NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.

Chronic Kidney Disease

Satyanarayana R. Vaidya; Narothama R. Aeddula.

Author Information and Affiliations

Last Update: October 24, 2022.

Continuing Education Activity

Chronic kidney disease (CKD) is defined as the presence of kidney damage or an

estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 square
meters, persisting for 3 months or more. It is a state of progressive loss of kidney
function ultimately resulting in the need for renal replacement therapy (dialysis
or transplantation). This activity reviews the etiology, evaluation, and
management of chronic kidney disease and emphasizes the roles of the
interprofessional team in caring for patients with chronic kidney disease.

Objectives:

Describe the risk factors for developing chronic kidney disease.

Review the pathophysiology of chronic kidney disease.

Outline the treatment and management options available for chronic kidney
disease.

Explain interprofessional team strategies for enhancing care coordination

and communication to advance the management of chronic kidney disease
and improve patient outcomes.

Access free multiple choice questions on this topic.

Introduction

Chronic kidney disease (CKD) is defined as the presence of kidney damage or an

estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 mt2,
persisting for 3 months or more, irrespective of the cause.[1] It is a state of
progressive loss of kidney function ultimately resulting in the need for renal
replacement therapy (dialysis or transplantation). Kidney damage refers to
pathologic abnormalities either suggested by imaging studies or renal biopsy,
abnormalities in urinary sediment, or increased urinary albumin excretion rates.
The 2012 KDIGO CKD classification recommends details about the cause of the
CKD and classifies it into 6 categories based on glomerular filtration rate (G1 to G5
with G3 split into 3a and 3b). It also includes the staging based on three levels of
albuminuria (A1, A2, and A3), with each stage of CKD being sub-categorized
according to the urinary albumin-creatinine ratio in (mg/gm) or (mg/mmol) in an
early morning “spot” urine sample.[2]

The 6 categories include:

G1: GFR 90 ml/min per 1.73 m2 and above

G2: GFR 60 to 89 ml/min per 1.73 m2

G3a: GFR 45 to 59 ml/min per 1.73 m2

 G3b: GFR 30 to 44 ml/min per 1.73 m2

G4: GFR 15 to 29 ml/min per 1.73 m2

G5: GFR less than 15 ml/min per 1.73 m2 or treatment by dialysis

The three levels of albuminuria include an albumin-creatinine ratio (ACR)

A1: ACR less than 30 mg/gm (less than 3.4 mg/mmol)

A2: ACR 30 to 299 mg/gm (3.4 to 34 mg/mmol)

A3: ACR greater than 300 mg/gm (greater than 34 mg/mmol).

The improved classification of CKD has been beneficial in identifying prognostic

indications related to decreased kidney function and increased albuminuria.
However, a downside of the use of classification systems is the possible
overdiagnosis of CKD, especially in the elderly.

Etiology

The causes of CKD vary globally, and the most common primary diseases causing
CKD and ultimately end-stage renal disease (ESRD) are as follows[3]:

Diabetes mellitus type 2 (30% to 50%)

Diabetes mellitus type 1 (3.9%)

Hypertension (27.2%)

Primary glomerulonephritis (8.2%)

Chronic Tubulointerstitial nephritis (3.6%)

Hereditary or cystic diseases (3.1%)

Secondary glomerulonephritis or vasculitis (2.1%)

Plasma cell dyscrasias or neoplasm (2.1)

Sickle Cell Nephropathy (SCN) which accounts for less than 1% of ESRD
patients in the United States[4]

CKD may result from disease processes in any of the three categories: prerenal
(decreased renal perfusion pressure), intrinsic renal (pathology of the vessels,
glomeruli, or tubules-interstitium), or postrenal (obstructive).

Prerenal Disease

Chronic prerenal disease occurs in patients with chronic heart failure or cirrhosis
with persistently decreased renal perfusion, which increases the propensity for
multiple episodes of an intrinsic kidney injury, such as acute tubular necrosis
(ATN). This leads to progressive loss of renal function over time.

Intrinsic Renal Vascular Disease

The most common chronic renal vascular disease is nephrosclerosis, which

causes chronic damage to blood vessels, glomeruli, and tubulointerstitium.

The other renal vascular diseases are renal artery stenosis from atherosclerosis
or fibro-muscular dysplasia which over months or years, cause ischemic
nephropathy, characterized by glomerulosclerosis and tubulointerstitial fibrosis.
[5]
Intrinsic Glomerular Disease (Nephritic or Nephrotic)

A nephritic pattern is suggested by abnormal urine microscopy with red blood

cell (RBC) casts and dysmorphic red cells, occasionally white blood cells (WBCs),
and a variable degree of proteinuria.[6] The most common causes are post-
streptococcal GN, infective endocarditis, shunt nephritis, IgA nephropathy, lupus
nephritis, Goodpasture syndrome, and vasculitis. [7]

A nephrotic pattern is associated with proteinuria, usually in the nephrotic range

(greater than 3.5 gm per 24 hours), and an inactive urine microscopic analysis
with few cells or casts. It is commonly caused by minimal change disease, focal
segmental glomerulosclerosis, membranous GN, membranoproliferative GN
(Type 1 and 2 and associated with cryoglobulinemia), diabetic nephropathy, and
amyloidosis.

