80

Clinical Evaluation and Management of

Chronic Kidney Disease
Laurie A. Tomlinson, David C. Wheeler

Although many patients with chronic kidney disease (CKD) progress with potential kidney involvement (e.g., systemic lupus erythematosus),
to end-stage renal disease (ESRD) and require renal replacement therapy a family history of category G5 CKD, or hereditary kidney disease—and
(RRT), the majority die of nonrenal causes, particularly premature after opportunistic detection of hematuria or proteinuria.5
cardiovascular (CV) events.1 Early diagnosis of CKD is therefore impor-
tant because it provides opportunities to delay progression of CKD Evaluation of Chronic Kidney Disease
(see Chapter 79) and prevent CV complications (see Chapter 81). Establishing Chronicity
When eGFR of less than 60 ml/min/1.73 m2 is detected, careful atten-
tion should be paid to previous blood and urine test results and the
DEFINITIONS clinical history to determine if this is a result of AKI; that is, an abrupt
Chronic kidney disease is defined as abnormalities of kidney structure decrease in kidney function or CKD that has been present but asymp-
or function, present for at least 3 months, with implications for health tomatic for some time.
(Table 80.1). The Kidney Disease: Improving Global Outcomes (KDIGO) A detailed medical history covering issues, including other medical
guidelines recommend classification of CKD based on cause, category conditions, family history of kidney disease, prescribed medication,
of glomerular filtration rate (GFR), and albuminuria (see Fig. 79.1).2 and recreational drug use, may suggest an underlying cause. There may
Because of the impracticalities of using radioisotopes and 24-hour urine be hints of a history of kidney problems (e.g., hypertension, proteinuria,
collections, the KDIGO classification system recommends that kidney microhematuria) or symptoms suggestive of prostatic disease. The
function be assessed by estimating GFR (eGFR) from the serum cre- physical examination findings are not usually helpful, although skin
atinine concentration using an appropriate equation, except in circum- pigmentation, scratch marks, left ventricular hypertrophy, and hyper-
stances in which eGFR estimations are known to be less accurate, such tensive fundal changes favor a chronic presentation (Fig. 80.1). Details
as when there is significant muscle wasting. Initially, the Modification of the social and personal circumstances are also crucial, particularly
of Diet in Renal Disease (MDRD) equation was used, but this has for patients with progressive kidney disease in whom RRT is likely to
predominantly been replaced by the Chronic Kidney Disease Epidemi- be required.
ology Collaboration (CKD-EPI) equation, which more accurately cat- Blood tests for other conditions can be helpful because they may
egorizes the risk for mortality and progression to ESRD (see Chapter indicate evidence of an acute illness that could be the cause of kidney
3).3 Although staging systems for CKD based on eGFR have limitations, failure, such as systemic vasculitis or multiple myeloma. A normochromic
they have proved useful in many clinical settings and are now deeply normocytic anemia is usual in CKD, but also may be a feature of acute
embedded in guidelines developed for CKD management and research. systemic illnesses and therefore is not discriminatory. Low serum calcium
The evidence base for the management of CKD is constantly evolv- and raised phosphate levels also have little discriminatory value, but
ing. Although every effort has been made to ensure this chapter reflects normal levels of parathyroid hormone (PTH) are more in keeping with
current recommendations, the reader is advised to check for any relevant AKI. Patients with grossly abnormal biochemical values—for example,
guideline updates. blood urea nitrogen higher than 140 mg/dl, serum creatinine above
13.5 mg/dl (>1200 µmol/l), or blood urea greater than 300 mg/dl
(>50 mmol/l)—who appear relatively well and are still passing normal
CLINICAL PRESENTATION volumes of urine are much more likely to have CKD than AKI.
CKD is usually asymptomatic until late stage G4 or stage G5 and is
commonly detected by routine blood testing. Symptoms of CKD are Assessment of Glomerular Filtration Rate
nonspecific and need to be asked about directly (Table 80.2). There is For patients in whom the distinction between AKI and CKD is
some evidence that early diagnosis with appropriate management may unclear, repeat testing of kidney function should be performed within
slow the rate of decline of kidney function and reduce CV risk.4 Screen- 2 weeks of the initial finding of an eGFR below 60 ml/min/1.73 m2.
ing of the general population for CKD is not recommended, but in the However, if previous results confirm that this is a chronic finding, or if
United Kingdom the National Institute for Health and Care Excellence repeated blood test results over a 3-month period are consistent, CKD
(NICE) proposes offering testing to people with conditions associated is confirmed. Other tests (such as cystatin C or an isotope-clearance
with an increased prevalence of CKD—those with diabetes, hypertension, measurement of GFR) may be required for confirmation of CKD in
previous acute kidney injury (AKI), CV disease (CVD), structural renal circumstances in which eGFR based on serum creatinine is known to be
tract disease, renal calculi, prostatic hypertrophy, multisystem diseases less accurate.

