Chronic Kidney Disease¶
Chapter 322 | Part 9: Disorders of the Kidney and Urinary Tract
KEY CLINICAL POINTS¶
- Chronic kidney disease (CKD) is defined by abnormal kidney function with progressive decline in GFR, often accompanied by albuminuria.
- Staging of CKD is based on estimated GFR (eGFR) and urinary albumin-to-creatinine ratio (UACR), with stage 5 CKD requiring renal replacement therapy.
- Key risk factors include diabetes, hypertension, genetic mutations (e.g., APOL1, COL4A3/4), and environmental exposures (e.g., NSAIDs, heavy metals).
- Management focuses on controlling blood pressure (target <130/80 mmHg), reducing proteinuria with RAS inhibitors/SGLT2 inhibitors, and addressing complications like anemia and mineral metabolism disorders.
- Early detection and intervention are critical to slow CKD progression and reduce cardiovascular risk.
1. DEFINITION & OVERVIEW¶
Chronic kidney disease (CKD) encompasses a spectrum of pathophysiological processes associated with abnormal kidney function, often with progressive decline in glomerular filtration rate (GFR). The term 'end-stage renal disease' (ESRD) refers to stage 5 CKD, requiring dialysis or transplantation. CKD is staged based on GFR and albuminuria, with staging reflecting risk for progression and complications.
Table 322-1: Risk Factors for Chronic Kidney Disease (CKD)¶
| Risk Factor | Description |
|---|---|
| Diabetes | Leading cause, often with diabetic nephropathy |
| Hypertension | Both risk and consequence of CKD |
| Genetic Mutations | e.g., APOL1, COL4A3/4, UMOD |
| Environmental Exposures | NSAIDs, heavy metals, radiographic contrast agents |
| Demographic Factors | Age, male sex, population ancestry |
Table 322-2: Monogenic Risk Loci for CKD¶
| Gene | Associated Condition |
|---|---|
| ADPKD1/2 | Autosomal Dominant Polycystic Kidney Disease |
| COL4A3/4 | Type IV Collagen-Associated Nephropathy |
| UMOD | Autosomal Dominant Tubulointerstitial Kidney Disease |
| APOL1 | Focal Segmental Glomerulosclerosis (FSGS) in African Ancestry |
Table 322-3: Equations for Estimating GFR¶
| Equation | Formula |
|---|---|
| Modification of Diet in Renal Disease (MDRD) Equation | 1.86 × (Scr)^-1.154 × (Age)^-0.203 × 0.742 (women) |
| CKD-EPI Equation | 141 × min(Scr/kappa, 1)^a × max(Scr/kappa, 1)^-1.209 × 0.993^Age |
Table 322-4: Leading Causes of CKD¶
| Cause | Description |
|---|---|
| Diabetic Nephropathy | Most common cause in type 2 diabetes |
| Glomerulonephritis | Inflammatory kidney disease |
| Hypertension-Associated CKD | Vascular and ischemic kidney disease |
| Autosomal Dominant Polycystic Kidney Disease (ADPKD) | Genetic disorder with cyst formation |
| Cystic/Tubulointerstitial Nephropathy | Non-diabetic causes like obstructive uropathy |
1.1 Pathophysiology¶
CKD pathophysiology involves two mechanisms: (1) specific initiating mechanisms (e.g., genetic, immune, metabolic, vascular, or tubulointerstitial damage) and (2) nonspecific mechanisms like hyperfiltration and hypertrophy of remaining nephrons. Hyperfiltration leads to glomerular hypertension, which promotes sclerosis and loss of nephrons.
1.2 Staging¶
CKD is staged (Fig. 322-1) based on eGFR and albuminuria. Stages 1–3 are asymptomatic, while stages 4–5 involve complications like fluid overload, electrolyte imbalances, and cardiovascular disease. Staging helps guide management and prognosis.
2. EPIDEMIOLOGY¶
CKD affects ~15% of the global population, with higher prevalence in older adults and those with diabetes/hypertension. In the U.S., ~15% of adults have CKD (stages 1–4), with stage 5 CKD requiring dialysis. Risk factors include age, male sex, African ancestry, and comorbidities like diabetes and hypertension.
2.1 Prevalence¶
Global prevalence of CKD is ~10–15%, with stage 5 CKD affecting ~2% of adults. In the U.S., ~15% of adults have CKD, with higher rates in older populations and those with diabetes/hypertension.
2.2 Demographics¶
CKD is more common in males, older adults, and individuals of African ancestry. Diabetes and hypertension are leading causes, with genetic factors (e.g., APOL1 variants) contributing to higher risk in certain populations.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
CKD arises from diverse etiologies, including diabetes, hypertension, glomerular diseases, and genetic disorders. Pathophysiology involves hyperfiltration, tubulointerstitial injury, and systemic inflammation, leading to progressive loss of nephrons and impaired kidney function.
