Diagnostic Criteria

• Reduced GFR: A GFR of <60 mL/min/1.73 m², sustained for at least three months.
• Evidence of Kidney Damage, including:
  • Albuminuria or proteinuria.
  • Abnormalities in urine sediment, such as haematuria.
  • Electrolyte imbalances due to tubular dysfunction.
  • Structural abnormalities visible on imaging (e.g., polycystic kidneys, hydronephrosis).
  • Histological abnormalities found on kidney biopsy.
  • History of kidney transplantation.
    
    

Functional Impact

Classification System

• Cause (C): Underlying condition causing kidney impairment (e.g., diabetic kidney disease, hypertensive nephrosclerosis).
• GFR Category (G1–G5):
  • G1: ≥90 mL/min/1.73 m² (normal or high)
  • G2: 60–89 mL/min/1.73 m² (mildly decreased)
  • G3a: 45–59 mL/min/1.73 m² (mild to moderate)
  • G3b: 30–44 mL/min/1.73 m² (moderate to severe)
  • G4: 15–29 mL/min/1.73 m² (severely decreased)
  • G5: <15 mL/min/1.73 m² (kidney failure)
• Albuminuria Category (A1–A3):
  • A1: AER <30 mg/day or ACR <3 mg/mmol (normal to mildly increased)
  • A2: AER 30–300 mg/day or ACR 3–30 mg/mmol (moderately increased)
  • A3: AER >300 mg/day or ACR >30 mg/mmol (severely increased)

Nephrotic Proteinuria

• Defined as protein excretion >3.5 g/day.
• Often associated with hypoalbuminaemia, oedema, and hyperlipidaemia.
  
  

Implications for Health

Major Global Causes of CKD

• Type 2 diabetes mellitus: 30–50% of CKD cases.
• Hypertension: Accounts for approximately 27%.
• Primary glomerulonephritis: 8–10%.
• Chronic tubulointerstitial nephritis: 3–4%.
• Polycystic kidney disease and other hereditary causes: 3%.
• Secondary glomerular diseases or vasculitis: ~2%.
• Plasma cell dyscrasias or haematological malignancies: ~2%.
• Sickle cell nephropathy: Rare (<1% in the US).
  
  

Pathophysiological Categories

• Congestive heart failure
• Cirrhosis and hepatorenal syndrome

• Vascular:
  • Hypertensive nephrosclerosis is the most common form, especially in the elderly and in Black populations.
  • Renal artery stenosis (from atherosclerosis or fibromuscular dysplasia) may cause ischaemic nephropathy characterised by glomerulosclerosis and interstitial fibrosis.
  • Vasculitides: ANCA-positive (e.g., granulomatosis with polyangiitis), ANCA-negative vasculitides, and thrombotic microangiopathies (e.g., TTP, HUS).
• Glomerular:
  • Nephritic patterns show active urine sediment with red cell casts, dysmorphic RBCs, and varying proteinuria. Causes include post-infectious glomerulonephritis, infective endocarditis, IgA nephropathy, lupus nephritis, and anti-GBM disease.
  • Nephrotic patterns present with heavy proteinuria (>3.5 g/day), bland sediment, and hypoalbuminaemia. Common causes include:
    • Diabetic nephropathy
    • Minimal change disease
    • Focal segmental glomerulosclerosis (FSGS)
    • Membranous nephropathy
    • Amyloidosis
    • Light chain deposition disease
• Tubulointerstitial:
  • Chronic tubulointerstitial nephritis can result from:
    • Autoimmune disorders: Sjögren syndrome, sarcoidosis
    • Drug-induced injury: NSAIDs, antibiotics (e.g., sulfonamides), allopurinol
    • Infections: viral, bacterial, parasitic
    • Inherited conditions: polycystic kidney disease, cystinosis
    • Other: chronic hypokalaemia, hypercalcaemia, heavy metals, multiple myeloma cast nephropathy

• Benign prostatic hyperplasia
• Urolithiasis
• Urethral strictures
• Pelvic or abdominal malignancies
• Neurogenic bladder
• Congenital abnormalities: e.g., posterior urethral valves, ureteropelvic junction obstruction
• Rare causes: retroperitoneal fibrosis

Additional Contributory Factors

• Diabetes mellitus: The most frequent cause in adults. Around one-third of diabetic patients develop CKD within 15 years of diagnosis, with earlier onset in type 2 diabetes.
• Hypertension: Both a cause and consequence of CKD, particularly when other aetiologies are excluded.
• Genetic predisposition: A family history is present in roughly 30% of CKD cases, suggesting inherited components (e.g., PKD, Alport syndrome, APOL1 risk alleles in Black populations).
• Climate and environmental exposures: Heat stress, toxins, and poor water quality contribute significantly to CKD in agricultural communities in Central America, Sri Lanka, and South Asia.
• Unresolved acute kidney injury (AKI): Severe or repeated episodes of AKI can lead to permanent renal impairment and chronic kidney disease.
  
  
  
  

Adaptive Hyperfiltration and Compensatory Mechanisms

• Each human kidney contains approximately 1 million nephrons. When nephron loss occurs, the surviving nephrons undergo hypertrophy and hyperfiltration to maintain overall glomerular filtration rate (GFR).
• Despite ongoing nephron injury, plasma levels of solutes such as urea and creatinine remain stable until GFR declines by around 50%. A doubling of plasma creatinine often signifies a 50% reduction in GFR.
• Although initially compensatory, this hyperfiltration increases intraglomerular pressure, which damages glomerular capillaries and accelerates nephron loss via focal segmental and global glomerulosclerosis.
  