Some patients may be assigned to one of these two categories.

Intrinsic Tubular and Interstitial Disease

The most common chronic tubulointerstitial disease is polycystic kidney disease

(PKD). Other etiologies include nephrocalcinosis (most often due to
hypercalcemia and hypercalciuria), sarcoidosis, Sjogren syndrome, reflux
nephropathy in children and young adults, [8]

There is increased recognition of the relatively high prevalence of CKD of

unknown cause among agricultural workers from Central America and parts of
Southeast Asia called Mesoamerican nephropathy,[9]

Postrenal (Obstructive Nephropathy)

Chronic obstruction may be due to prostatic disease, nephrolithiasis or

abdominal/pelvic tumor with mass effect on ureter(s) are the common causes.
Retroperitoneal fibrosis is a rare cause of chronic ureteral obstruction.

Epidemiology

The true incidence and prevalence of CKD are difficult to determine because of
the asymptomatic nature of early to moderate CKD. The prevalence of CKD is
around 10% to 14% in the general population. Similarly, albuminuria
(microalbuminuria or A2) and GFR less than 60 ml/min/1.73 mt2 have a
prevalence of 7% and 3% to 5%, respectively.[10]

Worldwide, CKD accounted for 2,968,600 (1%) of disability-adjusted life-years and

2,546,700 (1% to 3%) of life-years lost in 2012.[3]

Kidney Disease Outcomes Quality Initiative (KDOQI) mandates that for labeling of
chronicity and CKD, patients should be tested on three occasions over a 3-month
period with 2 of the 3 results being consistently positive.[11]

Natural History and Progression of CKD

CKD diagnosed in the general population (community CKD) has a

significantly different natural history and the course of progression compared to
the CKD in patients referred to the nephrology practices (referred CKD).

Community CKD is seen mainly in the older population. These individuals have
had lifelong exposure to cardiovascular risk factors, hypertension, and diabetes
which can also affect the kidneys. The average rate of decline in GFR in this
population is around 0.75 to 1 ml/min/year after the age of 40 to 50 years. [12] In a
large study of community-based CKD by Kshirsagar et al., only 1% and 20% of
patients with CKD stages G3 and G4 required renal replacement therapy (RRT),
however, 24% and 45% respectively died predominantly from cardiovascular
disease (CVD), suggesting that cardiac events rather than progressing to ESRD is
the predominant outcome in community-based CKD.[13]

In contrast to community CKD, patients with referred CKD present at an early age
because of hereditary (autosomal dominant polycystic kidney disease ADPKD) or
acquired nephropathy (glomerulonephritis, diabetic nephropathy, or
tubulointerstitial disease) causing progressive renal damage and loss of function.
The rate of progression in referred CKD varies according to the underlying
disease process and between individual patients. Diabetic nephropathy has
shown to have a rapid rate of decline in GFR averaging around 10 ml/min/year. In
nondiabetic nephropathies, the rate of progression is usually faster in patients
with chronic proteinuric GN than in those with a low level of proteinuria.
Patients with ADPKD and renal impairment, CKD stage G3b and beyond, may
have a faster rate of progression compared to other nephropathies. In patients
with hypertensive nephrosclerosis, good blood pressure control and minimal
proteinuria are associated with very slow progression.

Risk Factors for Progression of CKD

Non-Modifiable CKD Risk Factors

Older age, male gender, a non-Caucasian ethnicity which includes African

Americans, Afro-Caribbean individuals, Hispanics, and Asians (South Asians and
Pacific Asians) all adversely affect CKD progression.

Genetic factors which affect CKD progression have been found in different
Kidney diseases. In a population-based cohort study by Luttropp et al., single
nucleotide polymorphisms in the genes TCF7L2 and MTHFS were associated with
diabetic nephropathy and CKD progression. In the same study, polymorphisms of
genes coding for mediators of renal scarring and renin-angiotensin-aldosterone
system (RAAS) were found to influence CKD progression.[14]

Modifiable CKD Risk Factors

These include systemic hypertension, proteinuria, and metabolic factors.[15]

Systemic hypertension is one of the main causes of ESRD worldwide and the
second leading cause in the United States after diabetes. The transmission of
systemic hypertension into glomerular capillary beds and the resulting
glomerular hypertension is believed to contribute to the progression of
glomerulosclerosis.[16] Night-time and 24-hour blood pressure measurement
(ABPM) appear to correlate best with the progression of CKD. Systolic rather than
diastolic BP seems to be predictive of CKD progression and has also been
associated with complications in CKD.

