for tenderness.

F.Make neurological exam:

1.Assess for sensation and vibratory sense on both feet.

Diagnostic Tests

Age alone is not a reason for CKD screening.

Laboratory testing is critical in ascertaining the stage, course, chronicity, and complications (and associated comorbid conditions) of CKD:

A.Routine kidney function tests:

1.Serum creatinine.

2.Blood urea nitrogen (BUN).

3.Urinalysis.

4.eGFR is the best marker for CKD. Measuring GFR: The severity of CKD should be classified based on the level of the eGFR. Serum creatinine alone should not be used as a measure of kidney function. Kidney function in patients with CKD should be assessed by formula-based estimation of GFR (eGFR), preferably using the four-variable Modification of Diet in Renal Disease (MDRD) equation. Clinicians who do not have access to an automated tool may use the web-based tool at www.nkdep.nih.gov/professionals/gfr_calculators/index.htm. Calculate eGFRs using the actual MDRD equation: eGFR = 186 × [SCr] − 1.154 × [age] − 0.203 × [0.742 if female] × [1.210 if Black], where SCr is serum creatinine concentration

B.Assessing proteinuria:

1.When screening adults at increased risk for CKD, albumin in the urine should be measured in a spot urine sample using either:

a.Albumin-specific dipstick, or

b.Albumin-to-creatinine ratio (ACR).

i.It is usually not necessary to obtain a timed urine collection (overnight or 24 hours).

ii.First morning specimens are preferred, but random specimens are acceptable if first morning specimens are not available.

iii.In most cases, screening with urine sticks is acceptable for detecting proteinuria.

iv.Standard urine dipsticks are acceptable for detecting increased total urine protein.

v.Albumin-specific dipsticks are acceptable for detecting albuminuria.

2.Patients with a positive dipstick test (1 or greater) should undergo confirmation of proteinuria by a quantitative measurement (protein-to-creatinine ratio [PCR] or ACR) within 3 months.

3.Patients with two or more positive quantitative tests spaced apart by 1 to 2 weeks should be diagnosed as having persistent proteinuria and undergo further evaluation and management for CKD.

Other Tests to Determine CKD Complications

A.Complete blood count (CBC).

B.If hemoglobin (Hgb) level is less than 12 g/dL in females, and Hgb levels are less than 13.5 g/dL in adult males, also do blood cell indices, absolute reticulocyte count, serum iron, total iron-binding capacity, percent transferrin saturation, serum ferritin, white blood cell (WBC) count and differential, platelet count, and testing for blood in stool.

C.Lipid profile and triglycerides.

D.Comprehensive metabolic profile (serum total protein, serum albumin, glucose, calcium, sodium, potassium, chloride, bicarbonate, BUN, creatinine, alkaline phosphatase, alanine amino transferase [ALT], aspartate amino transferase [AST], bilirubin).

E.Prealbumin.

F.Phosphorus.

G.Parathyroid hormone.

H.Urine immunofixation study.

I.Antinuclear antibody (ANA), antineutrophil cytoplasmic autoantibody (ANCA), and complement 3 and complement 4 (C3-C4):

a.Test is done to rule out autoimmune disorder, lupus, vasculitis, and cancer.

b.No fasting is needed.

J.Hepatitis B surface antigen and hepatitis C antibody.

K.Anti-GBM antibody.

L.Renal ultrasound to rule out postobstructive uropathy.

M.Renal Doppler to rule out renal artery stenosis.

Differential Diagnoses

Evaluation is meant to determine whether kidney disease is acute or chronic and to determine prerenal, intrarenal, or postrenal causation.

A.CKD.

B.Acute kidney disease.

Plan

The treatment plan will focus on patients in earlier stages of CKD—Stages 1, 2, and 3. Persons with Stages 4 and 5 CKD need specialized interventions provided by nephrologists and should be referred immediately.

A.General interventions:

1.Provide support to the patient.

3.For Stage 4 or 5 CKD, access devices for hemodialysis, such as a primary arteriovenous fistula or graft, require months to mature and should be in place for 6 months prior to the start of dialysis.

B. See Section III: Patient Teaching Guide Chronic Kidney Disease (CKD):

1.Instruct the patient in how kidneys work and how his or her body is affected by the CKD.

2.Emphasize the importance of following instructions to prevent further kidney damage:

a.Follow medication management instructions as carefully as possible.

b.No OTC medications should be taken that are not approved by the provider.

c.Keeping diabetes and HTN under control is crucial to maintaining kidney function.

d.Preventing cardiovascular complications by lowering cholesterol and BP is more important when you have CKD.

e.Smoking cessation is an important way to prevent worsening kidney function.

f.Routine follow-ups with provider are necessary to monitor kidney function. Patients should be educated and encouraged to keep all appointments.

g.Follow dietary instructions regarding protein, fats, sodium, and minerals.

h.Dietary intake of protein is usually restricted to 0.8 to 1.0 g/kg/d of high biologic value protein.

i.Dietary sodium should be restricted to no more than 2 g daily.

j.Potassium should be restricted to 40 to 70 meq/d.

k.Calories should be restricted to 35 kcal/kg/d; if the body weight is greater than 120% of normal or the patient is older than 60 years of age, a lower amount may be prescribed.

l.Fat intake should be about 30% to 40% of total daily caloric intake.

m.Phosphorus should be restricted to 600 to 800 mg/d.

n.Calcium should be restricted to 1,400 to 1,600 mg/d.

o.Magnesium should be restricted to 200 to 300 mg/d.

