Chronic Kidney Disease (CKD) - Overview
Understanding the disease for better management
Definition of Chronic Kidney Disease
According to KDIGO 2024 (Kidney Disease: Improving Global Outcomes)
Chronic Kidney Disease (CKD) is defined as abnormalities in kidney structure or function persisting for more than 3 months, with implications for health.
Diagnostic criteria (either one):
- Abnormal kidney function: GFR (glomerular filtration rate) < 60 mL/min/1.73m² persisting for ≥ 3 months
- Abnormal kidney structure or markers:
- Proteinuria (albumin/creatinine ratio ≥ 30 mg/g)
- Abnormal urine sediment (hematuria, leukocyturia)
- Electrolyte disorders due to tubular disease
- Structural abnormalities on ultrasound or CT (cysts, scarring, atrophy)
- History of kidney transplantation
Global significance
According to the Global Burden of Disease 2021 study, CKD affects approximately 674 million people worldwide and is a leading cause of death with over 1.5 million deaths per year.
Stages of Chronic Kidney Disease
Classification by GFR (KDIGO 2024)
| Stage | Description | GFR (mL/min/1.73m²) | Severity |
|---|---|---|---|
| Stage 1 | Normal or increased kidney function with kidney damage | ≥ 90 | Normal to high |
| Stage 2 | Mildly decreased kidney function | 60-89 | Mildly decreased |
| Stage 3a | Mild-to-moderately decreased kidney function | 45-59 | Mild-to-moderate decrease |
| Stage 3b | Moderate-to-severely decreased kidney function | 30-44 | Moderate-to-severe decrease |
| Stage 4 | Severely decreased kidney function | 15-29 | Severely decreased |
| Stage 5 | End-stage kidney failure | < 15 | End-stage kidney failure |
Albuminuria classification (also important)
KDIGO also classifies CKD by albuminuria level: A1 (< 30 mg/g - normal), A2 (30-300 mg/g - moderately increased), A3 (> 300 mg/g - severely increased). High albuminuria is a risk factor for rapid progression and cardiovascular complications.
Time of Progression to End Stage
Rate of progression varies greatly between patients
Research from the Chronic Renal Insufficiency Cohort (CRIC Study, 2019) shows that the time of progression from CKD stage 3 to stage 5 (requiring dialysis) varies widely, depending on many factors.
Median time at each stage (according to the CRIC study):
- CKD 3a (GFR 45-59): Median 7.9 years at this stage (IQR: 2.3 - >12 years). With good blood pressure and proteinuria control, time from CKD 3a to ESKD can be >24 years; with uncontrolled proteinuria only about 7 years [Ku et al. 2018]
- CKD 3b (GFR 30-44): Median 5.0 years at this stage (IQR: 1.8 - 11.5 years) [Ku et al. 2018]
- CKD 4 (GFR 15-29): Median 4.2 years at this stage (IQR: 2.4 - 6.6 years) [Ku et al. 2018]
- CKD 5 (GFR <15): Median 0.8 years before requiring dialysis (IQR: 0.3 - 1.6 years) [Ku et al. 2018]
Note on variability
According to Baek et al. (2012) studying 347 CKD stage 3 patients followed for 10 years: 48.1% did not progress to a more advanced stage, 17.3% progressed to stage 4, 34.6% progressed to stage 5, and 26.2% required dialysis. [Baek et al. 2012]
Factors affecting the rate of progression:
Accelerating progression:
- Poorly controlled diabetes (HbA1c > 7%)
- Untreated hypertension (BP > 140/90 mmHg)
- High proteinuria (> 1g/day)
- Smoking
- Obesity (BMI > 30)
- Untreated anemia
- Recurrent urinary tract infections
- Use of nephrotoxic drugs (NSAIDs, nephrotoxic antibiotics)
Slowing progression:
- Good blood glucose control (HbA1c < 7%)
- Target blood pressure control (< 130/80 mmHg)
- Use of RAAS inhibitors (ACEi/ARB)
- Controlled low-protein diet
- Salt restriction (< 5g/day)
- Regular exercise
- Smoking cessation
- Maintaining a healthy weight
Scientific evidence on nutritional intervention
Regarding low-protein diet: Cochrane Review (2020) analyzed 17 studies involving 2,996 participants and found that a low-protein diet (0.5-0.6 g/kg/day) compared to normal protein (≥0.8 g/kg/day) may slightly reduce the risk of progression to kidney failure (low to moderate quality evidence). However, the real-world effectiveness remains debated and needs to be individualized for each patient. [Hahn et al. 2020, Cochrane]
Causes of Chronic Kidney Disease
Common causes (accounting for > 90% of cases)
1. Diabetes (Diabetic Nephropathy) - 40-50%
Diabetes is the leading cause of CKD globally. Prolonged high blood sugar damages small blood vessels in the kidneys, leading to decreased filtration function.
