116

Chronic Kidney Disease

Ajay K. Singh, MD
DEFINITION
Chronic kidney disease (CKD) is a defined as a clinical syndrome characterized
by a progressive decline in kidney function such that the kidneys ability to
adequately excrete waste products and to contribute to the constancy of the bodys
homeostatic functions becomes progressively impaired. CKD at its mildest stage
is asymptomatic; at its most severe stage, it is characterized by uremia. End-stage
kidney failure denotes CKD that necessitates kidney replacement therapy (dialysis
or transplantation). The National Kidney Foundation has developed a consensus
definition of CKD that has been widely accepted. CKD is defined as an absolute
reduction in glomerular filtration rate (GFR) to below 60 ml/min/1.73 m2 for 3
months or more, with or without other evidence of kidney damage; or the
presence of kidney damage for 3 months or more, as evidenced by structural or
functional abnormalities of the kidney, with or without reduction in GFR. Kidney
damage can be manifested by pathologic changes on kidney biopsy speciments,
abnormalities in the composition of the blood or urine (such as proteinuria or
changes in the urine sediment examination), or abnormalities in imaging tests.
This definition of CKD does leave unaddressed the significance of a reduced GFR
below 60 ml/min/1.73 m2 in certain subgroups, such as the elderly, the
undernourished, and those of specific ethnic groups. For example, elderly
individuals with reduced GFR may never develop end-stage renal disease.
However, the classification serves as a useful starting point in evaluation of a
patient with depressed GFR and provides an impetus either to refer the patient to a
nephrologist for further workup or to identify a patient at higher risk for
development of kidney disease.
CKD is classified into five stages, depicted in Table 116-1. Each stage has a
corresponding level of GFR. Patient with stage V CKD have advanced kidney
disease; this includes patients receiving dialysis and those with a kidney
transplant. Approximately 98% of patients beginning dialysis for CKD in the
Unite States have an estimated GFR of less than 15 ml . min -1 per 1.73 m2.
Nevertheiess, this definition is not synonymous with end-stage kidney failure
defined earlier. In essence, end-stage renal disease (ESRD) is an administrative

term in the United States signifying eligibility for coverage by Medicare for
payment for dialysis and transplantation.
The incidence of kidney failure in the United States is approximately 268 cases
per 1 million population per year.1 However, the incidence of CKD is greater
among black Americans (829 per million population per year, compared with 199
per million population per year among white Americans). The major causes of
CKD in the United States are diabetes mellitus (40%), hypertension (30%),
glomerular disease (15%), polycystic kidney disease, and obstructive uropathy
(Table 116-2).1 Elsewhere in the world, where the incidence of diabetes mellitus
has not reached epidemic proportion (e.g., in Europe and parts of the developing
world), chronic glomerulonephritis (20%) and chronic reflux nephropathy (25%)
are the most common causes of CKD. The progessive decline in kidney function
in individuals with CKD is variable and depends on both the cause of the
underlying insult and patient-specific factors. Furthermore, evidence also points to
the importance of several factors in modulation of kidney disease progression.
These include proteinuria, the presence of systemic hypertension, age, gender,
genetic factors, and smoking.2

TABLE 116-1. National Kidney Foundation

Classification of Chronic Kidney Disease
Stage I
Stage II
Stage III
Stage IV
Stage V

Kidney damage with normal or supranormal GFR

Kidney damage with mild reduction in GFR
Moderate reduction in GFR
Severe reduction in GFR
Kidney failure or on dialysis

GFR 90
GFR 60-89
GFR 30-59
GFR 15-29
GFR < 15

At an early stage, insidious effects on target organs may be manifested. For

example, patients may have mild to moderate hypertension, mild anemia, left
ventricular hypertrophy, and subtle changes in bone structure due to kidney
osteodystrophy. It is imperative to investigate the abnormal kidney function and to
refer the patient to a nephrologist. As kidney function gradually declines further,
with the GFR reaching 10 to 30 mL/min, hypertension usually present and subtle
biochemical and hematologic abnormalities may become evident, such as mild
hyperkalemia, mild hypobicarbonatemia (from uremic acidosis), and anemia of
chronic disease.3