  

Cellular and Molecular Pathways of Progressive Injury

• Glomerular injury increases permeability to macromolecules (e.g., proteins, fatty acids, inflammatory cytokines), leading to mesangial expansion, TGF-β–mediated fibrosis, and glomerular scarring.
• Renin-angiotensin system activation increases angiotensin II levels, promoting TGF-β expression and collagen deposition.
• Tubulointerstitial injury involves hypoperfusion and immune infiltration, resulting in tubular atrophy and interstitial fibrosis.
• Inflammation and oxidative stress contribute to the perpetuation of renal injury.
  
  

• Glomeruli: sclerosis
• Tubules and interstitium: fibrosis and atrophy
• Vessels: vascular sclerosis
  
  
  

Additional Mechanisms Driving Progression

• Proteinuria not only marks CKD but directly contributes to tubular injury.
• Nephrotoxins (NSAIDs, contrast agents), systemic hypertension, and recurrent AKI episodes aggravate nephron loss.
• Metabolic factors like hyperlipidaemia and hyperphosphataemia promote endothelial and tubular damage.
• Environmental contributors include smoking, lead exposure, obesity, and analgesic overuse.
  
  

Special Populations and Physiologic Considerations

• CKD in children is uncommon and typically due to congenital malformations (e.g., posterior urethral valves) or genetic disorders (e.g., FSGS).
• GFR matures by age 2–3 and must be adjusted for body surface area.
• Children with CKD are at risk of growth disturbances, hypertension, and poor bone mineralisation (“renal rickets”).
  
  

• Ageing is associated with a natural decline in GFR due to glomerular dropout, glomerulosclerosis, and decreased renal mass.
• Altered renal vasculature contributes to reduced renal perfusion and a blunted vasodilatory response, despite preserved vasoconstrictive capacity.
  
  

Genetic and Molecular Influences

• Monogenic causes include:
  • ADPKD, Alport syndrome, nephronophthisis, Dent disease
  • Atypical HUS (complement dysregulation)
• Polymorphisms and GWAS findings:
  • APOL1: Two risk alleles in Black individuals increase susceptibility to hypertension-attributable ESKD and FSGS.
  • FGF23: Variants associated with elevated FGF-23 levels, linked to increased risk of ESKD and mortality.
  • SHROOM3, SLC47A1, CDK12, CASP9, and others identified via genome-wide association studies contribute to altered GFR or albuminuria.
  • Variants in RAS genes (ACE A2350G, AGTR1 C573T) may predispose to CKD.
    
    
    

Electrolyte and Metabolic Derangements

• Hyperkalaemia typically emerges when GFR <20–25 mL/min/1.73 m² and is worsened by acidosis, diabetes, or medications (ACE inhibitors, NSAIDs).
• Hypokalaemia is rare and generally due to diuretics or GI losses.
  
  

• Develops as ammoniagenesis declines, with an increased anion gap in advanced CKD.
• Consequences include:
  • Negative nitrogen balance
  • Muscle catabolism
  • Protein-energy malnutrition
  • Progression of renal fibrosis
  • Impaired bone metabolism (renal osteodystrophy)
    
    

Fluid and Salt Handling

• As GFR drops below 10–15 mL/min/1.73 m², sodium and water retention leads to extracellular volume expansion, oedema, and hypertension.
• Tubulointerstitial diseases may initially cause salt-wasting and polyuria before eventual volume overload.
  
  

Anaemia of CKD

• Caused by:
  • Decreased erythropoietin production
  • Reduced RBC lifespan
  • Uraemic platelet dysfunction
  • Nutritional deficiencies
  • Chronic inflammation
• Normochromic normocytic anaemia begins early and worsens with declining GFR.
  
  

CKD-Mineral and Bone Disorder (CKD-MBD)

• Types of renal osteodystrophy:
  • High-turnover (osteitis fibrosa due to secondary hyperparathyroidism)
  • Low-turnover (adynamic bone disease, osteomalacia)
  • Dialysis-related amyloidosis (beta-2 microglobulin)
• Biochemical drivers:
  • Hyperphosphataemia
  • Hypocalcaemia
  • Low calcitriol
  • Elevated PTH → bone resorption, hyperplasia of parathyroid glands
    
    

Calciphylaxis

• Calcific uremic arteriolopathy primarily affects dialysis patients.
• Presents with painful purpura, progressing to necrosis and secondary infection.
• Carries a high mortality rate (45–80% at 1 year), even when calcium-phosphate levels appear normal.
  
  
  

Global Prevalence and Incidence

• CKD affects approximately 9% to 13% of the adult population worldwide.
• In 2017, global prevalence was estimated at 697.5 million cases (9.1%), with a 29.3% increase since 1990, mainly attributable to population ageing and higher rates of diabetes and hypertension.
• The estimated distribution by CKD stage (2017):
  • Stage 1–2: 5%
  • Stage 3: 3.9%
  • Stage 4: 0.16%
  • Stage 5: 0.07%
  • Dialysis: 0.041%
  • Transplantation: 0.011%
• CKD was responsible for approximately 1.2 million deaths globally in 2017 and contributed significantly to disability-adjusted life-years (DALYs), particularly in low- and middle-income countries.
  