- Mechanism: Hyperglycemia causes protein glycation, glomerular damage, and increased filtration pressure
- Prevention: Control HbA1c < 7%, blood pressure < 130/80 mmHg, use ACEi/ARB
- Research: DCCT/EDIC Study (2019) showed that good blood glucose control reduces kidney disease risk by 50%
2. Hypertension (Hypertensive Nephrosclerosis) - 25-30%
Long-term high blood pressure causes sclerosis and damage to renal blood vessels, reducing blood flow to the kidneys.
- Mechanism: High pressure thickens blood vessel walls, reduces elasticity, and causes glomerulosclerosis
- Prevention: Control BP < 130/80 mmHg (KDIGO 2021), reduce salt < 5g/day
- Research: SPRINT Trial (2015) - reducing BP < 120 mmHg decreased CKD progression risk by 28%
3. Glomerulonephritis - 10-15%
A group of diseases causing inflammation and direct damage to the glomeruli, which can be autoimmune, infectious, or of unknown cause.
- IgA nephropathy, Focal segmental glomerulosclerosis (FSGS), Membranous nephropathy
- Treatment: Immunosuppressive drugs, corticosteroids as prescribed by a specialist
Less common causes (5-10%)
4. Polycystic Kidney Disease (PKD)
A hereditary disease causing the formation of multiple fluid-filled cysts in the kidneys, causing the kidneys to enlarge and gradually lose function.
- ADPKD: Autosomal dominant inheritance, symptoms usually appear at age 30-40
- Progression: 50% of patients require dialysis by age 60
- Treatment: Tolvaptan (new drug) slows kidney growth and GFR decline (TEMPO 3:4 Trial, 2012)
5. Recurrent kidney stones
Repeated recurrence of kidney stones can cause obstruction, infection, and long-term kidney damage.
- Mechanism: Urinary tract obstruction → increased back pressure → kidney atrophy
- Prevention: Adequate hydration (2-3 liters/day), limit oxalate and sodium
- Research: Rule et al. (2009) and subsequent meta-analyses showed that recurrent kidney stones increase CKD risk by approximately 47%
6. Hyperuricemia (High Uric Acid)
Hyperuricemia is common in CKD patients and has been associated with disease progression in observational studies. However, a clear causal relationship has not been established.
- Causes: Gout, purine metabolism disorders, purine-rich diet, reduced excretion due to kidney failure
- Treatment: Allopurinol, Febuxostat - indicated when gout symptoms are present
- KDIGO 2024 recommendation: Does NOT recommend using uric acid-lowering drugs in CKD patients with asymptomatic hyperuricemia to slow CKD progression
- Evidence: Major clinical trials (CKD-FIX 2020, PERL, FEATHER) all showed no kidney-protective benefit from lowering uric acid in patients without gout symptoms
7. Dyslipidemia (Lipid Disorders)
High cholesterol and triglycerides cause renal artery atherosclerosis, reduced blood flow, and glomerular damage.
- Mechanism: Oxidized LDL deposits in glomeruli → inflammation → fibrosis
- Target: LDL < 100 mg/dL (< 70 if cardiovascular disease is present)
- Treatment: Statins (atorvastatin, rosuvastatin)
- Research: SHARP Trial (2011) - Statins reduced cardiovascular event risk by 17% in CKD patients
Note on multifactorial causes
Many CKD patients have more than one cause (e.g., diabetes + hypertension + dyslipidemia). Treatment needs to address all risk factors simultaneously for the best outcomes.
