References from 21st edition of Nelson and 9th edition of Ghai

1. CHRONIC KIDNEY
DISEASE IN PEDIATRICS
Dr.Himanshu Dave
Department of Pediatrics
NRCH , New Delhi

2. Criteria for Definition of Chronic Kidney Disease (NKF KDOQI
Guidelines)
NKF KDOQI, National Kidney Foundation Kidney Disease Outcomes Quality Initiative.
• Patient has chronic kidney disease (CKD if either of the following
criteria are present:
• 1. Kidney damage for ≥3 months as defined by structural or
functional abnormalities of the kidney, with or without
decreased GFR,manifested 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

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

4. Stages of Chronic Kidney Disease
STAGE DESCRIPTION GFR
1 Kidney damage with normal or increased
GFR
≥90
2 Kidney damage with mild decrease in GFR 60-89
3 Moderate decrease in GFR 30-59
4 Severe decrease in GFR 15-29
5 Kidney failure <15 or on
dialysis

5. • CKD prevalence is approximately 18 per 1 million children.
• Childhood-onset ESRD still carries significant morbidity and a
30-fold increased mortality rate as compared with healthy
peers, with cardiovascular and infectious diseases as the
leading causes of death.

6. ETIOLOGY
• In children< 5 yr of age, CKD is most commonly a result
of congenital abnormalities of the kidney and urinary
tract (i.e., renal hypoplasia, dysplasia, or obstructive
uropathy) and is often diagnosed with prenatal
ultrasonography.
• In children older than 5 yr of age, acquired or inherited
forms of glomerulo-nephritis predominate.

7. NONGLOMERULAR
• Aplastic, hypoplastic, and dysplastic kidneys
• Cystinosis
• Medullary cystic kidney disease/juvenile nephronophthisis
• Obstructive uropathy (e.g.,PUV , cloaca, neurogenic bladder)
• Oxalosis
• Autosomal dominant and autosomal recessive polycystic
kidney disease (ADPKD, ARPDK)
• Pyelonephritis/interstitial nephritis/reflux nephropathy
• Renal infarct Syndrome of agenesis of abdominal musculature
(Eagle Barrett syndrome)
• Wilms tumor

8. GLOMERULAR
• Chronic glomerulonephritis (Including FSGS)
• Congenital nephrotic syndrome (CNS)
• Hemolytic-uremic syndrome (HUS)
• Henoch-Schönlein nephritis (HSPnephritis)
• Idiopathic crescentic glomerulonephritis
• IgA nephropathy (IGAN)
• Membranoproliferative glomerulonephritis (MPGN)
• Membranous nephropathy
• Sickle cell nephropathy
• Systemic immunologic disease (e.g., SLE, Wegener
granulomatosis)
• Hereditary nephritis (Alport syndrome)

9. PATHOGENESIS
A) Hyperfiltration injury : Final common pathway of glomerular
destruction, independent of the underlying cause of renal
injury.
• As nephrons are lost, the remaining nephrons undergo
structural and functional hypertrophy & an increase in
glomerular blood flow.
• This compensatory hyperfiltration temporarily preserves total
renal
function.
* It cause progressive damage to surviving glomeruli,by direct
effect of the elevated hydrostatic pressure on integrity of the
capillary wall and/or the toxic effect of increasedprotein
traffic across the capillary wall.

10. • Over time, the remaining nephrons suffer an increased
excretory burden, resulting in a vicious cycle of increasing
glomerular blood flow and hyperfiltration injury.

11. B) Proteinuria: Itself can contribute to renal functional decline.
• Proteins that traverse the glomerular capillary wall can exert a
direct toxic effect on tubular cells and recruit monocytes and
macrophages, enhancing the process of glomerular sclerosis
and tubulo interstitial fibrosis.

12. C) Uncontrolled hypertension : Can exacerbate the disease
progression by causing arteriolar nephrosclerosis and by
increasing the hyperfiltration injury.
D) Hyperphosphatemia: Can increase the progression of
disease by leading to calcium phosphate deposition in the
renal interstitium and blood vessels.

