Chronic kidney disease

Definition

Chronic kidney disease (CKD) is a disorder of kidney structure or function present for at least 3 months. The most reliable evidence is an eGFR < 60 mL/min/1.73 m² for ≥ 3 months; with a normal GFR, persistent markers of damage such as albuminuria, an abnormal urinary sediment or structural or hereditary kidney disease on imaging or histology are sufficient. The disease usually progresses slowly and may lead to kidney failure in its end stage.

Classification

GFR and albuminuria categories

Staging combines the GFR category (G) with the albuminuria category (A):

• G1: GFR ≥ 90 mL/min/1.73 m² with markers of damage
• G2: 60–89 mL/min/1.73 m²
• G3a: 45–59 mL/min/1.73 m²
• G3b: 30–44 mL/min/1.73 m²
• G4: 15–29 mL/min/1.73 m²
• G5: < 15 mL/min/1.73 m² (kidney failure)
• A1: albumin excretion < 30 mg/24 h (normal to mildly increased)
• A2: 30–300 mg/24 h (moderately increased, formerly microalbuminuria)
• A3: > 300 mg/24 h (severely increased)

Occurrence & epidemiology

CKD is common: in the United States, its prevalence in adults (eGFR < 60 mL/min/1.73 m² or albumin-to-creatinine ratio ≥ 30 mg/g) was recently estimated at about 14%. The most common causes are diabetic nephropathy and hypertensive nephrosclerosis, followed by primary and secondary glomerulopathies.

Aetiopathogenesis

Causes and pathophysiology

Other causes include chronic tubulointerstitial nephritis, hereditary diseases (polycystic kidney disease, Alport syndrome), chronic urinary tract obstruction and vesicoureteral reflux, and renal artery stenosis. Metabolic syndrome with hypertension and type 2 diabetes is of growing importance.

Pathophysiologically, the remaining nephrons initially compensate for the loss of function, so that few abnormalities are noticeable for a long time. The ability to concentrate urine is lost early, later the excretion of phosphate, acid and potassium. Reduced calcitriol production and phosphate retention lead to secondary hyperparathyroidism and renal osteodystrophy; erythropoietin deficiency causes renal anemia.

Clinical features

Early stages are usually asymptomatic. Nocturia is common, mainly due to the declining ability to concentrate urine. Fatigue, lassitude, anorexia and decreased mental acuity are often the earliest signs of uremia.

• Advanced CKD (eGFR < 15 mL/min/1.73 m²): nausea, vomiting, weight loss, stomatitis, unpleasant taste, pruritus, yellow-brown dry skin, muscle twitches and cramps, restless legs syndrome, peripheral neuropathy, seizures
• Cardiovascular: hypertension in > 80% in advanced stages, heart failure with edema and dyspnea, pericarditis
• Hematologic and metabolic: normochromic, normocytic anemia from stage G3, metabolic acidosis, hyperkalemia, calcium-phosphate disturbances, undernutrition

Diagnosis

• eGFR from creatinine (CKD-EPI 2021 equation, without a race coefficient), ideally combined with cystatin C; cystatin C is particularly helpful in unusual muscle mass
• Urine: albumin-to-creatinine or protein-to-creatinine ratio in a spot urine, urine sediment; broad and waxy casts are common in advanced renal failure
• Blood: electrolytes, urea, creatinine, calcium, phosphate, parathyroid hormone, blood count, blood gases (bicarbonate usually 15–20 mmol/L in moderate acidosis)
• Ultrasound: usually small kidneys (< 10 cm) with thinned, hyperechoic cortex; normal-sized or enlarged kidneys e.g. in diabetic nephropathy, polycystic kidney disease, amyloidosis or myeloma
• Kidney biopsy to determine the cause, not in small, fibrotic kidneys

Distinguishing CKD from acute kidney injury is important: findings favoring CKD are previously known impaired kidney function, small kidneys, subperiosteal erosions on radiographs and chronic symptoms such as pruritus, nocturia and hypertension.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Chronic Kidney Disease
2. MSD Manual Professional: Evaluation of the Patient With Renal Issues
3. KDIGO 2024 Clinical Practice Guideline: Evaluation of Chronic Kidney Disease (CKD)

Cross-references