Multiple studies in patients with diabetic and nondiabetic kidney diseases have
shown that marked proteinuria (albuminuria A3) is associated with a faster rate
of CKD progression. Also, a reduction in marked proteinuria by RAS blockade or
by diet is associated with a better renal outcome. However, in large intervention
studies like Avoiding Cardiovascular Events Through Combination Therapy in
Patients Living with Systolic Hypertension (ACCOMPLISH)[17] and Ongoing
Telmisartan Alone and in Combination with Ramipril Global End Point Trial
(ONTARGET),[18] significant declines in GFR were noted despite a marked
reduction in albuminuria. Therefore, moderate level albuminuria (A2) is not a
reliable surrogate marker for CKD progression, and reduction in albuminuria can
be associated with both improving and worsening of CKD progression.

Multiple studies have linked the RAAS system in the pathogenesis of

hypertension, proteinuria, and renal fibrosis throughout CKD. Subsequently,
interventions targeting RAAS have proved effective in slowing the progression of
CKD. This has led to the widespread use of RAAS blockers in proteinuric and
diabetic kidney disease.

Obesity and smoking have been related to the development and progression of
CKD. Also, metabolic factors such as insulin resistance, dyslipidemia, and
hyperuricemia have been implicated in the development and progression of CKD.
[19][20]

Recommendations for CKD Screening

Screening, mostly targeting high-risk individuals is being implemented

worldwide. The KDOQI guidelines recommend screening high-risk populations
which include individuals with Hypertension, Diabetes mellitus, and those older
than 65 years. This should include urinalysis, a urine albumin-creatinine ratio
(ACR), measurement of serum creatinine and estimation of GFR preferably by
chronic kidney disease epidemiology collaboration (CKD-EPI) equation. It is the
most cost-effective approach, and there is no evidence to justify screening
asymptomatic individuals in the general population for CKD.

Pathophysiology

Unlike acute kidney injury (AKI), where the healing process is complete with
complete functional kidney recovery, chronic and sustained insults from chronic
and progressive nephropathies evolve to progressive kidney fibrosis and
destruction of the normal architecture of the kidney. This affects all the 3
compartments of the kidney, namely glomeruli, the tubules, the interstitium, and
the vessels. It manifests histologically as glomerulosclerosis, tubulointerstitial
fibrosis, and vascular sclerosis.

The sequence of events which lead to scarring and fibrosis are complex,
overlapping, and are multistage phenomena.

Infiltration of damaged kidneys with extrinsic inflammatory cells

Activation, proliferation, and loss of intrinsic renal cells (through apoptosis,

necrosis, mesangiolysis, and podocytopenia)

Activation and proliferation of extracellular matrix (ECM) producing cells

including myofibroblasts and fibroblasts

Deposition of ECM replacing the normal architecture

Mechanisms of Accelerated Progression of CKD

Systemic and intraglomerular hypertension

Glomerular hypertrophy

Intrarenal precipitation of calcium phosphate

Altered prostanoid metabolism

All these mechanisms lead to a histological entity called focal segmental

glomerulosclerosis.[21]
Clinical risk factors for accelerated progression of CKD are proteinuria,
hypertension, black race, and hyperglycemia. Also, environmental exposures
such as lead, smoking, metabolic syndrome, possibly some analgesic agents, and
obesity have also been linked to accelerated progression of CKD.[22]

History and Physical

Early CKD stages are asymptomatic, and symptoms manifest in stages 4 or 5. It is

commonly detected by routine blood or urine testing. Some common symptoms
and signs at these stages of CKD are:

Nausea

Vomiting

Loss of appetite

Fatigue and weakness

Sleep disturbance

Oliguria

Decreased mental sharpness

Muscle twitches and cramps

Swelling of feet and ankles

Persistent pruritus

Chest pain due to uremic pericarditis

Shortness of breath due to pulmonary edema from fluid overload

Hypertension that's difficult to control

Physical examination is often not helpful, but patients may have

Skin pigmentation

Scratch marks from pruritus

Pericardial friction rub due to uremic pericarditis

Uremic frost, where high levels of BUN result in urea in sweat

Hypertensive fundal changes suggesting chronicity

Evaluation

Establishing Chronicity

When an eGFR of less than 60 ml/min/1.73m is detected in a patient, attention

needs to be paid to the previous blood and urine test results and clinical history
to determine whether this is a result of AKI or CKD that has been present but
asymptomatic. The following factors would be helpful.

1. History of long-standing chronic hypertension, proteinuria,

microhematuria, and symptoms of the prostatic disease

2. Skin pigmentation, scratch marks, left ventricular hypertrophy, and

hypertensive fundal changes
 3. Blood test results of other conditions like multiple myeloma, systemic
vasculitis would be helpful.

4. Low serum calcium and high phosphorus levels have little discriminatory
value, but normal Parathyroid hormone levels suggest AKI rather than CKD

5. Patients who have very high blood urea nitrogen (BUN) values greater than
140 mg/dl, serum creatinine greater than 13.5 mg/dl, who appear relatively
well and still passing normal volumes of urine are much more likely to have
CKD than acute kidney disease.

Assessment of Glomerular Filtration Rate

For patients in whom the distinction between AKI and CKD is unclear, kidney
function tests should be repeated in 2 weeks of the initial finding of low eGFR
below 60 ml/min/1.73 m.

