CKD

Approach to Chronic Kidney Disease

• Chronic kidney disease (CKD) frequently progresses to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT).
• Patients with CKD often 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 for more than 3 months.
• National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) also defines CKD as kidney damage for more than 3 months.
• Kidney damage is a structural or functional abnormality of the kidney, confirmed by urinalysis or imaging studies or renal biopsy. This can exist with or without decreased glomerular filtration rate (GFR).

CKD Criteria

• CKD is characterized by kidney damage, assessed as reduced kidney function, for more than 3 months.
• A glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2, with or without kidney damage, is another criterion.
• Structural abnormalities other than reduced GFR are also indicators for CKD.

Pathophysiology of CKD

Initiating Mechanism

• CKD arises from specific underlying etiologies, encompassing:
  • Genetically determined abnormalities during kidney development.
  • Immune complex depositions in glomerulonephritis.
  • Inflammation in various types of glomerulonephritis.
  • Toxin exposure impacting renal tubules and interstitium.

Progressive Mechanism

• Progressive CKD involves a reduction of functional nephrons, mediated by vasoactive hormones, cytokines, and growth factors.
• Early adaptations like hyperfiltration and hypertrophy of remaining nephrons eventually turn maladaptive.
• This leads to glomerular architecture distortion, sclerosis, and nephron loss.
• Increased renin-angiotensin activity contributes to the initial adaptive hyperfiltration and subsequently to maladaptive hypertrophy and sclerosis.
• Ultimately, CKD results in a reduced renal mass and progressive decline in renal function over time.

Epidemiology

• In 2017, CKD was prevalent in about 850 million individuals globally.
• The prevalence rate was 11.1% in 2017.
• CKD is a leading cause of death, ranking 19th globally in 1990, 11th in 2019, and 5th in 2040.
• This ranking is closely tied to the prevalent causes such as 2 times more frequency of diabetes and 20 times more frequency of cancer and HIV/AIDs.

Etiology

• Common causes of CKD include:
  • Diabetic glomerular disease.
  • Hypertensive nephropathy.
  • Primary glomerulopathy with hypertension.
  • Vascular and ischemic renal disease.
  • Glomerulonephritis.
  • Urinary tract disease.
  • Polycystic kidney disease.
  • Lupus nephropathy.
  • Analgesic nephropathy.
  • Tubulointerstitial nephropathy.

Risk Factors

Susceptibility

• Factors associated with increased risk of CKD but not proven to cause it:
  • Advanced age
  • Reduced kidney mass
  • Low birth weight
  • Socioeconomic status
  • Racial/ethnic minority
  • Family history

Initiation

• Factors directly causing CKD and potentially modifiable by therapy:
  • Diabetes
  • Hypertension
  • Autoimmune disease
  • Polycystic kidney disease
  • Drug toxicity

Progression

• Factors contributing to faster decline in kidney function:
  • 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 below 60 mL/min/1.73 m2 is associated with a high risk of CKD complications such as:
  • Drug toxicity
  • Metabolic endocrine complications
  • Cardiovascular disease
  • Death

Normal GFR

• Normal GFR in young adults is approximately 120 to 130 mL/min/1.73 m2
• GFR declines with age
• Variations exist based on sex and body size.
• The average annual GFR decline with age is ~1 mL/min/year/1.73m2.
• Mean GFR reaches around 70 mL/min/1.73 m2 by age 70.
• Women generally have lower mean GFR compared to men.

Albuminuria/Proteinuria

• Albuminuria (proteinuria) is a marker of chronic kidney damage.
• Albuminuria's value lies in its prognostic significance in CKD progression and independent association with cardiovascular risk.
• For initial albuminuria assessment, KDIGO recommends:
  • Urine albumin to creatinine ratio (ACR).
  • Urine protein to creatinine ratio (PCR).
  • Reagent strip urinalysis (for total protein).

Systematic Approach

• Assessing and managing CKD involves a systematic approach comprising:
  • Gathering detailed medical history
  • Conducting a thorough physical examination
  • Performing clinical assessment
  • Conducting relevant investigations

History Taking

• Medical history taking for CKD includes:
  • Prenatal/natal/postnatal history
  • History of hypertension.
  • History of diabetes.
  • Pregnancy-related information.
  • Family history (heritable kidney diseases).
  • Previous abnormal lab results (urea, creatinine).
  • Asymptomatic changes in urine (hematuria, proteinuria).
  • Urinary frequency and urgency (obstructive uropathy).
  • Changes in urine color/appearance (frothy urine).

