Chronic Kidney Disease Overview

Approach to Chronic Kidney Disease

• Chronic kidney disease (CKD) often progresses to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT).
• Most patients with CKD 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 outcome (KDIGO) defines CKD as abnormalities of kidney structure or function lasting >3 months, impacting health.
• National Kidney Foundation, Kidney Disease Outcomes Quality Initiative (KDOQI) defines CKD as kidney damage (>3 months) with or without decreased glomerular filtration rate (GFR) evidenced by urinalysis, imaging studies, or renal biopsy.

Criteria for CKD

• Reduced kidney function or damage for more than 3 months.
• Glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 with or without kidney damage.
• Structural abnormalities other than decreased GFR.

Pathophysiology of CKD

Initiating Mechanism

• Genetic abnormalities in kidney development.
• Immune complex deposition.
• Inflammation in types of glomerulonephritis.
• Toxin exposure in renal tubules and interstitium.

Progressive Mechanism

• Reduction in nephron number due to vasoactive hormones, cytokines, and growth factors.
• Short-term adaptations like hyperfiltration and hypertrophy of viable nephrons.
• Long-term maladaptive responses with glomerular architecture distortion, sclerosis, and nephron loss.
• Increased intrarenal activity of renin-angiotensin axis contributes to both initial adaptive hyperfiltration and subsequent maladaptive hypertrophy and sclerosis.
• Eventually, a decline in renal mass and function occurs over many years.

Etiology of CKD

• 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 for CKD

Susceptibility (not proven to cause CKD):

• Advanced age.
• Reduced kidney mass.
• Low birth weight.
• Racial/ethnic minority.
• Family history.
• Low socioeconomic status.

Initiation (directly cause CKD):

• Diabetes.
• Hypertension.
• Autoimmune disease.
• Polycystic kidney disease.
• Drug toxicity.

Progression (result in faster CKD decline):

• Hyperglycemia.
• Elevated blood pressure.
• Proteinuria.
• Smoking.

Significance of GFR and Albuminuria

• Glomerular filtration rate (GFR) is the best overall index of kidney function.
• Decreases in GFR correlate with increasing symptoms and metabolic abnormalities.
• GFR <60 mL/min/1.73 m2 is associated with high risk of complications like drug toxicity, metabolic endocrine complications, and cardiovascular disease/death.
• Albuminuria (protein in urine) is a marker of chronic kidney damage and an independent cardiovascular risk factor.

Normal GFR

• Normal GFR in young adults is approximately 120-130 mL/min/1.73 m2.
• GFR declines with age.
• GFR varies with sex and body size.
• Annual mean decline in GFR with age is approximately 1 mL/min/1.73 m2/year.
• Mean GFR is lower in women than in men.

Albuminuria/Proteinuria

• Marker of chronic kidney damage.
• Prognostic value in CKD progression.
• Independent cardiovascular risk factor.
• KDIGO recommends urine albumin/creatinine ratio (ACR), urine protein/creatinine ratio (PCR), and reagent strip urinalysis for total protein for initial testing (early morning urine preferred).

CKD Classification (GFR Stages)

•  GFR stages are categorized by G1 (normal/high) to G5 (kidney failure).
• Each stage corresponds to a specific GFR range.
• Other classifications exist based on albuminuria/proteinuria (A1 to A3).

Systematic Approach to CKD

• Detailed history taking, physical examination, clinical evaluation, and investigations are essential.

History Taking

• Prenatal/natal/postnatal history, birth weight, recurrent infections (UTI).
• Hypertension details, history of diabetes, pregnancy-related complications.
• Family history of heritable kidney diseases.
• Previous abnormal urea/creatinine levels.
• History of urine abnormalities (hematuria, proteinuria).
• History of urinary frequency/urgency, changes in urine appearance.
• History of exposures to nephrotoxic drugs, herbal remedies, or natural supplements.
• History of uremic symptoms (loss of appetite, weight loss, nausea, hiccups, metallic taste, burning epigastrium, pruritus, muscle cramps, edema, nocturia).

Drug History

• History of current medications, dosage changes and new medications.
• History of any exposure to nephrotoxic drugs, chemotherapy, NSAIDs, or aminoglycosides, and recent contrast procedures.

Clinical Features

• Patients with CKD are often asymptomatic at early stages.
• Symptoms such as anemia, nausea, hyperkalemia, tiredness, fluid retention, pruritus, and anorexia typically occur in advanced stages.
• Severe CKD can manifest with neuropathy signs, altered consciousness, seizures, pericarditis, or deposits of urea/urate on skin & mucous membranes.

Physical Examination

• Appearance (skin, edema, pallor, uremic fetor).
• Vitals (blood pressure, pulse, saturation).
• Fundoscopy (hypertension/diabetes retinopathy).
• Cardiovascular (apex beat, left ventricular heave, pericardial rub, S4).
• Abdomen (distension, renal angle mass, aortic bruit, renal bruit).
• Central nervous system (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.
• Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), HIV.
• Parathyroid hormone (PTH).
• Serum iron, vitamin B12, folate levels.
• Albumin/creatinine ratio (ACR).
• Glomerular filtration rate (GFR).
• Renal ultrasound.
• Renal biopsy.

AKI vs CKD

• Important to differentiate AKI (acute kidney injury) from CKD (chronic kidney disease) based on history, clinical examination, and sequential creatinine measurements.
• Renal ultrasound can help.

CKD Screening

• Screening the general population for CKD is not generally recommended.
• Specific groups are recommended to undergo CKD testing, including patients with hypertension, diabetes, cardiovascular disease, hematuria, proteinuria, nephrotoxic drug use, structural renal disease, renal calculi, or prostatic hypertrophy or those with a family history of kidney disease.

Management of CKD

• Prevention of CKD progression by lifestyle modifications including lowering protein/sodium intake, lifestyle changes to control blood pressure and blood glucose.
• Comprehensive management of complications such as cardiovascular disease, hypertension, metabolic acidosis, anaemia, fluid overload, mineral imbalance, and the potential need for renal replacement therapy (RRT) or dialysis.
• Identifying patients at risk of progression to end-stage renal disease and preparing for dialysis or kidney transplantation are key in management.
• Management of diabetes, control of blood pressure and blood glucose.
• Vaccination to prevent infections (especially pneumonia/influenza).
• Dietary modifications (reduced salt/protein).
• Monitoring of relevant laboratory values (electrolytes, urea, creatinine, GFR).
• Medication adjustments based on the progression of CKD (and GFR values).

Cardiovascular Complications in CKD

• Cardiovascular disease is a significant cause of mortality and morbidity in patients with Chronic Kidney Disease (CKD).
• Albuminuria is an important predictor of cardiovascular risk in patients with CKD.
• Ischemic vascular disease is related to classical risk factors, and also to hemodialysis related issues (hypotension/hypovolemia) that exacerbate ischemia.
• Cardiac troponins are frequently elevated in patients with CKD, even without overt acute ischemia.

Hypertension in CKD

• Hypertension is a common complication of CKD.
• Hypertension may drive the progression of CKD and/or impact left ventricular hypertrophy.
• Low blood pressure may be associated with worse prognoses than high blood pressure in CKD patients.

KDIGO BP guidelines

• Target blood pressure (BP) recommendations vary based on presence of diabetes and proteinuria in CKD.
• Personalized BP management tailored to patient factors are key to reduce risks.

Preferred Antihypertensive Agents

• ACE inhibitors or ARBs are the preferred first-line agents for blood pressure management in CKD patients.

Diabetic Management

• Target HbA1c levels are important (7.0% or lower).

Dialysis/Renal Replacement Therapy (RRT)

• Indications include uremic symptoms, severe hyperkalemia, refractory acidosis, fluid overload, or bleeding tendency and eGFR <10 mL/min/1.73 m2).
• Treatment options include intermittent hemodialysis, continuous renal replacement therapy (CRRT), or hybrid approaches.

Anemia Management

• Anemia is common in CKD patients.
• Decreased erythropoietin production is the primary cause & related to low GFR.
• Treatment options involve the administration of erythropoiesis-stimulating agents (ESAs).

Mineral and Bone Disorder (MBD) Management

• Management of MBD in CKD patients involves treatment of hyperparathyroidism.

Fluid and Electrolyte Abnormalities

• Maintaining euvolemia through dietary salt restriction and/or diuretics.
• Fluid overload management with loop diuretics is critical.

Metabolic Acidosis Management

• Treatment of metabolic acidosis in CKD frequently involves sodium bicarbonate supplementation.

Drug Dosing in CKD

• Drugs must be dosed based on CKD progression and/or patient’s specific health factors.
• Multiple factors including other medications, and GFR/CrCl must be considered in drug dosing.

Uremia Pericarditis/Pericardial Effusion

• Uremia pericarditis and pericardial effusion can occur particularly in advanced CKD stages.
• Pericarditis is associated with retrosternal pain, dyspnea, and changes in ECG.
• Pericardial effusion is associated with shortness of breath, elevated jugular venous pressure, muffled heart sounds, and low QRS voltage on ECG.

Prevention Progression

• Lowering protein intake (<0.8 g/kg/day).
• Controlled blood pressure and diabetes.
• Encourage physical activity.
• Lifestyle modifications including smoking cessation, avoiding excessive sodium/salt intake.

Other key topics

• The presentation also touches upon the importance of dialysis/RRT.
• Treatment of cardiovascular complications.
• Complications related to various treatment modalities (AKI, hyperkalemia).

This quiz covers the key concepts related to chronic kidney disease (CKD), including its definition, criteria for diagnosis, and potential complications. Understanding CKD is vital for early intervention and management to prevent progression to end-stage renal disease. Enhance your knowledge of kidney health and related conditions through this informative quiz.