  
  

National Prevalence (United States Focus)

• CKD affects more than 1 in 7 adults (14%), totalling over 35 million people.
• The prevalence increases with age:
  • 18–44 years: 6%
  • 45–64 years: 12%
  • ≥65 years: 34%
• The adjusted incidence of end-stage kidney disease (ESKD) declined by 8.9% from 2000 to 2019, yet the absolute number of patients on treatment increased by 37.8%.
• In 2023, over 808,000 people in the U.S. were living with ESKD.
• The U.S. Healthy People 2030 initiative outlines national goals for CKD prevention, early detection, and reduction in morbidity and mortality.
  
  

Epidemiologic Trends in Other Regions

• European studies report CKD prevalence ranging from 3.3% in Norway to 17.3% in Northeast Germany.
• In Denmark (2006–2013), CKD stages 3–5 had a prevalence of ~4.8%, predominantly affecting women.
• A 2021 Chinese study reported a crude CKD prevalence of 10.1%.
• In Mexico, CKD prevalence nearly doubled between 2003–2004 and 2015–2016.
  
  

Community vs Referred CKD

• Community CKD:
  • Primarily affects older adults with long-standing cardiovascular risk factors.
  • Typically shows slow progression: GFR declines at 0.75–1 mL/min/year after age 40–50.
  • Mortality (primarily cardiovascular) exceeds progression to ESKD in stages 3–4.
• Referred CKD:
  • Often diagnosed earlier due to genetic or secondary nephropathies (e.g., glomerulonephritis, ADPKD).
  • Faster GFR decline is observed, especially with diabetic nephropathy (~10 mL/min/year) or heavy proteinuria.
    
    

Risk Factors for CKD Progression

• Older age, male sex
• Ethnic minorities: higher prevalence in Black, Hispanic, Asian, and Native American populations
• Family history of kidney disease
• Genetic predispositions, including:
  • SNPs in TCF7L2, MTHFS, and RAAS genes (ACE, AGTR1)
  • APOL1 variants in individuals of African descent
    
    

• Hypertension:
  • Strongly linked to CKD progression via transmission of systemic pressure to glomerular capillaries.
  • Ambulatory blood pressure monitoring (ABPM) is more predictive of CKD outcomes than office measurements
• Proteinuria/Albuminuria:
  • Strong predictor of rapid decline in both diabetic and non-diabetic nephropathies.
  • RAAS blockade and dietary sodium/protein restriction can reduce progression.
• Metabolic factors:
  • Insulin resistance, dyslipidaemia, and hyperuricaemia contribute to CKD progression.
• Lifestyle factors:
  • Smoking and obesity are associated with both incident CKD and faster progression.
    
    

Sex- and Race-Related Demographics

• Stages 1–4 CKD are more common in women (14%) than men (12%).
• However, men have a 60.6% higher incidence of ESKD, likely due to more rapid progression.

• Non-Hispanic Black adults: 19.5%
• Non-Hispanic Asians and Hispanics: 13.7%
• Non-Hispanic Whites: 11.7%
• Black patients have nearly 4× the incidence of ESKD compared to Whites.
• FSGS is more prevalent in Hispanic and Black populations; IgA nephropathy is rare in Black individuals but more frequent in Asians.
  
  
  

CKD in Children

• CKD is rarer in children, with congenital causes (e.g., posterior urethral valves, renal dysplasia) being predominant.
• Boys are more commonly affected due to congenital urological anomalies.
• Clinical manifestation often occurs later in life, though underlying structural abnormalities are present from birth.
  
  
  

Screening Recommendations

• Targeted screening is recommended for high-risk populations:
  • Patients with hypertension, diabetes, age >65
  • Tests should include:
    • Urinalysis and urine albumin-to-creatinine ratio (ACR)
    • Serum creatinine and eGFR estimation (using CKD-EPI equation)
• General population screening remains unsupported due to insufficient evidence of benefit.
  
  
  

Early Stages (CKD Stages 1–3)

• Asymptomatic course: Most individuals with a GFR >30 mL/min/1.73 m² do not experience overt symptoms.
• Negative symptoms absent: Electrolyte disturbances, fluid imbalance, or uremic signs are typically not clinically apparent.
• Incidental diagnosis: CKD is often discovered via routine screening, especially in high-risk populations.
  
  

Symptoms Indicative of CKD Progression (Stages 4–5)

• Fatigue, lethargy, reduced exercise tolerance due to anaemia and metabolic waste accumulation
• Pruritus, metallic taste, and anorexia linked to uraemic toxin build-up
• Nausea and vomiting, often worsening with progression
• Restless leg syndrome and sleep disturbance, reflecting uraemic neuromuscular irritability
• Cognitive slowing, daytime somnolence, and reduced concentration
• Peripheral neuropathy or encephalopathy, especially in end-stage renal disease
  
  

• Peripheral oedema (ankles, periorbital), worsening with hypoalbuminaemia or salt retention
• Pulmonary oedema and dyspnoea, with or without orthopnoea
• Hypertension, exacerbated by fluid overload and RAAS activation

• Dry skin, ecchymoses, and uremic frost (rare, in advanced uraemia)
• Malnutrition due to reduced intake and metabolic acidosis
• Gastrointestinal complaints: Diarrhoea, anorexia, early satiety

• Uremic pericarditis: May present with chest pain; rarely leads to tamponade
• Erectile dysfunction, amenorrhoea, and reduced libido
  
  
  

Risk Factors and Associated History

• Diabetes mellitus:
  • Present in up to 40% of people with diabetes within 15 years of diagnosis
  • Type 2 diabetes may have CKD at diagnosis
• Hypertension:
  • Both a cause and consequence of CKD
  • Long-standing uncontrolled hypertension accelerates glomerular injury
• Age >50 years:
  • Normal ageing decreases GFR; risk is amplified with comorbidities
• Childhood kidney disease:
  • History of congenital anomalies, glomerular disorders, or pyelonephritis confers a four-fold increased risk of adult CKD or ESKD
    
    

• Black or Hispanic ethnicity:
  • Increased risk linked to both socio-demographic and genetic factors (e.g., APOL1 variants)
• Obesity:
  • Promotes diabetes, sleep apnoea, glomerular hyperfiltration, and sclerosis
• Family history:
  • Suggests genetic predisposition to conditions such as polycystic kidney disease, Alport syndrome, and glomerulonephritis
• Autoimmune diseases:
  • Includes lupus, Sjögren syndrome, sarcoidosis, and rheumatoid arthritis
• NSAID use:
  • Long-term use associated with analgesic nephropathy
• Smoking:
  • Exacerbates vascular damage and accelerates CKD progression
• Elevated uric acid:
  • Associated with CKD progression, though urate-lowering therapy shows limited renal benefit
    
    

Less Common Features to Elicit in History

• Foamy or cola-coloured urine:
  • Suggestive of proteinuria or haematuria
• Arthralgia or rashes:
  • May indicate underlying systemic autoimmune disease
• Seizures:
  • Reflect severe uraemia or electrolyte disturbances
• Menstrual abnormalities or infertility
• Symptoms of infection:
  • Hepatitis B/C, HIV, or streptococcal infections may signal secondary glomerulopathies
    
    

Screening History Points

• Prior episodes of acute kidney injury
• Exposure to nephrotoxic agents (e.g., aminoglycosides, contrast)
• Recurrent urinary tract infections or renal calculi
• Use of traditional/herbal medicines in certain regions
• History of low birth weight or prematurity, increasing long-term CKD risk
  
  

General Principles

• Silent early disease: CKD stages 1–3 (GFR >30 mL/min/1.73 m²) are usually asymptomatic; examination may be unremarkable.
• Physical findings become more apparent in stages 4–5 (GFR <30 mL/min/1.73 m²), particularly when complications of uraemia or volume overload develop.
• Systemic clues: Examination should focus on identifying:
  • Signs of CKD complications (e.g., anaemia, pericarditis)
  • Evidence of causative systemic disease (e.g., lupus, vasculitis)
  • Volume status abnormalities

Skin and Mucosal Findings

• Scratch marks and excoriations from uraemic pruritus
• Dry skin (xerosis) and pallor due to anaemia
• Uraemic frost: Rare; white urea crystals on the skin in advanced CKD
• Ecchymoses and purpura: Suggest platelet dysfunction or uraemia-related coagulopathy
• Butterfly malar rash: Suggestive of systemic lupus erythematosus
• Hyperpigmentation: Seen in long-standing CKD due to retention of urochromes
  
  
  

Cardiovascular Examination

• Hypertension: Common in all stages; may be severe or treatment-resistant
• Pericardial friction rub: Indicative of uraemic pericarditis, particularly in underdialysed patients
• Raised jugular venous pressure and displaced apex beat: Signs of fluid overload or left ventricular hypertrophy
• Gallop rhythm or murmurs: From anaemia-related high-output states or valvular calcification
• Peripheral oedema: Pitting oedema in legs and sacrum due to fluid retention
• Pulmonary oedema: May present with basal crackles or decreased breath sounds if pleural effusions are present
  
  

Neurological and Neuromuscular Findings

• Hyperreflexia, tremor, or asterixis in uraemia
• Peripheral neuropathy: Often distal, symmetrical; results in sensory deficits
• Restless leg syndrome: Common in all CKD stages
• Seizures or encephalopathy: Late manifestations of severe uraemia
  
  

Abdominal and Genitourinary Findings

• Palpable kidneys: Seen in polycystic kidney disease
• Abdominal masses: May indicate obstructive uropathy or malignancy
• Enlarged prostate (on digital rectal exam): May suggest obstructive cause
• Ascites or hepatomegaly: In patients with cardiorenal or hepatorenal syndromes
  
  

Ophthalmological Findings

• Hypertensive or diabetic retinopathy:
  • Arteriovenous nicking, cotton wool spots, hard exudates, or neovascularisation
  • Important to assess for microvascular disease in diabetic or hypertensive patients
• Pale conjunctivae: Indicative of anaemia
  
  

Respiratory Findings

• Crackles at lung bases: Suggest fluid overload or pulmonary oedema
• Pleural rub: Rare but can occur in uraemic pleuritis
  
  

Musculoskeletal and Growth Abnormalities

• Muscle wasting: Related to protein-energy malnutrition or metabolic acidosis
• Bone tenderness or deformity:
  • May indicate renal osteodystrophy
  • Skeletal deformities or short stature may be seen in children with longstanding CKD
    
    

Reproductive and Endocrine Findings

• Gynaecomastia, testicular atrophy, or amenorrhoea in end-stage disease
• Decreased libido and erectile dysfunction
  
  

Screening for Depression in CKD

• Up to 45% of adults with CKD exhibit depressive symptoms by the time dialysis is initiated.
• Somatic symptoms like fatigue, anorexia, and sleep disturbance may overlap with uraemia.
• Tools such as:
  • Beck Depression Inventory (BDI) – cutoff score ≥11
  • Quick Inventory of Depressive Symptomatology (QIDS-SR16) – cutoff score ≥10
     have shown utility in detecting major depressive episodes in CKD patients.

Initial Laboratory Evaluation

• Serum urea and creatinine: Elevated in CKD, but creatinine alone is a poor estimator of GFR, especially in elderly or malnourished patients.
• Electrolytes: Abnormalities may indicate tubular dysfunction. Progressive acidosis typically develops as GFR falls below 30 mL/min/1.73 m².
• Serum bicarbonate: Low levels suggest metabolic acidosis in advanced disease.
• Serum potassium: Hyperkalaemia may occur in advanced CKD or with certain medications.
  
  

• Anaemia is typically normochromic normocytic due to reduced erythropoietin. Iron studies and vitamin B12/folate levels may help exclude other causes.

• Hypoalbuminaemia may result from urinary protein loss or malnutrition.
• Lipid profile: Dyslipidaemia is common and contributes to cardiovascular risk.
  
  

• Serum phosphate, calcium, alkaline phosphatase, 25-hydroxyvitamin D, and parathyroid hormone (PTH) levels should be checked to assess for renal osteodystrophy and secondary hyperparathyroidism.
  
  

Assessment of Kidney Function

• Use CKD-EPI equation (2021 version without race variable) to calculate GFR.
• The MDRD formula may be used but underestimates GFR >60 mL/min/1.73 m².
• In the elderly, GFR should be calculated rather than inferred from creatinine alone due to reduced muscle mass.
  
  

• Cystatin C is unaffected by muscle mass and useful in individuals with low or high muscle mass (e.g., bodybuilders, elderly).
• The CKD-EPI Cystatin C equation or combined creatinine–cystatin C equation offers improved accuracy.
  
  

Urinalysis and Proteinuria Assessment

• Screens for haematuria and proteinuria; positive results warrant confirmation.
  
  

• Preferred over total protein as a sensitive marker of glomerular injury.
• Moderately increased albuminuria (A2: ACR 30–300 mg/g) is a risk factor for CKD progression.
• Severely increased albuminuria (A3: ACR >300 mg/g) requires full diagnostic evaluation.
  
  

• Used if albumin-specific measurement is not available or if ACR >500–1000 mg/g.

• RBCs and RBC casts: Suggest proliferative glomerulonephritis.
• WBC casts or eosinophils: Suggest interstitial nephritis or infection.
  
  

Immunological and Serological Investigations

• ANA and anti-dsDNA: Lupus nephritis
• Complement levels (C3, C4): Depressed in lupus, MPGN
• ANCA (C-ANCA, P-ANCA): Vasculitides (e.g., granulomatosis with polyangiitis, microscopic polyangiitis)
• Anti-GBM antibodies: Goodpasture syndrome
• Serum/urine electrophoresis and free light chains: Myeloma kidney
• Hepatitis B/C, HIV, syphilis: Infection-associated glomerulonephritides
  
  

Imaging Studies

• First-line modality for assessing kidney size, echogenicity, and obstruction.
• Small, echogenic kidneys: Indicate irreversible damage.
• Normal or large kidneys in diabetes, amyloidosis, or infiltrative disease.
• Detects hydronephrosis, stones, polycystic kidneys.
  
  

• Best for evaluating renal masses, cysts, or stones.
• Use non-contrast CT to avoid contrast nephropathy in reduced GFR.
• IV contrast use requires caution; prophylactic hydration may be considered.
  
  

• Used when contrast CT is contraindicated.
• MRA evaluates renal artery stenosis; gadolinium-based contrast carries a risk of nephrogenic systemic fibrosis in CKD patients.

• Assess differential renal function and screen for renal artery stenosis (captopril-enhanced).
• Not reliable if GFR <30 mL/min/1.73 m².
  
  

• Plain abdominal radiograph: Detects radiopaque stones.
• Voiding cystourethrogram (VCUG): Gold standard for vesicoureteral reflux.
  
  

Renal Biopsy

• Indicated when:
• CKD aetiology is unclear.
• Nephrotic-range proteinuria or rapidly progressive renal failure is present.
• There is suspicion of treatable glomerulonephritis (e.g., lupus nephritis).
• Contraindicated in patients with small, scarred kidneys.
• Main risk: bleeding; open surgical biopsy may be considered in high-risk cases.
  
  

Special Considerations

• Use updated Schwartz formula (with or without cystatin C) to calculate GFR.
• Ultrasound is the preferred imaging modality.
  
  

• GFR declines physiologically with age; serum creatinine may underestimate disease.
• Always calculate eGFR for dose adjustment and diagnosis.
  
  

Screening Recommendations

• Recommended for individuals with:
  • Diabetes
  • Hypertension
  • Cardiovascular disease
  • Family history of CKD
  • Age >65 years
• Use:
  • Urine ACR
  • Serum creatinine and eGFR
    
    

• Routine screening of asymptomatic individuals without risk factors is not currently supported by strong evidence (ACP recommendation).
• The American Society of Nephrology advocates broader screening due to CKD’s asymptomatic nature and potential for early intervention.
  
  

Acute Kidney Injury (AKI)

• Sudden decline in renal function
• Often reversible if underlying cause is treated
  
  

• Recent illness, hypotension, nephrotoxic exposure
• Normal kidney size on imaging
• Rapid changes in serum creatinine and urine output
• Absence of chronic features such as anaemia or small kidneys
  
  
  

Diabetic Kidney Disease

• History of type 1 diabetes (usually >10 years) or type 2 diabetes (may be present at diagnosis)
• Often coexists with diabetic retinopathy and other microvascular complications
  
  

• HbA1c >53 mmol/mol (7%)
• Persistent albuminuria (microalbuminuria early)
• Bland urine sediment
• Small, atrophic kidneys only in late disease
• Early stages may show normal creatinine with increased albumin-to-creatinine ratio (ACR)
  
  

Hypertensive Nephrosclerosis

• Long-standing poorly controlled hypertension
• More common in Black individuals

• Sub-nephrotic proteinuria (<2 g/day)
• Bland urine sediment
• Bilateral small kidneys on ultrasound
• Absence of active urinary sediment (no haematuria or casts)
  
  

Ischaemic Nephropathy

• Atherosclerotic disease, tobacco use, dyslipidaemia
• Sudden worsening of hypertension or renal function

• Asymmetry in kidney size (>2.5 cm difference)
• Renal duplex ultrasonography showing elevated resistive index
• CT angiography, MR angiography, or renal arteriography confirming renal artery stenosis
  
  

Obstructive Uropathy

• More common in older men due to prostatic enlargement or malignancy
• Symptoms include hesitancy, frequency, weak stream, incomplete voiding

• Post-void residual volume
• Hydronephrosis on renal ultrasound
• May be complicated by recurrent urinary tract infections
  
  

Nephrotic Syndrome

• Sudden or worsening oedema (periorbital, peripheral)
• Accelerated hypertension

• Proteinuria >3.5 g/day
• Hypoalbuminaemia, hyperlipidaemia
• Bland urine sediment
• Renal biopsy to classify glomerular pathology
• Serology: ANA (lupus), HIV (FSGS), hepatitis B/C (membranous), SPEP/UPEP (amyloidosis)
  
  

Glomerulonephritis (Nephritic Syndrome)

• Acute hypertension, oedema, and renal dysfunction
• Haematuria and variable proteinuria
  
  

• Urinalysis with dysmorphic RBCs and RBC casts
• Elevated creatinine
• Relevant serologies:
  • ANA/dsDNA: Lupus nephritis
  • C3/C4: Low in MPGN or lupus
  • ANCA: Vasculitis
  • Anti-GBM: Goodpasture syndrome
  • ASO titre: Post-streptococcal GN
  • HBV, HCV, HIV testing for secondary causes
• Renal biopsy required for definitive diagnosis
  
  

Rapidly Progressive Glomerulonephritis (RPGN)

• Rapid loss of renal function over days to weeks
• May present with nephritic features and systemic illness

• High creatinine, nephritic urine sediment
• Biopsy reveals crescent formation
• Often requires urgent immunosuppression
  
  

Alport Syndrome

• Hereditary nephritis (X-linked or autosomal)
• Haematuria from childhood, sensorineural hearing loss, anterior lenticonus

• Family history
• Biopsy with electron microscopy: GBM thinning/splitting
• Genetic testing may confirm diagnosis
  
  

Anti-Glomerular Basement Membrane (Anti-GBM) Disease

• Presents with pulmonary–renal syndrome (haemoptysis + haematuria)

• Anti-GBM antibody positivity
• Linear IgG deposition on renal biopsy
  
  

Nephrolithiasis (Chronic Obstructive Pattern)

• Flank pain, intermittent obstruction
• May result in chronic kidney damage with recurrent episodes

• Non-contrast CT: Gold standard for stone detection
• Ultrasound: Shows hydronephrosis or obstructive pattern
  
  

Multiple Myeloma

• Older adults with unexplained CKD, anaemia, bone pain

• Serum/urine protein electrophoresis, free light chain assay
• Bence-Jones proteinuria
• Skeletal survey or low-dose whole-body CT for lytic lesions
• Renal biopsy shows cast nephropathy or amyloid deposits
  
  

Goals of Management

• Slow or halt the decline in kidney function.
• Manage systemic and metabolic complications.
• Reduce cardiovascular morbidity and mortality.
• Delay or avoid the need for dialysis or transplantation.
• Prepare for renal replacement when required.
• Optimise quality of life.
  
  

General Measures

• G1–G2: Normal/mildly decreased GFR with markers of kidney damage.
• G3a–G3b: Moderate decline (45–59 / 30–44 mL/min/1.73 m²).
• G4: Severe reduction (15–29 mL/min/1.73 m²).
• G5: Kidney failure (<15 mL/min/1.73 m² or dialysis).
  
  

• Smoking cessation and weight loss reduce progression and cardiovascular risk.
• Physical activity: Target ≥30 minutes, 5 days/week.
• Salt restriction: <5–6 g/day unless salt-wasting conditions are present.
• Protein intake: 0.8 g/kg/day in CKD ≥G3; avoid severe restriction unless GFR <20 mL/min.
• Dietary monitoring: Low potassium/phosphate diets as needed; renal dietitian referral recommended.
  
  

Pharmacologic Therapy

• Target BP: KDIGO recommends <120 mmHg systolic (if tolerated).
• First-line: ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), especially in proteinuria.
• Second-line: Thiazide diuretics, calcium-channel blockers, beta-blockers
• Avoid: Combination of ACEI + ARB due to hyperkalaemia risk.
  
  

• HbA1c target: 6.5–8.0%, individualised.
• Preferred agents:
  • SGLT2 inhibitors: Empagliflozin, dapagliflozin, canagliflozin (renal and cardiovascular benefit).
  • GLP-1 receptor agonists: Semaglutide, liraglutide (benefit in CV and renal outcomes).
  • Metformin: Safe if eGFR ≥30 mL/min/1.73 m².
  • Finerenone: Non-steroidal mineralocorticoid receptor antagonist for diabetic CKD with albuminuria.
    
    

• Statins: Recommended in CKD stages 1–4.
• Combination therapy: Statin + ezetimibe in G3–G4.
• Avoid initiating statins in dialysis-dependent CKD unless previously on therapy.
  
  

Management of Complications

• Evaluate: Iron, B12, folate deficiency.
• Treat if Hb <100 g/L with erythropoiesis-stimulating agents (e.g., darbepoetin).
• Target Hb: 100–110 g/L; avoid normalisation due to increased cardiovascular risk.
• Vadadustat: HIF stabiliser approved for dialysis-dependent anaemia.

• Monitor: Calcium, phosphate, PTH every 6–12 months (G3–G5).
• Vitamin D:
  • Replace 25(OH)D if <75 nmol/L with ergocalciferol.
  • Use active vitamin D analogues in progressive hyperparathyroidism.
• Phosphate Binders:
  • First-line: Calcium acetate (per NICE).
  • Non-calcium binders (e.g., sevelamer) preferred to reduce vascular calcification.
• Calcimimetics (e.g., cinacalcet): Lower PTH without increasing calcium.
• NHE3 Inhibitor (e.g., tenapanor): Reduces phosphate in dialysis-dependent CKD.
  
  

• Sodium bicarbonate: Maintains serum bicarbonate >22 mmol/L.
  Slows CKD progression, improves nutritional status, and reduces hospitalisations.
  
  

Cardiovascular Risk Reduction

• Statins and blood pressure control reduce cardiovascular events.
• Aspirin may be used with caution due to higher bleeding risk.
• NOACs preferred over warfarin in early-stage CKD for atrial fibrillation.
  
  

Specific Stage-Based Management

• Begin education on CKD progression and RRT options.
• Monitor and treat anaemia and secondary hyperparathyroidism.
  
  

• Referral for vascular access placement (fistula) or transplant evaluation.
• Patient education on dialysis modalities (haemodialysis vs peritoneal).
• Monitor metabolic acidosis and consider oral bicarbonate therapy.
  
  

• Initiate renal replacement therapy in presence of uraemia, electrolyte abnormalities, fluid overload, or failure to thrive.
• Consider transplantation for eligible patients (eGFR <20 mL/min).
• For patients >80 years or with significant comorbidities, consider palliative care.
  
  

Renal Replacement Therapy (RRT)

• Symptomatic uraemia
• Refractory hyperkalaemia
• Metabolic acidosis
• Volume overload
• Malnutrition or failure to thrive
• GFR <9 mL/min/1.73 m², if asymptomatic

• Haemodialysis
• Peritoneal dialysis
• Kidney transplantation (preferred due to survival benefit)
  
  

Additional Considerations

• Avoid NSAIDs, IV contrast, nephrotoxic antibiotics.
• Adjust doses based on eGFR.
  
  

• Monitor serum albumin, weight, and protein intake regularly.
• Avoid excessive protein restriction to prevent malnutrition.
  
  

• High prevalence in CKD, particularly in dialysis patients.
• Screening recommended due to its association with disease progression.
  
  

Natural History and Disease Progression

• CKD typically progresses gradually, leading to ESKD in a subset of patients.
• Major determinants of progression:
  • Lower baseline GFR
  • High levels of albuminuria
  • Younger age
  • Male sex
  • Low serum bicarbonate, calcium, and albumin
  • High serum phosphate
• Predictive Tools:
  • The Tangri risk calculator uses age, sex, eGFR, albuminuria, and biochemical markers to estimate 2- and 5-year risk of kidney failure.
    
    

Mortality Risk

• Overall mortality is significantly elevated in CKD patients compared with the general population, with rates rising sharply in those with ESKD.
• In 2019, adjusted mortality rates:
  • CKD: 94.5 per 1000 person-years
  • Non-CKD: 41.5 per 1000 person-years
  • ESKD: 128.5 per 1000 person-years
• Key factors linked to mortality:
  • Protein-energy malnutrition (hypoalbuminaemia)
  • Vitamin D deficiency (25(OH)D <15 ng/mL)
  • Anaemia
  • Cardiovascular disease (most common cause of death)
  • Hyperkalaemia (frequent cause of sudden death)
• Mortality patterns:
  • Highest within the first 6 months of dialysis initiation
  • 5-year survival on dialysis: ~35% overall, ~25% in diabetic patients
  • ESKD patients aged ≥65 have a 6-fold higher mortality risk than age-matched general population
    
    

Morbidity and Hospitalisation

• CKD patients are 3–5 times more likely to be hospitalised than the general population.
• Leading causes of admission: cardiovascular disease and bacterial infections.
• ESKD patients average 1.7 admissions and 3 emergency visits per year.
  
  

Impact of Dialysis Modality on Prognosis

• Haemodialysis vs Peritoneal Dialysis:
  • Haemodialysis associated with longer median survival (36.7 months vs 20.4 months).
  • Frequent (6-day/week) dialysis increases risk of vascular access complications by 76%.
• Hyperkalaemia is a leading cause of sudden death in patients on dialysis, especially following missed sessions or dietary indiscretion.
  
  

 Cardiovascular Risk and Progression

• CKD is a strong independent risk factor for cardiovascular disease.
• Cardiovascular mortality is 10–20 times higher in dialysis patients than in the general population.
• Optimisation of BP (e.g., <120 mmHg systolic) and glycaemic control reduces risk.
• SGLT2 inhibitors reduce cardiovascular and renal outcomes in type 2 diabetes.
  