If previous tests confirm that the low eGFR is chronic or the repeat blood test
results over 3 months are consistent, CKD is confirmed.

If eGFR based on serum creatinine is known to be less accurate, then other

markers like cystatin-c or an isotope-clearance measurement can be undertaken.

Assessment of Proteinuria

KDIGO recommends that proteinuria should be assessed by obtaining an early

morning urine sample and quantifying albumin-creatinine ratio (ACR). The
degree of albuminuria is graded from A1 to A3, replacing previous terms such as
microalbuminuria.

Some patients may excrete proteins other than albumin and urine protein-
creatinine ratio (PCR) may be more useful for certain conditions.[23]

Imaging of Kidneys

If an ultrasound examination of kidneys shows small kidneys with reduced

cortical thickness, increased echogenicity, scarring, or multiple cysts, this suggests
a chronic process. It may also be helpful to diagnose chronic hydronephrosis
from obstructive uropathy, cystic enlargement of the kidney in ADPKD.

Renal ultrasound Doppler can be used in suspected renal artery stenosis to

evaluate the renal vascular flow

Computerized tomography: A low dose of non-contrast CT is used to diagnose

renal stone disease. It is also used to diagnose suspected ureteric obstruction
which cannot be seen by ultrasonography.

Renal angiography has its role in the diagnosis of polyarteritis nodosa where
multiple aneurysms and irregular areas of constriction are seen.

Voiding cystourethrography is mainly used when chronic vesicourethral reflux is

suspected as the cause of CKD.[8] It is used to confirm the diagnosis and estimate
the severity of reflux.

Renal scans can give sufficient information about the anatomy and function of
kidneys. They are used predominantly in children as they are associated with
lesser radiation exposure compared to CT scan. Radionuclide renal scans are used
to measure the difference in function between the kidneys.

Establishing an Accurate Diagnosis

An accurate cause of CKD needs to be established such as when there is an
underlying treatable condition that requires appropriate management, for
example, lupus nephritis, ANCA vasculitis, among others. In addition, certain
diseases carry a higher frequency of recurrence in the kidney after
transplantation and accurate diagnosis will influence later management. A
kidney biopsy is used to diagnose the etiology of CKD, and it also gives
information about the extent of fibrosis in the kidney.

Treatment / Management

General Management

Adjusting drug doses for the level of estimated glomerular filtration rate
(GFR)

Preparation of renal replacement therapy by placing an arteriovenous

fistula or graft

Treat the Reversible Causes of Renal Failure

The potentially reversible causes of acute kidney injury like infection, drugs that
reduce the GFR, hypotension such as from shock, instances that cause
hypovolemia such as vomiting, diarrhea should be identified and intervened.

Patients with CKD should be evaluated carefully for the use of intravenous
contrast studies, and any alternatives for the contrast studies should be utilized
first. Other nephrotoxic agents such as aminoglycoside antibiotics and NSAIDs
should be avoided.

Retarding the Progression of CKD

The factors which result in progression of CKD should be addressed such as

hypertension, proteinuria, metabolic acidosis, and hyperlipidemia. Hypertension
should be managed in CKD by establishing blood pressure goals. Similarly, the
proteinuria goal should be met.

Multiple studies have shown that smoking is associated with the risk of
developing nephrosclerosis and smoking cessation retards the progression of
CKD.[24]

Protein restriction has also been shown to slow CKD progression. However, the
type and amount of protein intake are yet to be determined.

Bicarbonate supplementation for the treatment of chronic metabolic acidosis has

been shown to delay the CKD progression as well. [25] Also, intensive glucose
control in diabetics has been shown to delay the development of albuminuria and
also the progression of albuminuria to overt proteinuria.[26]

Preparation and Initiation of Renal Replacement Therapy

Once the CKD progression is noted, the patient should be offered various options
for renal replacement therapy.

Hemodialysis (home or in-center)

Peritoneal dialysis (continuous or intermittent)[27]

Kidney transplantation (living or deceased donor): It is the treatment of

choice for ESRD given better long-term outcomes.
 Patients who do not want renal replacement therapy should be provided
with information about conservative and palliative care management.

The hemodialysis is performed after stable vascular access is placed in a

nondominant arm. In this arm, intravenous cannulas are avoided to
preserve the veins. The preferred vascular access is AV fistula. The other
hemodialysis access options are AV graft and tunneled hemodialysis
catheters. The patency rates of AV fistula is good, and infections are very
infrequent. Higher flows can be achieved through AV fistula, and there is
less chance of recirculation.