935
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936 SECTION XVI Chronic Kidney Disease and the Uremic Syndrome

TABLE 80.1 Criteria for Definition of

Chronic Kidney Disease (CKD)
CKD is defined as abnormalities of kidney structure or function, present
for more than 3 months, with implications for health. These may include
the following:
Markers of Albuminuria (AER ≥30 mg/24 h; uACR ≥30 mg/g
kidney damage [≥3 mg/mmol])
Urine sediment abnormalities
Electrolyte and other abnormalities caused by tubular
disorders
Abnormalities detected through histology
Structural abnormalities detected through imaging
History of kidney transplantation
Decreased GFR GFR <60 ml/min/1.73 m2

From reference 2.
AER, Albumin excretion rate; GFR, glomerular filtration rate;
uACR, urinary albumin-to-creatinine ratio.
Fig. 80.1 Uremic pigmentation. Diffuse brown pigmentation as seen
here suggests chronic kidney disease rather than acute kidney injury.

TABLE 80.2 Symptoms and Signs of a further measurement of urinary protein excretion. Proteinuria is an
Severe Chronic Kidney Disease important diagnostic and prognostic marker, and its presence indicates
a higher risk for both progression of kidney disease and CV complica-
Symptoms Signs tions.7 KDIGO guidelines recommend that the preferred method of
Difficulty sleeping Altered respiration including assessing proteinuria is by measurement of the urinary albumin-to-
Kussmaul breathing and creatinine ratio (uACR) using an early morning urine sample.2 The
Cheyne-Stokes respiration degree of albuminuria is graded by the A1 to A3 category system, replac-
Nocturia Icteric sclera or “red eye” due to ing previous terms such as microalbuminuria (see Fig. 79.1). However,
calcium deposition it is important to be aware that some patients will excrete proteins
Headache Muscle weakness
other than albumin, and a urine protein-to-creatinine ratio (uPCR)
may be more useful for certain conditions.8 Serial uPCR measurements
Restless leg syndrome Oral lesions including gingival
may be particularly useful in glomerular disease because of the higher
bleeding or petechiae, xerostomia,
variability of uACR and the greater cost of determining albumin in
periodontitis, and candidiasis
urine. Where appropriate, urine tests for Bence Jones protein (immu-
Metallic taste in the mouth Pericardial and/or pleural rub noglobulin light chains) may be required because this is not detected
Shortness of breath on exertion Pulmonary and peripheral edema by standard proteinuria or albuminuria testing.
or at rest, paroxysmal
nocturnal dyspnea Kidney Imaging
Fatigue, often profound Skin changes including xerosis Imaging of the kidneys with ultrasound is useful for a number of reasons.
(abnormal dryness), scratch Small kidneys with reduced cortical thickness, showing increased echo-
marks, pallor, sallow coloration or genicity, scarring, or multiple cysts, suggest a chronic process. Structural
hyperpigmentation abnormalities such as autosomal dominant polycystic kidney disease
Muscle cramps and twitches Uremic flap (asterixis) (ADPKD), hydronephrosis caused by obstruction, or coarse renal scar-
ring may be detected. NICE guidelines propose that kidney ultrasound
Seizures Uremic fetor: Ammonia or urine-like
scanning is important only in certain circumstances and suggests coun-
odor to the breath
seling patients if ADPKD is suspected before imaging.5 In some situa-
Lack or loss of appetite for Uremic frost: Crystallized urea tions, imaging with computed tomography, magnetic resonance, or
food, abdominal pain, nausea, deposits that can be found on the angiography may be useful, taking into account the risks of administering
vomiting, and weight loss skin contrast media (see Chapter 5).
Itch, particularly on the trunk
and worse at night Further Investigations
Establishing the cause of CKD is important whenever possible, and
further specific testing, as indicated by the history and results of initial
investigations, may be required. There may be an underlying treatable
condition that requires appropriate management, or there may be a
Assessment of Proteinuria genetic cause such as ADPKD, for which counseling should be offered.
Dipstick testing of the urine and urine culture is important.6 This may Furthermore, some kidney diseases may recur after transplantation (see
reveal microhematuria, which can be a useful pointer toward an under- Chapter 108) and an accurate diagnosis may therefore influence later
lying diagnosis. Workup of hematuria is discussed in Chapters 4 and management. Despite thorough investigation, however, the cause of
59. Whether or not proteinuria is detected by dipstick, there should be CKD is often unclear, with an unhelpful medical history, minimal