  

Modifiable Risk Factors and Interventions

• Proteinuria: Reduction with ACEI/ARB therapy slows progression and improves survival.
• Vitamin D: Low levels are independently associated with higher all-cause mortality.
• Serum bicarbonate: Low levels correlate with increased inflammation and mortality; oral bicarbonate slows CKD progression.
• Finerenone, a mineralocorticoid receptor antagonist, reduces renal and cardiovascular outcomes in diabetic CKD.
  
  

Demographic Factors Affecting Prognosis

• Sex: Men have consistently higher mortality than women across all CKD stages.
• Ethnicity:
  • In Medicare CKD patients ≥66 years, White patients had slightly higher mortality than Black patients.
  • US dialysis population has higher morbidity/mortality than in other countries due to broader inclusion criteria.
    
    

Children and CKD

• Prognosis in children is better than in adults, but morbidity and mortality still exceed those in healthy peers.
• Transplantation is preferred over dialysis due to better long-term outcomes and growth potential.
  
  

Reproductive Health in Advanced CKD

• Delayed puberty, menstrual irregularities, and infertility are common in both sexes.
• Pregnancies in women with advanced CKD are high-risk, associated with poor fetal outcomes and accelerated renal decline.
  
  

Long-Term Outlook

• Many patients with CKD will die from cardiovascular complications before reaching ESKD.
• Early intervention with renoprotective agents, lifestyle changes, and management of comorbidities can alter the natural history of disease.
  
  

Fluid and Electrolyte Disturbances

• Common in CKD stages 4–5.
• Presents as peripheral oedema, pulmonary oedema, or hypertension.
• Management: sodium restriction (<2 g/day) and loop diuretics.
  
  

• May reflect volume expansion or increased RAAS activity.
• Target blood pressure: <120 mmHg systolic (KDIGO 2021); <130/80 mmHg (ACC/AHA 2017).
• Requires tailored antihypertensive regimens, often involving multiple agents.
  
  

• Caused by reduced excretion, RAAS blockade, acidosis, or aldosterone deficiency.
• ECG findings (e.g., peaked T waves) signal severity
• Treatment: intravenous calcium, insulin–dextrose, beta-agonists, potassium binders (patiromer, sodium zirconium cyclosilicate), or dialysis in severe cases.
  
  

• Occurs as bicarbonate excretion fails with GFR <50 mL/min.
• Contributes to bone disease, protein catabolism, and impaired growth in children.
• Treatment: oral bicarbonate supplementation to maintain serum bicarbonate >20–22 mmol/L.

Anaemia of CKD

• Normocytic, normochromic anaemia due to reduced erythropoietin production.
• Screening:
  • Stage 3: annually
  • Stage 4–5: every 6 months
  • Dialysis: monthly
• Treatment:
  • Erythropoiesis-stimulating agents if Hb <100 g/L and symptomatic.
  • Iron repletion if ferritin <200 ng/mL or transferrin saturation <20%.
  • Target Hb: 100–110 g/L. Avoid normalisation >130 g/L due to increased cardiovascular risk.
    
    

Mineral and Bone Disorder (CKD-MBD)

• Begins in stages G3–G5.
• Due to phosphate retention and reduced vitamin D activation.
• Elevated PTH contributes to renal osteodystrophy and vascular calcification.

• Monitor serum phosphate, calcium, and PTH regularly.
• Vitamin D:
  • Supplement 25(OH)D if <75 nmol/L.
  • Use active analogues (e.g., calcitriol) in progressive hyperparathyroidism.
• Phosphate binders:
  • Calcium-based (first-line)
  • Non-calcium-based (e.g., sevelamer) for high-risk vascular calcification.
• Calcimimetics (e.g., cinacalcet): Suppress PTH without raising calcium.
  
  

Cardiovascular Disease (CVD)

• Leading cause of death in CKD.
• Independent of traditional CVD risk factors.
• Associated with insulin resistance, chronic inflammation, vascular calcification.
• Prevention strategies:
  • Statins (CKD stages 1–4)
  • Aspirin for secondary prevention
  • Blood pressure and glycaemic control
  • Smoking cessation
    
    

Malnutrition and Protein–Energy Wasting

• Caused by anorexia, dietary restrictions, inflammation, metabolic acidosis.
• Recommended intake:
  • Non-dialysis CKD: 0.6–0.8 g/kg/day
  • Dialysis: 1.0–1.2 g/kg/day
• Dietitian involvement is crucial to maintain nutritional status and avoid sarcopenia.
  
  

Uraemic Complications

• Caused by platelet dysfunction.
• Treated with desmopressin (DDAVP), cryoprecipitate, conjugated oestrogens, or initiation of dialysis.

• Encephalopathy, restless legs syndrome, peripheral neuropathy.
• Stroke and seizure risk increase in both ESKD and post-transplant patients.

• Results from volume overload.
• Loop diuretics and combination regimens are first-line; dialysis if refractory.
  
  

End-Stage Renal Disease (ESRD) Complications

• Malnutrition, hyperkalaemia, metabolic acidosis, and uraemia frequently necessitate dialysis initiation.
• Frequent complications of dialysis:
  • Access failure
  • Cardiovascular instability
  • Infection
    
    

Post-Transplant Complications

• Infectious: CMV, BK virus, fungal infections.
• Metabolic: Hypertension, diabetes, dyslipidaemia.
• Cardiovascular: CAD, arrhythmias, heart failure.
• Malignancy: Post-transplant lymphoproliferative disorder, skin cancer.
• Neurological: PRES, stroke, seizures.
  
  

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