Dr. Hussein Mahdi's Specialization Quiz

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 CKD diagnosis is vital to delay progression and prevent cardiovascular complications.

Defining CKD

• Kidney Disease Improving Global Outcomes (KDIGO) defines CKD as abnormalities in kidney structure or function lasting 3 months, impacting health.
• National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) also defines CKD.
• CKD is kidney damage for more than 3 months. This damage is structural or functional abnormality of the kidney, with or without reduced glomerular filtration rate (GFR), documented via urinalysis, imaging, or kidney biopsy.

CKD Criteria

• CKD involves kidney damage or reduced kidney function.
• Kidney damage (or reduced function) must persist for 3+ months.
• GFR less than 60 mL/minute/1.73 m2, with or without kidney damage, meets the criterion.
• Structural/functional abnormalities beyond decreased GFR are also considered for CKD diagnosis.

Pathophysiology of CKD

Initiating Mechanism

• CKD's initiating phase is specific to the underlying cause.
• Causes include genetic abnormalities in kidney development, immune complex deposition, glomerulonephritis inflammation, or toxin exposure affecting renal tubules and interstitium.

Progressive Mechanism

• The progressive phase is influenced by vasoactive hormones, cytokines, and growth factors, reducing nephron numbers.
• Initially, compensatory hyperfiltration and hypertrophy of remaining nephrons occur as an adaptive response.
• Ultimately, this response becomes maladaptive leading to glomerular architecture distortion, sclerosis, and nephron dropout.
• The renin-angiotensin system plays a crucial role in both initial adaptation and subsequent maladaptive changes.
• A reduction in renal mass, from isolated insult, causes progressive decline in renal function over time.

CKD Pathophysiology Diagram

• Renal injury leads to decreased nephron number.
• Systemic hypertension and proteinuria occur.
• Glomerular hypertension and hypertrophy occur.
• Macrophage recruitment is triggered.
• Phenotypic changes develop within intrinsic glomerular cells.
• Cytokines and growth factors are released.
• Increased extracellular matrix (ECM) production contributes to glomerulosclerosis.
• These factors lead to the development of chronic kidney disease.

CKD Epidemiology

• Approximately 850 million individuals globally had CKD in 2017, with a 11.1% prevalence.
• CKD had become the 19th leading cause of death (in 1990), the 11th leading cause of death (in 2019), and projected as the 5th leading cause of death (in 2040).
• CKD's prevalence is 2 times that of diabetes and 20 times higher than cancer and HIV/AIDS.

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

• Advanced age, reduced kidney mass, low birth weight, racial or ethnic minority status, and low socioeconomic status are associated with increased risk but are not proven causes of CKD. These are mostly not modifiable.

Initiation

• Diabetes, hypertension, autoimmune diseases, polycystic kidney diseases, and drug toxicity directly cause CKD. Some of these are modifiable by drug therapy.

Progression

• Hyperglycemia, elevated blood pressure, proteinuria, and smoking contribute to a faster decline in kidney function.

Significance of GFR and Albuminuria

• Glomerular filtration rate (GFR) measures overall kidney function.
• Decreasing GFR correlates with increasing symptoms and metabolic abnormalities.
• GFR less than 60 mL/min per 1.73 m2 is a significant risk factor for CKD complications like drug toxicity, endocrine/metabolic complications, and cardiovascular disease.
• Albuminuria (protein in urine) is a marker of chronic kidney damage and poor prognosis for CKD.

Normal GFR

• Normal GFR in young adults is approximately 120-130 mL/min/1.73m².
• GFR declines with age.
• GFR varies according to sex and body size.
• The average yearly decline in GFR with age is ~1 mL/min/year for 1.73 m².
• Mean GFR at age 70 is around 70 mL/min/1.73m^2.
• Women typically have a lower average GFR than men.

Albuminuria/Proteinuria

• Albuminuria/proteinuria is a marker for chronic kidney damage.
• It's a prognostic factor (predicts the progression of CKD).
• It's an independent risk factor for cardiovascular disease.
• Assessment includes urine albumin-to-creatinine ratio (ACR), urine protein-to-creatinine ratio (PCR), and reagent strip urinalysis of total protein.

Use of GFR and Albuminuria

• GFR measures kidney function.
• Albuminuria detects chronic kidney damage.
• Clinical decision-making, diagnosis, and staging rely on both to monitor CKD progression, recommend treatment (e.g., dialysis), assess medication safety for patients with CKD.

CKD Classification

• G1: Normal/high GFR (≥90 mL/min/1.73m²)

• G2: Mildly decreased GFR (60-89 mL/min/1.73m²)

• G3a: Mild-moderately decreased GFR (45-59 mL/min/1.73m²)

• G3b: Moderately-severely decreased GFR (30-44 mL/min/1.73m²)

• G4: Severely decreased GFR (15-29 mL/min/1.73m²)

• G5: Kidney failure (GFR <15 mL/min/1.73m² or end-stage renal disease).

