Pediatric Nephrology Lecture Notes

Urinary Tract Infection (UTI)

• Bacteriuria in a significant amount & urinary symptoms (e.g., dysuria).
• Etiology:
  1. E.coli:
     • Ascending from bowel flora.
     • Accounts for 85% of first infections.
  2. Klebsiella
  3. Pseudomonas Aeruginosa:
     • In patients using indwelling catheters.
  4. Staphylococcus saprophyticus
  5. Serratia
  6. Proteus (associated with a high urinary pH)
  7. Enterococcus
  8. Viruses:
     • Not treated unless generalized symptoms are present.
     • Include:
       1. Adenovirus → Hemorrhagic cystitis
       2. Coxsacki virus
       3. Echoviruses
• H. influenza DO NOT cause UTI
• Risk factors:
  • Age below one year
  • Sex: female
  • Race/ethnicity: white children
  • Genetic factors
  • Urinary obstruction
  • An abnormal elimination pattern (frequent or infrequent voids, urgency, constipation)
  • Withholding maneuvers
  • Bladder and/or bowel incontinence
  • Constipation
  • VesicoUreteral Reflux
  • Sexual activity
  • The risk of UTI increases with the increasing duration of bladder catheterization
  • Uncircumcised boys

Clinical Features of UTI

• Age-specific symptoms:
  • Neonates:
    • Failure to thrive
    • Feeding problems
    • Fever
    • Irritability
    • Lethargy
    • Direct hyperbilirubinemia secondary to gram-negative endotoxins
  • Infants (1 month to 2 years of age):
    • Feeding problems
    • Failure to thrive
    • Diarrhea
    • Vomiting
    • Unexplained fever
  • At 2 years of age:
    • Urgency
    • Dysuria
    • Frequency
    • Abdominal pain
    • Back pain
    • New-onset urinary incontinence
• Lower UTI:
  • Urinary frequency
  • Urinary urgency
  • Dysuria
  • Hematuria
  • Pyuria
• Upper UTI:
  • Fever, chills
  • Flank pain
  • Nausea, vomiting
  • Costovertebral angle tenderness
  • Leukocytosis
  • Pyuria
• Uncomplicated UTI:
  • Symptoms and signs are limited to simple cystitis (bladder infection).
  • Dysuria, frequency, urgency, and suprapubic pain.
  • Common in healthy children
  • No systemic findings like fever, chills, or sepsis.
• Complicated UTI:
  • Infection in patients with risk factors for infection, treatment failure, or serious outcomes, including:
    • Male sex
    • Children with features of atypical pediatric UTI
    • Significant anatomical or functional abnormalities
    • Immunosuppression
    • Renal failure
    • Metabolic disorders (e.g., diabetes)
  • Infection associated with recent instrumentation or medical devices, e.g.:
    • Cystoscopy
    • Indwelling catheters
    • Drainage devices (e.g., ureteral stents, nephrostomy tubes)

Diagnosis of UTI

• Dipstick (88% sensitive):
  • Protein:
    • Not specific for UTI
  • Nitrites:
    • Most specific for UTI
    • Staphylococcus saprophyticus cannot generate nitrites.
  • WBCs:
    • In uncentrifuged sample: $≥ 10$ WBCs per mmᶟ
    • In centrifuged sample: $≥ 5$ WBCs per high power field
    • Not specific for UTI
  • Leukocyte esterase:
    • This enzyme found in Neutrophil
    • Result of WBCs destruction
• Urine culture:
  • Gold standard
  • Significant colony counts depend on the culture method:
    • Suprapubic aspiration → Any growth
    • Sterile urethral catheterization → $≥10,000$ colonies
    • Clean-catch technique → $≥50,000–100,000$ colonies
• Imaging:
  1. Ultrasound:
     • The least important in differentiating between upper and lower UTI
     • All children under 6 months old with a UTI should receive an abdominal USS within 6 weeks
  2. Voiding CystoUrethroGram:
     • Look for VesiculoUretheral Reflux
     • Used to rule out posterior urethral valve in neonate:
       • Congenital anomalies occur in males
       • Signs & symptoms:
         • Palpable kidney
         • Distended bladder with dullness on percussion
         • Weak urinary stream
  3. DMSA scan:
     • Look for renal scar

