Chronic Kidney Disease (CKD)

Chronic Kidney Disease (CKD), also known as chronic renal disease, has been recognized as a significant health issue since the 19th century. Today, it has reached a global scale. While CKD predominantly affects adults, its impact on children is substantial. CKD in children is associated with a mortality rate 30 to 150 times higher than their peers. It not only affects their growth but also impacts their overall quality of life, putting significant psychosocial stress on families.

Chronic kidney disease is a broad term encompassing various disorders that impact kidney structure and function. The definition of CKD is based on the presence of kidney damage (such as albuminuria) or decreased kidney function (glomerular filtration rate [GFR] <60 mL/min per 1.73 m²) for a period of 3 months or more, regardless of clinical diagnosis.

Definition of CKD

Although CKD has been recognized for a long time, its definition and classification were proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) just over a decade ago. This definition was later revised by Kidney Disease: Improving Global Outcomes (KDIGO) in 2012. Both definitions have significantly impacted the understanding of CKD's epidemiology, with KDIGO's revised 2012 classification including albuminuria.

CKD is characterized by:

• Kidney damage lasting ≥ 3 months, indicated by structural or functional abnormalities of the kidney, with or without decreased GFR.
• Pathological abnormalities or markers of kidney damage, including blood or urine composition abnormalities or imaging test irregularities.
• GFR < 60 ml/min/1.73m² for ≥ 3 months, with or without kidney damage.

Criteria for Defining CKD According to K/DOQI (2003)

A patient is considered to have Chronic Kidney Disease (CKD) if they meet either of the following criteria:

1. Kidney damage for ≥ 3 months, indicated by structural or functional abnormalities of the kidney, with or without decreased GFR, demonstrated by one or more of the following features:

   • Abnormalities in the composition of the blood or urine
   • Abnormalities in imaging tests
   • Abnormalities on kidney biopsy

2. GFR < 60 mL/min/1.73 m² for ≥ 3 months, with or without the other signs of kidney damage described above.

Other Old Terminology

Several older terms were used to describe different stages of chronic kidney disease:

• Chronic Renal Disease (CRD): A complex of clinical, chemical, and metabolic disturbances resulting from chronic reduction in renal function, with reduced GFR being the essential feature.

• Chronic Renal Insufficiency (CRI): Defined as a reduction of GFR to between 25% and 50% of normal (N). It often progresses to CRF despite attempts to correct or arrest the primary cause.

• Chronic Renal Failure (CRF): Can be defined as a reduction of GFR to below 25% of normal (N) that has been present for at least 3 months.

Stages of CKD According to the US National Kidney Foundation and KDIGO

• Stage 1: Kidney damage (pathological abnormalities or markers of damage including abnormalities in blood or urine tests or in imaging studies) with normal or raised GFR (>90 mL/min per 1.73 m²)

• Stage 2: Glomerular filtration rate 60–89 mL/min per 1.73 m² with evidence of kidney damage

• Stage 3: Glomerular filtration rate 30–59 mL/min per 1.73 m²

• Stage 4: Glomerular filtration rate 15–29 mL/min per 1.73 m²

• Stage 5: End-stage renal failure; glomerular filtration rate <15 mL/min per 1.73 m²

K/DOQI STRATIFIES CHRONIC KIDNEY DISEASE INTO FIVES TAGES BASED ON THE GFR AND METABOLIC CONSEQUENCES

Stages of Chronic Kidney Disease: A Clinical Action Plan

KDIGO CLASSIFICATION

• CKD Risk and Mortality: CKD carries a risk of mortality 30 to 150 times that of the general pediatric population.

• Data Availability: While data are available for adults in developed countries, there is a paucity of data for children with CKD.

• From the US:

  • The prevalence of CKD in children is unknown but estimated at 82 cases per million per year.
  • The incidence of pediatric end-stage kidney disease (ESKD), the worst form of CKD, is 15 cases per million per year.
  • The 10-year survival rate for adolescent-onset ESKD is 80%.

• African Countries:

  • Lack of data with few hospital-based studies.
  • Anochie and Eke (2003) reported an annual incidence of 3 per million among children seen at Port Harcourt.
  • Ibadin et al (2004) reported an estimated incidence of 1.7 new cases per million-child population and a prevalence of 4 per million populations.

