Dr. Hussein Mahdi: Professional Role Quiz

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 Outcomes (KDIGO) defines CKD as abnormalities of kidney structure or function lasting longer than 3 months, with implications for health.
• The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) also defines CKD based on chronic kidney damage lasting longer than 3 months.
• Kidney damage encompasses structural or functional abnormalities confirmed by urinalysis, imaging, or kidney biopsy, with or without reduced glomerular filtration rate (GFR).

CKD Criteria

• CKD is defined by kidney damage or reduced kidney function.
• Kidney damage must persist for at least 3 months, as documented.
• GFR less than 60 mL/minute/1.73 m2, with or without kidney damage qualifies as CKD.
• Structural or functional abnormalities besides reduced GFR can indicate CKD.

Pathophysiology of CKD

Initiating Mechanism

• CKD's initial phase is specific to the underlying cause.
• Genetic abnormalities in kidney development are one cause
• Immune complex deposition and inflammation in glomerulonephritis are other causes of CKD initiation
• Toxin exposure affecting renal tubules and interstitium.

Progressive Mechanism

• Reduction in nephron number (the functional units of the kidney) due to vasoactive hormones, cytokines, and growth factors leads to progressive kidney damage.
• Initially, viable nephrons undergo hyperfiltration and hypertrophy (increased size and function) as compensatory mechanisms.
• These adaptive responses, however, become maladaptive, leading to sclerosis (scarring) and dropout of nephrons.
• Increased activity of the renin-angiotensin axis contributes to the initial adaptive response and subsequent deterioration.
• Ultimately, a reduction in renal mass due to an initial insult leads to a progressive decline in kidney function over a significant period.

CKD Risk Factors

Susceptibility

• Associated with an increased risk of CKD but not directly causing it. These factors are often non-modifiable. They include: Advanced age, reduced kidney mass, low birth weight, racial/ethnic minority status, family history, and low socioeconomic status.

Initiation

• These factors directly contribute to CKD development and are potentially modifiable. They include, but are not limited to, diabetes, hypertension, autoimmune disorders, polycystic kidney disease, and drug toxicity.

Progression

• Factors that expedite kidney function decline and lead to faster CKD progression are modifiable. These include, but are not limited to, hyperglycemia (high blood sugar), elevated blood pressure, proteinuria (protein in urine), and smoking.

Significance of GFR and Albuminuria

• Glomerular filtration rate (GFR) is the best overall indicator of kidney function.
• Decreasing GFR results in increasing symptoms and metabolic abnormalities.
• A GFR below 60 mL/min/1.73 m2 signifies a high risk of complications, including drug toxicity, metabolic and endocrine issues, and cardiovascular disease and death.

Normal GFR

• Normal GFR in young adults is typically 120–130 mL/min per 1.73 m2.
• GFR naturally declines with age.
• GFR varies based upon body size and sex.
• The average annual decline in GFR is about 1 mL/min per year per 1.73 m2, resulting in a mean value of around 70 mL/min/1.73 m2 by age 70.

Albuminuria/Proteinuria

• A marker of chronic kidney damage.

• Provides prognostic information on CKD progression.

• An independent risk factor for cardiovascular issues.

• KDIGO recommends urine albumin-to-creatinine ratio (ACR), urine protein-to-creatinine ratio (PCR), and reagent strip urinalysis for total protein as initial tests for proteinuria detection.

CKD Classification (GFR)

• Categorizes CKD severity based on GFR values with corresponding terms for each class.

CKD Classification (Albuminuria)

• Classifies CKD by albumin excretion rate as either normal, mild, moderate, or severe.

Prognosis of CKD by GFR and Albuminuria Categories (KDIGO 2012)

• Risk stratification chart for CKD prognosis dependent upon GFR and Albuminuria categories.

