Approach to Chronic Kidney Disease

Approach to Chronic Kidney Disease

• Chronic kidney disease (CKD) often progresses to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT).
• Patients with CKD frequently die from non-renal causes, particularly cardiovascular events.
• Early diagnosis of CKD is crucial to delay progression and prevent cardiovascular complications.

Defining CKD

• Kidney Disease Improving Global Outcomes (KDIGO) defines CKD as structural or functional kidney abnormalities lasting for at least three months, impacting health.
• The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) also defines CKD.
• CKD is characterized by kidney damage (structural or functional abnormalities) for three or more months. This is often evident through urinalysis, imaging studies, or renal biopsy and may or may not include a decreased glomerular filtration rate (GFR).

Criteria for CKD

• CKD is diagnosed with kidney damage or reduced kidney function.
• The duration of kidney damage or reduced function must be three or more months.
• A glomerular filtration rate (GFR) below 60 mL/minute/1.73 m2, either with or without kidney damage, is a diagnostic criterion for CKD.
• Other structural or functional abnormalities beyond decreased GFR are also considered for diagnosis

Pathophysiology of CKD

Initiating Mechanism

• The initiating mechanisms of CKD are specific to the underlying etiology.
• Genetic abnormalities in kidney development are a possibility.
• Immune complex deposition can occur.
• Inflammation, specific to glomerulonephritis, is one factor.
• Toxin exposure, affecting renal tubules and interstitium, is another contributing factor.

Progressive Mechanism

• Reduction in nephron number, alongside vasoactive hormones, cytokines, and growth factors, leads to CKD progression.
• Initially, adaptive mechanisms like hyperfiltration and hypertrophy of remaining nephrons occur.
• These eventually become maladaptive and cause glomerular architecture distortion, sclerosis, and nephron dropout.
• The renin-angiotensin system is involved both in adaptive and maladaptive mechanisms.
• Ultimately, a reduction in renal mass causes a progressive decline in renal function.

Significance of GFR and Albuminuria

• Glomerular filtration rate (GFR) is the best overall index of kidney function.
• Decreasing GFR correlates with increasing symptoms and metabolic abnormalities.
• A GFR below 60 ml/min per 1.73 m² is associated with a higher risk of CKD complications like metabolic/endocrine complications and cardiovascular disease related death.

Normal GFR

• Normal GFR for young adults is typically between 120 and 130 mL/min per 1.73 m².
• GFR diminishes with age.
• Sexual differences and body size may also influence GFR.
• The average decline in GFR per year is around 1 mL/min per 1.73 m² for adults.
• At age 70, the average GFR is 70 mL/min per 1.73 m².

Albuminuria/Proteinuria

• Albuminuria/proteinuria is a marker of chronic kidney damage.
• Albuminuria/proteinuria has a prognostic value in CKD progression.
• Albuminuria/proteinuria is an independent risk factor for cardiovascular disease.
• Urine albumin-to-creatinine ratio (ACR) and urine protein-to-creatinine ratio (PCR) are initial tests for proteinuria. A reagent strip urinalysis for total protein is also used.

Etiology

• Diabetic glomerular disease
• Hypertensive nephropathy
• Primary glomerulopathy with hypertension
• Vascular and ischemic renal disease
• Glomerulonephritis
• Urinary tract disease
• Polycystic kidney disease
• Lupus and analgesic nephropathy
• Tubulointerstitial nephropathy

Risk Factors

Susceptibility

• Advanced age, reduced kidney mass, low birth weight, racial/ethnic minority status, and family history, and low socioeconomic status are susceptibility factors. These are largely not modifiable.

Initiation

• Diabetes, hypertension, autoimmune diseases, polycystic kidney diseases, and drug toxicity—modifiable—directly contribute to the onset of CKD.

Progression

• Factors like hyperglycemia, elevated blood pressure, proteinuria, and smoking speed up kidney function decline. These are modifiable.

Systematic Approach to CKD

History Taking

• Ante/Natal/Postnatal history, including birth weight, IUGR, recurrent URI, are reviewed.
• Hypertension (duration, type of medications), Diabetes mellitus (duration, severity), and pregnancy history are also taken into consideration.
• History of hereditary kidney diseases (e.g., Alport, Fabry) and previous abnormal lab results (urea, creatinine).
• Asympotomatic urinary abnormalities (hematuria/proteinuria), urinary frequency/urgency (obstructive uropathy), and changes in urine appearance are also assessed.