Peritoneal dialysis is performed after placing a peritoneal catheter.[27]

Indications for Renal Replacement Therapy

Pericarditis or pleuritis (urgent indication)

Progressive uremic encephalopathy or neuropathy, with signs such as

confusion, asterixis, myoclonus, and seizures (urgent indication)

A clinically significant bleeding diathesis is attributable to uremia (urgent

indication)

Hypertension is poorly responsive to antihypertensive medications

Fluid overload is refractory to diuretics

Metabolic disorders that are refractory to medical therapy such as

hyperkalemia, hyponatremia, metabolic acidosis, hypercalcemia,
hypocalcemia, and hyperphosphatemia

Persistent nausea and vomiting

Evidence of malnutrition

Renal transplantation is the best treatment option of ESRD due to its survival
benefit compared to long-term dialysis therapy. The patients with CKD become
eligible to be listed for Deceased donor renal transplant program when the eGFR
is less than 20 ml/min/1.73m2

Conservative management of ESRD is also an option for all patients who decide
not to pursue renal replacement therapy. Conservative care includes the
management of symptoms, advance-care planning, and provision of
appropriate palliative care. This strategy is often underutilized and needs to be
considered for very frail patients with poor functional status with numerous
comorbidities. For facilitating this discussion a 6-month mortality score calculator
is being used which includes variables such as age, serum albumin, the presence
of dementia, peripheral vascular disease, and (yes/no) answer to a question by a
treating nephrologist "would I be surprised if this patient died in the next year?"

When to Refer to a Nephrologist

Patients with CKD should be referred to a nephrologist when the estimated GFR is
less than 30 ml/min/1.73 mt2. This is the time to discuss the options of renal
replacement therapy.

Differential Diagnosis

Acute kidney injury

 Alport syndrome

Antigiomerular basement membrane disease

Chronic glomerulonephritis

Diabetic nephropathy

Multiple myeloma

Nephrolithiasis

Nephrosclerosis

Rapidly progressive glomerulonephritis

Renal artery stenosis

Staging

The 6 categories include:

G1: GFR 90 ml/min per 1.73 m2 and above

G2: GFR 60 to 89 ml/min per 1.73 m2

G3a: GFR 45 to 59 ml/min per 1.73 m2

G3b: GFR 30 to 44 ml/min per 1.73 m2

G4: GFR 15 to 29 ml/min per 1.73 m2

G5: GFR less than 15 ml/min per 1.73 m2 or treatment by dialysis

The 3 levels of albuminuria include albumin-creatinine ratio (ACR):

A1: ACR less than 30 mg/gm (less than 3.4 mg/mmol)

A2: ACR 30 to 299 mg/gm (3.4 to 34 mg/mmol)

A3: ACR greater than 300 mg/gm (greater than 34 mg/mmol)

Prognosis

Significant racial and ethnic differences exist in the incidence and prevalence
rates of ESRD. The highest incidence is found in African Americans; followed by
American Indians and Alaska Natives; followed by Asian Americans, Native
Hawaiians, and other Pacific Islanders; followed by whites. Hispanics have higher
incidence rates of ESRD than non-Hispanics.

Early-stage CKD and ESRD are associated with increased morbidity and health
care utilization rates. A review of the USRDS 2009 annual data report suggests
that the number of hospitalizations in ESRD patients is 1.9% per patient-year. In a
study by Khan SS et al., the prevalence of cardiovascular disease, cerebrovascular
disease, and peripheral vascular disease in earlier stages of CKD was comparable
to those in the US dialysis population. It was also found that patients with CKD
had 3-fold higher rates of hospitalization and hospital days spent per patient-year
compared to the general US population.[28] CKD patients are at a higher risk of
hospitalization and cardiovascular diseases and the risk increases with a decline
in GFR.
Patients with CKD and particularly end-stage renal disease (ESRD) are at
increased risk of mortality, particularly from cardiovascular disease. A review of
USRDS 2009 data suggests that 5-year survival probability in a patient on
dialysis is only around 34%.

Complications

Treatment of Complications of Chronic Kidney Disease

Patients with CKD have diminished ability to maintain a fluid balance after a
rapid sodium load and becomes more apparent in stages IV and V of CKD. These
patients respond to sodium restriction and a loop diuretic. The 2012 KDIGO
guidelines recommend all CKD patients should be sodium restricted to less than 2
gm per day.

Hyperkalemia in CKD can occur specifically in oliguric patients and in whom

where aldosterone secretion is diminished. Dietary intake of potassium, tissue
breakdown and hypoaldosteronism could result in hyperkalemia. Drugs such as
ACE inhibitors and nonselective beta-blockers could also result in hyperkalemia.

Metabolic acidosis is a common complication of advanced CKD due to the

increased tendency of kidneys in CKD to retain H. Chronic metabolic acidosis in
CKD would result in osteopenia, increased protein catabolism, and secondary
hyperparathyroidism. These patients should be treated with bicarbonate
supplementation to target serum bicarbonate of equal to 23.

CKD is a significant risk factor for CVD and risk increases with increased severity
of the CKD. Considerable evidence indicates a significant association between
Epicardial adipose tissue (EAT) thickness and the incidence of CVD events in CKD
patients. In CKD patients, EAT assessment could be a reliable parameter for
cardiovascular risk assessment.[29].

