Chronic Kidney Disease (CKD)

NKF-K/DOQI Definition of CKD KDIGO Modifications (Amsterdam 2004)

Structural or functional abnormalities of the kidneys for ≥ 3 months, as manifested by either:

1. Kidney damage, with or without decreased GFR, as defined by:

• Pathologic abnormalities
• Markers of kidney damage
• Urinary abnormalities (proteinuria, haematuria)
• Blood abnormalities (Creatinine, Urea)
• Imaging abnormalities
• Kidney transplantation

2. GFR <60 ml/min/1.73 m

Definition of CKD by KDIGO

CKD is defined as abnormalities of kidney structure or function, present for >3 months, with implications for health. (Not Graded)

Criteria for CKD (either of the following present for >3 months)

• Markers of kidney damage (one or more)
  • Albuminuria (AER ≥ 30mg/24 hours; ACR ≥ 30mg/g [≥3mg/mmol])
  • Urine sediment abnormalities
  • Electrolyte and other abnormalities due to tubular disorders
  • Abnormalities detected by histology
  • Structural abnormalities detected by imaging
  • History of kidney transplantation
• Decreased GFR (GFR < 60 ml/min/1.73 m

Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate.

The different stages of CKD form a continuum. The stages of CKD are classified as follows

• Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m 2)
• Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m 2)
• Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m 2)
• Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m 2)
• Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m 2)
• Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m 2 or dialysis)

By itself, measurement of GFR may not be sufficient for identifying stage 1 and stage 2 CKD, because in those patients the GFR may in fact be normal or borderline normal. In such cases, the presence of one or more of the following markers of kidney damage can establish the diagnosis:

• Albuminuria (albumin excretion > 30 mg/24 hr or albumin:creatinine ratio > 30 mg/g [> 3 mg/mmol])
• Urine sediment abnormalities
• Electrolyte and other abnormalities due to tubular disorders
• Histologic abnormalities
• Structural abnormalities detected by imaging
• History of kidney transplantation

Hypertension is a frequent sign of CKD but should not by itself be considered a marker of it, because elevated blood pressure is also common among people without CKD.

In an update of its CKD classification system, Kidney Disease: Improving Global Outcomes (KDIGO) advised that GFR and albuminuria levels be used together, rather than separately, to improve prognostic accuracy in the assessment of CKD. More specifically, the guidelines recommended the inclusion of estimated GFR and albuminuria levels when evaluating risks for overall mortality, cardiovascular disease, ESKD, acute kidney injury, and the progression of CKD.

KDIGO guidelines recommend referral to a kidney specialist for patients with any of the following:

• GFR < 30 mL/min/1.73 m 2
• A consistent finding of significant albuminuria (albumin-to-creatinine ratio ≥ 300 mg/g [≥ 30 mg/mmol] or albumin excretion rate ≥ 300 mg/24 hours, approximately equivalent to urine protein-to-creatinine ratio ≥ 500 mg/g [≥50 mg/mmol] or protein excretion rate ≥ 500 mg/24 hours)
• Progression of CKD

NON-Modifiable

• Age- prevalence of CKD increases dramatically with age.
• Gender- CKD in children is somewhat more common in boys, because posterior urethral valves, the most common birth defect leading to CKD, occur only in boys. The incidence of end stage kidney disease (ESRD) is 50% higher in adult men than in women, even though there is a higher prevalence of chronic kidney disease (CKD) in women
• Genetics
• Race- the incidence rate of ESRD among Blacks in the United States is nearly 4 times that for Whites
• Family Hx of CKD

Modifiable

• Hypertension
• Diabetes
• Obesity
• Infections (HIV)
• Analgesics, NSAIDs
• Nephrotoxins
• Smoking
• Poverty

Patients with CKD stages 1-3 are generally asymptomatic. Typically, it is not until stages 4-5 (GFR < 30 mL/min/1.73 m²) that endocrine/metabolic derangements or disturbances in water or electrolyte balance become clinically manifest.

Signs of metabolic acidosis in stage 5 CKD include the following:

• Protein-energy malnutrition
• Loss of lean body mass
• Muscle weakness

Signs of alterations in the way the kidneys are handling salt and water in stage 5 include the following:

• Peripheral edema
• Pulmonary edema
• Hypertension

Anemia in CKD is associated with the following:

• Fatigue
• Reduced exercise capacity
• Impaired cognitive and immune function
• Reduced quality of life
• Development of cardiovascular disease
• New onset of heart failure or the development of more severe heart failure
• Increased cardiovascular mortality

Other manifestations of uremia in ESKD, many of which are more likely in patients who are being inadequately dialyzed, include the following:

• Pericarditis: Can be complicated by cardiac tamponade, possibly resulting in death if unrecognized
• Encephalopathy: Can progress to coma and death
• Peripheral neuropathy, usually asymptomatic
• Restless leg syndrome
• Gastrointestinal symptoms: Anorexia, nausea, vomiting, diarrhea
• Skin manifestations: Dry skin, pruritus, ecchymosis
• Fatigue, increased somnolence, failure to thrive
• Malnutrition
• Erectile dysfunction, decreased libido, amenorrhea
• Platelet dysfunction with tendency to bleed

Screen adult patients with CKD for depressive symptoms; self-report scales at initiation of dialysis therapy reveal that 45% of these patients have such symptoms, albeit with a somatic emphasis.