Drug History

• Previous infections (systemic or recurrent).
  • Recent endoscopic GI procedures.
    • Exposure to nephrotoxic drugs (chemotherapy, antibiotics etc.)
  • Recent changes in medication doses, and newly started drugs.
  • Over-the-counter medications (herbal/natural supplements)

History of Uremia

• Assessment of uremia symptoms:
  • Loss of appetite
  • Loss of weight
  • Nausea
  • Hiccups
  • Metallic taste
  • Burning epigastrium
  • Pruritus
  • Muscle cramps
  • Edema (limbs, abdomen, or facial).
  • Nocturia

Clinical Features

• Patients with CKD often remain asymptomatic until disease progresses.
• Diminished kidney function (lower GFR) often leads to specific symptoms or signs.
• GFR values and their associated presenting features:
  • GFR less than 30 mL/min/1.73m2: anemia, nausea
  • GFR less than 25 mL/min/1.73m2: hyperkalemia
  • GFR 15-20 mL/min/1.73m2: tiredness, fluid retention
  • GFR less than 15 mL/min/1.73m2: pruritus, anorexia, weight loss, vomiting, hiccups
  • Extremely low GFR (<5 mL/min/1.73m2): neuropathy, altered consciousness, seizures, uremic pericarditis, uremic frost (urate deposits on skin and mucous membranes)

Physical Examination

• Physical examination of a CKD patient may reveal:
  • Appearance (skin, edema, pallor, uremic odor)
  • Vital signs (blood pressure, pulse, saturation).
  • Fundoscopy (hypertension/diabetes retinopathy)
  • Cardiovascular findings (apex beat, heave, pericardial rub, S4)
  • Abdominal examination (distension, renal angle issues, masses, bruits)
  • Neurological assessments (flapping tremor/sensory polyneuropathy)

Investigations

• CKD investigations frequently include:
  • Complete blood count (CBC)
  • Urinalysis (dipstick and microscopic)
  • 24-hour urine protein.
  • Serum creatinine and urea.
  • Coagulation profile
  • Electrolytes (sodium, potassium, calcium, phosphorus)
  • Liver and viral markers (hepatitis B, C, HIV)
  • Parathyroid hormone (PTH)
  • Iron, vitamin B12, folate
  • Albuminuria/proteinuria assessments (ACR, PCR).
  • GFR assessment.
  • Renal ultrasound
  • Renal biopsy

CKD Classification

• GFR categories are essential for classifying CKD severity. GFR levels classify stages of CKD and their corresponding GFR levels are given.
• Albuminuria categories are assessed with urine albumin to creatinine ratio (ACR) to classify the severity
• The combination of both classifications are used in combination to establish the prognosis of CKD.

AKI vs CKD

• Differentiating between acute kidney injury (AKI) and CKD is vital in appropriate patient management.
• Historical clinical information like sequential creatinine values, detailed medical history, and renal ultrasound are useful in this distinction.
• CKD patients are prone to AKI development.

Screening for CKD

• Universal CKD screening is not recommended for the entire population.
• Specific groups with elevated risk should be screened, such as:
  • Patients with hypertension
  • Patients with diabetes (type 1 or 2)
  • Individuals with cardiovascular disease.
  • Individuals found incidentally to have hematuria/proteinuria,
  • Patients receiving nephrotoxic medication
  • Patients with structural renal disease, renal calculi, or prostatic hypertrophy.
  • People with family history or known genetic variants associated with CKD.

Heart in CKD

• Cardiovascular complications are a significant mortality and morbidity driver in CKD.
• Albuminuria is a strong predictor of cardiovascular risk.
• Ischemic vascular disease, hypertension, and related complications (e.g., cardiac troponin elevation, heart failure, pulmonary edema) are common issues in affected patients.

Hypertension in CKD

• Hypertension is the most frequent complication in CKD.
• Hypertension's association with left ventricular hypertrophy and rapid renal function loss mandates effective management.
• Absence of hypertension can signify poor left ventricular function.
• Systolic blood pressure is a more important target than diastolic blood pressure in managing hypertension within CKD patients.

KDIGO Guidelines

• Kidney Disease: Improving Global Outcomes (KDIGO) guidelines tailor blood pressure (BP) targets for CKD patients based on the presence and level of albuminuria.
• BP treatment protocols are personalized to individual patient characteristics (age, comorbidities, risk of CKD progression) to optimize treatment efficacy and tolerance.

Preferred Antihypertensive Agents

• ACE inhibitors or ARBs are preferred antihypertensive agents in managing CKD, based on clinical benefits and reduction in CKD progression risk.
• Avoiding specific medications (e.g. dihydropyridine calcium channel blockers) as first-line treatment options is crucial.
• Monitoring serum creatinine and potassium levels in patients receiving ACE inhibitors or ARBs is essential.

Management of CKD

• CKD management is multi-faceted encompassing: prevention of CKD progression and addressing complications like:
  • Proteinuria - limiting protein intake
  • Cardiovascular concerns - controlling blood pressure & blood sugar, encouragement of physical activity, limiting salt intake, and smoking cessation
  • Metabolic issues- monitoring and controlling electrolytes,
  • Management of complications like anemia, management of bone mineral disease.
  • Preparation for renal replacement therapy (e.g., dialysis) in advanced or severely declining disease stages.

Glycemic Control

• Maintaining optimal glycemic control (<7.0% HbA1c) is critical for preventing microvascular complications (such as diabetic kidney disease) linked to diabetes.
• Insulin therapy requirements may increase in CKD patients; management of dosage requires careful and progressive reductions as renal function worsens.
• Metformin discontinuation is commonly required when GFR drops below 30 mL/min/1.73 m2.
• Contraindicated if contrast studies are pending.

Dialytic Therapy

• Dialytic therapy is a treatment for certain severe stages of CKD.
• Indications include:
  • Uremia symptoms.
  • Hyperkalemia unresponsive to medical measures.
  • Persistent fluid volume increase.
  • Severe acidosis responsive to medical measures.
  • Bleeding diathesis.
  • eGFR below 10 mL/min/1.73 m2.
• Modes of dialysis include (specific options depend on patient factors).
  • Hemodialysis (intermittent and continuous).
  • Renal replacement therapy (SLED-sustained low efficiency dialysis).
  • Peritoneal dialysis.

Metabolic Acidosis

• Metabolic acidosis is a common feature of advanced CKD.
• It arises from impaired renal ammonia production and urinary acidification.
• Often coupled with hyperkalemia, often requiring intervention and requiring treatment.
• Treatment for this complication often involves monitoring bicarbonate levels and correcting the underlying electrolyte disturbance.

Drug Dosing in CKD

• Drug selection must consider toxicity risks that are especially significant in the presence of CKD.
• Medication adjustments are necessary based on CKD severity and type of replacement therapy (RRT) in use or anticipated use by the patient.
• Accurate estimation of creatinine clearance (CrCl) using the Cockcroft-Gault equation is essential for appropriate drug dosing adjustments.

Pericardial Disease

• Uremia-related pericarditis typically presents with retrosternal chest pain exacerbated by lying and relieved by sitting upright. Associated symptoms include dyspnea and tachycardia, with characteristic electrocardiogram (ECG) changes including widespread ST-T-wave abnormalities, PR segment depression, and possible reciprocal changes .
• Pericardial effusion, another related complication, may exhibit symptoms such as shortness of breath (SOB), elevated jugular venous pressure (JVP), hypotension, and muffled heart sounds, accompanied by specific ECG findings (low QRS voltage, tachycardia).

Anemia

• Anemia in adults is diagnosed when hemoglobin (Hb) levels are lower than 13 g/dL in men and 12 g/dL in women.
• Decreased erythropoietin production is the primary cause.
• Additional potential causes include blood loss during dialysis, iron deficiency, and anemia associated with chronic disease or renal osteodystrophy

Management of Mineral and Bone Disorder (MBD)-CKD

• Vitamin D and Vitamin D analogs reduce parathyroid hormone (PTH).
• Calcium regulation is crucial in CKD. Calcimimetics, like cinacalcet, may be used to reduce PTH elevation.
• Monitoring serum calcium levels during medication intervention is important, and therapy initiation should be cautiously considered to avoid hypocalcemia, an unexpected complication of these treatments.

Fluid and Electrolyte Abnormalities

• CKD often presents with fluid overload or hyponatremia.
• Dietary modifications (limiting salt, sodium), diuretic use, and adjusting fluid intake are essential and individualized approaches to these symptoms.
• Careful monitoring and control of potassium levels also contribute to better outcomes.