3.Instruct when to notify the provider with urgent signs/symptoms or changes in kidney function:

a.Changes in urine volume.

b.Anorexia, nausea, and vomiting.

c.Increased edema.

d.Shortness of breath (SOB).

e.Increased fatigue.

f.Difficulty concentrating.

g.Muscle weakness, cramping, or twitching.

h.Fever.

i.Chest pain.

C.Pharmaceutical therapy:

General principles of medications used to prevent progression of CKD and to manage symptoms of complications of CKD:

1.Always prescribe the smallest effective dose of any medication.

2.Start with a low dose and gradually increase. Adjust drugs according to kidney function using the eGFR. Dosage intervals may need to be extended.

3.Obtain regular measurements of Cr/eGFR, at least every 6 months after any change in medications (e.g., angiotensin converting enzyme [ACE] inhibitor, angiotensin II receptor blocker (ARB), or diuretics), medical intervention, or clinical status.

4.Monitor potassium:

a.Measure after change in medications, medical intervention, or clinical status with particular attention to potassium.

b.Check Cr and potassium prior to starting ACE inhibitors or ARBs, within 7 to14 days of starting, and within 7 to14 days after dose increase.

c.Cr rise greater than 20% or eGFR decrease greater than 15% after dose increase should be followed by further measurements within 7 to14 days.

5.Provide education to the patient of signs/symptoms to report to the provider immediately regarding drug therapy.

6.Diabetes:

a.Long-acting sulfonylureas may be associated by hypoglycemia with an unstable eGFR, especially those below 45.

b.If recurrent hypoglycemia, or unstable eGFR, consider using short-acting sulfonylureas or nonsulfonylureas.

c.In patients with an unstable eGFR or acute changes in clinical condition, metformin should be held, avoided, or reduced.

7.Avoid use of nephrotoxic radiographic contrast materials to prevent nephrogenic systemic fibrosis. If radiocontrast material use cannot be avoided because the benefit outweighs the risks, protect the kidney with acetylcysteine (Mucomyst) 600 mg orally twice daily on the day of intravenous (IV) contrast.

8.For patients with an extensive list of drugs, evaluate the need for dosage adjustment, contraindications, or nephrotoxicity. There are several classifications of the medications requiring dose adjustment. Classes may be used with the mnemonic BANDD CAMP.

B: Beta-blockers.

A: Ace inhibitors/angiotensin II receptor blockers (ACE/ARBs).

N: NSAIDs, cyclooxygenase-2 (COX-2) inhibitors, opioids.

D: Diuretics.

D: Diabetic medications.

C: Cholesterol medications.

A: Antibiotics-Aminoglycosides should be avoided or used in caution in patients with any degree of CKD. Kidney function should be monitored if they are used.

M: Miscellaneous.

P: Psychotropics.

9.Immunizations: Some vaccines in usual doses provide protection, whereas other vaccines require more frequent dosing, or larger doses, to achieve and maintain protective antibodies. Protective antibody titers may fall and booster doses should be given if appropriate. In general the recommendations are the following:

a.Annual influenza vaccination.

b.Pneumococcal vaccine with a single booster dose 5 years after the initial dose.

c.Hepatitis B vaccine series for patients prior to starting dialysis.

10.HTN control and kidney protection: It is recommended that HTN therapy achieve a goal of BP of 130/80 or less. Use of an ACE inhibitor or ARB therapy in early stages of CKD with persons who have proteinuria can preserve kidney function. The clinician should monitor serum potassium upon initiation of the therapy. It is common for the serum potassium to initially rise, then return to normal levels in 2 to 3 months. Follow-up serum potassium levels are recommended. In the early stages of CKD, with no proteinuria, the ACE inhibitors and ARBs have not been shown to be effective in protecting kidney function. HTN control can still be achieved with the ACE/ARB drugs, but other antihypertensive drugs can be used as well.

11.Fluid overload: Occurs when sodium intake exceeds sodium excretion. The combination of sodium restrictions and a loop diuretic can lower intraglomerular pressure and provide some kidney protection.

12.Hyperkalemia:

a.Hyperkalemia is managed with a low-potassium diet in combination with prescribing a

loop diuretic such as furosemide. If a patient is on an ACE or ARB, the addition of the loop diuretic will compensate for the elevation of serum potassium related to the ACE/ARB treatment.

13.Metabolic acidosis: Buildup of hydrogen ions causes bicarbonate levels to fall below acceptable levels. Sodium bicarbonate in a daily dose of 0.5 to 1 meq/kg/d is often given. This prevents the symptoms of metabolic acidosis, which can increase muscle mass loss and worsen bone disease.