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 CHAPTER 80 Clinical Evaluation and Management of Chronic Kidney Disease 937

abnormalities on urinalysis, and small kidneys on ultrasound. In such accelerated progression as a sustained decrease in GFR of 15 ml/
patients, investigation should not be pursued relentlessly because the min/1.73 m2 per year.2 In patients with CKD progression, consideration
implications for treatment are often minimal. Attempting to obtain should be given to detection of reversible causes (e.g., renal tract obstruc-
biopsy material from small kidneys is associated with risk, and even if tion) and specialist referral may be required.
a biopsy is performed, histologic assessment may simply show nonspe-
cific chronic scarring rather than diagnostic features that explain the When to Refer to the Nephrologist
cause of kidney damage. Chronic management of patients with early nonprogressive CKD is
becoming the responsibility of primary care physicians in many well-
developed health care systems, with follow-up in secondary care for
PREDICTING PROGNOSIS those likely to progress to ESRD and require RRT. However, early assess-
With the cause of CKD established if possible, the GFR and the level ment by nephrologists is useful for all patients newly diagnosed with
of proteinuria measured, and other comorbidities categorized, it may CKD in whom a treatable underlying cause is suspected, even in those
be possible to estimate the risk for CKD progression and likely future with advanced disease at presentation to rule out treatable causes. Timely
need for RRT. KDIGO recommends consideration of the GFR and the referral of those with progressive CKD allows preparation for dialysis,
albuminuria categories according to a “heatmap” of risk (see Fig. 79.1).2 kidney transplantation, or initiation of a palliative approach if more
Other factors associated with CKD progression will help inform prog- appropriate. Substantially similar criteria for referral have been devel-
nosis. These include the cause of CKD, age, sex, ethnicity, dyslipidemia, oped by NICE and KDIGO (Table 80.3). Such criteria are not absolute
smoking, obesity, history of CVD, ongoing exposure to nephrotoxic but should provide a guide to the primary care physician as to which
agents, and degree of control of hypertension and hyperglycemia. patients are likely to benefit from specialist care. For example, many
However, often the best guide to future change in kidney function is patients with stable category G4 CKD are successfully managed in the
the previous pattern of decline, highlighting the importance of con- community, often after initial assessment by or with advice from sec-
sidering results of previous blood and urine testing during the initial ondary care colleagues.
assessment. Unfortunately, a substantial proportion of patients with advanced
CKD are referred late, often when they need dialysis. Late referral is
Monitoring and Defining Progression often avoidable, although in some cases, patients may have had a truly
Once CKD has been identified, arrangements should be made to ensure silent illness or an acute presentation of a disease with rapid decline in
regular monitoring of kidney function and proteinuria. In patients at kidney function.9 Over recent years the introduction of routine report-
low risk for rapidly declining eGFR, this can be done annually. However, ing of eGFR in some health care systems has facilitated better com-
assessment should be undertaken more regularly if the trajectory of munication between primary and secondary care providers and has led
the disease is not clear and in patients at higher risk for progression. to a substantial fall in late referrals.10
Determining a true change in kidney function may be difficult because Late presentation is disadvantageous to the patient because it limits
small fluctuations in eGFR are common and not necessarily indicative the time to select the mode of dialysis or to be listed for “preemptive”
of progression. They may be caused by reversible factors, such as intra- kidney transplantation. There may be increased psychological stress,
vascular depletion or high meat intake, so repeat testing may be required. making it difficult for the patient to come to terms with the illness.
Both NICE and KDIGO guidelines define accelerated progression as a Furthermore, because an arteriovenous fistula takes several weeks to
sustained decrease in GFR of 25% or more and a change in GFR cat- mature, patients presenting late start hemodialysis with central venous
egory within 12 months.2,5 In addition, the NICE guidance refers to catheters. Catheters are prone to infectious complications and inevitably