13. E) Hyperlipidemia: A common condition in CKD patients, can
adversely affect glomerular function through oxidant-
mediated injury.
* Regardless of the etiology , the progression of
tubulointerstitial fibrosis is the primary determinant of CKD
progression.

14. Pathophysiology of Chronic Kidney
Disease
1) Accumulation of nitrogenous waste products -- Due to
decrease in glomerular filtration rate.
2) Acidosis –Decreased ammonia synthesis
--Impaired bicarbonate reabsorption
--Decreased net acid excretion

15. 3) Sodium wasting – Solute diuresis
--Tubular damage
4) Urinary concentrating defect
-- Solute diuresis
--Tubular damage
5) Hyperkalemia
-Decrease in glomerular filtration rate –Metabolic acidosis
-Excessive potassium intake
-Hyporeninemic hypoaldosteronism

16. 6) Renal osteodystrophy
-Impaired renal production of
1,25dihydroxycholecalciferol (1,25OH2 D)
-Hyperphosphatemia
-Hypocalcemia
-Secondary hyperparathyroidism

17. 7) Growth retardation:
- Inadequate caloric intake
- Renal osteodystrophy
- Metabolic acidosis
-Anemia
-Growth hormone resistance

18. 8) Anemia
- Decreased erythropoietin production
- Iron, folate, and/or vitamin B12 deficiency
- Decreased erythrocyte survival
9) Bleeding tendency- Defective platelet function

19. 10) Infection
-Defective granulocyte function
-Impaired cellular immune functions
-Indwelling dialysis catheters
11) Decreased academic achievement, attention regulation,
or executive functioning
-Hypertension
- Low birth weight

20. 12) Gastrointestinal symptoms (feeding intolerance, abdominal
pain)
-Gastroesophageal reflux
- Decreased gastrointestinal motility
13) Hypertension
- Volume overload
-Excessive renin production

21. 14) Hyperlipidemia
- Decreased plasma lipoprotein lipase activity
- Abnormal HDL-C
15) Cardiomyopathy
-Hypertension
-Anemia
-Fluid overload
16) Glucose intolerance
-Tissue insulin resistance

22. CLINICAL FEATURES OF CKD
• Appearance : Pallor secondary to anemia
• Hypertension
• Shortness of breath: fluid overload, anemia or
cardiomyopathy
• Kidneys: B/L small with thinned cortices suggests intrinsic
disease (Glomerulo nephritis)
: U/L small kidney – Renal arterial
disease
: Clubbed cortices & cortices scar- chronic
infection
: Enlarged cystic kidneys

23. • Itch and cramps.
• Cognitive changes.
• Gatrointestinal symptoms- Anorexia, vomiting and taste
disturbances
-Uremic odour due to breakdown of urea by
saliva.
* Urine output changes-
Polyuria: tubular concentrating ability is damaged.
Oliguria
Persistently froathy urine: Proteinuria.

24. • Hematuria: Immune injury to glomerular capillary wall.
(Microscopy showing dysmorphic red cells and casts , hence
differentiated from lower tract bleeding)
• Proteinuria:
# Tubular damage- low grade proteinuria (<2 gm ) , low MW
proteins.
# Glomerular damage- loss of selectivity to proteinuria , > 3.5
gm (Nephrotic range).

25. • Peripheral oedema:
- Due to renal sodium retention

26. Laboratory Findings
• Elevations in BUN and Creatinine.
• Hyperkalemia
• Hyponatremia (secondary to either renal salt wasting
versus volume overload)
• Hypernatremia (loss of free water)
• Acidosis
• Hypocalcemia
• Hyperphosphatemia
• Elevation in uric acid.

27. • Heavy proteinuria may lead to hypoalbuminemia.
• CBC: Normochromic,Normocytic anemia.
• Dyslipidemia.
• In children with glomerulonephritis the urinalysis shows :
Hematuria and proteinuria.
• In children with congenital lesions (renal dysplasia) urinalysis
s/o low specific gravity with minimal other abnormalities.