Indications of Imaging & Management of UTI

• Indications of imaging (US and MCUG):
  • Acute pyelonephritis
  • Male at any age with 1st UTI
  • All boys with recurrent UTI
  • Female < 3 years with first UTI
  • Female > 3 years with 1st UTI & failure to respond to therapy
  • Not responsive to treatment (no lowering of fever after 48 hrs of appropriate antibiotic)
  • With predisposing factors
  • Poor growth & hypertension
  • Impaired renal function
  • Family history of UTI or congenital anomaly
• Management:
  • Hospital Admission Criteria:
    • Infant less than 3 months to start Start IV ampicillin & gentamicin
    • Immunocompromised patient
    • Patients who are toxemic or septic
    • Patients with signs of urinary obstruction or significant underlying disease
    • Patients unable to tolerate adequate oral fluids or medications
    • Infants younger than 2 months with febrile UTI (presumed pyelonephritis)
    • All infants younger than 1 month with suspected UTI, even if not febrile
  • Empiric antibiotic therapy:
    • Should be started in symptomatic patients with a suspicious urinalysis while culture results are pending.
    • Oral antibiotics → trimethoprim–sulfamethoxazole or cephalexin, cefixime
    • IV antibiotic → cefazolin, ceftriaxone, or ampicillin plus gentamicin
  • Prophylaxis is indicated in high-risk conditions for the development of renal scarring or urosepsis:
    • Dilated VUR
    • Severe obstruction
    • Recurrent symptomatic UTI
    • Infective stones

Acute Renal Failure (ARF)

• Sudden loss of renal function
• Causes:
  1. Pre-renal ARF (Most common)
  2. Intrinsic ARF
  3. Post-renal ARF

Phases of Acute Renal Failure

• Acute interstitial nephritis:
  • Drug-induced hypersensitivity involving the interstitium and tubules
  • Causes include:
    • NSAIDs
    • Penicillin
    • Diuretics
  • Presents as:
    • Oliguria
    • Fever
    • Rash days to weeks after starting a drug
    • Eosinophils may be seen in urine
  • Resolves with cessation of drug
  • May progress to renal papillary necrosis

Acute Tubular Necrosis (ATN) & Chronic Renal Failure

• Acute tubular necrosis:
  • Injury and necrosis of tubular epithelial cells
  • Most common cause of intrinsic AKI
  • Etiology may be:
    1. Ischemia:
       • Decreased blood supply results in necrosis of tubules.
       • Often preceded by prerenal AKI
    2. Nephrotoxic:
       • Toxic agents result in necrosis of tubules.
       • Causes include:
         • Aminoglycosides (most common)
         • Heavy metals (e.g., lead)
         • Myoglobinuria (e.g., from crush injury to muscle)
         • Ethylene glycol (associated with oxalate crystals in urine)
         • Radiocontrast dye
         • Urate
• Chronic Renal Failure:
  • Abnormality of kidney structure or function that persists for > 3 months
  • Causes:
    • Congenital Anomalies of the Kidney & Urinary Tract → the most common
    • Diabetic nephropathy
    • Hypertensive nephropathy
    • Glomerulonephritis
    • Idiopathic

Clinical Features & Complications of CKD

• Clinical features:
  • Causes of SOB:
    • ARDS-like
    • Pulmonary edema → Loop diuretic, water restriction, O2
    • Acidosis
    • Chest infection
  • Electrolytes disturbances:
    • Elevated Electrolytes:
      • Potassium, phosphate & magnesium
      • Creatinine, Sulfate, cholesterol
      • Urea, uric acid
      • Amino acids
    • Decreased Electrolytes:
      • Sodium, calcium, chloride, albumin
    • Acid/Base:
      • High Anion gap metabolic acidosis
• Complications of CKD & treatment:

Indications for Dialysis, Acute vs Chronic Renal Failure, and Polycystic Kidney Disease

• Absolute indications for dialysis (AEIOU):
  1. Acidosis (pH <7.1)
  2. Electrolytes:
     • Refractory (resistance) hyperkalemia
  3. Intoxication
     • Toxic alcohol, salicylates, lithium
  4. Overload:
     • Congestive heart failure
  5. Uremia:
     • Pericarditis, encephalopathy, anorexia, platelet dysfunction
• Acute vs chronic renal failure:

• Polycystic Kidney Disease (PKD):
  • Is an inherited disorder characterized by the development of multiple cysts in the kidneys.
  • It is classified into two distinct disorders:

Bilateral Renal Agnesis, Stones, and Hypertension

• Bilateral renal agenesis:
  • Most probably die from Respiratory failure
• Stones:

• Hypertension:

Glomerular Filtration Rate & Barrier

• Glomerular Filtration Rate:
  • $= K * (Height / Serum creatinine)$
  • K → constant depend on child’s sex & age
  • The best investigation for renal function and GFR is creatine clearance
• Glomerular filtration barrier:
  • Responsible for filtration of plasma according to size and charge selectivity
  • Composed of:
    • Fenestrated capillary endothelium
    • Glomerular Basement Membrane with type IV collagen
    • Podocyte foot processes (epithelial cells)
  • A Charger barrier:
    • Glomerular filtration barrier contains ⊝ charged that prevent entry of ⊝ charged molecules (e.g., albumin)
  • Size barrier:
    • Fenestrated capillary endothelium, prevents entry of:
      • $> 100$ nm molecules
      • Red blood cells
    • Slit diaphragm
    • Filtration slit:
      • Between the feet of the podocytes
      • Prevents entry of molecules $> 40–50$ nm

Urine Analysis & Hematuria

• Urine analysis:
  • Urine sample should be examined within 2 hours
  • Should be refrigerated if not read immediately
  • Methods to collect urine sample:
    1. For children who are toilet trained:
       • Mid-Stream Urine sample (MSU):
         • Cleaning of the external genitalia
         • Then child needs to start passing urine into the toilet:
           • The initial portion of the urine → escape
           • Then his mother or the nurse catch some of the middle part of the urine stream in a sterile container
    2. For children who are not toilet trained:
       • Clean catch:
         • Give your infant a drink or breastfeed to help fill the bladder
         • Clean the child’s genital area with soap and water
         • Leave your child’s nappy off and wait for them to urinate and quickly
         • Catch a small amount in a sterile container
       • Bag collection:
         • You attach a plastic bag over your baby’s genital area after cleaning very well with soap and water
         • Urine collects in the bag when your baby urinates.
         • Transfer the urine sample from the bag into the sterile container
         • A bag urine sample is often contaminated by germs from the skin:
           • This can make it look like the child has a UTI, even if he doesn’t really
       • Catheter sample:
         • A doctor or nurse passes a fine plastic tube (catheter) into the urethra and bladder so that they can collect a urine sample into a sterile container
       • SupraPubic Aspirate (SPA):
         • Involves putting a needle into the bladder just above the pubic bone
         • Urine is collected straight from the bladder via the needle into the syringe
• Hematuria:
  • Five or more RBCs per high-power microscope
  • The most common cause in children is UTI

Nephritic Syndrome

• Definition:
  • Inflammation in the glomerulus
• Characterized by:
  • Gross hematuria
  • “Cola-colored” urine
  • Hypertension
  • Signs of fluid overload from renal insufficiency
• Post-Infectious GN:
  • Most common cause of acute GN presenting as nephritic syndrome
  • Seen 10 days after group A streptococcal pharyngitis
  • Seen 4-6 weeks after skin infection (impetigo)
  • Resolve spontaneously
  • Low serum complement (C3) & normal C4:
    • Is present but transient and normalizes within 8–12 weeks
    • If not normalize → do renal biopsy
  • Detection of prior streptococcal infection
    • Anti-Streptolysin O titer:
      • Is positive in 90% of children after streptococcal pharyngitis
      • Is positive in only 50% of patients with impetigo.
  • Light microscopy: Enlarged and hypercellular glomeruli
  • Electron microscopy: Subepithelial Immune Complex humps (Pathognomonic for PIGN)
  • Immunofluorescence: Granular (“starry sky”) appearance (“lumpy-bumpy”)
  • Prompt antibiotic treatment of infections with nephritogenic strains of group A streptococcus:
    • Does not reduce the risk of PSGN
    • It will reduce the risk of rheumatic fever
• IgA nephropathy:
  • Most common cause of chronic GN at all ages
  • Seen at the same time of infection (respiratory tract infection or GI tract infection)
  • Around 50% of them develop renal failure at the age of adulthood
  • Risk of renal failure increase with:
    • Increasing creatinine
    • Hypertension
    • Gross hematuria
    • Azotemia
  • High IgA is not diagnostic