• A1: Normal/mild albumin excretion (<30 mg/day, <30 mg/g creatinine)

• A2: Moderate albumin excretion (30-299 mg/day, 30-299 mg/g creatinine)

• A3: Severe proteinuria (>300 mg/day, >300 mg/g creatinine)

Systematic Approach

• History taking (ante-natal, natal, post-natal, hypertension, diabetes, pregnancies, family history, symptoms)
• Physical examination (vital signs, CVS, abdomen, CNS)
• Clinical evaluation
• Investigations (CBC, urinalysis, 24-hour urine protein, blood urea nitrogen, creatinine, electrolytes)

History Taking

• Ante-natal/natal/post-natal history (IUGR, birth weight, recurrent urinary tract infections (UTIs)).
• Hypertension (duration, medication, compliance)
• Diabetes mellitus (duration, severity, organ damage).
• Pregnancy history (pre-eclampsia, pregnancy loss).
• Family history of inheritable CKD (e.g., Alport syndrome, Fabry disease)
• Previous documentation of abnormal urea and creatinine levels.
• Asymptomatic urinary abnormalities (hematuria, proteinuria)
• Urinary frequency, urgency (suggestive of obstructive uropathy).
• Changes in urine character/appearance (color, frothy).

Drug History

• History of systemic infections, recurrent illnesses.
• History of gastrointestinal (GI) endoscopic procedures (potential for acute phosphate nephropathy due to phosphate-containing enemas).
• Use of contrast requiring procedures.
• Previous exposure to nephrotoxic drugs (chemotherapy, NSAIDs, aminoglycosides).
• Recent changes in drug doses, newly started medications.
• Use of over-the-counter medications (herbal, natural supplements).
• Uremia symptoms (loss of appetite, weight loss, nausea, hiccups, metallic taste, etc.)

Clinical Features

• Patients may be asymptomatic initially.
• Reduced GFR is associated with symptoms like anemia (GFR < 30mL/min), nausea, hyperkalemia (GFR < 25), tiredness, fluid retention(GFR 15-20), pruritus, anorexia, weight loss, vomiting, and hiccups (GFR <15), and neurological problems (GFR below 5 mL/min).

Physical Examination

• Physical traits (appearance, edema, pallor, uremic odor).
• Vital signs (blood pressure, pulse, oxygen saturation).
• Fundoscopy (look for retinopathy associated with hypertension or diabetes).
• Cardiovascular examination (apex beat, heave, cardiac rub, presence of murmurs, rhythm)
• Abdominal examination (distention, masses, tenderness, bruits)
• Neurological examination (sensory neuropathy)

Investigations

• Complete blood count (CBC)
• Urinalysis, microscopic exam, 24 hour urine protein.
• Blood urea nitrogen (BUN) and creatinine.
• Electrolytes (sodium, potassium, calcium, phosphorus).
• Coagulation profile.
• Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), human immunodeficiency virus (HIV)
• Parathyroid hormone (PTH)
• Serum iron, vitamin B12, folate.
• Urine albumin-to-creatinine ratio (ACR), urine protein-to-creatinine ratio(PCR).
• Glomerular filtration rate (GFR).
• Renal ultrasound for assessment of kidney size.

Renal Ultrasound

• Bilateral shrunken kidneys, asymmetry, scar from reflux nephropathy are signs of previous damage.
• Normal or large-size kidneys might indicate different underlying causes like diabetic nephropathy, amyloidosis, HIV nephropathy, or polycystic kidney disease.
• Unilateral small kidneys might suggest conditions like unilateral obstruction or inflammatory lesions.

AKI vs CKD

• Distinguish acute kidney injury (AKI) from chronic kidney disease (CKD) by history (detailed clinical history, previous sequential creatinine results), physical exam, and kidney ultrasound.
• Patients with CKD are at increased risk of AKI.

CKD Management

• Prevent CKD progression by reducing protein intake (< 0.8 g/kg/day in adults with GFR < 30 mL/min/1.73m²).
• Lifestyle modifications (encourage physical activity, stop smoking, and control blood pressure and blood sugar).
• Implement vaccination strategies.
• Specific interventions for CKD stage 3, 4, and 5 include managing anemia in CKD 3a/b, controlling electrolyte disorders (hyponatremia, hyperkalemia) at CKD 4, and preparing for renal replacement therapy (RRT) at CKD 5.