TABLE 80.3 Suggested Criteria for Referral of Patients With Chronic Kidney Disease to
a Nephrologist
NICE 2014 KDIGO 2012
Advanced CKD Category G4 and G5 CKD Category G4 and G5 CKD
Proteinuria High proteinuria: uACR ≥70 mg/mmol unless known to be Consistent proteinuria: uACR ≥300 mg/g
caused by diabetes and appropriately treated (≥30 mg/mmol)
Hematuria Proteinuria (uACR ≥30 mg/mmol) together with hematuria Urinary red cell casts, RBCs >20 per high-
power field sustained; not readily explained
Progression of CKD Rapidly declining eGFR: Progression of CKD:
Sustained decrease in GFR of 25% or more, and a change in Sustained decrease in GFR of 25% or more,
GFR category within 12 mo and a change in GFR category within 12 mo
Sustained decrease in GFR of 15 ml/min/1.73 m2 or more Sustained decrease in GFR of 5 ml/min/1.73 m2
within 12 mo or more within 12 mo
Uncontrolled hypertension Hypertension that remains poorly controlled despite the use CKD and hypertension refractory to treatment
of at least four antihypertensive drugs at therapeutic doses with four or more antihypertensive agents
Hereditary kidney disease Known or suspected rare or genetic causes of CKD Hereditary kidney disease
Other conditions Suspected renal artery stenosis Recurrent or extensive nephrolithiasis
Persistent abnormalities of serum potassium
Data from references 2 and 5.
CKD, Chronic kidney disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; NICE, National
Institute for Health and Care Excellence; PTH, parathyroid hormone; RBC, red blood cell; uACR, urinary albumin-to-creatinine ratio.

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938 SECTION XVI Chronic Kidney Disease and the Uremic Syndrome