Alport Syndrome & Rapidly Progressive Glomerulonephritis

• Alport syndrome:
  • Caused by mutations in genes encoding type IV collagen:
    • Lead to the construction of abnormal Glomerular Basement Membrane (GBM) in the kidneys and ears.
  • The most common inheritance pattern is X linked
  • Progressive disease
  • Males with Alport syndrome present with:
    • Painless microscopic or macroscopic hematuria
    • Progressive proteinuria
    • Hypertension
    • Loss of kidney function
    • Sensorineural hearing loss.
  • Females typically have a more benign course:
    • Microscopic hematuria
• Thin basement membrane (benign familial hematuria):
  • Caused by autosomal dominant collagen mutations
  • Lead to isolated GBM thinning & persistent hematuria.
  • There is often a family history of benign hematuria in first-degree relatives.
  • Usually has an excellent prognosis.
  • Not a Progressive disease
• Rapidly Progressive GlomeruloNephritis (RPGN):
  • More severe form of acute GN with a rapid loss of kidney function over days to weeks.
  • RPGN may be seen in any form of acute GN.
  • A common feature on renal biopsy is:
    • Glomerular epithelial cell proliferation with crescents

Nephrotic Syndrome

• Is defined as:
  • Hypoalbuminemia (serum albumin
  • Hypercholesterolemia ($>250$mg/dL)
  • Edema → from decreased oncotic pressure

Minimal Change Disease & FSGS

• Minimal Change disease:
  • The most common cause of NS in children.
  • Males are affected more frequently than females (2:1)
  • The peak age of presentation is in the preschool years.
  • Usually idiopathic
  • Associated with Hodgkin lymphoma → cytokine-mediated damage
  • Excellent response to steroids (prednisone)
  • Absent of hypertension or hematuria
  • In light microscopy → normal
  • Immunofluorescence → negative
  • In electron microscopy → effacement of podocyte foot
• Focal Segmental GlomeruloSclerosis (FSGS):
  • Focal → some of the glomeruli become scarred
  • Segmental → only segment of the glomerulus become scarred
  • Most common cause of nephrotic syndrome in adults
  • More than 35% of children with FSGS progress to end-stage kidney disease
  • 35% of children respond to steroid
  • If ESKD develop, steroid has no role & start ACE inhibitor
  • In light microscopy → Segmental sclerosis and hyalinosis
  • Immunofluorescence → negative
  • In electron microscopy → effacement of podocyte foot
• Treatment:
  • 1st line → steroid:
    • 90% of the patient respond to steroids in pediatric ages.
      • 2/3 of those who respond to steroids have recurrent illness "relapse".
      • 1/3 of those who respond to steroids will improve completely
    • Avoid live vaccine while on steroid
    • If not response to steroid → suspect FSGN
  • 2nd line → cyclophosphamide:
    • Used in patients with frequent relapses who are not steroid dependent
    • Cause hemorrhagic cystitis

Indications for Renal Biopsy

• Indications for renal biopsy:
  • Age of onset less than 12 months
  • Gross hematuria
  • Persistent microscopic hematuria
  • Elevated blood pressure
  • Low blood C3 for more than 3 months
  • Impaired renal function
  • Proteinuria despite appropriate steroid therapy (not respond to steroid)
  • Acute RF not known cause yet
  • Absent evidence of streptococcal infection.
  • Initially normal complement levels in Post Streptococcus glomerulonephritis
  • Rapidly progressive GN
• Nephrotic syndrome

Arterial Blood Gas & Acidosis

Acid-Base Disorders & RTA

• Acid-Base disorders
  • $CO<em>2 → H^+ + HCO</em>3^-$
  • $CO_2 → pH$ (Respiratory)
    • Maintained by the lung:
      • Hypoventilation → $CO_2$↑ → pH↓ → Acidosis
      • Hyperventilation → $CO_2$↓ → pH↑ → alkalosis
  • $HCO_3^- → pH$ (Metabolic)
    • Determined the pH
    • Maintained by the kidney:
      • Loss $HCO_3^-$ → Acidosis
      • Gain $HCO_3^-$ → alkalosis
• Renal Tubular Acidosis: