Chronic kidney disease

Last updated: September 13, 2024

Summary

Chronic kidney disease (CKD) is defined as an abnormality of kidney structure or function that persists for > 3 months. The most common causes of CKD in the United States are diabetes mellitus, hypertension, and glomerulonephritis. The kidney's efficient compensatory mechanisms and significant renal reserve mean that most patients remain asymptomatic until their kidney function is severely impaired. While patients are most commonly initially identified because of gradual asymptomatic elevation in serum creatinine, at advanced disease stages, patients may present with symptoms of fluid overload (e.g., peripheral edema) and/or uremia (e.g., fatigue, pruritus). Patients with CKD also have a significantly increased risk of developing atherosclerotic cardiovascular disease (ASCVD). Laboratory studies may show metabolic complications, such as hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis. The goal of management is to slow CKD progression and prevent and manage complications. This includes treatment of the underlying disease, avoiding nephrotoxic substances, maintaining adequate hydration and nutrition, management of ASCVD (e.g., using statin therapy and adequate treatment of diabetes mellitus), and addressing complications such as anemia of chronic kidney disease and CKD-mineral and bone disorder. Renal replacement therapy (i.e., dialysis or kidney transplantation) is required if CKD progresses to end-stage renal disease (ESRD).

See also “Acute kidney injury” (AKI) and “Diabetic kidney disease.”

Epidemiology

Prevalence ^[1]
- An estimated 37 million individuals (15%) in the US have CKD.
- 726,000 individuals have ESRD.
Incidence: > 350 cases of ESRD per million individuals annually ^[1]
Risk factors for CKD ^[1]
- Diabetes
- Hypertension
- Obesity
- Advanced age (> 60 years of age) ^[2]
- Substance use (smoking, alcohol, recreational drugs)
- Acute kidney injury
- Family history of CKD
- African American or Hispanic descent ^[3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Diabetic nephropathy (38%)
Hypertensive nephropathy (26%)
Glomerulonephritis (16%)
Other causes (15%, e.g., polycystic kidney disease, analgesic misuse, amyloidosis)
Idiopathic (5%)

Pathophysiology

Pathophysiology depends on the underlying condition, any of which will eventually lead to progressive nephron loss, structural damage, and impaired kidney function.

Underlying conditions

Diabetic nephropathy ^[6]

Hyperglycemia → nonenzymatic glycation of proteins → varying degrees of damage to all types of kidney cell.
Pathological changes include:
- Hypertrophy and proliferation of mesangial cells, GBM thickening, and ECM protein accumulation → eosinophilic nodular glomerulosclerosis
- Thickening and diffuse hyalinization of afferent and efferent arterioles/interlobular arteries
- Interstitial fibrosis, TBM thickening, and tubular hypertrophy

Hypertensive nephropathy

Caused by protective autoregulatory vasoconstriction of preglomerular vessels, increases in systemic blood pressure do not normally affect renal microvessels. ^[7]
Increased systemic blood pressure (e.g., due to chronic hypertension) below the protective autoregulatory threshold → benign nephrosclerosis (sclerosis of afferent arterioles and small arteries) → ↓ perfusion → ischemic damage
In case BP exceeds threshold → acute injury → malignant nephrosclerosis (petechial subcapsular hemorrhages, visible infarction with necrosis of mesangial and endothelial cells, thrombosis of glomeruli capillaries, luminal thrombosis of arterioles, and red blood cell extravasation and fragmentation) → failure of autoregulatory mechanisms → ↑ damage

Glomerulonephritis (GN)

Noninflammatory GN (e.g., minimal change GN, membranous nephropathy, focal segmental glomerulosclerosis)
Inflammatory GN (e.g., lupus nephritis, poststreptococcal GN, rapid progressive GN, hemolytic uremic syndrome)

Consequences

Reduced GFR

↓ Production of urine → ↑ extracellular fluid volume → total-body volume overload
↓ Excretion of waste products (e.g., urea, drugs)
↓ Excretion of phosphate → hyperphosphatemia
- During the early stages of CKD, plasma phosphate levels will typically be normal due to the increased secretion of fibroblast growth factor 23 (FGF23). ^[8]
  - FGF23 is produced by osteoblasts in response to initial hyperphosphatemia and increased calcitriol.
  - Increased secretion of FGF23 leads to increased phosphate secretion and suppressed conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.
  - In advanced CKD, the effects of FGF 23 subside (most likely due to development of resistance in target tissues). ^[8]
↓ Maintenance of acid-base balance; → metabolic acidosis
↓ Maintenance of electrolyte concentrations → electrolyte imbalances (e.g., Na⁺ retention)

Reduced endocrine activity

↓ Hydroxylation of calcifediol → ↓ production of calcitriol → (in combination with ↓ excretion of phosphate) → ↓ serum Ca²⁺ → ↑ PTH
↓ Erythropoietin → ↓ stimulation of erythropoiesis

Reduced gluconeogenesis

↑ Risk of hypoglycemia

Clinical features

Patients are often asymptomatic until later stages due to the exceptional compensatory mechanisms of the kidneys.

Manifestations of Na⁺/H₂O retention

Hypertension and heart failure
Pulmonary; and peripheral edema

Manifestations of uremia

Definition: Uremia is defined as the accumulation of toxic substances due to decreased renal excretion. These toxic substances are mostly metabolites of proteins such as urea, creatinine, β₂ microglobulin, and parathyroid hormone.
Constitutional symptoms
- Fatigue
- Weakness
- Headaches
Gastrointestinal symptoms
- Nausea and vomiting
- Loss of appetite
- Uremic fetor: characteristic ammonia- or urine-like breath odor
Dermatological manifestations
- Pruritus
- Skin color changes (e.g., hyperpigmentation, pallor due to anemia)
- Uremic frost: uremia leads to high levels of urea secreted in the sweat, the evaporation of which may result in tiny crystallized yellow-white urea deposits on the skin.
Serositis
- Uremic pericarditis: a complication of chronic kidney disease that causes fibrinous pericarditis
  - Clinical features: chest pain worsened by inhalation
  - Physical examination findings
    - Friction rub on auscultation
    - ECG changes normally seen in nonuremic pericarditis (e.g., diffuse ST-segment elevation) are not usually seen.
- Pleuritis
Neurological symptoms
- Asterixis
- Signs of uremic encephalopathy
  - Seizures
  - Somnolence
  - Coma
- Peripheral neuropathy → paresthesias
Hematologic symptoms
- Anemia
- Leukocyte dysfunction → ↑ risk of infection
- ↑ Bleeding tendency caused by abnormal platelet adhesion and aggregation ^[9]

Kidney OUTAGES: hyperKalemia, renal Osteodystrophy, Uremia, Triglyceridemia, Acidosis (metabolic), Growth delay, Erythropoietin deficiency (anemia), Sodium/water retention (consequences of chronic kidney disease)

Uremic frost Fibrinous pericarditis in uremia Chronic kidney disease fact sheet

Diagnostic criteria and classification

Diagnostic criteria ^[5]

Criteria for chronic kidney disease (CKD) include the persistence of eGFR < 60 mL/min/1.73 m² (≥ G3a) and/or of any of the following markers of kidney damage for > 3 months:
- Albuminuria: e.g., urine albumin-to-creatinine ratio (UACR) > 30 mg/g (≥ A2)
- Urine sediment abnormalities: e.g., hematuria
- Abnormalities due to tubulointerstitial dysfunction, e.g.:
  - Electrolyte and acid-base imbalances
  - Retention of nitrogenous wastes
  - Reduced production of erythropoietin, 1,25-dihydroxyvitamin D, and/or renin
- Histological abnormalities on biopsy
- Imaging showing structural abnormalities: e.g., polycystic kidney disease
- History of renal transplant
CKD progression is the presence of either of the following:
- A decline in renal function, leading to a change in eGFR category
- A sustained decline in eGFR of > 5 mL/min/1.73 m² per year
End-stage renal disease (ESRD) ; ^[10]
- Irreversible kidney dysfunction with eGFR < 15 mL/min/1.73 m²
- AND manifestations of uremia requiring chronic renal replacement therapy with either dialysis (hemofiltration or hemodiafiltration) or renal transplantation
- Prognosis: approx. 50% of individuals with ESRD die of cardiovascular disease.