Physical Examination

• Appearance, skin, edemas, pallor, uremic odor are evaluated.
• Vital signs like blood pressure, pulse, and saturation are measured.
• Fundoscopy for hypertension and diabetic retinopathy is performed.
• Cardiovascular assessment (apex beat, LV heave, pericardial rub/S4), abdominal examination (distension, renal angle/mass, bruits), and neurologic assessment (flapping tremor, sensory polyneuropathy)

Investigations

• Complete blood count (CBC)
• Urinalysis (dipstick and microscopic exam)
• 24-hour urine protein
• Serum creatinine
• Urea
• Coagulation profile
• Electrolyte panel (sodium, potassium, calcium, phosphorus)
• Liver function tests (LFTs)
• Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), HIV
• Parathyroid hormone (PTH), serum iron, vitamin B12, and folate levels
• Albumin-to-creatinine ratio (ACR)
• Glomerular filtration rate (GFR)
• Renal ultrasonography (USG)—to evaluate renal size and symmetry, the presence of scars
• Biopsy to aid with diagnoses

Classification of CKD

• G1: ≥90 mL/min/1.73m² (Normal/high GFR)
• G2: 60-89 mL/min/1.73m² (Mildly decreased GFR)
• G3a: 45-59 mL/min/1.73m² (Mild to moderately decreased GFR)
• G3b: 30-44 mL/min/1.73m² (Moderate to severely decreased GFR)
• G4: 15-29 mL/min/1.73m² (Severely decreased GFR)
• G5: <15 mL/min/1.73m² (Kidney failure)

Albuminuria Classification

• A1: <30 mg/g (Mild/Normal)
• A2: 30-299 mg/g (Moderate)
• A3: >300 mg/g (Severe)

AKI vs CKD

• Differentiating AKI from CKD is crucial, especially in a patient with renal impairment.
• A detailed clinical history, previous sequential creatinine results, and renal ultrasound help in the distinction.
• Patients with CKD are at an increased risk of AKI.

Screening for CKD

• Screening the general population for CKD isn't recommended.
• Certain patient groups should be screened, including those with hypertension, diabetes, cardiovascular disease (CVD), hematuria/proteinuria from incidental investigations, patients receiving nephrotoxic drugs, structural renal disease, renal calculi, or prostatic hypertrophy, and those with a family history of kidney disease.

Cardiovascular Complications of CKD

• Leading causes of mortality and morbidity throughout all stages of CKD.
• Albuminuria is a crucial risk factor for CVD.
• Ischemic vascular disease involves a complex interaction of classical and CKD-related factors. Hemodilution, hypotension, and volume depletion are complications of hemodialysis, aggravating ischemia.
• Cardiac troponin levels are often elevated in CKD even without evident acute ischemia.
• Elevated cardiac function and salt and water retention can lead to heart failure.

Hypertension in CKD

• Hypertension is a prevalent complication in CKD, often associated with LVH (left ventricular hypertrophy) and rapid renal function decline.
• The absence of hypertension can indicate poor left ventricular function, with low BP carrying a worse prognosis than high BP.
• Systolic blood pressure is a more significant marker of CKD progression than diastolic blood pressure.

KDIGO Guideline for BP

• BP targets depend on the presence/absence of diabetes and level of albumin excretion.
• In patients with CKD and urine albumin excretion <30 mg/24 h, a target BP of <140/90 mmHg is recommended.
• In patients with CKD and urine albumin excretion >30 mg/24 h, a target BP of <130/80 mmHg is recommended.
• Treatment adjustments should align with the patient's age, comorbidities, and potential risks of CKD progression. Addressing retinopathy, electrolyte/tolerance issues, and any acute/orthostatic hypotension is crucial.

Preferred Antihypertensive Agents

• ACE inhibitors or ARBs are the preferred first-line antihypertensive agents in CKD to slow disease progression.
• If the target BP is not reached after 2-4 weeks at the maximum dose, additional medications can be considered.
  • Add amlodipine (start at 2.5mg/day, titrate up to 5mg/day) if proteinuria is low.
  • Add NDHP-CCB (diltiazem 180mg/day) if the proteinuria is high.
  • If target BP is not reached after 2-4 weeks of medication titration, a detailed assessment to rule out secondary causes for hypertension or add aldosterone (e.g., spironolactone 25mg or eplerenone 50mg daily) is required.

Other Management Considerations

Pericardial Disease

• Uremia-related pericarditis involves retrosternal chest pain, dyspnea, and tachycardia.
• ECG findings include widespread concave ST elevation, PR segment depression in most leads, and reciprocal changes in AVR.
• Sinus tachycardia can also be present
• Pericardial effusion is characterized by shortness of breath, Beck's triad (elevated jugular venous pressure, hypotension, muffled heart sounds), and specific ECG findings (low QRS voltage, tachycardia, electrical alternans).