28. Measurement of renal function
• By measuring GFR
• INULIN CLEARANCE is the Gold standard( not readily
available)
• Other methods for GFR in clinical practice include using
iohexol or radioisotopes
(99m Tc-DTPA, 51 Cr-EDTA or 125 Iothalamate).

29. • Estimating GFR by endogenous markers (e.g., creatinine
and/or cystatin C) : Most utilized method to understand the
severity of renal disease.
• Bedside creatinine-based estimating equation of estimated
GFR (mL/min/1.73 m2 )
=0.43 ×height (cm) / serum creatinine (mg/dL)
# validated in pediatric CKD population of children aged 1-16
yr and whose GFR was between 15 and 90 mL/min/1.73 m2.

30. • In Original Schwartz formula constant K values:
• Infant (LBW < 1 year) = 0.33
• Infant ( Term < 1 year) = 0.45
• Child or adolescent girl = 0.55
• Adolescent boys =0.70
• In Revised Schwartz formula value of K is 0.413

31. Management of CKD
• CKD treatment is supportive
• Aim : To screen for and treat various metabolic complications
of CKD to improve quality of life and potentially slow the
progression of renal dysfunction.

32. • Close monitoring of blood studies, urine studies (quantitative
measurement for proteinuria using a spot urine protein/urine
creatinine ratio or 24 hr urine collection).
• Ambulatory blood pressure monitoring (ABPM) over 24 hr,
the gold standard of blood pressure evaluation (especially
masked hypertension).

33. • Masked hypertension : Defined as a normal office blood
pressure but abnormal ABPM.
• Is seen in up to 35% of pediatric predialysis CKD patients .
• 4-fold increased risk of having left ventricular hypertrophy
(LVH).

34. 1) Nutritional management
• Patients should receive 100% of the estimated
energy requirement
- for age
- individually adjusted for the physical activity body mass
index & response in the rate of weight gain or loss.
• Tube feeding (by nasogastric tubes or gastrostomy tubes) may
be considered.

35. • Dietary protein restriction is not suggested because of the
concern about adverse effects on growth and
development.
• Children with CKD stages 2-5 should receive 100% of the
daily requirement of vitamins and trace elements.
• Water-soluble vitamin supplements are often required for
patients receiving dialysis.

36. 2) CKD Mineral and Bone Disorder
(CKD-MBD)
• Disorders of calcium, phosphorus, PTH, and vitamin D
metabolism leads to:
- Bone disorders (renal osteodystrophy)
- Vascular and soft tissue calcification

37. Elevated FGF23 results in
Increased urinary phosphate excretion
and
suppression of 1-αhydroxylase activity
leading to reduced 1,25-
dihydroxycholecalciferol(1,25OH2 D)
and
increased PTH secretion.

38. • Elevated FGF23 is the first sign of altered osteocyte function
in pediatric and adult CKD.
• Seen as early as CKD stage 2 (GFR 60-90 mL/min/1.73m2) and
occurs despite normal calcium, phosphorus, PTH, and
1,25OH2 levels.
• Further FGF23 elevation results in secondary hyper –
parathyroidism (low 1,25OH2 D,
hypocalcemia,hyperphosphatemia, and elevated PTH values).

39. • Renal osteodystrophy : Abnormalities in bone turnover (high
versus low),mineralization,and bone volume.
• High-turnover bone disease is osteitis fibrosa cystica.
• Low-turnover bone disease is adynamic renal osteodystrophy

40. Osteitis Fibrosa Cystica
• Most common condition seen in advanced pediatric CKD.
• Laboratory findings:
Hypocalcemia, hyperphosphatemia and elevated alkaline
phosphatase and PTH values.
• Radiographic findings :
Subperiosteal bone resorption
& metaphyseal widening.

41. • C/F: Bone pain, fractures with minor trauma, and various
bony abnormalities (rachitic changes,varus and valgus
deformities of the long bones, and slipped capital
femoral epiphyses).