CGA classification of chronic kidney disease ^[4]^[5]

CKD is classified according to the cause, eGFR category, and albuminuria category; this is referred to as the CGA classification.

Clinical uses
- Standardized documentation of CKD stages
- Identification of CKD progression
- Determination of the frequency of patient monitoring
Interpretation: Higher stages correlate with a poorer prognosis. ^[11]
- Increased risk of CKD progression and mortality (e.g., all-cause mortality, cardiovascular mortality)
- Increased risk of developing complications (e.g., AKI, CKD-mineral and bone disorder)

Cause ^[5]

Systemic vs. primary cause: Determine if kidney disease is associated with a systemic disease (e.g., diabetes) or if it is primary kidney disease (e.g., polycystic kidney disease).
Location: Determine the location (presumed or confirmed) of the damage within the kidney.
- Glomerular
- Tubulointerstitial
- Vascular
- Cystic and congenital

eGFR and albuminuria ^[5]

Risk of progression and complications of CKD based on eGFR and albuminuria category ^[5]
eGFR category (mL/min/1.73 m²)		Albuminuria category (UACR)
eGFR category (mL/min/1.73 m²)		A1: < 30 mg/g or < 3 mg/mmol (normal to mildly increased)	A2: 30–300 mg/g or 3–30 mg/mmol (microalbuminuria)	A3: > 300 mg/g or > 30 mg/mmol (macroalbuminuria)
Stage G1 CKD: ≥ 90 (normal or high)		Low risk*	Moderate risk	High risk
Stage G2 CKD: 60–89 (mildly low)		Low risk*	Moderate risk	High risk
Stage G3 CKD	G3a: 45–59 (mildly to moderately low)	Moderate risk	High risk	Very high risk
Stage G3 CKD	G3b: 30–44 (moderately to severely low)	High risk	Very high risk
Stage G4 CKD: 15–29 (severely low)		Very high risk
Stage G5 CKD: < 15 (kidney failure)		Very high risk
*Stages G1A1 and G2A1 do not indicate CKD in the absence of other markers of kidney damage.

Diagnosis

The goals of the diagnostic evaluation include confirming the chronicity of kidney dysfunction and identifying the cause of kidney disease.

Approach ^[5]

Order initial laboratory studies.
- Determine if the patient meets the criteria for CKD.
- Stage CKD according to the CGA classification.
- Order further tests (e.g., electrolytes, CBC) to establish if complications are present.
Rule out AKI or acute on chronic kidney injury.
Identify the etiology of CKD and possible contributing factors.
- Perform a comprehensive chart review, history, and physical examination.
- Consider an initial renal ultrasound for all patients with CKD.
Consider further investigations for specific underlying causes of CKD.
If any indications for acute dialysis are identified, proceed with urgent renal replacement therapy.

The diagnosis of CKD requires the persistence of eGFR < 60 mL/min/1.73 m² and/or of a marker of kidney damage for more than 3 months.

A rapid rise in creatinine level (i.e., over days rather than weeks or months), recent onset of uremia, and/or oliguria or anuria suggest AKI (with or without underlying CKD).

Initial laboratory studies

Parameters of renal function

Serum markers: ↑ creatinine and BUN; (alternatively, ↑ cystatin C)
Glomerular filtration rate: ↓ eGFR
- Serum creatine-based eGFR (preferred): e.g., CKD-EPI equation, MDRD equation
- Serum cystatin C-based eGFR
  - Used to confirm eGFR when creatinine-based estimation may be inaccurate or the diagnosis of CKD is in doubt ^[5]
  - E.g., CKD-EPI creatinine-cystatin C, CKD-EPI cystatin C

eGFR using CKD-EPI MDRD eGFR Equation

Urine studies

↑ Spot UACR: used to determine the albuminuria category for CKD staging. ^[5]
↑ Spot urine protein-to-creatinine ratio (UPCR): Nephrotic-range proteinuria may be seen.
Urine dipstick: : may show hematuria or proteinuria
Urine microscopy: : may show abnormal urine sediment, e.g., the presence of waxy casts

If the UPCR is significantly higher than the UACR, plasma cell dyscrasia should be suspected. Send a urine sample for protein electrophoresis to identify urine proteins other than albumin (e.g., Bence Jones protein).

Other

Hemostasis: ↑ bleeding time, normal PT, PTT and platelet count (see “Diagnostic workup of bleeding disorders”)

Ultrasound of the kidneys and urinary tract

First-line imaging technique for the assessment of kidney structure
Consider obtaining for all patients to further support the diagnosis and help determine the etiology.
Findings that suggest chronic kidney damage include: ^[12]
- ↓ Kidney length (< 10 cm)
- ↓ Parenchymal and/or cortical thickness
- ↑ Cortical echogenicity
- Cysts
- Calcifications
Findings that suggest specific etiologies
- Ureteral or renal pelvic dilation suggests obstructive nephropathy.
- Bilaterally enlarged kidneys with multiple cysts suggest polycystic kidney disease.
- Cortical nephrocalcinosis suggests chronic glomerulonephritis or chronic pyelonephritis. ^[13]

Ultrasound in chronic renal disease

Consider obtaining an ultrasound of the kidneys and urinary tract as part of the routine evaluation of all patients with CKD.

Additional investigations to identify underlying causes

Additional investigations should be considered based on clinical suspicion or if an underlying cause of CKD is not apparent following an initial assessment.

Integration of information from the patient's clinical presentation, laboratory tests, imaging, and in some cases, pathology, is needed to determine the underlying cause.

Noninvasive testing

Investigations for specific underlying causes of CKD
Examples	Suggestive features	Common additional studies
Diabetes	Symptoms of diabetes mellitus Age > 35 years and/or the presence of other risk factors for type 2 diabetes mellitus Nephrotic syndrome or nephrotic-range proteinuria	Fasting plasma glucose HbA1c See also “Diabetic kidney disease.”
Glomerulonephritis	Evidence of extrarenal disease (e.g., clinical features of SLE, anti-GBM disease, pauci-immune glomerulonephritis) History of IV drug use Nephritic syndrome or nephrotic syndrome Urinalysis abnormalities (any of the following): Nephritic sediment Nephrotic sediment Nephrotic-range proteinuria	Serology, e.g.: ANA ANCA anti-GBM antibody Viral serology (e.g., HIV, HBV, HCV) Complement levels
Multiple myeloma	CRAB criteria	Serum protein electrophoresis Urine Bence Jones protein Serum and urine free light chains
Renal artery stenosis	Treatment-resistant hypertension Abdominal bruit heard over the flank or epigastrium Evidence of other atherosclerotic diseases (e.g., CAD, PAD)	Duplex ultrasonography of the renal arteries
Amyloidosis	History of a chronic inflammatory condition (e.g., IBD, RA) or chronic infectious disease (e.g., tuberculosis, osteomyelitis) History of plasma cell dyscrasia Evidence of other organ involvement (e.g., macroglossia, restrictive cardiomyopathy, hepatosplenomegaly, malabsorption)	Serum protein electrophoresis Urine Bence Jones protein Serum and urine free light chains

Renal biopsy ^[5]^[14]

Not routinely indicated
Consider in either of the following situations:
- Rapid and unexplained decline in eGFR
- Need for diagnostic confirmation of the underlying etiology (e.g., glomerulonephritis) prior to initiating disease-specific therapy

Renal biopsy is only indicated in patients in whom the underlying cause of CKD is still unclear after noninvasive testing, the results are likely to influence management, and the potential benefits are thought to outweigh the risks.

Management

The following guidance applies to patients with CKD category G1–G5 who are not on dialysis and have not had a kidney transplant.

Approach

The goals of treatment are to delay the progression of CKD and prevent and manage complications.

Treat the underlying causes of CKD (if identified).
Start comprehensive management.
- Provide recommendations regarding nutrition and vaccinations, and adjust current medications as required.
- Primary prevention of ASCVD.
- Assess for evidence of metabolic complications and start management under specialist guidance.
Monitor for CKD progression and continuously evaluate the need for advanced care.

If CKD progression or complications are detected during follow-up, review the current management and assess for reversible causes of progression (e.g., nephrotoxin exposure, medications affecting glomerular perfusion, urinary tract obstruction).