As kidney dysfunction becomes severe (GFR in the range of 10 to 15 mL/min),

the syndrome of uremia is invariably present. Uremia reflects the accumulation of
metabolic toxins, some characterized and others unknown, that influences the
functioning of a variety of organ systems. In this late stage, the need for kidney
replacement therapy is imminent, and dialysis or transplantation is required to
sustain life. The indication for initation of kidney replacement therapy include
severe refractory abnormalities in biochemistry (severe hyperkalemia and
acidosis), severe pulmonary edema, bleeding metabolic encephalopathy, and
pericarditis.4 More subtle but no less important indications include malnutrition
and severe disability (marked tiredness and lethargy).
TABLE 116-2. Causes of Chronic Kidney Disease
Prekidney
Cardiogenic
Severe cardiac failure
Vascular
Kidney artery stenosis
Kidney
Immunologic
Glomerulonephritis (primary or secondary)
Neoplastic
Multiple myeloma
Toxic
Gold, pencillamine, cyclosporine
Tubulointerstitial
Infection or reflux
Cystic disease
Polycystic kidney disease
Postkidney
Stones
Pelviureteric obstruction
Retroperitoneal fibrosis
Prostatic hypertrophy

SYMPTOMS
CKD may be asymptomatic when kidney function is only mildly impaired; when
the GFR is markedly reduced, the patient is usually symptomatic and may be
severely disabled. Early in kidney disease, individuals may present simply with

elevated serum creatinine and blood urea nitrogen levels but no symptoms. These
individuals are usually unaware that they have any abnormalities in kidney
function and usually fail to register on the radar screen of thier clinicians.
Edema may also be observed for the first time, reflecting the kidneys inability to
excrete salt and water. With a further decline in kidney function, there is often a
concomitant decline in cognitive and physical functioning. This is usually due to
anemia, kidney osteodystrophy, and onset of the uremic syndrome. In addiction,
appetite declines, and there is often a significant loss of lean body mass.

PHYSICAL EXAMINATION
One or more of a spectrum of abnormalities that reflect the multisystem nature of
the uremic syndrome may be manifested on physical examination of patients with
CKD. Patients may appear generally ill, gaunt, and pale. Mucous membranes may
be pale from anemia, and poor platelet function may result in easy bleeding of the
gums. The cardiovascular system may exhibit no abnormality, or there may be
evidence of hypertension extracellular fluid overload (elevated jugular venous
pressure, pulmonary venous congestion manifested by rales, and pitting edema),
and acute pericarditis. The presence of a pericardial rub on physical examination
is usually highly sugesstive of uremic pericarditis. The pulmonary system may
demonstrate rales from fluid overload on physical examination. Gastrointestinal
abnormalities include stomatitis, cheilosis, and halitosis. Patients may also
experience epigastric tenderness compatible with gastritis secondary to uremia.
Abnormalities in the musculoskeletal system may include generalized weakness
on physical examination. Proximal weakness may be an early sign of kidney
osteodystrophy. Patients with dialysis-associated amyloidosis may experience
bone tenderness, carpal tunnel syndrome, and amyloid accumulations or tumors in
various parts of the body, such as the skin. Hematologic abnormalities evident on
physical examination may include bruising from platelet function abnormalities.
Findings of the neurologic examination may, quite commonly, be abnormal in
patients with uremia. Patients may have mild abnormalities, such as intermittent
confusion, or more severe manifestations, such as delirium, seizure activity, and
psychosis. In extreme cases, the patient may become comatose. Common
abnormalities on physical examination include evidence of confusion, a flapping
tremor (asterixis), and fasciculations. A peripheral neuropathy is quite rare
because most patients have started dialysis treatment before a neuropathy has time
to develop.
It is unclear why some patients demonstrate the flu-blown physical
abnormalities of the uremic syndrome, whereas others exhibit relatively mild

findings on physical examination. The physical examination is important in the

diagnosis of uremia. In particular, abnormalities such as encephalopathy, acute
pericarditis, and pulmonary edema are indications for initiation of kidney
replacement therapy.

FUNCTIONAL LIMITATIONS
Functional limitations in individuals with CKD depend on the degree of lethargy,
fatigue, and neuropsychological symptoms that are present. Individuals may go
from being mobile to nonmobile because of weakness. Elderly individuals with
underlying comorbidities may be the most affected. Endurance and the ability to
perform activities of daily living may be reduced, and modifications in lifestyle
may become necessary, including a change from full-time to part-time work,
reduction in travel, and discontinuation of driving.5-7 In diabetic patients, the onset
of symptomatic CKD in the setting of other underlying complications of diabetes
mellitus, including impaired visual acuity and peripheral neuropathy, presents
challenging functional limitations.