42. Adynamic Renal Osteodystrophy
• PTH over suppression (Due to therapies containing high
calcium contents).
• Hypercalcemia
• Low alkaline phosphatase activity
• More common in pediatric dialysis patients receiving
treatment for secondary hyperparathyroidism.
# Most pediatric CKD patients have normal to high bone volume
unless exposed to prolonged corticosteroids

43. 3) Vascular calcification in CKD-MBD
• Occurs within the vascular media
(In contrast to the atherosclerotic plaques
that form within the vascular intima).
• Associated with hypercalcemia, hyperphosphatemia, and an
elevated calcium-phosphorus product (Ca×PO4) .
• Noted vascular calcification despite normal serum calcium
and phosphorus values.

44. • Pathophysiology of vascular calcification involves the
transition of vascular smooth muscle cells to osteoblast-like
cells in response to trigger.
• The goal of treatment:
* Normalize mineral metabolism with the goal of
improving growth, reducing bone deformities and fragility,
and reducing vascular and other soft tissue calcification.
* Accomplished with reduced phosphorus intake,
normalization of 25OH vitamin D.

45. • Low phosphorous diet for all patients of CKD.
Low-phosphorus formula for infant (Similac PM60/40).

46. Phosphate binders
• Given with meals.
• Enhance GI phosphate excretion.
• Calcium-based : Calcium carbonate, Calcium acetate (0.5-1gm
/ day with meals)
• Non–calcium-based: Sevelamer (100 mg/kg/day in 3 divided
doses) and ferric citrate.
• Aluminum may be absorbed from the GI tract and can lead to
aluminum toxicity, So aluminum-based binders should be
avoided.

47. • Correcting 25OH Vitamin D insufficiency can delay the onset
of secondary hyperparathyroidism.
• US-based pediatric CKD treatment guidelines define 25OH
vitamin D sufficiency as a serum value of ≥ 30 ng/mL.
• Ergocalciferol OR cholecalciferol are typically recommended
to treat insufficient 25OH vitamin D.
• Dosage of Calcitriol: 20-50 ng / kg / day)
• Dosage of 1-Alpha hydroxyD3: 25-50 ng/kg/day)

48. Active vitamin D sterols (Calcitriol, alfacalcidiol and
doxercalciferol) have been traditionally indicated when:
• (1) 1,25OH2 D levels fall below the established goal range
for the child's particular stage of CKD.
• (2) PTH levels increase above the established goal range for
CKD stage (after correcting for insufficient 25OH vitamin D)
• (3) In patients with elevated PTHlevels and hypocalcemia

49. • Vitamin D sterols increase calcium and phosphorus
absorption from the GI tract and are effective in reducing PTH
values.

50. 4) Fluid and Electrolyte Management
• Infants and children with renal dysplasia may be polyuric, with
significant urinary sodium and free water losses. Benefited
from high-volume, low-caloric-density feedings with sodium
supplementation.
• Children with high blood pressure or oedema benefit from
sodium restriction and diuretic therapy.

51. HYPERKALEMIA:
• Develop with severe deterioration in renal function
• Excessive dietary potassium intake
• Severe acidosis
• Hyporeninemic hypoaldosteronism (related to destruction of
the renin-secreting juxtaglomerular apparatus).

52. • Treated by the restriction of dietary potassium intake,
administration of oral alkalinizing agents, and/or use of
Kayexalate.
• Sodium zirconium and patiromer: Oral agents used in adults.

53. • Metabolic acidosis : Because of decreased net acid excretion
by failing kidneys.
• Bicitra (1mEq sodium citrate/mL) OR
• Sodium bicarbonate tablets (650 mg = 8mEq of base) used to
maintain serum bicarbonate level ≥ 22 mEq/L.

54. 5) LINEAR GROWTH
• Short stature is a significant long-term sequel of childhood
CKD.
• CKD results:
Apparent growth hormone–resistant state, with elevated
growth hormone levels but decreased insulin-like growth
factor 1 levels and abnormalities of insulin-like growth factor–
binding proteins.