Bone and Mineral Disorders

Hyperphosphatemia is a frequent complication of CKD due to a decreased filtered

load of phosphorous. This leads to increased secretion of a Parathyroid hormone
(PTH) and causes secondary hyperparathyroidism. Hyperparathyroidism results
in the normalization of phosphorous and calcium but at the expense of bone. This
results in renal osteodystrophy. Therefore, phosphorus binders along with dietary
restriction of phosphorus are used to treat secondary hyperparathyroidism.

Hypertension is a manifestation of volume expansion in CKD. Patients in CKD do

not always have edema to suggest volume expansion. Therefore, all patients with
CKD should have a loop diuretic added to control the blood pressure which needs
to be titrated before considering an increase in antihypertensive therapy.

Anemia in CKD is usually normocytic normochromic. It is primarily due to

reduced erythropoietin production from reduced functioning renal mass and also
due to reduced red cell survival. Hemoglobin should be checked at least yearly in
CKD 3, every 6 months in CKD IV and V, and every 3 months in dialysis patients.
Erythropoietin stimulating agents (ESA) in CKD patients should be considered
when Hb is less than 10 and provided iron saturation is at least 25% and ferritin
greater than 200 ng/mL. In dialysis patients, the goal Hb concentration is 10 to
11.5 gm/dl.

Treatment of Complications of ESRD

Malnutrition in ESRD is due to anorexia and poor protein intake. The diet in ESRD
should provide at least 30 to 35 Kcal/kg per day. A low plasma albumin
concentration is suggestive of malnutrition.

Uremic bleeding is a complication resulting from impaired platelet function. It

results in prolonged bleeding time. Asymptomatic patients are not treated.
However, correction of uremic platelet dysfunction is needed during active
bleeding, need for a surgical procedure. Some interventions used are
desmopressin (dDAVP), cryoprecipitate, estrogen, and initiation of dialysis.

Uremia can present as uremic pericarditis and is an indication for initiation of

dialysis. Uremic pericarditis is treated with dialysis and responds well.

Complications of Renal Transplantation

Complications related to cardiovascular, renal, neurologic, and gastrointestinal

systems.[30][31]

Common complications include hypertension, dyslipidemia, coronary artery

disease from new-onset diabetes mellitus and renal failure, left ventricular
hypertrophy, arrhythmias,[31] and heart failure. Neurologic complications
include stroke and posterior reversible encephalopathy syndrome, central
nervous system (CNS) infections, neuromuscular disease, seizure disorders, and
neoplastic disease. GI complications include infection, malignancy
(posttransplant lymphoproliferative disorder), mucosal injury, mucosal
ulceration, perforation, biliary tract disease, pancreatitis, and diverticular
disease.

Consultations

Nephrology should be consulted for all patients with CKD where GFR is less
than 30 ml/min/1.73 m.

Urology consultation is needed for obstructive uropathy.

Relieve obstruction with retrograde ureteral catheters or percutaneous

nephrostomy.

Interventional radiology consults for placement of permanent tunneled

hemodialysis catheter.

Vascular surgery is suggested for placing arterio-venous fistula(AVF) or

grafts (AVG) along with peritoneal dialysis catheters.

Deterrence and Patient Education

All high-risk groups of patients such as Diabetic patients, hypertensives, should

not only be screened for CKD but also be counseled about the symptoms and signs
of CKD. Patients with CKD should be taught about the following interventions at
home

Eighty percent to 85% of patients with CKD have hypertension, and they should
be instructed to measure blood pressure daily and to keep a log of blood pressure,
daily weights. They should be prescribed a diuretic as a part of an
antihypertensive regimen.

Teaching patients with advanced CKD of home administration of subcutaneous

erythropoietin stimulating agents.
There should be a discussion held with patients by nutritionists or physicians
about low protein diet which may slow the progression of CKD and potassium-
containing foods.

All patients with advanced CKD should be instructed about the need to control
phosphorus levels. They should be instructed to take phosphate binders with each
meal.

CKD patients who are pregnant should be educated that pregnancy may worsen
the CKD and how reduced kidney function can adversely affect pregnancy.

Pearls and Other Issues

1. Chronic kidney disease (CKD) is defined as kidney damage or an estimated

glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m persisting for
three months or more irrespective of the cause.

2. CKD is usually asymptomatic till stages IV and V.

3. The KDOQI guidelines recommend screening high-risk populations which

include individuals with hypertension, diabetes mellitus, and those older
than 65 years with a urinalysis, a urine albumin-creatinine ratio (ACR),
measurement of serum creatinine, and estimation of GFR preferably by
chronic kidney disease epidemiology collaboration (CKD-EPI) equation.

4. Calcium and phosphorus are not useful to distinguish AKI from CKD.
However, normal PTH suggests AKI rather than CKD.

5. Systemic hypertension, proteinuria, hyperlipidemia, and metabolic acidosis

cause progression of CKD and need to be treated aggressively.

6. Bicarbonate supplementation to reach a serum bicarbonate target equal to

23 delays the progression of CKD.

7. All CKD patients need to be evaluated for anemia, hypertension, metabolic

acidosis, and bone and mineral disorders.

