Chronic kidney disease (CKD) is defined as an abnormality of the kidney structure or function for ≥ 3 months. The most common causes of CKD in the United States are diabetes mellitus, hypertension, and glomerulonephritis. Since the kidneys have exceptional compensatory mechanisms, most patients remain asymptomatic until kidney function is significantly impaired. Patients typically present with symptoms of fluid overload (e.g., peripheral edema) and uremia (e.g., fatigue, pruritus). Laboratory studies show hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis. Management focuses mainly on treating the underlying disease and preventing possible complications, e.g., treating hypertension, avoiding nephrotoxic substances, and maintaining adequate hydration. If chronic kidney disease progresses to end-stage renal disease (ESRD), renal replacement therapy (i.e., dialysis or kidney transplantation) becomes necessary.
- Chronic kidney disease is defined as an eGFR < 60 mL/min/1.73 m2 and/or persistence ≥ 3 months findings indicating irreversible kidney damage, such as:
- 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.
- Diabetic nephropathy (38%)
- Hypertensive nephropathy (26%)
- Glomerulonephritis (16%)
- Other causes (15%, e.g., polycystic kidney disease; , analgesic misuse, amyloidosis)
- Idiopathic (5%)
Diabetic nephropathy 
- Hyperglycemia → nonenzymatic glycation of proteins → varying degrees of damage to all types of kidney cell.
- Pathological changes include:
Hypertensive nephropathy: Due to 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
- Glomerulonephritis (GN)
- ↓ 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
- Reduced gluconeogenesis: ↑ 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
- Chronic kidney disease is staged according to the CGA classification based on GFR and albuminuria categories.
- Higher categories are associated with poorer prognosis.
- There are two main categories: systemic causes and primary kidney disease
- Further differentiation based on location within the kidney (glomerular, tuberointerstitial, vascular, or cystic and congenital)
Categories and staging
|Estmiated glomerular filtration rate (eGFR) categories |
|Category||eGFR (mL/min/1.73 m2)|| |
|G1||> 90||Normal or high|
|G3a||45–59||Mildly to moderately decreased|
|G3b||30–44||Moderately to severely decreased|
|G5||< 15||Kidney failure|
|Albuminuria categories |
|Category||Urinary albumin excretion||Description|
|A1||< 30||< 3||Normal to mildly increased|
|A2||30–300||3–30||Moderately increased (microalbuminuria)|
|A3||> 300||> 30||Severely increased (macroalbuminuria)|
|Staging of CKD|
|GFR category|| |
< 30 mg/g or < 3 mg/mmol
30–300 mg/g or 3–30 mg/mmol
> 300 mg/g or > 30 mg/mmol
Diagnosing CKD requires the integration of information from clinical presentation, laboratory tests, imaging, and, if necessary, pathology. The following steps should be included in the process:
- Thorough review of patient medical records for information suggesting CKD and potential underlying conditions
- Physical examination with fluid status, thorough abdominal status, exploration of signs of common comorbidities, and clues of underlying conditions
- Laboratory tests (see below) to assess kidney function
- Imaging (see “Doppler ultrasound” below) to assess kidney structure
- If necessary, kidney biopsy
- Complete blood count: normochromic, normocytic anemia
- Basic metabolic panel
- Coagulation screen
- Lipid panel: dyslipidemia (↑ triglycerides are common)
- Blood pH: metabolic acidosis 
- Hormones: ↑ PTH
- Vitamins: ↓ calcitriol
- Parameters of renal function
- Serology: may be necessary to identify underlying condition (e.g., ↑ complement levels, ↑ ANA)
- Urine dipstick
- Spot urine microalbumin: ↑ albumin-to-creatinine ratio
- Urine microscopy: : abnormal urine sediment, e.g., presence of waxy casts
Doppler ultrasound 
- Pathological findings
- Renal biopsy: indicated when diagnosis by other means remains inconclusive regarding the underlying condition
Kidney OUTAGES: hyperKalemia, renal Osteodystrophy, Uremia, Triglyceridemia, Acidosis (metabolic), Growth delay, Erythropoietin deficiency (anemia), Sodium/water retention (consequences of chronic kidney disease)
In chronic renal disease, close surveillance of serum potassium, calcium, and phosphate levels is essential.
- Fluid intake: monitor appropriate fluid intake
Protein and energy consumption 
- Mediterranean diet, ↑ fruit and vegetable intake
- Protein restriction to 0.55–0.6 g/kg/day
- Sodium restriction
- Potassium intake adjustment (e.g., avoidance of high-potassium foods) to reduce the risk of hyperkalemia (see “”)
- Phosphorus restriction
- Micronutrients: vitamin D supplementation with cholecalciferol/ergocalciferol 
Avoidance of nephrotoxic substances
- Antifungals (e.g., amphotericin B)
- Platinum-based chemotherapeutic agents (e.g., cisplatin, carboplatin)
- Immunosuppressants (e.g., cyclosporine)
- Inhalational anesthetics
- Recommended immunizations: influenza, Pneumococcus, and varicella zoster
- MMR and varicella for individuals who were vaccinated as infants or currently do not have immunity
- General: Well-controlled blood pressure is essential to prevent progression of CKD and complications resulting from cardiovascular disease (CVD).
- Goal: < 130/80 mmHg 
- First-line treatment: inhibitors of the renin-angiotensin-aldosterone system
- Second-line treatment
- General: Individuals with CKD often have dyslipidemia (e.g., ↑ LDL, ↓ HDL) due to alterations in lipoprotein metabolism.
- Preferred substances: statins
Chronic kidney disease-mineral and bone disorder (CKD-MBD)
- Definition: abnormalities of the mineral or bone metabolism in the setting of chronic kidney disease
- Chronic kidney disease results in hypocalcemia via different mechanisms
- Chronically decreased calcium levels can cause (which can progress to )
- Clinical features
- Diagnostics: x-ray may show rugger-jersey spine
- Treatment: See “Treatment” above and “ .”
- Can be treated surgically (e.g., parathyroidectomy) or with calcimimetics (e.g., cinacalcet)
- See “.”
Anemia of chronic kidney disease
- Pathophysiology: ↓ synthesis of erythropoietin → ↓ stimulation of RBC production → normocytic, normochromic anemia
- Laboratory findings: ↓ hemoglobin, but normal MCV
- Goal: target hemoglobin concentration should be > 10.0 g/dl 
- Treatment: synthetic EPO
End-stage renal disease (ESRD)
- Definition: irreversible kidney dysfunction requiring renal replacement therapy
Growth delay and developmental delay in children
- Contributing factors include:
We list the most important complications. The selection is not exhaustive.
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