Pay attention to the prevention of AKI, as this may further compromise kidney function.

If there are indications for acute dialysis, urgently initiate renal replacement therapy.

Nephrology consultation ^[5]

Indications (any of the following):
- CKD progression
- High risk of CKD progression: i.e., eGFR category G4–G5 and/or albuminuria category A3 (macroalbuminuria)
- Treatment-resistant hypertension or persistent hyperkalemia
- Hematuria, nephrolithiasis, or hereditary kidney disease
- During an AKI episode

Nutritional management ^[15]

Fluid intake: Ensure appropriate fluid intake and avoid dehydration.
Protein and energy consumption
- Mediterranean diet, ↑ fruit and vegetable intake
- Protein restriction (e.g., 0.55–0.60 g/kg/day) in patients with CKD category G3–G5
Electrolytes
- Sodium restriction (< 2.3 g/day): for individuals with CKD category G3–G5
- Potassium intake adjustment: avoidance of high-potassium foods in patients with CKD category G4–G5 to reduce the risk of hyperkalemia
- Phosphorus intake adjustment: as needed to maintain serum phosphate levels in the normal range
Micronutrients: Consider multivitamin supplementation; for patients with inadequate dietary vitamin (e.g., vitamin D) intake. ^[15]

Dietary protein restriction must ONLY be prescribed under close clinical supervision and in consultation with a nutritionist.

Obtain a nutritionist consult for all patients with CKD.

Vaccinations

Patients with CKD are at an increased risk of vaccine-preventable infections.

Live attenuated vaccines: Consider offering the MMR vaccine and varicella vaccine to patients who have not been vaccinated since infancy or do not have immunity.
Non-live vaccines
- Ensure influenza, pneumococcal, and hepatitis B vaccinations are up-to-date. ^[16]
- See “Immunization schedule” for recommendations on indications, timing, and frequency.

Patients with CKD may be immunocompromised. Decisions regarding the use of live vaccines should therefore take into account the patient's current immune status and be made in consultation with a specialist. ^[5]

Medication management ^[5]^[14]

Renally cleared medications: Adjust dosing based on the patient's eGFR (CKD-EPI equation is preferred).
Potentially nephrotoxic substances
- Avoid use (except when the benefits outweigh the risks).
- Frequently monitor renal function and electrolytes and, when indicated, measure drug levels. ^[5]
- Contrast imaging
  - The risk of contrast-induced nephropathy is highest in patients with eGFR < 30 mL/min/1.73 m².
  - For information on prevention, see “Contrast-induced nephropathy.”

Weigh the risks and benefits of potentially nephrotoxic substances on a case-by-case basis.

Given the increased risk of AKI in acutely ill patients with CKD, consider temporarily holding renally cleared medications and medications that can detrimentally affect glomerular perfusion (e.g., NSAIDs, ACEIs, ARBs).

Renal replacement therapy ^[5]

Nonoperative (hemodialysis or peritoneal dialysis)
- Indications include:
  - Hemodynamic or metabolic complications that are refractory to medical therapy, e.g.:
  - Serositis: e.g., uremic pericarditis
  - Other symptoms of uremia: e.g., signs of encephalopathy
  - Refractory deterioration in nutritional status
Operative: kidney transplantation

Monitoring and management of ASCVD risk factors

Specific recommendations for ASCVD risk management in patients with CKD are reviewed below; see also “Hypertension,” “Lipid disorders,” “Diabetes,” and “ASCVD.”

ASCVD risk assessment

Perform for all patients (untreated CKD is an ASCVD risk-enhancing factor).
Includes:

Management of ASCVD not only reduces cardiovascular morbidity and mortality, but also helps prevent CKD progression.

