Chronic Kidney Disease (CKD)

Chronic Kidney Disease (CKD) is a progressive condition characterized by structural or functional abnormalities of the kidneys that persist for more than three months, with or without a reduction in glomerular filtration rate (GFR). CKD is associated with increased risks of cardiovascular disease, kidney failure, and premature mortality. Early identification and appropriate management are essential to delay disease progression, prevent complications, and improve patient outcomes.

Screening of individuals at high risk—including those with hypertension, diabetes mellitus, glomerular diseases, HIV infection, and other predisposing conditions—is crucial for early diagnosis. Once the underlying cause has been identified and an individualized care plan established, adults with CKD stages 1–3 can often be managed effectively at the primary healthcare level with regular monitoring.

Epidemiology

Chronic Kidney Disease is a major global public health problem affecting approximately 10–15% of the adult population worldwide. The burden of CKD continues to increase due to the rising prevalence of diabetes mellitus, hypertension, obesity, population aging, and cardiovascular disease. In sub-Saharan Africa, including Tanzania, CKD commonly affects younger adults compared with high-income countries, with hypertension, diabetes mellitus, chronic glomerular diseases, HIV-associated kidney disease, and infectious diseases being important contributors. Many patients present late with advanced disease due to limited access to screening and specialized nephrology services.

Risk factors

Common risk factors for CKD include:

• Diabetes mellitus

• Hypertension

• Chronic glomerular diseases

• HIV infection

• Hepatitis B and Hepatitis C infection

• Cardiovascular disease

• Family history of chronic kidney disease

• Older age

• Obesity

• Smoking

• Recurrent acute kidney injury

• Prolonged use of nephrotoxic medications

• Autoimmune diseases

• Obstructive uropathy

Pathophysiology

Chronic Kidney Disease results from progressive and irreversible loss of functional nephrons due to persistent kidney injury. As nephron loss increases, the remaining nephrons undergo adaptive hyperfiltration to maintain overall kidney function. Over time, this compensatory mechanism leads to increased intraglomerular pressure, glomerulosclerosis, and further nephron loss.

Progressive decline in glomerular filtration rate results in impaired excretion of metabolic waste products, disturbances in fluid and electrolyte balance, metabolic acidosis, anemia due to reduced erythropoietin production, disorders of calcium-phosphate metabolism, secondary hyperparathyroidism, and increased cardiovascular risk. Without appropriate treatment, CKD may progress to end-stage kidney disease requiring kidney replacement therapy.

Clinical presentation

Clinical manifestations depend on the stage and severity of kidney disease. Early CKD is frequently asymptomatic and may only be detected through laboratory screening.

Patients with advanced CKD may present with:

• Anorexia

• Malaise

• Nausea

• Vomiting

• Fatigue

• Reduced urine output (oliguria)

• Absence of urine (anuria)

• Generalized body swelling

• Shortness of breath

• Pruritus

• Muscle cramps

• Nocturia

• Weight loss

• Reduced exercise tolerance

Clinical signs may include:

• Hypertension

• Peripheral oedema

• Pallor due to anemia

• Features of fluid overload

• Signs of uremia in advanced disease

• Altered mental status in severe kidney failure

Diagnostic criteria

Chronic Kidney Disease is diagnosed when structural or functional abnormalities of the kidneys persist for more than three months, with or without a reduction in glomerular filtration rate.

Evidence supporting the diagnosis includes one or more of the following:

• Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m² for more than three months.

• Persistent albuminuria or proteinuria.

• Persistent abnormalities on urinalysis.

• Structural abnormalities detected on renal imaging.

• Histological abnormalities where kidney biopsy has been performed.

• History of kidney transplantation.

The underlying cause of CKD should always be identified whenever possible, particularly in patients being considered for kidney transplantation.

Staging of chronic kidney disease

CKD should be staged using estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI equation without the ethnicity factor.

Investigations

Recommended investigations include:

Assessment of kidney function

• Serum creatinine

• Blood urea nitrogen (BUN)

• Estimated glomerular filtration rate (eGFR)

• Kidney function tests at diagnosis monthly for three months, then according to disease stage

Urine investigations

• Urinalysis for:

  • Protein

  • Red blood cells

  • Cast cells

• Quantification of proteinuria using:

  • Urine Albumin-Creatinine Ratio (ACR)

  • Urine Protein-Creatinine Ratio (PCR)

  • Esbach test where available

Blood investigations

• Full blood count (especially haemoglobin)

• Serum electrolytes:

  • Potassium

  • Sodium

  • Calcium

  • Phosphate

• Serum albumin

• Serum bicarbonate

• Parathyroid hormone (Stage 5 CKD on dialysis)

• Alkaline phosphatase (ALP)

Imaging

• Kidney-Ureter-Bladder (KUB) ultrasound

• Chest X-ray

Cardiac assessment

• Electrocardiogram (ECG)

Additional investigations

Additional investigations should be guided by the suspected underlying cause of CKD and assessment for kidney transplantation where appropriate.