Treatment and Management of Chronic Kidney Disease
1. Medical Treatment - The Role of Nephrologists
Treatment of chronic kidney disease is a complex process requiring the specialized management of nephrologists. The main goals are to treat the underlying cause and slow disease progression.
A. Treating underlying causes
- Diabetes: Blood glucose control (HbA1c < 7%), use of SGLT2i (empagliflozin, dapagliflozin), GLP-1 agonists
- Hypertension: Target BP < 130/80 mmHg, prefer ACEi/ARB
- Glomerulonephritis: Immunosuppressive treatment according to specialist protocol
- High uric acid: Uric acid-lowering drugs (allopurinol, febuxostat)
- Lipid disorders: High-dose statins
B. Kidney Protection (Renoprotection)
- RAAS inhibitors: ACE inhibitors (enalapril, ramipril) or ARBs (losartan, telmisartan) - reduce proteinuria, protect kidneys
- SGLT2 inhibitors: Empagliflozin, dapagliflozin - DAPA-CKD study (2020) showed 39% reduction in CKD progression risk
- GLP-1 receptor agonists: Semaglutide, liraglutide - provide kidney and cardiovascular protection
- Finerenone: New mineralocorticoid receptor antagonist - FIDELITY Analysis (2022) showed 23% reduction in CKD progression risk
C. Treating complications
- Anemia: Erythropoiesis-stimulating agents (ESA), iron supplementation
- Mineral bone disorder: Vitamin D, phosphate binders, calcimimetics
- Hyperkalemia: Dietary modification, potassium binders (patiromer, sodium zirconium cyclosilicate)
- Metabolic acidosis: Sodium bicarbonate
Evidence on medical treatment efficacy
Large studies have proven the efficacy of each drug class: SGLT2 inhibitors reduce CKD progression risk by 39-44% (DAPA-CKD 2020), Finerenone reduces CKD progression risk by 23% (FIDELITY 2022), and ACE inhibitors/ARBs reduce proteinuria and protect kidneys. Combining multiple interventions according to KDIGO 2024 guidelines can optimize treatment outcomes, but needs to be individualized based on each patient's specific condition.
2. Nutritional Therapy - Important Supportive Role
Appropriate nutrition plays a SUPPORTIVE role to medical treatment, not replacing medications and medical interventions, but has great significance in slowing disease progression.
Nutritional principles according to KDOQI 2020:
- Protein: 0.55-0.6 g/kg/day for CKD 3-5 without diabetes; 0.6-0.8 g/kg/day for those with diabetes (KDOQI 2020)
- Sodium (salt): < 2.3g sodium/day or 100 mmol/day (< 5.8g table salt) according to KDOQI 2020; < 2g for CKD with diabetes according to KDIGO 2020
- Potassium: 2-3g/day if hyperkalemia is present
- Phosphorus: 800-1000 mg/day
- Energy: 30-35 kcal/kg/day to prevent malnutrition
Benefits of appropriate diet:
- Reduces filtration burden on kidneys (decreases proteinuria)
- Reduces accumulation of urea toxins
- Controls electrolytes (Na, K, P)
- Lowers blood pressure
- Improves symptoms (nausea, fatigue)
Scientific evidence
The MDRD study showed: Each 0.2 g/kg/day reduction in protein helps reduce the rate of GFR decline by about 1.15 ml/min/1.73m²/year (equivalent to 29% of the average GFR decline rate) and reduces the risk of kidney failure or death by 50% [MDRD Study 1996]. The Garneata (2016) study on 207 CKD 4-5 patients: VLPD (0.3 g/kg/day) + ketoanalog reduced dialysis requirement from 30% to 11% (P<0.001), particularly effective in the eGFR<20 ml/min group (NNT=2.7) [Garneata et al. 2016].
3. The Role of Ketoanalogs in CKD Treatment
Ketoanalogs (α-keto acids) are essential amino acid analogues that are metabolized into amino acids in the body without producing nitrogen (urea).