Cardiovascular disease (e.g., coronary artery disease, stroke) is the leading cause of death in patients with CKD. The risk of cardiovascular events is higher in patients with more advanced stages of CKD. ^[5]

Blood pressure control ^[17]

Systolic blood pressure (SBP) target
- SBP < 120 mm Hg is recommended (if tolerated). ^[17]
- Consider higher targets (e.g., < 130–140 mm Hg) for selected patients.
Pharmacological therapy
- Consider for patients with SBP above target, particularly if they are in albuminuria categories A2–A3.
- First-line therapy: RAAS inhibitors (i.e., ACEI or ARB)
  - Benefits: nephroprotection and reduced proteinuria
  - Risks: may cause hyperkalemia and/or an initial decline in GFR
- Consider combination therapy (e.g., RAAS inhibitor PLUS a calcium channel blocker and/or a thiazide diuretic) :
  - For patients with an initial SBP ≥ 20 mm Hg above target
  - For patients who do not reach the target while on monotherapy at the optimal dose
- Second-line agents include:
  - Loop diuretics or thiazide diuretics
  - Calcium channel blockers (CCBs)
  - Beta-blockers: usually reserved for patients with cardiovascular comorbidities
  - Aldosterone receptor antagonists: usually reserved for treatment resistant hypertension
- See “Antihypertensive therapy” for information on medication dosages and contraindications.
Nonpharmacological management: Recommend for all patients; see “Lifestyle changes for managing hypertension.”

Avoid any combination of an ACEI, ARB, and/or direct renin inhibitor because of the increased risk of hyperkalemia and AKI.

Good blood pressure control is essential to prevent ASCVD complications, reduce mortality, and help delay disease progression in patients with CKD.

Lipid management ^[18]^[19]

Goal: reduction of ASCVD risk
Fasting lipid panel
- Order at diagnosis and repeat only if the results may alter management.
- May show dyslipidemia (↑ triglycerides are common)
Statin therapy; indications include:
- Prevention of ASCVD in patients with CKD ^[19]^[20]^[21]
  - Start for all patients ≥ 50 years of age.
  - Consider for patients 18–49 years of age with concomitant diabetes mellitus and/or 10-year ASCVD risk > 10%.
- Management of ASCVD
Nonpharmacological management: Recommend as adjunctive therapy for all patients with hypercholesterolemia.

For patients with eGFR < 60 mL/min/1.73 m² (eGFR category G3–G5), adjustments to the recommended statin doses are required to reduce their potential for toxicity.

Individuals with CKD often have dyslipidemia (e.g., ↑ triglycerides, ↑ LDL, ↓ HDL) due to alterations in lipoprotein metabolism.

Diabetes management ^[22]

HbA1c may not accurately reflect glycemic control in patients with CKD and eGFR < 30 mL/min/1.73 m²; correlate with results from ambulatory glucose monitoring.
Medications may need to be reduced or stopped as eGFR declines.
See “Diabetic kidney disease” for further information on managing DM in patients with renal impairment.

SGLT-2 inhibitors and GLP-1 receptor agonists have been shown to slow CKD progression and reduce urinary albumin excretion and ASCVD events. ^[22]^[23]

In patients with CKD category G4–G5 who were previously on metformin and/or an SGLT-2 inhibitor, metformin should be discontinued; the SGLT-2 inhibitor may be continued if tolerated.

Antiplatelet therapy

Usually indicated for management of ASCVD
May be considered for primary prevention of ASCVD in high-risk individuals (e.g., patients with CKD and diabetes) ^[5]^[23]

Monitoring for complications

Screening tests for complications are indicated in all patients with CKD at diagnosis to establish a baseline.
Patients with CKD categories G3–G5 require repeat testing at regular intervals.

In CKD, close surveillance of serum potassium, calcium, and phosphate levels is essential.

Overview of screening for CKD complications ^[5]
Screening test		Screening frequency (CKD category G3–G5)	Potential findings	Management
CBC		Every 6–12 months	Normochromic, normocytic anemia	See “Anemia of chronic kidney disease.”
Potassium ^[14]		Repeat as needed.	Hyperkalemia: usually seen in advanced CKD	See “Chronic hyperkalemia” in “Therapeutic approach to hyperkalemia.”
Mineral and bone disorder panel ^[24]	PTH	Every 3–12 months	↑ PTH Suggests secondary hyperparathyroidism May be seen with any stage of CKD and worsens as GFR declines	See “Management” in “CKD-MBD.”
	Phosphate and total calcium	Every 1–12 months	Hyperphosphatemia and hypocalcemia : typically seen in patients with eGFR < 30 mL/min/1.73 m² ^[24]
	Vitamin D	Calcidiol: Repeat as needed. Calcitriol: No specific indication or monitoring frequency exists.	↓ Calcidiol ↓ Calcitriol ^[24]
Coagulation screen		Measure in case of bleeding or if symptoms of uremia are present.	Normal PT, PTT, and platelet count ↑ Bleeding time due to uremic platelet dysfunction	See “Hemostasis and bleeding disorders.”
Blood gases		Repeat as needed.	May show metabolic acidosis ^[25]	Consider oral bicarbonate supplementation for patients with serum bicarbonate < 22 mEq/L.