Disorders that Increase the Risk of CKD

• Family history of polycystic kidney disease or other genetic kidney disease
• Small birth weight infants
• Children with a history of AKI resulting from perinatal hypoxemia or other acute insults to the kidneys
• Renal dysplasia or hypoplasia
• Urologic disorders—especially obstructive uropathies
• Vesicoureteral reflux associated with recurrent urinary tract infections and scars in the kidneys
• Prior history of acute nephritis or nephrotic syndrome
• Prior history of hemolytic uremic syndrome
• Prior history of Henoch-Scho¨nlein Purpura
• Diabetes mellitus
• Systemic lupus erythematosus
• Prior history of hypertension, e.g., from renal artery or renal vein thrombosis in the neonatal period

• Chronic glomerulenephritis
• Chronic pyelonephritis
• Renal dysplasia
• Cystic diseases
• Urologic abnormalities
• Obstructive uropathies
• Reflux nephropathy
• Urinary tract malformations
• Systemic – SLE, H.S.P.
• Vascular – HUS
• Tumours – Bilateral Wilms

Once a critical level of deterioration is reached, the progression of chronic kidney disease can involve:

• Hyperfiltration
• Phosphate retention
• Proteinuria

Mechanism of renal scarring

Chronic kidney disease (CKD) in children can present with various clinical features, including:

• Antenatal detection of conditions that can cause CRF
• Failure to thrive
• Short stature
• History of recurrent urinary tract infections (UTI)
• Enuresis
• History of recurrent body swelling

When evaluating a child with chronic kidney disease (CKD), a series of investigations are commonly performed:

Group 1 (To assess severity of CKD)

• Biochemistry:
  • U&E (urea and electrolytes)
  • Creatinine
  • Calcium
  • Phosphate (P04)
  • Alkaline phosphatase
  • Albumin
• GFR (glomerular filtration rate): Reduced GFR is a key indicator of impaired kidney function.
• PTH (parathyroid hormone): Elevated PTH levels may suggest secondary hyperparathyroidism due to CKD-related mineral imbalances.
• X-ray of hand and wrist: Evaluates bone age and potential renal osteodystrophy, a common CKD complication.
• Chest X-ray (CXR): Screens for pulmonary congestion and fluid accumulation associated with advanced CKD.
• Electrocardiogram (ECG): Detects cardiac complications often seen in CKD, such as electrolyte imbalances and cardiac hypertrophy.
• Echocardiogram (Echo): Assesses cardiac structure and function, as heart changes are common in CKD.

Group 2 (To find the underlying cause of CKD)

• Renal ultrasound (USS): Identifies kidney size, shape, and structural abnormalities that can contribute to CKD.
• Micturating cystourethrogram (MCUG): Reveals vesicoureteral reflux and obstructive uropathies, which can lead to CKD.
• Technetium-99m dimercaptosuccinic acid (DMSA) scan: Assesses kidney structure and function, helping to identify damaged areas.
• Urinalysis + microbiological culture and sensitivity (m/c/s): Detects urinary tract infections and possible renal involvement in CKD.
• Immunology panel:
  • C3 - Low levels may indicate immune complex-related kidney damage.
  • C4 - Low levels suggest autoimmune-related kidney involvement.
  • ANF (antinuclear factor) - Detects autoimmune disorders potentially causing CKD.
  • DsDNA (double-stranded DNA) - Positive results may indicate lupus-related kidney involvement.
  • ANCA (antineutrophil cytoplasmic antibody) - Detects vasculitis-associated autoimmune activity.
• Renal biopsy: Provides detailed information about kidney tissue, helping to diagnose the specific cause of CKD.
• Computed tomography (CT) or magnetic resonance imaging (MRI) scan : Offers detailed images for identifying structural abnormalities or tumors linked to CKD.

When managing chronic kidney disease (CKD) in children, the following strategies are employed:

Pre-terminal Objectives:

• Make the child feel and appear normal among peers.
• Slow down the progression of CKD to end-stage kidney disease (ESKD).
• Maintain normal growth and development.
• Preserve a normal family environment.
• Prepare the family for the management of ESKD.

