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).
- 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 
- Risk factors for CKD 
Epidemiological data refers to the US, unless otherwise specified.
- Hyperglycemia → nonenzymatic glycation of proteins → varying degrees of damage to all types of kidney cell.
- Pathological changes include:
- Caused by protective autoregulatory vasoconstriction of preglomerular vessels, increases in systemic blood pressure do not normally affect renal microvessels. 
- 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
- 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)
- ↓ 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). 
- 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). 
- During the early stages of CKD, plasma phosphate levels will typically be normal due to the increased secretion of fibroblast growth factor 23 (FGF23). 
- ↓ 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
- ↑ Risk of hypoglycemia
Patients are often asymptomatic until later stages due to the exceptional compensatory mechanisms of the kidneys.
Manifestations of Na+/H2O retention
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.
- Gastrointestinal symptoms
- Dermatological manifestations
- Uremic pericarditis: a complication of chronic kidney disease that causes fibrinous pericarditis
- Neurological symptoms
- Hematologic symptoms
Kidney OUTAGES: hyperKalemia, renal Osteodystrophy, Uremia, Triglyceridemia, Acidosis (metabolic), Growth delay, Erythropoietin deficiency (anemia), Sodium/water retention (consequences of chronic kidney disease)
Diagnostic criteria 
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.:
- 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:
- End-stage renal disease (ESRD) ; 
CGA classification of chronic kidney disease 
- Clinical uses
- Interpretation: Higher stages correlate with a poorer prognosis. 
- 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.
- Cystic and congenital
eGFR and albuminuria 
|Risk of progression and complications of CKD based on eGFR and albuminuria category |
|eGFR category (mL/min/1.73 m2)||Albuminuria category (UACR)|
A1: < 30 mg/g or < 3 mg/mmol
(normal to mildly increased)
A2: 30–300 mg/g or 3–30 mg/mmol
A3: > 300 mg/g or > 30 mg/mmol
|Stage G1 CKD: ≥ 90 (normal or high)||Low risk*||Moderate risk||High risk|
|Stage G2 CKD: 60–89 (mildly low)|
|Stage G3 CKD||G3a: 45–59 (mildly to moderately low)||Moderate risk||High risk||Very high risk|
|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)|
*Stages G1A1 and G2A1 do not indicate CKD in the absence of other.
- Order initial laboratory studies.
- Rule out or .
- Identify the etiology of CKD and possible contributing factors.
- Consider further investigations for specific underlying causes of CKD.
- If any urgent renal replacement therapy. are identified, proceed with
Initial laboratory studies
- Serum markers: ↑ creatinine and BUN; (alternatively, ↑ cystatin C)
- : ↓ eGFR
- ↑ Spot UACR: used to determine the for . 
- ↑ Spot urine protein-to-creatinine ratio (UPCR): 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).
- 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: 
- Findings that suggest specific etiologies
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.
|Investigations for specific underlying causes of CKD|
|Examples||Suggestive features||Common additional studies|
|Multiple myeloma|| |
|Renal artery stenosis|
Renal biopsy 
- Not routinely indicated
- Consider in either of the following situations:
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.
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.
- Monitor for 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 kidney function., as this may further compromise
If there are , urgently initiate .
Nephrology consultation 
- Indications (any of the following):
Nutritional management 
- Fluid intake: Ensure appropriate fluid intake and avoid dehydration.
- Protein and energy consumption
- 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. 
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.
Patients with CKD are at an increased risk of vaccine-preventable infections.
- Live attenuated vaccines: Consider offering the and to patients who have not been vaccinated since infancy or do not have immunity.
- Non-live vaccines
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. 
Medication management 
- Renally cleared medications: Adjust dosing based on the patient's eGFR (. 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. 
- Contrast imaging
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).
Nonoperative (hemodialysis or peritoneal dialysis)
- Indications include:
- Operative: kidney transplantation
- Perform for all patients (untreated CKD is an ).
- (e.g., using )
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. 
Blood pressure control 
Systolic blood pressure (SBP) target
- SBP < 120 mm Hg is recommended (if tolerated). 
- Consider higher targets (e.g., < 130–140 mm Hg) for selected patients.
- 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)
- 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:
- See “Antihypertensive therapy” for information on medication dosages and contraindications.
- Nonpharmacological management: Recommend for all patients; see “ .”
Good blood pressure control is essential to prevent ASCVD complications, reduce mortality, and help delay disease progression in patients with CKD.
Lipid management 
- Goal: reduction of
- Fasting lipid panel
Statin therapy; indications include:
Prevention of ASCVD in patients with CKD 
- Start for all patients ≥ 50 years of age.
- Consider for patients 18–49 years of age with concomitant and/or > 10%.
- Prevention of ASCVD in patients with CKD 
- Nonpharmacological management: Recommend as adjunctive therapy for all patients with hypercholesterolemia.
Diabetes management 
- 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.
- Usually indicated for
- May be considered for diabetes)  in high-risk individuals (e.g., patients with CKD and
- 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.
|Overview of screening for CKD complications |
|Screening test|| |
(CKD category G3–G5)
|CBC|| || || |
|Potassium || || || |
|Mineral and bone disorder panel ||PTH|| || |
|Phosphate and total calcium|| |
|Coagulation screen|| || |
|Blood gases|| || |
Screening and periodic monitoring for complications are indicated in all patients with CKD and eGFR < 60 mL/min/1.73 m2.
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 
- Pulmonary edema
- Infection 
- See also “ ” and “ .”
- Definition: a rare but potentially life-threatening condition characterized by dermal and subcutaneous arteriolar calcifications that cause painful skin necrosis
- Risk factors
- Clinical features
- 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. 
Anemia of chronic kidney disease 
- Pathophysiology: : ↓ synthesis of erythropoietin → ↓ stimulation of RBC production → normocytic, normochromic anemia
- Laboratory findings
- Manage correctable causes of anemia.
Consider erythropoietin-stimulating agents (ESAs): for patients with Hb < 10.0 g/dL ; 
- 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)
Chronic kidney disease-mineral and bone disorder (CKD-MBD) 
- CKD-MBD refers to abnormalities in mineral and/or bone metabolism in CKD.
- Renal osteodystrophy refers specifically to issues with bone metabolism due to CKD.
- CKD results in hypocalcemia via different mechanisms.
- Chronically decreased calcium levels can cause , which can progress to .
- Histological classification
- Clinical features (may be asymptomatic initially)
- Diagnostics 
Treatment (under specialist guidance): The goal is to normalize phosphate, calcium, and PTH levels. 
- Treatment of hyperphosphatemia, e.g.:
- , e.g.:
Growth delay and developmental delay in children
- Contributing factors include:
We list the most important complications. The selection is not exhaustive.
Special patient groups
Chronic kidney disease in pregnancy 
- Prevalence of CKD in women of childbearing age is estimated to be 0.1–4%.
- Research suggests that pregnancy negatively affects kidney function in women with CKD (as evidenced by, e.g., doubling of creatinine, progression to next stage).
- CKD negatively influences pregnancy outcomes by increasing the risk of maternal and fetal complications (see below).
- Physiological anatomic (e.g., dilation of the renal collecting system, changes in kidney length and volume) and hemodynamic changes (e.g., decreased mean arterial pressure) can pose a challenge to monitoring kidney function and diagnosing complications.
- Maternal complications
- Fetal complications
- Patients should be cared for by a multidisciplinary team, including nephrologists, neonatologists, and health care personnel specialized in high-risk obstetrics.
- Optimization of blood pressure (i.e., < 140/90 mm Hg) to reduce the risk of preeclampsia and other complications (see “ ” for details)
- Minimization of proteinuria: Treatment depends on the underlying etiology (e.g., pregnancy-safe immunosuppression with prednisone or calcineurin inhibitors in lupus nephritis).
- Consideration of anticoagulation in individuals with severe proteinuria
- Prevention of preeclampsia with aspirin before 16 weeks of gestation and calcium and vitamin D supplementation throughout the pregnancy
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