damage central veins, leading to thromboses and stenoses, which may decline of kidney function, so in early CKD, weight loss may be appro-
manifest at a later stage when venous return from one or the other arm priate. However, in advanced CKD, malnutrition is common (see Chapter
is increased by the subsequent construction of an arteriovenous fistula 86). The causes are multifactorial but include anorexia, acidosis, insulin
(see Chapter 91).11 Late presentation of CKD also precludes effective resistance, inflammation, oxidative stress, and urinary protein loss.
treatment of complications such as hypertension and anemia, which Biochemical indicators may demonstrate a decrease in serum albumin,
may contribute to CV damage and ultimately limit life span.12 Most transferrin, and cholesterol. Weight should be monitored in patients
important, late referral is associated with greater subsequent costs of who progress to CKD categories G4 and G5. Serum creatinine concen-
medical care and a worse prognosis.13 trations, which in part reflect muscle mass, may stop rising despite a
progressive loss of kidney function, because of compromised nutritional
PREVENTION OF CHRONIC KIDNEY status.
In light of this, recommendations to restrict protein intake have
DISEASE PROGRESSION been controversial. Although there is evidence that reduced protein
Management of CKD should be aimed at slowing the rate of decline intake may slow progression of decline of kidney function, many patients
of kidney function and minimizing the effects of other complications. develop protein-calorie malnutrition on a low-protein diet.21 KDIGO
Except for specific management of the underlying kidney disease where has recommended that protein intake should be lowered to 0.8 g/kg/
possible, the most effective intervention is control of blood pressure day in adults with CKD and GFR below 30 ml/min/1.73 m2, whereas
(BP), including (in patients with albuminuria) use of angiotensin- high protein intake (>1.3 g/kg/day) should be avoided in adults with
converting enzyme (ACE) inhibitors or angiotensin receptor blockers CKD at risk for progression. When this recommendation is followed,
(ARBs) (see Chapter 79). Control of glycemia for patients with diabetes detailed dietary assessment and supervision are needed to ensure that
and CKD is covered in Chapter 32. malnutrition is prevented.
One of the earliest effects of CKD is to limit the ability of the kidney
Hypertension to compensate for large changes in sodium and water intake (see Chapter
Hypertension is very common in patients with CKD, and the level of 7). Salt and water retention are major factors contributing to hyperten-
BP is associated with the rate of loss of kidney function14 while control sion in CKD patients and, in more advanced stages, to morbidity and
slows the rate of decline (see Chapter 79). BP targets have changed to mortality through systemic or pulmonary edema. Therefore sodium
reflect the available evidence, from a focus on “the lower, the better” intake ideally should be restricted to less than 90 mmol/day (5 g/day
toward less-intensive and individualized BP control.15 With the results of sodium chloride), except in salt-wasting conditions. Advice about
of the SPRINT trial, the pendulum may be swinging back again to optimal fluid intake at each stage of CKD is needed to prevent volume
lower BP goals.16 Guidelines by both NICE and KDIGO have considered overload. Salt substitutes containing potassium should be avoided because
management of hypertension in patients with CKD in depth.5,17 Both of the risk for hyperkalemia. In categories G4 and G5 CKD, education
sets of guidelines emphasize the importance of considering coexistent and advice about restriction of potassium and phosphate may be required.
CVD, other comorbidities, and side effects when choosing medications
and BP targets, particularly for elderly patients. Lifestyle modifications MANAGEMENT OF COMPLICATIONS OF
should be encouraged, including maintenance of a healthy weight, reduc-
tions in salt and alcohol intake, and regular exercise (see Chapter 35).
CHRONIC KIDNEY DISEASE
Although current recommendations are based on office BP record- A detailed discussion of the complications of CKD is provided in Chap-
ings, recent studies suggest that readings obtained from home and ters 81 to 88. With the exception of hypertension, there are usually few
ambulatory monitoring correlate better with CV and kidney outcomes.18 clinical manifestations associated with CKD categories G1 and G2 (GFR
It is alarming to note that up to 30% of CKD patients who were thought >60 ml/min/1.73 m2). Other complications (discussed in the following
to have hypertension have normal BPs at home, and 40% of patients sections) tend to develop progressively as GFR declines below 60 and
who were thought to be normotensive (or to have adequately treated in particular below 30 ml/min/1.73 m2 (i.e., during CKD categories
hypertension) were hypertensive at home.19 Although ambulatory moni- G4 and G5).
toring is not yet universally recommended, there should be a very low
threshold for undertaking 24-hour monitoring or asking patients to Anemia
undertake self-measurements at home if they prefer. Anemia is common in CKD categories G3a to G5 and is caused by a
Target BP levels and antihypertensive therapy in CKD patients are relative deficiency of erythropoietin, although reduced availability of
discussed in Chapter 79. ACE inhibitors or ARBs are recommended as iron and chronic inflammation are frequent contributory factors (see
first-line agents for patients with evidence of proteinuria, but usually Chapter 82). Anemia may have multiple adverse effects, including wors-
multidrug regimens are required to obtain good control. Patients with ening cardiac dysfunction by increasing cardiac output and exacerbating
CKD are vulnerable to drug side effects, particularly during intercurrent left ventricular hypertrophy, exacerbating the decline of kidney function,
illness, when they may develop hyperkalemia and AKI.20 The KDIGO and reducing cognition and concentration. However, clear evidence
guidelines recommend the temporary discontinuation of potentially that reversal of anemia using erythropoiesis-stimulating agents (ESAs)
nephrotoxic drugs and those excreted by the kidney (including ACE is associated with improved clinical outcomes is lacking, and random-
inhibitors, ARBs, aldosterone inhibitors, direct renin inhibitors, diuret- ized trials have suggested that in some circumstances these agents may
ics, nonsteroidal antiinflammatory drugs, metformin, lithium, and cause harm. A promising new avenue for the treatment of renal anemia
digoxin) in patients with a GFR below 60 ml/min/1.73 m2 (CKD cat- is the development of oral small-molecule stabilizers of hypoxia induc-
egories G3a to G5) who have serious intercurrent illness. ible factor. These offer the possibility of simple and cheaper therapy
compared with ESAs, with potential benefits beyond increases in hemo-
Dietary Advice globin (Hb) level.22
Detailed dietary advice and education, along with ongoing support The relevant KDIGO guideline recommends that all patients identi-
from an appropriately trained professional, are important in the man- fied as having CKD categories G3a and below should have their Hb
agement of patients with CKD. Obesity is associated with a more rapid levels monitored annually, increasing to twice a year for categories G4