Multi-disciplinary Team:

Collaborative management involving various specialists and professionals:

• Nephrologist
• Specialist Nurse
• Dietitian
• Social Worker
• Psychologist/Psychiatrist
• Teacher
• Play Specialist

Growth:

• Assess and address growth failure as many children experience it before CKD diagnosis.
• Use recombinant growth hormone (GH) to promote growth.

Nutrition:

• Ensure adequate calorie intake (100-120 calories/kg).
• Restrict phosphate intake.
• Maintain normal protein intake.

Fluid and Electrolyte Balance:

Monitor and manage fluid and electrolyte imbalances.

Metabolic Acidosis:

• Treat metabolic acidosis to support growth and prevent bone demineralization.
• Use sodium bicarbonate (NaHCO3) at 2 mmol/kg.

Bone Health (Renal Osteodystrophy):

• Use phosphate binders, such as calcium carbonate, to manage bone mineral disturbances.
• Consider 1,25-dihydroxycholecalciferol at a dose of 0.02 micrograms/kg/day, titrated with parathyroid hormone (PTH).

Hypertension:

• Manage hypertension with diuretics and angiotensin-converting enzyme inhibitors (ACEIs).
• In some cases, nephrectomy may be necessary.

Anemia:

• Ensure adequate iron and folate stores.
• Use erythropoietin (EPO) at a dose of 50 IU/kg three times per week to manage anemia.

Merits of Recombinant Human Erythropoietin Therapy

ESKD MANAGEMENT:

• RRT is initiated when GFR falls below 10 ml/min per 1.73 m².
• Other indications for RRT initiation are consistent with those enumerated in acute kidney injury (AKI).
• When poor growth is unresponsive to conservative management, RRT may be necessary.

Renal Replacement Therapy (RRT):

RRT options are chosen based on clinical factors:

• Peritoneal Dialysis (PD), Continuous Cycler Peritoneal Dialysis (CCPD), or Continuous Ambulatory Peritoneal Dialysis (CAPD).
• Haemodialysis: Typically involves three to four-hour sessions per week.
• Access for haemodialysis includes arteriovenous (A-V) fistula, graft, or central venous catheters (subclavian or internal jugular).

Renal Transplantation:

Renal transplantation is the ultimate goal for managing ESKD in children:

• Living related donor transplant involves a kidney donation from a family member.
• Cadaveric transplant involves a kidney from a deceased donor.

The prognosis of CKD in children has improved in the last 25 years in developed countries. However, unfortunately, end-stage kidney disease (ESKD) still represents a dire prognosis for Nigerian children.

Renal osteodystrophy is a systemic disorder of mineral and bone metabolism that arises due to CKD. It is characterized by the presence of one or a combination of the following manifestations:

• Abnormalities in calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism
• Abnormalities in bone turnover, mineralization, volume, linear growth, or strength
• Calcification in blood vessels or other soft tissues

Clinical Features of Renal Osteodystrophy

Renal osteodystrophy can manifest with various clinical features that reflect its impact on bone and mineral metabolism:

• Muscle weakness
• Bone pain
• Increased susceptibility to fractures with minor trauma
• In growing children, rachitic changes, varus and valgus deformities of the long bones, and slipped capital femoral epiphyses

Laboratory studies often reveal specific abnormalities that contribute to the clinical presentation:

• Decreased serum calcium level
• Increased serum phosphorus level
• Increased alkaline phosphatase
• Normal parathyroid hormone (PTH) level (or potentially elevated in certain cases)

Radiographic Findings and Skeletal Pathology

Radiographs of the hands, wrists, and knees can reveal characteristic changes associated with renal osteodystrophy:

• Subperiosteal resorption of bone
• Widening of the metaphyses

These radiographic changes reflect the skeletal pathologic finding known as osteitis fibrosa cystica, which is a distinctive manifestation of renal osteodystrophy. It results from the derangement of mineral and bone metabolism due to chronic kidney disease.

The prevention and management of chronic kidney disease in childhood necessitates early identification of risk factors. Children with low birth parameters are particularly susceptible to adult morbidity, including chronic kidney disease, aligning with Brenner and Barker’s hypothesis. The escalating prevalence of kidney failure and early stages of chronic kidney disease, coupled with the considerable expenses and unsatisfactory outcomes of treatment, pose a significant global public health challenge.

For further exploration, you can refer to the article:

https://doi.org/10.31450/ukrjnd.1(69).2021.08