Systemic Approach to CKD

• History taking (detailed clinical history, including past medical history related to risk factors, symptoms)
• Physical examination
• Clinical evaluation (assessing symptoms further)
• Investigations (diagnostic tests like blood tests, urine tests, imaging)

History Taking

• Ante/Natal/Postnatal history(important information about pregnancy, birth, and early life)
• Hypertension (duration, medication, and blood pressure)
• Diabetes Mellitus (duration, severity, and any complications)
• Previous pregnancy issues (Pre-eclampsia, pregnancy loss)
• Family history (of CKD, Alport syndrome, or any other inherited kidney conditions)
• Previous abnormal urea/creatinine levels or other related reports
• Any symptomatic urinary abnormalities (hematuria, proteinuria)
• History of frequent urination (urgency)/ urinary tract issues/obstructive uropathy
• Any changes in urine color/ appearance (Frothy urine)

Drug History

• Prior exposure to any toxic or nephrogenic medications.
• Indications of recent (or past) use for any prescribed medications of concern for causing kidney damage.)
• Details about recent procedures involving contrast agents

History of Uremia

• Uremia-related symptoms, including appetite loss, weight loss, nausea, hiccups, metallic taste sensations, heartburn in the epigastrium, itching (pruritus), muscle spasms, swelling (edema), and frequent night urination (nocturia).

Clinical Features of CKD

• CKD patients often present with no symptoms initially.
• As CKD advances:
  • GFR below 30 mL/min/1.73 m2: anemia, nausea
  • GFR below 25 mL/min/1.73 m2 : hyperkalemia (high potassium levels)
  • GFR below 15 to 20 mL/min/1.73 m2: fatigue, fluid overload
  • GFR below 15 mL/min/1.73 m2: pruritus, anorexia, weight loss, vomiting, hiccups
  • Extremely low GFR (<5 mL/min/1.73 m2): neuropathy, altered consciousness, seizures, uremic pericarditis, uremic deposits on skin/mucosal membranes.

Physical Examination

• Skin appearance (edema, pallor, uremic fetor)
• Vital signs (blood pressure, pulse, oxygen saturation)
• Fundoscopy (examination of the eye's retina)
• Cardiovascular assessment (heart sounds, apical impulse, murmurs)
• Abdominal examination (kidney size/ masses)
• Neurological assessment (sensory/ motor polyneuropathy)

Investigations

• CBC (Complete blood count)
• Urinalysis (dipstick and microscopic examination)
• 24-hour urine protein
• Serum creatinine
• Serum urea
• Serum electrolytes (sodium, potassium, calcium, phosphorus)
• Renal ultrasound
• Coagulation profile
• Blood sugar
• Hepatitis B/C, HIV
• Parathyroid hormone (PTH)
• Serum iron
• Vitamin B12, folate
• Albumin-to-creatinine ratio (ACR)

Renal Ultrasound

• B/L (both sides) shrunken or asymmetric kidneys.
• Scars due to reflux nephropathy are detectable.
• Normal or large-sized kidneys may indicate specific conditions (diabetes nephropathy, amyloidosis, HIV nephropathy, polycystic kidney disease).

AKI vs CKD

• Differentiating acute kidney injury (AKI) from chronic kidney disease (CKD) is important because initial treatment differs from each other.
• Key details to consider when differentiating: Detailed clinical history, evaluating previous sequential creatinine results, and performing a renal ultrasound

Screening for CKD

• Universal screening for CKD in the general population is not recommended.
• High-risk groups, however, should undergo screening, which includes those with: Hypertension, diabetes (types1 and 2), cardiovascular disease, hematuria or proteinuria, use of nephrotoxic drugs, individuals with structural kidney abnormalities, renal calculi, prostatic hypertrophy, and family history of CKD.

Heart in CKD

• Cardiovascular complications are a leading cause of mortality/morbidity across every CKD stage.
• Albuminuria is a prominent risk factor for cardiovascular disease.
• Ischemic vascular disease (interplay of classical and kidney-related risk factors) frequently leads to hypotension/hypovolemia.
• Cardiac troponin levels are often elevated in CKD without acute ischemia, creating diagnostic challenges.
• Dysregulation in cardiac function, elevated left ventricular hypertrophy, salt/water retention, and resultant heart failure; may lead to pulmonary edema.

Hypertension with CKD

• Frequent CKD complication; associated with decreased kidney function.
• Absence of hypertension may be an indicator of a poorly functioning left ventricle.
• Lowering blood pressure is vital in CKD management to prevent disease progression.
• Systolic blood pressure is a preferred target measure in CKD patients.

KDIGO Guidelines

• KDIGO recommendations for managing blood pressure (BP) in diabetes and non-diabetes with CKD dependent upon urine albumin excretion rates.
• BP treatment regimens and agents must be tailored to the patient's age, comorbidities, progression risk factors (kidney disease stage, presence of retinopathy), tolerance to treatment (electrolyte issues, drug reaction), acute/chronic deterioration in kidney function/orthostatic hypotension/ and drug side effects.

Preferred Antihypertensive Agents

• ACE inhibitors or ARBs are strongly recommended as first-line antihypertensive agents, particularly for CKD patients.
• If systolic blood pressure (SBP) exceeds the target goal by more than 20 mmHg, additional antihypertensive agents may be needed.
• ACE inhibitors and ARBs are known to slow CKD progression.
• Every 10 mmHg reduction in SBP markedly reduces major cardiovascular disease occurrences.

Management of CKD

• Prevention of CKD progression (Lowering protein intake, reducing sodium intake).
• Managing complications
• Encourage physical activity compatible with cardiovascular health.
• Stop smoking.
• Control high blood pressure and blood sugar.
• Specific management for complications based on stage (CKD 3a-5)

Management of CKD Complications

• Vaccination, blood glucose management, treatment and monitoring of anemia, electrolyte management, prepare for renal replacement therapy

Glycemic Control

• Target HbA1c below 7.0% to minimize diabetes-related complications, including diabetic nephropathy.
• Insulin levels in CKD patients tend to rise, requiring progressive reductions to prevent complications and kidney function deterioration.
• Metformin should be discontinued in CKD patients with a GFR below 30 mL/min/1.73 m2.

Dialytic Therapy

• To correct fluid and electrolyte imbalances and remove toxic waste products in kidney failure, dialysis procedures may be necessary.
• Indicators for the implementation of dialysis procedures may include the occurrence of uremic symptoms, unresponsive hyperkalemia (high potassium levels) to conservative measures, persistent extracellular volume expansion Despite diuretic administration, and acidosis resistant to medical treatments.

Anemia

• Anemia in adults is characterized by low hemoglobin/red blood cell count (<13 g/dL in men and <12 g/dL in women). Low hemoglobin concentration.
• Decreased erythropoietin production is the primary cause; other causes include blood loss during dialysis and conditions like iron deficiency.

Metabolic Acidosis

• Common in advanced CKD due to impaired kidney's ammonia production and acid excretion.
• Often combined with hyperkalemia (high potassium) and hyperchloremic metabolic acidosis.
• Treat symptoms, including hyperkalemia, and raise bicarbonate levels to target levels (22 mEq/L), to mitigate acidosis potential.

Drug Dosing in CKD

• Drug selections and dosages to prevent toxicity must be modified to reflect CKD stage, whether receiving renal replacement therapy, and the complexity of assessing drug absorption.
• CKD patients frequently take multiple medications, further complicating drug interactions and potential adverse reactions.
• Patient history and clinical data are crucial.
• Renal function is assessed using creatinine clearance (Cockcroft-Gault formula).
• Adjustments for individual medications may be needed.

Pericardial Disease

• Uremia-associated pericarditis (inflammation around the heart): characterized by Retrosternal chest pain (exacerbated by lying down but reduced by sitting upright) and related symptoms.
• ECG findings: widespread concave ST elevation, PR segment depression across multiple limb/precordial leads with reciprocal changes seen in lead aVr.
• Sinus tachycardia may occur.
• Pericardial effusion: symptoms include shortness of breath, Beck's triad (increased jugular venous pressure, hypotension, muffled heart sounds), low voltage/ electrical alternans on ECG .

Additional Topics

• Specific disease considerations (Diabetes, Hypertension, Vascular Disease, Infections, Drug use History)
• Treatment considerations/Management strategies in CKD.

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