Enhancing Healthcare Team Outcomes

CKD has a multitude of manifestations and is optimally managed by an

interprofessional team of health care professionals who practice at a single
location such as a CKD clinic. These clinics focus on guideline-driven kidney care,
evaluate and treat complications, suggest patient lifestyle modifications, and
provide adequate patient education regarding the various modalities of dialysis.
Fishbane et al. compared a standard care model with a healthy transitions
program where a nurse care manager works with a protocol-driven informatics
system that provides daily reports with incomplete steps of the process for each
patient.[32] It showed a reduction in hospitalizations, increased use of AV fistulas,
a decrease in emergent dialysis, and less use of catheters. Such models decrease
the overall cost of health care by saving billions of dollars.

The interprofessional CKD clinics have access to a nutritionist who assesses the
nutritional status of a patient and also formulates a meal plan. Similarly, a
pharmacist performs a medication check and screens for nephrotoxic
medications and adjusts the non-nephrotoxic medications to the patient’s renal
function. The nurse practitioner evaluates the blood pressure and adjusts the
blood pressure medications accordingly. The primary care provider educates the
patient on the importance of discontinuing smoking, eating healthy and
maintaining healthy body weight. The dialysis nurse assists the team by
providing education on how to look after the dialysis catheters or AV fistulas. A
vascular access nurse also evaluates appropriate patients for hemodialysis access.
Finally, a renal transplantation nurse provides information on the procedure and
the criteria for selecting patients for the procedure.

Evidence shows that an interprofessional approach to chronic renal failure

avoids duplication of studies, is cost-effective, results in less patient morbidity,
and ensures better outcomes.[33] [Level 5]

Review Questions

Access free multiple choice questions on this topic.

Comment on this article.