Management

Management aims to:

• Treat reversible causes of kidney dysfunction.

• Slow progression of chronic kidney disease.

• Prevent cardiovascular complications.

• Treat complications of kidney failure.

• Prepare patients requiring kidney replacement therapy.

Non-pharmacological treatment

General measures include:

• Reduce dietary salt intake.

• Treat underlying diseases such as hypertension, diabetes mellitus, HIV infection, and glomerular diseases.

• Reduce cardiovascular risk factors.

• Maintain healthy body weight.

• Encourage smoking cessation.

• Avoid nephrotoxic medications where possible.

• Monitor kidney function regularly.

• Restrict dietary protein to no more than 1 g/kg/day in patients with CKD stages 4 and 5.

• Manage significant proteinuria.

Significant proteinuria is defined as:

• Proteinuria greater than +2 on urine dipstick, or

• Spot urine protein-creatinine ratio greater than 0.1 g/mmol, or

• Albumin-creatinine ratio greater than 100 g/mol,

confirmed on at least two of three occasions in the absence of urinary tract infection, heart failure, or menstruation.

Pharmacological treatment

Reduction of proteinuria

In patients with established CKD and significant proteinuria, irrespective of the presence or absence of hypertension:

Before initiating ACE inhibitors:

• Assess kidney function.

• Measure serum potassium.

• Correct dehydration before treatment.

• Monitor serum creatinine and potassium after initiation.

ACE inhibitors are contraindicated in:

• Hyperkalaemia

• Known hypersensitivity to ACE inhibitors

Begin with a low dose and gradually titrate while monitoring blood pressure, kidney function, and proteinuria.

Recommended treatment:

Adults

Enalapril 10–20 mg orally every 12 hours.

OR

Lisinopril 5–10 mg orally once daily, titrated gradually up to a maximum of 40 mg once daily as tolerated.

Management of hypertension should follow the hypertension treatment guideline.

Hyperlipidaemia

Patients with co-existing hyperlipidaemia should be managed according to the dyslipidaemia treatment guideline to reduce cardiovascular risk.

Referral

Referral depends on disease stage and severity.

Refer patients to a physician or nephrologist when:

• CKD Stage 3 or higher.

• Rapid decline in kidney function.

• Persistent heavy proteinuria.

• Resistant hypertension.

• Electrolyte abnormalities.

• Suspected hereditary or glomerular kidney disease.

• Recurrent acute kidney injury.

• Preparation for kidney replacement therapy.

Patients with Stage 4 and Stage 5 CKD should be referred to nephrology services for assessment and preparation for dialysis or kidney transplantation.

Complications

Potential complications include:

• End-stage kidney disease

• Fluid overload

• Hypertension

• Hyperkalaemia

• Metabolic acidosis

• Anaemia of chronic kidney disease

• Mineral and bone disorders

• Secondary hyperparathyroidism

• Cardiovascular disease

• Pericarditis

• Malnutrition

• Increased susceptibility to infection

• Uraemic encephalopathy

• Death

Prognosis

The prognosis of CKD depends on the underlying cause, disease stage at diagnosis, degree of proteinuria, blood pressure control, and associated comorbidities. Early diagnosis and aggressive management of modifiable risk factors can significantly slow disease progression and reduce cardiovascular complications. Patients presenting with advanced CKD have an increased risk of kidney failure, cardiovascular events, hospitalization, and mortality.

Prevention

Preventive measures include:

• Routine screening of high-risk individuals, particularly those with diabetes mellitus, hypertension, HIV infection, and glomerular diseases.

• Early diagnosis and treatment of kidney disease.

• Optimal control of blood pressure.

• Good glycaemic control in patients with diabetes mellitus.

• Prompt treatment of urinary tract and kidney diseases.

• Avoidance of nephrotoxic medications whenever possible.

• Smoking cessation.

• Reduction of dietary salt intake.

• Maintenance of healthy body weight and regular physical activity.

• Management of dyslipidaemia and other cardiovascular risk factors.

• Regular monitoring of kidney function in individuals at increased risk.