Cardiovascular Complications in CKD

• Albuminuria is a significant cardiovascular risk factor in all stages of CKD.
• Ischemic vascular disease results from interplay of classical and CKD-related risk factors.
• Patients receiving dialysis are at high risk of low blood pressure and ischemia.
• Cardiac troponin elevation is common in CKD patients without acute ischemia, posing diagnostic challenges.
• Abnormalities in cardiac function (e.g., left ventricular hypertrophy) are frequently associated with CKD as is fluid retention and elevated blood pressure

Hypertension in CKD

• Hypertension is a common complication of CKD, often associated with left ventricular hypertrophy and rapid loss of renal function.
• Absence of hypertension can indicate poor left ventricular function and potentially a poorer prognosis.
• Low blood pressure can also carry worse prognosis compared to elevated blood pressure.
• Systolic blood pressure is the preferred target for blood pressure management in CKD to better correlate with CKD progression.
• It's important to customize blood pressure management based on age, comorbidities, risk of progression, presence of retinopathy and medication tolerability and adverse effects.

KDIGO Guidelines for Blood Pressure Management in CKD

• Different target blood pressure goals are recommended for diabetic and non-diabetic patients with CKD and varying levels of albuminuria excretion (protein in urine).
• The presence of retinopathy and electrolyte disorders requires careful consideration of blood pressure medications.
• Treatment strategies must be tailored to individual patients based on various factors.

Preferred Antihypertensive Agents in CKD

• ACE inhibitors or ARBs are the preferred antihypertensive agents in CKD due to their protective role in slowing CKD progression.
• Additional antihypertensive medications may be necessary to achieve blood pressure targets.
• Avoid first line use of dihydropyridine calcium channel blockers, particularly in those at risk for further renal complications.
• Patients receiving ACE inhibitors or ARBS should monitor serum creatinine and potassium levels as these drugs can affect these values.

AKI on CKD

• The sudden decline in renal function in known CKD patients requires immediate medical attention, considering it as an emergency situation.
• It has an increased risk of progression to End Stage Renal Disease (ESRD).
• Conditions like infections, drugs, dehydration, renal hypoperfusion, and metabolic conditions (DKA, hyperkalemia) could be triggering factors for AKI in patients with CKD.

Screening for CKD

• Routine screening of the general population for CKD is not beneficial or cost effective.
• Selective screening is recommended for appropriate population groups, including patients with hypertension, diabetes, cardiovascular disease (including peripheral vascular disease and cerebrovascular disease), hematuria, proteinuria, nephrotoxic medications, those with renal structural abnormalities, or a family history of renal disease.

Anemia in CKD

• Anemia in adults is defined by lower hemoglobin levels (<13 g/dL in males and <12 g/dL in females).
• Decreased erythropoietin production is the most important cause of anemia in CKD, along with blood loss during dialysis, iron deficiency and chronic disease.

Management of Mineral and Bone Disorders (MBD) in CKD

• Vitamin D and vitamin D analogs suppress parathyroid hormone (PTH) synthesis and reduce PTH levels.
• Calcimimetics (e.g., cinacalcet) are used in cases of high calcium and phosphate to regulate PTH levels.
• Close monitoring of serum calcium is critical to prevent hypocalcemia and hypercalcemia.

Fluid and Electrolyte Abnormalities in CKD

• Fluid overload and hyponatremia (low sodium) commonly manifest in CKD.
• Fluid overload is treated with diuretics.
• Dietary advice and drug choices (ACE inhibitors, ARBs) are needed for prevention and management of electrolyte imbalance, including hyperkalemia.

Diabetic Glycemic Control in CKD

• Maintaining a target HbA1c level below 7 % is recommended in patients with CKD to reduce microvascular complications of diabetes, including diabetic kidney disease.
• Insulin therapy may be required in patients with CKD and diabetes; it's worth noting that insulin levels may need to be adjusted progressively when kidney function deteriorates or worsens.
• Metformin should be discontinued in patients with GFR below 30 ml/min/1.73 m² or in cases where contrast studies are required; note that Metformin use is contraindicated in these patients.

Dialytic Therapy in CKD

• Dialysis is used for end-stage kidney failure to correct fluid and electrolyte imbalances and remove toxic products.
• Indication for dialysis include uremic symptoms, unresponsive hyperkalemia, persistent extracellular volume, refractory acidosis, bleeding diathesis and very low eGFR below <10 ml/min. Various dialysis methods exist.

Drug Dosing in CKD

• Selection and dosage of drugs must consider CKD stage, whether receiving renal replacement therapy (RRT), and the type of RRT for effective treatment and prevention of drug related toxicity.
• It is important to assess drug absorption and adjust doses based on kidney function.

Test your knowledge about Dr. Hussein Mahdi, his area of specialization, professional title, and the role he plays as a consultant physician. This quiz covers key aspects of his profession and contributions to the field.