References

1. Chapter 1: Definition and classification of CKD. Kidney Int Suppl (2011). 2013
Jan;3(1):19-62. [PMC free article: PMC4089693] [PubMed: 25018975]
2. Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M,
Feldman HI. KDOQI US commentary on the 2012 KDIGO clinical practice
guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014
May;63(5):713-35. [PubMed: 24647050]
3. Webster AC, Nagler EV, Morton RL, Masson P. Chronic Kidney Disease. Lancet.
2017 Mar 25;389(10075):1238-1252. [PubMed: 27887750]
4. Aeddula NR, Bardhan M, Baradhi KM. StatPearls [Internet]. StatPearls
Publishing; Treasure Island (FL): Sep 4, 2023. Sickle Cell Nephropathy.
[PubMed: 30252273]
5. Textor SC. Ischemic nephropathy: where are we now? J Am Soc Nephrol. 2004
Aug;15(8):1974-82. [PubMed: 15284283]
6. Kitamoto Y, Tomita M, Akamine M, Inoue T, Itoh J, Takamori H, Sato T.
Differentiation of hematuria using a uniquely shaped red cell. Nephron.
1993;64(1):32-6. [PubMed: 8502333]
7. Khanna R. Clinical presentation & management of glomerular diseases:
hematuria, nephritic & nephrotic syndrome. Mo Med. 2011 Jan-Feb;108(1):33-
6. [PMC free article: PMC6188440] [PubMed: 21462608]
8. Aeddula NR, Baradhi KM. StatPearls [Internet]. StatPearls Publishing; Treasure
Island (FL): May 22, 2023. Reflux Nephropathy. [PubMed: 30252311]
9. Madero M, García-Arroyo FE, Sánchez-Lozada LG. Pathophysiologic insight
into MesoAmerican nephropathy. Curr Opin Nephrol Hypertens. 2017
Jul;26(4):296-302. [PubMed: 28426518]
10. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic
kidney disease and decreased kidney function in the adult US population:
Third National Health and Nutrition Examination Survey. Am J Kidney Dis.
2003 Jan;41(1):1-12. [PubMed: 12500213]
11. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic
kidney disease: evaluation, classification, and stratification. Am J Kidney Dis.
2002 Feb;39(2 Suppl 1):S1-266. [PubMed: 11904577]
12. Muntner P. Longitudinal measurements of renal function. Semin Nephrol.
2009 Nov;29(6):650-7. [PubMed: 20006797]
13. Kshirsagar AV, Bang H, Bomback AS, Vupputuri S, Shoham DA, Kern LM,
Klemmer PJ, Mazumdar M, August PA. A simple algorithm to predict incident
kidney disease. Arch Intern Med. 2008 Dec 08;168(22):2466-73. [PMC free article:
PMC2849985] [PubMed: 19064831]
14. Luttropp K, Lindholm B, Carrero JJ, Glorieux G, Schepers E, Vanholder R,
Schalling M, Stenvinkel P, Nordfors L. Genetics/Genomics in chronic kidney
disease--towards personalized medicine? Semin Dial. 2009 Jul-Aug;22(4):417-
22. [PubMed: 19708993]
15. Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012 Jan
14;379(9811):165-80. [PubMed: 21840587]
16. Hyperfiltration in remnant nephrons: a potentially adverse response to renal
ablation. J Am Soc Nephrol. 2001 Jun;12(6):1315-1325. [PubMed: 11373357]
17. Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, Hester A, Gupte J,
Gatlin M, Velazquez EJ., ACCOMPLISH Trial Investigators. Benazepril plus
amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N
Engl J Med. 2008 Dec 04;359(23):2417-28. [PubMed: 19052124]
18. Vidt DG. Telmisartan, ramipril, or both in patients at high risk for vascular
events. Curr Hypertens Rep. 2008 Oct;10(5):343-4. [PubMed: 18775108]
19. Moorhead JF, Chan MK, El-Nahas M, Varghese Z. Lipid nephrotoxicity in
chronic progressive glomerular and tubulo-interstitial disease. Lancet. 1982
Dec 11;2(8311):1309-11. [PubMed: 6128601]
20. Johnson RJ, Nakagawa T, Jalal D, Sánchez-Lozada LG, Kang DH, Ritz E. Uric
acid and chronic kidney disease: which is chasing which? Nephrol Dial
Transplant. 2013 Sep;28(9):2221-8. [PMC free article: PMC4318947] [PubMed:
23543594]
21. Anderson S, Rennke HG, Brenner BM. Antihypertensive therapy must control
glomerular hypertension to limit glomerular injury. J Hypertens Suppl. 1986
Dec;4(5):S242-4. [PubMed: 3553475]
22. Yu HT. Progression of chronic renal failure. Arch Intern Med. 2003 Jun
23;163(12):1417-29. [PubMed: 12824091]
23. Methven S, Traynor JP, Hair MD, St J O'Reilly D, Deighan CJ, MacGregor MS.
Stratifying risk in chronic kidney disease: an observational study of UK
guidelines for measuring total proteinuria and albuminuria. QJM. 2011
Aug;104(8):663-70. [PubMed: 21382924]
24. Hallan SI, Orth SR. Smoking is a risk factor in the progression to kidney
failure. Kidney Int. 2011 Sep;80(5):516-23. [PubMed: 21677635]
25. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate
supplementation slows progression of CKD and improves nutritional status. J
Am Soc Nephrol. 2009 Sep;20(9):2075-84. [PMC free article: PMC2736774]
[PubMed: 19608703]
26. Diabetes Control and Complications Trial Research Group. Nathan DM,
Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect
of intensive treatment of diabetes on the development and progression of
long-term complications in insulin-dependent diabetes mellitus. N Engl J
Med. 1993 Sep 30;329(14):977-86. [PubMed: 8366922]
27. Sachdeva B, Zulfiqar H, Aeddula NR. StatPearls [Internet]. StatPearls
Publishing; Treasure Island (FL): Aug 8, 2023. Peritoneal Dialysis. [PubMed:
30422574]
28. Khan SS, Kazmi WH, Abichandani R, Tighiouart H, Pereira BJ, Kausz AT.
Health care utilization among patients with chronic kidney disease. Kidney
Int. 2002 Jul;62(1):229-36. [PubMed: 12081582]
29. Aeddula NR, Cheungpasitporn W, Thongprayoon C, Pathireddy S. Epicardial
Adipose Tissue and Renal Disease. J Clin Med. 2019 Mar 02;8(3) [PMC free
article: PMC6463003] [PubMed: 30832377]
30. Sen A, Callisen H, Libricz S, Patel B. Complications of Solid Organ
Transplantation: Cardiovascular, Neurologic, Renal, and Gastrointestinal. Crit
Care Clin. 2019 Jan;35(1):169-186. [PubMed: 30447778]
31. Thongprayoon C, Chokesuwattanaskul R, Bathini T, Khoury NJ, Sharma K,
Ungprasert P, Prasitlumkum N, Aeddula NR, Watthanasuntorn K, Salim SA,
Kaewput W, Koller FL, Cheungpasitporn W. Epidemiology and Prognostic
Importance of Atrial Fibrillation in Kidney Transplant Recipients: A Meta-
Analysis. J Clin Med. 2018 Oct 19;7(10) [PMC free article: PMC6210475]
[PubMed: 30347721]
32. Fishbane S, Agoritsas S, Bellucci A, Halinski C, Shah HH, Sakhiya V, Balsam L.
Augmented Nurse Care Management in CKD Stages 4 to 5: A Randomized
Trial. Am J Kidney Dis. 2017 Oct;70(4):498-505. [PubMed: 28396108]
33. Ghimire S, Lee K, Jose MD, Castelino RL, Zaidi STR. Adherence assessment
practices in haemodialysis settings: A qualitative exploration of nurses and
pharmacists' perspectives. J Clin Nurs. 2019 Jun;28(11-12):2197-2205.
[PubMed: 30786082]
Disclosure: Satyanarayana Vaidya declares no relevant financial relationships with ineligible
companies.

Disclosure: Narothama Aeddula declares no relevant financial relationships with ineligible

companies.

Copyright © 2023, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to
distribute the work, provided that the article is not altered or used commercially. You are not required to obtain
permission to distribute this article, provided that you credit the author and journal.

Bookshelf ID: NBK535404 PMID: 30571025