Anemia

• Anemia in adults is defined as hemoglobin (Hb) levels below 13 g/dL in males and 12 g/dL in females.
• Decreased erythropoietin production is the primary cause.
• Other contributing factors include blood loss during dialysis, iron deficiency, and anemia of chronic disease including renal osteodystrophy.
• Anemia workup is warranted when CrCl is below 60 mL/min/1.73m² or Hb is below 13 g/dL (men) or 12 g/dL (women).

Management of Mineral and Bone Disorders in CKD(MBD-CKD)

• Vitamin D analogs—like calcitriol (Calcijex, Rocaltrol) and paricalcitol (Zemplar)—are used to suppress parathyroid hormone (PTH) synthesis.
• Doxercalciferol (Hectorol) is used as another analog of vitamin D.
• Calcimimetics like cinacalcet hydrochloride (Sensipar) can be used when high calcium and phosphate concentrations persist despite adequate vitamin D analog therapy.
• Close monitoring of serum calcium levels (every 1-2 weeks) along with other pertinent parameters are essential to avoid hypocalcemia, which can be associated with hypocalcemia. Etelcalcetide (Parsabiv) is also available for calcium management.

Fluid and Electrolyte Abnormalities

• Fluid overload requires restriction of dietary salt and the use of loop diuretics (e.g., furosemide) or metolazone.
• Hyponatremia requires water restriction, and diuretics may be added when edema is present.
• Hyperkalemia requires dietary adjustments (avoiding high potassium foods like bananas, nuts, and certain dairy products) along with medication adjustments like drugs that spare potassium (e.g., ACE inhibitors, ARBs) and K+ sparing diuretics (e.g., spironolactone), and other medications like calcineurin inhibitors (e.g., cyclosporine).

Metabolic Acidosis

• Impaired renal ammonia production and urinary acidification are common in advanced CKD.
• Metabolic acidosis may be linked with hyperkalemia and hyperchloremic metabolic acidosis.
• Bicarbonate levels should be maintained within a target range 22 mmol/L.
• Hyperkalemia must be managed concurrently to prevent acidosis progressing to AKI.Sod bicarbonate supplementation is a part of treatment to correct acidosis.

Drug Dosing in CKD

• Drug selection and dosing should aim to prevent toxicity, taking into account factors like CKD stage, renal replacement therapy (RRT) status, drug absorption, and the patient's use of multiple medications.
• Patient history and clinical data should guide treatment.
• CrCI (using the Cockcroft-Gault equation) should be considered when adjusting medication dosages.
• Medications requiring modification should be identified using the above parameters.

Management of CKD

• Prevention of CKD progression: protein intake optimization (<0.8g/kg), salt intake (<2g/day).

• Management of CKD complications:

• CKD stage 3a warrants vaccination (hepatitis B, pneumococcal, influenza, zoster), which is helpful in prevention of some infections; metabolic bone disease management (e.g., calcium and phosphate management); blood sugar and blood pressure control, physical activity (compatible with cardiovascular health), smoking cessation

• CKD stages 3a/b indicate management for bone metabolism disease, diabetes, and hypertension

• CKD stage 4 recommends screening for and management of electrolytes and volumes; and prepare for treatment with renal replacement therapy (RRT) as needed.

• CKD stage 5 mandates initiation of renal replacement therapy (RRT) and optimization of any related complications including electrolytes, fluid and volumes to optimize treatment.

Glycemic Control

• Maintain HbA1c levels below 7%
• Insulin therapy may require careful titration up as needed because the level of insulin in the body slightly increases with CKD.
• Metformin discontinuation in CKD 3 patients is warranted when GFR reaches <30ml/min per 1.73m².

Dialytic Therapy

• Indicated for patients with uremic symptoms, hyperkalemia unresponsive to conservative measures, persistent extracellular fluid volume expansion despite diuretic therapy, acidosis refractory to medical therapy, or bleeding diathesis.
• It also becomes necessary when the eGFR drops below 10 ml/min per 1.73m².
• Various dialysis methods (e.g., intermittent hemodialysis, continuous renal replacement therapy, and hybrid therapies) are employed.

This quiz covers key concepts related to chronic kidney disease (CKD), including its definition, progression to end-stage renal disease, and the importance of early diagnosis. Participants will learn about criteria for diagnosing CKD and its implications for patient health, particularly concerning cardiovascular complications.