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 CHAPTER 80 Clinical Evaluation and Management of Chronic Kidney Disease 939

and G5.2 Anemia in adults is diagnosed when the Hb concentration calcium loss from bone where the hydrogen ions are buffered.28 Cor-
falls below 13.0 g/dl in men and below 12.0 g/dl in women. NICE rec- rection of metabolic acidosis may slow progression of kidney disease,
ommends that management of anemia should be considered in patients although larger trials are required to confirm this.29
with CKD when the Hb level is 11 g/dl or lower.5 In anemic patients, KDIGO recommends that in patients with CKD and serum bicar-
investigations for other causes should be conducted, including measure- bonate concentrations below 22 mmol/l (NICE recommends a threshold
ment of iron stores, serum vitamin B12, and folate levels. ESAs should of <20 mmol/l), oral bicarbonate supplementation should be given to
not be started until treatment of iron deficiency or other underlying maintain serum bicarbonate within the normal range, unless contra-
causes has been addressed and then only after considering the balance indicated. However, the associated sodium loading may aggravate
of benefits (from the reduced requirement for blood transfusions and hypertension and fluid retention, and severe metabolic acidosis associ-
abrogation of anemia-related symptoms) against the potential harms, ated with symptoms in a patient with CKD category G5 may be an
which may include an increased risk for stroke and malignancy. indication to start dialysis.2 Novel pipeline drugs include an oral polymer
If anemia does not respond to correction of underlying causes, such designed to remove acid from the body with high capacity and specific-
as iron deficiency, KDIGO recommends that ESAs be commenced when ity. This raises the possibility of treatment of acidosis without the prob-
Hb concentrations are below 10.0 g/dl, if indicated.23 Hb target ranges lems associated with increased sodium intake.
are discussed in Chapter 82.
Cardiovascular Risk
Bone and Mineral Metabolism Patients with CKD have an increased prevalence of CVD and are far
Hyperphosphatemia, together with a deficiency of 1,25-dihydroxyvitamin more likely to die from a CVD-related cause than to progress to ESRD
D3, contribute to secondary hyperparathyroidism and ultimately to the (see Chapter 81). Therefore appropriate management of existing CVD
development of renal bone disease. These biochemical and endocrine and minimization of future CV risk is vital for all patients with CKD.
changes, in association with the closely related histologic abnormalities Unfortunately, many trials of interventions for CVD have excluded
of bone and soft tissue calcification, are collectively termed the CKD– patients with CKD,30 and there is doubt about the relevance of existing
mineral and bone disorder (see Chapter 84).24 Bone disease already may standards of care of CVD to patients with CKD.31 Nonetheless, the level
be manifested in CKD category G3b and is well established in ESRD, of care for coronary heart disease offered to patients with CKD should
even though patients may remain asymptomatic. In addition to the not be prejudiced by their CKD. NICE suggests that antiplatelet drugs
need to prevent bone complications, active management of CKD–mineral should be offered to patients with CKD for the secondary prevention
and bone disorder may help prevent some of the CV complications of CVD, and some experts would extend this recommendation to primary
of CKD.25 prevention for those at risk for atherosclerotic events. However, there
KDIGO recommends measuring serum levels of calcium, phosphate, is an increased risk for minor bleeding, and a recent systematic review
PTH, and alkaline phosphatase activity in adults with GFR below 45 ml/ of antiplatelet agents for patients with CKD found that although the
min/1.73 m2 (GFR categories G3b through G5). Determining the optimal incidence of myocardial infarction is reduced, major bleeding is increased.
