Chronic Kidney Disease

Definition

• Functional abnormalities in Kidney Function with or without decrease in GFR with any one of
  • abnormal urine or blood values
  • abnormal imaging
  • abnormal kidney biopsy
    or
• decrease in GFR of less than 60 ml/min/1.73 m²
  for a period of more than 90 days

Staging of CKD

Causes

• CAKUT (congenital anomalies of the kidney and urinary tract)
• Glomerular diseases
  • FSGS
  • MPGN
  • IgA nephropathy
  • HUS
  • Alport
  • sickle cell nephropathy
  • cystic diseases of kidney
• Non glomerular causes
  • Obstructive uropathy (PUV)
  • Tumors - Wilms
  • Cystinosis, oxaluria
  • trauma
  • infracts

Pathophysiology

Intact nephron hypothesis

• loss of nephron
• compensatory hypertrophy of the remaining nephrons
• hyperfiltration of remaining nephrons
• increases glomerular capillary pressure
• Glomerular sclerosis and fibrosis
• progressive nephron damage

Proteinuria

• secondary to damage of glomerular capillary wall or decreased tubular absorption
• exerts direct toxic effects on tubular cells and initiate many inflammatory and pro-inflammatory pathways
• glomerular sclerosis and tubulointerstitial fibrosis

Hypertension

• arteriolar hypertension and increasing hyperfiltration injury

Hyperphosphatemia

• leads to deposition of calcium in the renal interstitium and blood vessels

Hyperlipidemia

• oxidant induced damage

Clinical features

General features

• metabolic bone disease
• Anemia
• Acidosis
• Uremia

CAKUT

• growth failure, stunting and vomiting

Glomerular diseases

• edema, hypertension, and proteinuria
• uremic symptoms - fatigue, weakness, nausea, vomiting and anorexia - in advanced stages

Cystic kidney diseases

• associated with wide range of extrarenal anomalies of kidney, liver, pancreas, skeletal system, eyes, CNS

Lab Findings

• increased BUN and creatinine
• decrease in GFR
  • estimation can be done by creatinine - bedside
    • Swartz formula = 0.413 x height / S. creatinine
    • not accurate
  • Inulin method
    • gold standard
    • not readily available
  • commonly used in clinical practise
    • with radioisotopes
      • ^99mTc-DTPA, ⁵¹Cr-EDTA, and ¹²⁵Iothalmate
    • newer biomarkers - cystatin C
      • complex calculation
      • online calculators available
• electrolyte abnormalities
  • hyperkalemia
  • hyponatremia
  • hypernatremia
  • hypocalcemia
  • hyperphosphatemia
  • increase in uric acid
• Dyslipidemia

Management

Nutrition

• 100% estimated energy requirement for age
• 100% RDA of protein or slightly less (as there is risk of growth failure with undernutrition)
• 100% supplementation of trace minerals and vitamins

Bone Mineral disease

• FGF 23, and its cofactor klotho plays a role
• causes increased urinary phosphate excretion and suppression of 1-α hydroxylase
• causes renal osteodystrophy
  • Osteitis fibrosa cystica
    • characterized by hypocalcemia, hyperphosphatemia, elevated alanine phosphate and PTH
    • subperiosteal bone resorption and metaphyseal bone widening
    • bone pain, fractures with minor trauma, varus and valgus deformities, Slipped capital femoral epiphysis
  • Adynamic renal osteodystrophy
    • PTH over suppression
    • hypercalcemia, low alanine phosphatase
    • seen in patients on dialysis
    • defective bone turnover - osteomalacia
  • Vascular calcification
    • in media - as opposed in intima in cardiovascular risk factors

Management

• low phosphate diet, low phosphate formula (Similac PM 60/40) for infants
• Phosphate binders - calcium based (calcium carbonate, calcium acetate) or non calcium based (sevelamer)
• Vitamin D3 supplementation

Fluid and Electrolyte balance

• Fluid overload
  • fluid restriction
• Hyperkalemia
  • restriction of dietary potassium intake
  • cation exchange resins - kayexalate, zirconium cyclosilicate and patiromer
• Metabolic acidosis
  • maintain bicarbonate above 22 mEq/L
  • Bicitra (1mEq sodium citrate/mL) or Sodium bicarbonate tablets used (650 mg = 7.7 mEq of sodium and 7.7 mEq of bicarbonate)

Growth stunting

• due to relative growth hormone resistance in the presence of insulin like growth factor 1 and IGF binding proteins
• long term recombinant growth hormone (rHuGH) given daily as s.c. injection until the patient reach the 50th percentile for mid-parental height

Anemia

• Erythropoietin stimulating agents
  • Erythropoietin
  • Darbepoetin alfa
• Iron, Vit B12 and Folic acid deficiency should be corrected with supplementation

Hypertension and proteinuria

• dietary sodium restriction of less than 2 g sodium in 24 hours
• ACE inhibitors and ARBs are first line as they slow the progression of CKD
• Thiazide and loop diuretics - useful in controlling salt and fluid retention

Immunizations

• Should receive all standard vaccines except live vaccines if receiving immunosuppressive medication
• yearly influenza and pneumococcal vaccine to be given

Drug dosage

• all drugs should be adjusted for CKD