Screening and periodic monitoring for complications are indicated in all patients with CKD and eGFR < 60 mL/min/1.73 m².

Complications

For recommendations on screening tests and frequencies, see “Monitoring for complications.” Specialist consultation (e.g., with a nephrologist) is advised for the management of complications.

Common acute complications ^[26]

Pulmonary edema
Hyperkalemia
Infection ^[27]
- Bacteremia secondary to UTI or pneumonia
- IV catheter-related infection
- Hemodialysis catheter-related infection
- Peritoneal dialysis-associated peritonitis
Drug toxicity ^[28]
See also “Complications of hemodialysis” and “Complications of peritoneal dialysis.”

Maintain a low threshold for suspecting infections and initiating empiric antibiotics, as signs of sepsis may be vague or absent in patients with CKD. ^[26]^[29]

Calciphylaxis ^[30]^[31]

Definition: a rare but potentially life-threatening condition characterized by dermal and subcutaneous arteriolar calcifications that cause painful skin necrosis
Risk factors
- Most commonly seen in patients with ESRD who are receiving dialysis
- Comorbidities: diabetes mellitus, obesity, CKD-mineral and bone disorder, warfarin therapy
Clinical features
- Intensely painful skin lesions, e.g.: livedo reticularis, purpura, plaques, nodules
- Necrotic skin ulcerations typically covered with black eschar
- Areas of firm, painful, subcutaneous tissue
- Secondary bacteremia and sepsis
Diagnosis
- A skin biopsy is required for definitive diagnosis but may provoke new lesions.
- Clinical diagnosis may be made in patients with ESRD with a typical presentation. ^[31]
Differential diagnosis
Treatment ^[30]^[31]
- Multidisciplinary care
- Supportive measures
  - Provide wound care and aggressive pain management.
  - Consider holding potentially offending medications: warfarin, calcium and iron supplements, vitamin D preparations.
  - Treat CKD-mineral and bone disorder.
  - Optimize renal replacement therapy.
  - Monitor for infection and initiate appropriate sepsis management if indicated.
- Pharmacotherapy: Consider a trial of sodium thiosulfate in consultation with a specialist. ^[30]^[31]

Calciphylaxis

Anemia of chronic kidney disease ^[5]^[32]^[33]

Pathophysiology: : ↓ synthesis of erythropoietin → ↓ stimulation of RBC production → normocytic, normochromic anemia
Laboratory findings
- ↓ Hemoglobin (Hb)
- MCV is usually normal.

Management

Manage correctable causes of anemia.
- Obtain diagnostic studies for iron deficiency.
  - Consider evaluation for underlying causes of iron deficiency (e.g., GI bleeding).
  - Consider iron therapy for iron deficiency anemia in patients with TSAT < 30% and ferritin < 500 ng/mL.
- Check for and potentially treat vitamin B₁₂ deficiency and folate deficiency.
Consider erythropoietin-stimulating agents (ESAs): for patients with Hb < 10.0 g/dL ; ^[33]
- Treatment target: usually Hb concentration between 11 and 12 g/dL (without intentionally exceeding 13 g/dL)
- Measure TSAT and ferritin at least every 3 months to determine if adjunctive iron replacement therapy is needed.
- Adverse effects include increased risk of thrombosis, an increase in blood pressure, and headache.
Avoid blood transfusions: particularly in patients eligible for renal transplantation (risk of alloimmunization)

Treatment with ESAs is not recommended for patients with Hb levels ≥ 10 g/dL because their use has been associated with increased mortality, stroke, and venous thromboembolism.