• Hypertension
• Glomerulonephritis
• Diabetes
• Polycystic kidney disease
• Chronic Interstitial nephritis
• Obstructive uropathy
• HIV
• SLE/Connective Tissue Diseases
• Sickle cell disease
• AKI lasting more than 3 months
• Uric acid nephropathy

Chronic Glomerulonephritis

• Majority of causes of GN in tropical setting have post-infective background
• Streptococcal tonsillitis or dermatitis (children and adolescent)
• Majority of AGN which developed sequel to these infections have spontaneous remission
• 5 – 10% progresses to chronic stage with proteinuria, haematuria, and granular casts.

Other causes CGN

• HBV
• HIV
• Leprosy and Syphilis
• Plasmodium malariae
• Schistosomiasis
• Connective tissue disease notably SLE
• Mercury-containing soaps and creams

Diabetic Nephropathy

• Diabetics also a global health problem.
• 171 million (2000) → 552 million (2030)
• 1/3 will develop diabetic nephropathy
• 3rd commonest cause of CKD in Nigeria.
• 43% in CKD in USA, commonest cause in developed countries.

Chronic Interstitial Nephritis

• Majority of the patients have small kidneys.
• One or both kidneys may be affected.
• Histology often shows normal glomeruli although these are sometimes destroyed. Tubules are absent, atrophied or ballooned while the interstitium contains inflammatory cells and fibrosis.

Causes of CIN

• Infection, especially following childhood ureteric reflux.
• Obstructive uropathy.
• Nephrotoxic agents: heavy metals such as mercury
• Analgesic abuse
• Nephrocalcinosis, nephrolithiasis
• Gout
• Inherited disease such as sickle-cell disease, polycystic diseases
• Malignancy
• Radiation nephritis.
• Sometimes, no cause is found (idiopathic cases)

• full Blood Count (FBC): Assesses for anemia, infection, or other blood disorders.
• Electrolytes, urea and creatinine: Evaluates electrolyte levels and kidney function.
• Urinalysis: Detects abnormalities like proteinuria, hematuria, and urinary tract infections.
• Serum Albumin Levels: May indicate malnutrition, protein loss, or inflammation.
• Lipid Profile: Assesses cardiovascular risk due to increased risk in CKD patients.

Evidence of Renal Bone Disease:

• Serum Calcium and Phosphate: Evaluates bone mineralization.
• 25-hydroxyvitamin D: Assesses vitamin D levels related to bone health.
• Alkaline Phosphatase: Indicates bone turnover.
• Intact Parathyroid Hormone (PTH) Levels: Reflects parathyroid function and bone health.

Additional Tests for Specific Conditions:

• Serum and Urine Protein Electrophoresis: Screens for multiple myeloma.
• Antinuclear Antibodies (ANA) and Double-stranded DNA Antibody Levels: Screens for lupus.
• Serum Complement Levels: Indicates activity of certain glomerulonephritides.
• Antineutrophil Cytoplasmic Antibody Levels (C-ANCA and P-ANCA): Aids in diagnosing granulomatosis with polyangiitis.
• Anti-glomerular Basement Membrane (anti-GBM) Antibodies: Suggests Goodpasture syndrome.
• Hepatitis B and C, HIV, VDRL Serology: Screens for infections associated with glomerulonephritides.

Imaging Studies for CKD Diagnosis:

• Renal Ultrasonography: Screens for hydronephrosis, kidney size, and structural abnormalities.
• Retrograde Pyelography: Diagnoses renal stones or obstruction not visible on ultrasound.
• Computed Tomography (CT) Scan: Identifies renal masses, cysts, and kidney stones.
• Magnetic Resonance Imaging (MRI): Alternative to CT scan, particularly useful in patients unable to receive contrast.
• Renal Radionuclide Scanning: Screens for renal artery stenosis and assesses renal function.

Biopsy:

Percutaneous kidney biopsy is indicated when kidney impairment and/or significant proteinuria are present, and diagnosis remains unclear after appropriate workup.

Early diagnosis and treatment of the underlying cause and/or institution of secondary preventive measures is imperative in patients with CKD. These may slow, or possibly halt, progression of the disease. The medical care of patients with CKD should focus on the following:

• Delaying or halting the progression of CKD: Treatment of the underlying condition, if possible, is indicated
• Diagnosing and treating the pathologic manifestations of CKD
• Timely planning for long-term renal replacement therapy

Conservative management

• dietary modification (low salt, low protein that increase nitrogenous wastes e.g. beans & its products)
• Control Hypertension and Diabetes
• Correct anaemia
• Correct Mineral Bone disorders
• Manage electrolyte imbalance and fluid retention
• Treat Infections

Treatment of ESKD

• Dialysis
• Kidney Transplantation

Indications for renal replacement therapy include the following:

• Severe metabolic acidosis
• Hyperkalemia
• Pericarditis
• Encephalopathy
• Intractable volume overload
• Failure to thrive and malnutrition
• Peripheral neuropathy
• Intractable gastrointestinal symptoms
• In asymptomatic patients, a GFR of 5-9 mL/min/1.73 m², [7] irrespective of the cause of the CKD or the presence or absence of other comorbidities

CKD in Nigeria

• Population figures are few
• Hospital admission rates 6 - 10%
• Mortality over 90% within 3 months
• Less than 1% able to RRT