Mechanism of action:
- Provides essential amino acids without increasing nitrogen burden on kidneys
- Helps maintain body protein when restricting dietary protein
- Reduces blood urea toxins
- Improves calcium-phosphorus metabolism
Indications for use:
- CKD stage 3b-5 patients not on dialysis
- Combined with very low protein diet (VLPD: 0.3-0.4 g/kg/day)
Research evidence:
- Garneata et al. (2016): Study of 207 CKD 4-5 patients over 15 months, VLPD (0.3 g/kg/day) + ketoanalog reduced dialysis requirement from 30% to 11% (P<0.001). Reached composite endpoint (dialysis or >50% eGFR decline) in 13% of KD group vs 42% of LPD group (P<0.001). No deaths in either group [Garneata 2016]
- Di Iorio et al. (2019): Ketoanalog combined with VLPD reduced uremic toxins, improved gut microbiome, decreased blood indoxyl sulfate and p-cresyl sulfate, without causing malnutrition [Di Iorio 2019]
- Cochrane Review (2016): Ketoanalog combined with low protein may slow progression to dialysis, but quality of evidence is low and larger studies are needed for confirmation
Important note
Ketoanalogs should ONLY be used under the supervision of a nephrologist and nutrition specialist. Close monitoring of nutritional status (weight, serum albumin) is needed to prevent malnutrition. The VLPD + ketoanalog regimen is not suitable for all patients.
4. Importance of Multidisciplinary Compliance
IMPORTANT: CKD patients need support from multiple specialists
To properly manage chronic kidney disease and related conditions, patients MUST follow the advice of ALL the following specialists:
Essential specialist team:
- Nephrologist: Primary treatment, kidney disease management, medication decisions
- Endocrinologist (if diabetic): Blood glucose control
- Cardiologist (if hypertensive or with heart disease): Blood pressure management, heart disease
- Renal Dietitian: Design personalized diet plan
- Pharmacist: Medication counseling, drug interactions, nephrotoxic drugs
- Medical Social Worker: Psychological and financial support
Why is compliance with all specialists necessary?
- CKD often comes with other conditions (diabetes, hypertension, cardiovascular disease, dyslipidemia)
- Each specialist has a unique role, complementing each other
- Incomplete treatment of one condition can worsen others
- Multidisciplinary coordination helps maximize time before dialysis is needed
Optimizing Time Before End Stage
Comprehensive strategy to maximize duration
When all kidney-damaging conditions are well-managed and combined with appropriate nutrition, the time to progression to end stage can be significantly extended.
Optimization steps:
1. Optimal medical treatment:
- Tight blood glucose control (HbA1c < 7%)
- Target blood pressure control (< 130/80 mmHg)
- Use kidney-protective drugs (SGLT2i, ACEi/ARB)
- Control blood lipids (LDL < 100 mg/dL)
- Treat anemia, mineral bone disorder
- Avoid nephrotoxic drugs (NSAIDs, certain antibiotics)
2. Appropriate nutrition:
- Controlled protein restriction (0.55-0.6 g/kg/day for non-diabetic, 0.6-0.8 g/kg/day for diabetic)
- Sodium restriction (< 2.3g/day per KDOQI 2020, < 2g/day for diabetic CKD per KDIGO 2020)
- Control potassium and phosphorus based on lab results
- Ensure adequate energy (prevent malnutrition)
- Consider ketoanalogs if available (in CKD 4-5)
3. Lifestyle changes:
- Complete smoking cessation
- Regular moderate exercise (30 minutes/day, 5 days/week)
- Maintain healthy weight (BMI 18.5-25)
- Adequate hydration (unless doctor advises restriction)
- Adequate sleep (7-8 hours/night)
- Stress management
4. Regular monitoring:
- Regular nephrologist visits (every 3-6 months)
- Blood tests: Creatinine, GFR, electrolytes, albumin (every 3-6 months)
- Urine tests: Proteinuria (every 6 months)
- Home blood pressure monitoring daily
- Track weight and dietary intake
Evidence on efficacy of individual interventions
Large clinical studies have proven the efficacy of each intervention: DAPA-CKD (2020) showed SGLT2i reduced the risk of CKD progression or kidney death by 39%, and reduced the risk of ≥50% GFR decline or ESKD by 44% [Heerspink et al. 2020]. SPRINT (2015) demonstrated intensive blood pressure control (<120 mmHg) reduced death risk by 25% and reduced cardiovascular events [SPRINT 2015]. Combining multiple interventions can optimize outcomes, but combined efficacy needs to be individualized for each patient.