14.Renal osteodystrophy: The development of renal osteodystrophy is caused by hyperphosphatemia and hypocalcemia that are secondary to the decreased kidney function. In order to compensate, the patient will develop secondary hyperparathyroidism. Dietary restriction of phosphate to 800 mg/d is recommended. In Stage 3 CKD, the patient will usually require an oral phosphate binder like calcium carbonate or calcium acetate to prevent hyperphosphatemia. Oral phosphate binders must be taken with meals to be effective. It is imperative to avoid phosphate binders that contain aluminum or magnesium. To suppress parathyroid hormone secretion, the patient is given calcitriol, a vitamin D analogue.

15.Anemia:

a.Use of elemental iron 200 mg such as ferrous sulfate 325 mg three times daily (65 mg elemental iron per dose) is recommended to maintain the percent transferrin saturation greater than 20%, and the serum ferritin level to be greater than 100 ng/mL.

b.Although primarily used in patients with ESRD, erythropoietic agents (EPO), such as epoetin alfa (Procrit), Epogen, and darbepoetin alfa (Aranesp), are also used to correct the anemia in those with CKD who do not yet require dialysis.

16.Dyslipidemia: Management of dyslipidemia has been shown to slow progression of CKD. Statins and fibrates are commonly prescribed to lower total cholesterol, low-density lipoprotein (LDL), and triglycerides. The incidence of untoward side effects with statins and fibrates is increased in persons with CKD; therefore, lower dosages and careful monitoring are required.

Follow-Up

A.Measure at least annually (more frequently with advanced CKD):

1.CBC and iron profiles (percent iron saturation).

2.Mineral metabolism (calcium, phosphorus).

3.Nutrition profile (albumin).

B.Diabetes:

1.Measure A1c every 3 to 6 months or as clinically indicated.

2.The American Diabetes Association 2018 Standards of Medical Care in Diabetes states that all hypertensive patients with diabetes monitor their BP at home to help identify potential discrepancies between office versus home BP, and to improve medication taking behavior.

Consultation/Referral

A.Rapid and sustained deterioration in kidney function (a decline of eGFR >10%–15% within a 12-month period) warrants urgent referral to a nephrologist or internist, irrespective of eGFR values.

B.Early referral to a nephrologist is recommended for anyone who has CKD. Referral to a nephrologist must be done as quickly as possible for symptomatic patients with Stage 4 or 5. Consultation with an endocrinologist or HTN specialist may be helpful in cases where DM and HTN continue to be poorly controlled.

C.Counseling on renal transplantation should be completed by a nephrologist, after the patient is evaluated as a candidate for kidney transplantation, on what types of transplant are available and how the transplant process works.

D.Referral to a dietitian for nutritional counseling and education to assist the patient to understand and follow complex dietary instructions is recommended.

E.Patients with Stage 4 or 5 CKD need counseling regarding the psychosocial and financial impact of progressive renal disease. Referral to a renal social worker or case manager can help the patient understand his or her health insurance benefits, how the transition to Medicare occurs after the health insurance benefit changes, and to help the patient deal with concerns about work or family life.

F.Patients should be referred to educational and support organizations for further education regarding CKD.

Individual Considerations

A.Although renal replacement therapy is widely available, some patients, especially the more debilitated elderly or those who have a terminal illness, may request end-of-life counseling, including advance directives.

B.Serum creatinine may be elevated after intense exercise or heavy intake of protein in the form of meat. Instruct patients who exercise vigorously to withhold strenuous exercise and large intake of meat protein at least 24 hours prior to evaluation of serum creatinine.

C.Geriatrics:

1.Risk for renal artery stenosis increases with age; if a sharp increase in creatinine occurs after beginning treatment with an ACE or ARB, obtain a duplex Doppler ultrasound.

2.Older adults treated for ESRD should be referred for a palliative care consult to provide guidance in discussing/determining goals of care for this life-limiting condition.

3.Patients on dialysis with limited life expectancies should not routinely be screened for cancer without active signs and symptoms.

Beers list caution: Refer to Appendix C, Tables C.2 and C.5 on medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults.

Resources

American Diabetes Association Standards of Medical Care in Diabetes: care.diabetesjournals.org/content/41/Supplement_1

Department of Veterans Affairs (VA)/Department of Defense (DoD) Clinical Practice Guidelines: www.healthquality.va.gov/guidelines/CD/CKD/GlobalRPh Commonly used agents for renal failure: www.globalrph.com/renalfx.htm

Creatinine clearance and CKD staging calculator: www.globalrph.com/multiple_crcl_2012.htm

Renal Dosing Database: www.globalrph.com/index_renal.htm

National Kidney Disease Education Program: www.nkdep.nih.gov

National Kidney Foundation: www.kidney.org

National Kidney Foundation: Kidney Disease Outcomes

Quality Initiative (KDOQI) Clinical Practice Guidelines: www.ajkd.org