level of PTH in CKD has been controversial. For patients with levels Thus the risks may outweigh benefits among individuals with low risk
of intact PTH above the upper normal limit of the assay, efforts should for CV events, including those with early stages of CKD who do not
be made to correct hyperphosphatemia, hypocalcemia, and vitamin D have clinically evident occlusive arterial disease.32
deficiency if present. KDIGO guidelines recommend that serum phos- For reduction of cardiovascular risk, KDIGO guidelines recommend
phate concentrations be maintained in the normal range according to that statin treatment be routinely offered to patients with CKD who
local laboratory reference values,26 whereas the United Kingdom Renal are older than 50 years and to younger patients with additional risk
Association support a level between 0.9 and 1.5 mmol/l for patients factors, irrespective of baseline lipid values.33 NICE recommends that
with category G4 and G5 CKD.27 Early advice on dietary phosphate all people with CKD should be offered atorvastatin 20 mg for the primary
management by a specialist dietician or other professional is important or secondary prevention of CVD.34
in helping patients achieve this. Phosphate-binding drugs may be
required, and their choice is discussed in Chapter 84. Prescription of Risk for Infections
vitamin D supplements or analogues, in the absence of documented Infection is the second most common cause of death after CVD in
deficiency, to suppress elevated PTH concentrations in patients with patients with ESRD. This is in part because of defects in both cellular
CKD not on dialysis is not routinely recommended. Calcimimetics are and humoral immunity, which make CKD a state of chronic immu-
a group of drugs that mimic the action of calcium on parathyroid nosuppression (see Chapter 83).35 T-cell responses to de novo antigens
glands by activation of the calcium sensing receptor and thus reduce are deficient, partly because of impaired antigen presentation by mono-
the release of PTH. At present, because of cost restraints, cinacalcet cytes. Neutrophil activation is defective, and although serum immu-
(the sole clinically available oral calcimimetic) and etelcalcetide (which noglobulin levels are normal, antibody responses to immunization may
is given intravenously) are generally used for patients who are unfit for be poor. Patients with CKD have an increased susceptibility to bacterial
surgical parathyroidectomy. Whether these drugs have additional health infection (particularly staphylococcal), increased risk for reactivation
benefits is not clear (see Chapter 84). of tuberculosis (typically with a negative tuberculin skin test response),
and failure to eliminate hepatitis B and C viruses after infection.
Metabolic Acidosis In view of these increased risks, the KDIGO guidelines recommend
The metabolic acidosis associated with CKD is caused by failure of that all adults with CKD be offered annual vaccination with influenza
hydrogen ion excretion and may be compounded by the accumulation vaccine unless contraindicated and that all adults with eGFR below
of organic acids and bicarbonate loss, particularly in interstitial kidney 30 ml/min/1.73 m2 (GFR categories G4 to G5) and those at high risk
diseases. Clinical symptoms resulting from acidosis are rare until patients for pneumococcal infection (e.g., patients with nephrotic syndrome,
reach CKD category G5, when dyspnea may occur as a result of respira- with diabetes, or who are receiving immunosuppression) receive vac-
tory compensation. Other causes of dyspnea in advanced CKD, such cination with polyvalent pneumococcal vaccine unless contraindicated.2
as anemia and pulmonary edema, should always be considered. Acidosis Patients who have received pneumococcal vaccination are offered revac-
aggravates hyperkalemia, inhibits protein anabolism, and accelerates cination within 5 years. In addition, those at high risk for progression

