Dr Hussein Mahdi Quiz

Approach to Chronic Kidney Disease

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

Defining CKD

• Kidney Disease Improving Global Outcome (KDIGO) defines CKD as persistent abnormalities of kidney structure or function for at least 3 months, impacting health.
• National Kidney Foundation, Kidney Disease Outcomes Quality Initiative (KDOQI) also defines CKD as kidney damage lasting 3+ months
• Kidney damage includes structural or functional abnormalities evidenced by urinalysis, imaging studies or a renal biopsy.

CKD Criteria

• Reduced kidney function or damage is key in diagnosing CKD.
• The damage or reduced function must last ≥3 months.
• A Glomerular Filtration Rate (GFR) <60 ml/min/1.73 m2 with or without kidney damage can indicate CKD.
• Additional structural/functional abnormalities beyond decreased GFR can also indicate CKD.

Pathophysiology of CKD

Initiating Mechanism

• CKD's initial phase is specific to the underlying cause.
• This can include genetic abnormalities during kidney development.
• Immune complex deposition, glomerulonephritis, or toxin exposure to renal tubules & interstitium can also initiate the progression of CKD.

Progressive Mechanism

• CKD progresses due to reductions in nephron number and the action of vasoactive hormones, cytokines, and growth factors.
• Short term responses include hyperfiltration and hypertrophy of remaining nephrons.
• These responses later become maladaptive leading to various distortions in glomerular architecture.
• Increased activity of the renin-angiotensin axis contributes to hyperfiltration and later sclerosis; which ultimately reduce renal mass and function.

Significant of GFR & Albuminuria

• GFR is the best overall index of kidney function.
• Decreasing GFR is linked to increasing symptoms and metabolic issues.
• A GFR below 60 ml/min/1.73 m2 is associated with high risk of complications, including drug toxicity, metabolic endocrine complications, and cardiovascular disease.
• Albuminuria is a significant marker of chronic kidney damage, and has a prognostic value for CKD. It is also a crucial independent cardiovascular risk factor and is considered a key measure when diagnosing CKD.

Normal GFR

• Normal GFR in young adults is typically between 120-130 mL/min per 1.73 m2.
• This value diminishes with age.
• GFR varies according to sex and body size.
• An average annual decline in GFR is estimated at ~1 mL/min per year per 1.73 m2.
• Reaching an annual mean value of ~70 ml/min per 1.73m2 at age 70 is a rough marker.
• Women generally have lower average GFR than men.

Albuminuria/Proteinuria

• Albuminuria (or proteinuria) is a marker of chronic kidney damage.
• It is a prognostic factor in CKD progression.
• Albuminuria is an independent cardiovascular risk factor.
• Initial testing should include urine albumin to creatinine ratio (ACR), urine protein to creatinine ratio (PCR), and reagent strip urinalysis for total protein (early morning samples are ideal).

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, family history, and low socioeconomic status may increase susceptibility to CKD, but not necessarily directly cause CKD.

Initiation

• The factors here directly cause CKD and may likely improve if addressed. These include diabetes, hypertension, autoimmune diseases, polycystic kidney diseases, and drug toxicity.

Progression

• Factors contributing to faster decline in kidney function include hyperglycemia, elevated blood pressure, proteinuria, and smoking.

CKD Classification

• G1-G5: CKD stages based on GFR values.
• A1-A3: Albuminuria classifications based on excretion rates, and categorized based on severity (mild, moderate, severe).

Systematic Approach

• History taking (including medical, family, and social history is necessary.)
• Physical examination
• Clinical evaluation (to assess physical status)
• Investigations (including blood tests, urine tests, imaging studies such as renal ultrasound).

History Taking

• Prenatal/natal/postnatal history: IUGR, birth weight, and recurrent urinary tract infections.
• Hypertension duration, medications, and history.
• Diabetes mellitus.
• Pregnancy history (pre-eclampsia, pregnancy loss.)
• Family history for inheritable CKD (e.g. Alport syndrome, Fabry disease).
• Any symptoms of previous renal abnormalities.
• Previous and current health issues.
• History of drug exposure.
• History of recent gastrointestinal endoscopy.

Drug History

• History of systemic infections/recurrent illnesses.
• History of gastrointestinal endoscopy procedures (e.g., phosphate-containing enemas).
• History of contrast-requiring procedures.
• Exposure to nephrotoxic drugs (chemotherapy, antibiotics, NSAIDs, aminoglycosides).
• Recent changes in drug dosage or recent new drug initiation.
• Herbal/natural supplements.

History of Uremia

• Symptoms like loss of appetite, weight loss, nausea, hiccups, metallic taste, burning epigastrium, pruritus, muscle cramps, edema (in limbs, abdomen, or face), and nocturia.

Clinical Features

• Initially, CKD patients are usually asymptomatic until it progresses.
• Patients eventually display symptoms such as anemia, nausea, hyperkalemia, tiredness, fluid overload, pruritus, anorexia, weight loss, vomiting, and hiccups.
• Severe cases of CKD present with signs of neuropathy, altered consciousness, seizures, uremic pericarditis, or uremic deposits on the skin and mucous membranes.

Physical Exam

• General appearance, skin examination for edema, pallor, or uremic fetor (smell).
• Vital signs, including blood pressure (for hypertension detection), pulse rate, oxygen saturation.
• Fundoscopy (for detection of retinopathy).
• Cardiovascular examination (including cardiac auscultation for murmurs/rubs, apex beat, and any signs of cardiac enlargement).
• Abdominal examination , including palpation for renal angle abnormality or mass, or bruits.
• Neurological examination to look for sensory neuropathies.

Investigations

• CBC
• Urinalysis: dipstick and microscopic examination.
• 24-hour urine protein.
• Serum creatinine, urea.
• Coagulation profile.
• Electrolytes (Na+, K+, Ca2+, and phosphorus).
• Liver function tests.
• Hepatitis B surface antigen, hepatitis C virus, HIV.
• Parathyroid hormone (PTH).
• Serum iron, vitamin B12 and folic acid levels.
• ACR
• GFR
• Renal Ultrasound
• Biopsy

Renal Ultrasound

• May show shrunken or enlarged kidneys, asymmetry, or scarring.

AKI vs CKD

• Identifying distinctions between acute kidney injury (AKI) and chronic kidney disease (CKD) is very important.
• In patients with marked renal impairment, distinguishing AKI from CKD is necessary.
• History assessment including previous sequentially observed creatinine results.
• Performing renal ultrasound.
• CKD patients are at increased risk for AKI.

Comparison of AKI and CKD in a Tabular Summary

• History (brief nature vs. long duration of illness)
• Examination (acutely ill vs. stable state)
• creatinine level increases rapidly vs. stable renal function declines over time
• Calcium (normal vs. various disturbances)
• Hb (normal vs. variation due to anemia/hemolysis).
• Renal ultrasound (possible hydroonephrosis vs. structural kidney abnormalities)

Management of CKD

• Preventing CKD progression; strategies for preventing more severe stages, and treatments for complications of CKD.
• Treating CKD complications (such as anemia, mineral and bone disorder (MBD), fluid and electrolyte abnormalities, metabolic acidosis, cardiovascular complications).
• Lifestyle modifications (including dietary changes, reduced salt intake, and increased physical activity).
• Complication management based on CKD stage and patient presentation.

Screening for CKD

• Screening the general population for CKD is not typically recommended.
• Selected high risk populations should be screened for CKD, these include individuals with diabetes, hypertension, cardiovascular disease, or who have hematuria or proteinuria found on incidental testing.

Heart in CKD

• Cardiovascular complications are a leading cause of mortality and morbidity in all stages of CKD.
• Albuminuria is a key risk factor for cardiovascular disease.
• Ischemic vascular disease may involve classical risk factors along with potential aggravation of factors by treatments like hemodialysis, in turn exacerbating the situation.
• Elevated troponin levels suggest potentially acute ischemia, which can complicate diagnosis.
• Cardiovascular function abnormalities (e.g., LVH, low blood pressure) affect disease progression and prognosis.

Hypertension in CKD

• Hypertension is a frequent complication of CKD; and is associated with heart (myocardial) hypertrophy and rapid decline in overall renal function.
• Lack of hypertension can sometimes be a sign of poor left ventricular function.
• Low blood pressure may have a worse prognosis than high blood pressure based on the progression of CKD in patients.
• Targeting systolic blood pressure has shown stronger correlation with CKD progression.

KDIGO Guidelines

• KDIGO (Kidney Disease Improving Global Outcomes) guidelines provide specific recommendations tailored to different patient populations with CKD, including individuals with diabetic and non-diabetic CKD and varying degrees of albumin excretion rates, based on their blood pressure consistently exceeding or not exceeding particular thresholds. Individualized approaches to treatment are essential.

Dialytic Therapy

• Dialytic therapy is used to correct fluid and electrolyte disturbances, and remove toxins in patients with kidney failure.
• This therapy is administered under certain indications, including uremic symptoms, hyperkalemia poorly responding to conservative measures, and prolonged extracellular fluid expansion. Other indications may consider severe acidosis, bleeding diathesis, or an eGFR that is exceptionally low (<10 ml/min per 1.73 m2)
• Different methods are used for initiating dialytic therapy, including intermittent hemodialysis, continuous renal replacement therapy, and peritoneal dialysis.

Glycemic Control

• Tight glycemic control (HbA1c <7.0%) slows progression of diabetes-related complications, including diabetic nephropathy, in CKD patients.
• Plasma insulin levels slightly increase in CKD, and progressive reduction of insulin therapy may be needed if CKD worsens.
• Metformin use may need to be discontinued if GFR falls below 30 ml/min/1.73 m2. It is also contraindicated in patients undergoing contrast studies who develop CKD.

Vitamin D and Vitamin D Analogues in CKD-MBD Management

• Vitamin D and analogues suppress parathyroid hormone (PTH) synthesis and reduce PTH levels.
• Calcitriol (Calcijex, Rocaltrol) and paricalcitol (Zemplar) are active vitamin D forms.
• Doxercalciferol (Hectorol) is another vitamin D analog used.
• Calcimimetics, such as cinacalcet hydrochloride (Sensipar), can benefit patients in whom vitamin D analogs aren't helpful for maintaining appropriate calcium and phosphate homeostasis. They help to control those very important mineral levels.

CKD-related Fluid and Electrolyte Abnormalities

• Manage fluid overload through dietary salt restriction, and use of loop diuretics (e.g., furosemide, bumetanide) or thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) as appropriate.
• Moderate hyponatremia via water restriction or addition of diuretics if edema is also present.
• Manage hyperkalemia by dietary restriction of dietary potassium-rich foods, and/or by administering drugs that promote potassium excretion (e.g. loop diuretics, sodium polystyrene sulfonate). Specific medical management is essential to evaluate and address these conditions.

Metabolic Acidosis in CKD

• Disturbed ammonia production and acidification of urine in CKD can result in metabolic acidosis.
• Addressing underlying factors like hyperkalemia can also be necessary.
• Target bicarbonate level is 22 mmol/L.
• Treating these disturbances is essential to treat CKD. Metabolic acidosis can precipitate AKI in CKD patients.

Drug Dosing in CKD

• Drug selection and dosing to prevent toxicity-
• Appropriate adjustment of medications is essential, depending on specific CKD stage and type of renal replacement therapy (RRT) if employed. Also important to consider drug absorption difficulties in CKD patients due to multiple medications.
• General recommendations include patient history, calculating creatinine clearance (e.g., Cockcroft-Gault equation) and identifying specific medications requiring dose modifications.

Uremia-related Complications, e.g. Pericarditis and Pericardial Effusion

• Uremia-related pericarditis or pericardial effusion involves significant clinical implications. Uremic pericarditis symptoms include retrosternal chest pain, symptoms worsen when lying down and better when sitting upright; may also include dyspnea and tachycardia. An ECG will display a widespread pattern of ST elevation or depression. Pericardial Effusion often displays Beck's Triad: Elevated Jugular Venous Pressure, muffled heart sounds, and hypotension (combined with other signs and symptoms).

Anemia in CKD

• Anemia is a frequent complication of CKD, with hemoglobin concentration frequently lower than 13 g/dL in males and 12 g/dL in females (reference ranges can sometimes vary).
• Anemia can be caused from decreased erythropoietin production, blood loss during dialysis, iron deficiency, and other underlying health issues (e.g. anemia of chronic disease, or renal osteodystrophy.)
• CKD-anemia is addressed when creatinine clearance (CrCl) falls below 60 mL/minute/1.73 m2, or if hemoglobin (Hb) falls below 13 g/dL in men or 12 g/dL in women (depending on reference range values)

Prevention Strategies (in regards to progressive CKD)

• Lowering protein intake (0.8 g/kg/day) in individuals with a GFR <30 ml/min is important preventive measure.
• Keeping salt intake below 2g daily is also helpful.
• Encouraging lifestyle modifications that improve cardiovascular health, including stopping smoking, controlling blood pressure and blood sugar.
• Addressing specific complications like anemia, bone disease (MBD), hyperkalemia, and fluid overload is also beneficial in the long term.

Additional Considerations

• CKD is often a long term health condition.
• Individuals with early and progressed stages of CKD may benefit from early intervention and preventive and/or therapeutic strategies

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