55. • Children with CKD who remain less than −2 SD for height
despite optimal medical support may benefit from treatment
with recombinant human growth hormone (rHuGH).
• rHuGH : Daily subcutaneous injections and continues until the
patient reaches 50th percentile for mid parental height,
achieves a final adult height, or undergoes kidney
transplantation.
• Dose of rHuGH: 0.024-0.070 mg/kg subcutaneously once a
day, 6-7 times a week ( max 0.35 mg/kg/week).

56. 6) ANEMIA IN CKD
• Inadequate erythropoietin production by failing kidneys and
typically manifests when renal function falls below
40 mL/min/1.73m2.
• Other factors for anemia in CKD include: Iron, folic acid,
and/or vitamin B12 deficiency, and decreased erythrocyte
survival secondary to uremia.

57. • Anemia in pediatric CKD patients is defined when Hb falls to <
5% for age and gender.
• Investigate for Iron , B 12 and Folic acid deficiency.
• Iron supplementation (oral or intravenous) is recommended
when : Transferrin saturation (TSAT) ≤20% and ferritin ≤ 100
ng/mL.

58. • Erythropoiesis-stimulating agents (ESAs) :
• Erythropoietin and Darbepoetin alfa may be given with oral
or intravenous iron supplementation.
• Resistant to ESA should be evaluated for bone marrow fibrosis
related to secondary hyperparathyroidism.
• Dose of Recombinant human erythropoietin: 50-150
U/Kg/dose subcutaneously or IV, 2-3 times a week.
• Dose of erythropoietin is targeted to keep Hb level of 11-12
g/dl.

59. 7) Hypertension and Proteinuria
• Hypertension in CKD may be due to:
1) Volume overload
2) Excessive Renin production due to glomerular disease.
* Both hypertension and proteinuria associated with more rapid
CKD

60. • Treatment for hypertension:
• Dietary sodium restriction (< 2g of sodium/24 hr) and lifestyle
modifications.
• Guidelines recommend initiating pharmacologic therapy
when systolic or diastolic blood pressures are > 90% for age,
gender, and height.
• Titrate medications to achieve a systolic and diastolic blood
pressure < 50% for age, gender, and height, especially for
those patients with proteinuria.

61. • ACE inhibitors (enalapril or lisinopril) and angiotensin II
receptor blockers (losartan) are medications of choice
irrespective of the level of proteinuria, because of their
potential ability to slow CKD.
• Closely monitor the renal function and electrolyte balance
while using ACEs or ARBs.

62. • Thiazide (hydrochlorothiazide, chlorothiazide) or loop
diuretics (furosemide) helpful in hypertension related to salt
and fluid retention.
• Thiazide ineffective when estimated GFR falls below 30
mL/min/1.73 m2 .

63. 8) IMMUNIZATION IN CKD
• Children with CKD should receive all standard immunizations
with an exception to withhold live virus vaccines from those
receiving immuno suppressive medications (i.e., kidney
transplant recipients and some patients with glomerulo
nephritis).
• It is critical to make every attempt to administer live virus
vaccines before kidney transplantation.
• All children with CKD should receive a yearly influenza
vaccine.

64. 9) Adjustment in Drug Dose
• Drugs excreted by the kidneys might need to be dose adjusted
in CKD patients to maximize their effectiveness and minimize
the risk of toxicity.

65. Progression of Disease
• The median loss of GFR in children enrolled in the Chronic
Kidney Disease in Children (CKiD) study is:
1.5 mL/min/1.73 m2 /yr
(nonglomerular CKD etiology)
versus
4.3 mL/min/1.73 m2 /yr
(glomerular CKD etiology)

66. • Nonmodifiable risk factors: older age, glomerular etiology of
renal disease, CKD severity, and onset of puberty.
• Modifiable risk factors: Elevated blood pressure , persistent
nephrotic range proteinuria, anemia, and dyslipidemia, as well
as no ACE/ARB use,were important predictors of CKD
progression.

67. • Treatment of infectious complications and episodes of
dehydration can minimize additional loss of renal
parenchyma.
• Tobacco avoidance, prevention of obesity, and
avoidance of potential nephrotoxic medications are important
recommendations in CKD.

68. THANK YOU