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940 SECTION XVI Chronic Kidney Disease and the Uremic Syndrome

of CKD with eGFR below 30 ml/min/1.73 m2 (GFR categories G4 and require dialysis, then superficialized for use once clinical circumstances
G5) should be immunized against hepatitis B and the response con- dictate.
firmed by appropriate serologic testing. This should happen as early as Early kidney transplantation may be associated with improved long-
possible to maximize the chances of seroconversion.36 term outcome,39 so patients should be assessed for their suitability and,
when feasible, activated on the waiting list before dialysis is commenced.
CARE OF THE PATIENT WITH PROGRESSIVE This maximizes the chances of the potential recipient remaining in
reasonable health. The availability of a living donor should be explored
CHRONIC KIDNEY DISEASE to increase the chances of preemptive transplantation before the patient
To optimize the care of patients with progressive CKD, management begins dialysis. The KDIGO guidelines recommend that living donor
is provided in a multidisciplinary setting where a range of professionals preemptive kidney transplantation in adults be considered when the
are able to provide education and information about diet, different GFR is below 20 ml/min/1.73 m2 and there is evidence of progressive
RRT modalities, transplant options, vascular access surgery, and social and irreversible CKD over the preceding 6 to 12 months.2
care. Psychological comorbidity is common among patients with CKD. Planned early initiation of dialysis is not associated with improve-
Health care professionals working with patients with CKD should take ment in outcomes compared with commencement when indicated by
account of the psychological aspects of coping with the condition and signs and symptoms of uremia.40 KDIGO suggests that dialysis be initi-
offer access to support groups, counseling, or a specialist nurse. The ated when one or more of the following are present: symptoms or signs
aim is to create an environment in which patients can become informed attributable to kidney failure (serositis, acid-base or electrolyte abnor-
and proactive in their care. malities, pruritus); inability to control volume status or BP; a progressive
deterioration in nutritional status refractory to dietary intervention;
Chronic Kidney Disease and Risk of Acute Kidney Injury or cognitive impairment.2 These problems often but not invariably
All patients with CKD are at increased risk for AKI, and AKI is associ- occur when the GFR is below 15 ml/min/1.73 m2 (see Chapter 90).
ated with the development and progression of CKD.37,38 Imaging studies
that require iodinated radiocontrast media carry a risk for AKI, and Conservative Management
the benefit of a diagnostic scan needs to be balanced against the risks. The potential burden of commencing RRT in terms of high short-term
If the investigation is needed, the lowest dose of radiocontrast should mortality rates, recurrent hospitalizations, time spent traveling, and
be used, the patient should be adequately hydrated, and potentially limited improvement in quality of life for some elderly patients and
nephrotoxic agents should be withdrawn before and after the procedure; those with multiple comorbid disease is increasingly recognized. This
however, the fear of radiocontrast-induced AKI should not prevent or has led to the practice of offering patients approaching ESRD the addi-
impair a necessary diagnostic workup. The potential risk for nephrogenic tional option of choosing not to start dialysis, but to maintain ongoing
systemic fibrosis from gadolinium-based contrast media and measures follow-up and symptomatic support through conservative management.
to reduce it are discussed in Chapter 5. Although dialysis may offer longer survival, those choosing conservative
Many commonly used medications increase the risk for AKI, and management may have as many hospital free-days as those who choose
the level of GFR should be considered when any drug is prescribed or hemodialysis.41 The symptoms of advanced uremia can be distressing,
its dosage determined. As discussed earlier, the need for temporary and it is important to ensure that patients who choose this pathway
cessation of all medications should be considered during periods of have access to members of the multidisciplinary team with expertise
severe intercurrent illness. Other causes of reduction in kidney perfu- in palliative care to facilitate a death free of suffering.
sion can lead to AKI, including volume depletion from excessive diuretics,
insufficient fluid intake in hot weather, diarrhea or vomiting, heart
failure, myocardial infarction, and tachyarrhythmias. Severe hypercal-
cemia, resulting from either coadministration of high doses of vitamin
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Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.
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 CHAPTER 80 Clinical Evaluation and Management of Chronic Kidney Disease 941.e1

SELF-ASSESSMENT
QUESTIONS
1. Which of the following is the most common cause of death for
people with chronic kidney disease (CDK) (estimated glomerular
filtration rate [eGFR] <60 ml/min/1.73 m2)?
A. Failure of dialysis access
B. Sepsis
C. Withdrawal from dialysis
D. Cardiovascular disease
E. Cerebrovascular disease
2. The equation recommended by Kidney Disease: Improving Global
Outcomes (KDIGO) for estimating GFR is:
A. The Modification of Diet in Renal Disease (MDRD) equation
B. The Cockcroft-Gault formula
C. The Chronic Kidney Disease–Epidemiology Collaboration
(CKD-EPI) formula
D. The Mayo Clinic Quadratic formula
E. The Schwartz formula
3. Which of the following variables is not needed to calculate eGFR
from the CKD-EPI formula?
A. Age
B. Weight
C. Race
D. Sex
E. Creatinine
4. Which of the following symptoms is suggestive of CKD, regardless
of cause?
A. Pain in the renal angle
B. Nocturia
C. Urinary frequency
D. Tremor
E. Anuria
5. In a well patient, which of the following biochemical or hematologic
abnormalities is suggestive of CKD rather than acute kidney injury?
A. Calcium 3.5 mmol/l
B. Potassium 7.5 mmol/l
C. Hemoglobin 10.7 g/dl
D. Creatinine 13.5 mg/dl
E. Sodium 132 mmol/l

Descargado para Natalia Rodriguez ([email protected]) en Pontifical Bolivarian University de ClinicalKey.es por Elsevier en julio 01, 2019.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.