3.1 Mechanisms¶
CKD pathophysiology includes: (1) specific initiating mechanisms (e.g., glomerular injury, tubulointerstitial damage), and (2) nonspecific mechanisms like hyperfiltration and hypertrophy of remaining nephrons. Hyperfiltration leads to glomerular hypertension, which promotes sclerosis and loss of nephrons.
3.2 Genetic Factors¶
Monogenic causes include ADPKD, APOL1-mediated kidney disease, and collagen disorders (e.g., COL4A3/4). Polygenic risk factors and environmental exposures (e.g., NSAIDs, heavy metals) also contribute.
4. CLINICAL FEATURES¶
CKD is often asymptomatic in early stages. Later stages present with fatigue, edema, hypertension, and complications like anemia, electrolyte imbalances, and cardiovascular disease. Uremic syndrome includes symptoms like pruritus, nausea, and neurological disturbances.
4.1 Symptoms¶
Early CKD is asymptomatic. Later stages may present with fatigue, decreased appetite, edema, hypertension, pruritus, and neurological symptoms (e.g., asterixis, seizures).
4.2 Complications¶
Complications include cardiovascular disease, anemia, electrolyte imbalances (hyperkalemia), metabolic acidosis, and bone disease (e.g., adynamic bone disease, secondary hyperparathyroidism).
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnosis includes prerenal azotemia, postrenal azotemia, acute kidney injury (AKI), and systemic diseases (e.g., lupus, vasculitis). CKD must be distinguished from acute renal failure and other systemic conditions.
5.1 Prerenal vs. Intrinsic CKD¶
Prerenal azotemia (e.g., dehydration) is reversible, while intrinsic CKD involves glomerular or tubulointerstitial damage. Urine sodium and fractional excretion of sodium (FeNa) help differentiate.
5.2 Systemic Diseases¶
Conditions like lupus nephritis, vasculitis, and diabetic nephropathy must be considered in differential diagnosis.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis involves measuring eGFR, urinary albumin-to-creatinine ratio (UACR), and ruling out reversible causes. Imaging (e.g., renal ultrasound) and biopsy may be required for specific etiologies.
6.1 Laboratory Tests¶
Key tests include serum creatinine, eGFR, UACR, electrolytes, BUN, and markers of bone and mineral metabolism (e.g., PTH, calcium, phosphorus).
6.2 Imaging¶
Renal ultrasound assesses kidney size, structure, and obstruction. CT/MRI may be used for vascular or structural abnormalities.
7. MANAGEMENT & TREATMENT¶
Management includes controlling blood pressure (target <130/80 mmHg), reducing proteinuria with RAS inhibitors/SGLT2 inhibitors, managing complications (e.g., anemia, hyperparathyroidism), and considering renal replacement therapy (dialysis/ transplantation) for stage 5 CKD.
7.1 Pharmacologic Therapy¶
ACE inhibitors/ARBs, SGLT2 inhibitors, and RAS blockers are first-line for reducing proteinuria and slowing progression. Iron supplementation and erythropoietin-stimulating agents (ESAs) manage anemia.
7.2 Non-Pharmacologic Therapy¶
Dietary sodium restriction, fluid management, and lifestyle modifications (e.g., exercise, smoking cessation) are critical. Patient education and multidisciplinary care are essential.
8. PROGNOSIS & COMPLICATIONS¶
CKD is associated with increased cardiovascular mortality, progressive renal failure, and complications like anemia, electrolyte imbalances, and bone disease. Early intervention improves outcomes.
8.1 Cardiovascular Risk¶
CKD patients have 10–200-fold higher cardiovascular risk due to hypertension, atherosclerosis, and uremic toxins. Cardiovascular disease is the leading cause of mortality in CKD.
8.2 Long-Term Outcomes¶
Progression to ESRD is common in advanced CKD. Early detection and management of risk factors (e.g., blood pressure, proteinuria) improve prognosis.
9. SPECIAL CONSIDERATIONS¶
Special populations (e.g., pregnancy, elderly, pediatric patients) require tailored management. CKD in pregnancy increases risks of preterm birth and maternal complications. Elderly patients may have reduced GFR and require dose adjustments for medications.
9.1 Pregnancy¶
CKD in pregnancy increases risks of preterm birth, preeclampsia, and maternal mortality. Dialysis may be required in severe cases. ESAs and antihypertensives must be carefully managed.
9.2 Pediatrics¶
Pediatric CKD may present with growth failure, hypertension, and renal failure. Management includes dietary adjustments, growth hormone therapy, and early referral for dialysis/ transplantation.
10. KEY POINTS & CLINICAL PEARLS¶
- CKD is staged by eGFR and UACR, with stage 5 requiring renal replacement therapy. 2. RAS inhibitors and SGLT2 inhibitors slow progression and reduce cardiovascular risk. 3. Anemia and mineral metabolism disorders are common complications. 4. Early detection and intervention are critical to prevent ESRD. 5. Patient education and multidisciplinary care improve outcomes.