6 - Pediatric Kidney Disorders

Nephrotic syndrome?

Nonspecific kidney disorder that increases the permeability across the glomerular filtration barrier

Symptoms and clinical features of nephrotic syndrome?

Symptoms → Edema, foamy urine, weight gain

Clinical features → Proteinuria, Hypoalbuminemia (< 3g/dL), Edema, Hyperlipidemia

What is the epidemiology of nephrotic syndrome?

Incidence → 1.15–16.9 new cases per 100,000 children/year

Typical onset → Ages 2–7 years

Disparities → African American and Hispanic children have higher incidence, more severe disease, and poorer prognosis

Primary Nephrotic Syndrome?

90% of cases

Idiopathic → Kidney problem without an identified underlying cause

Most commonly → Minimal Change disease

Others → FSGS, Membranous Nephropathy

Secondary Nephrotic Syndrome?

10% of cases

Kidney problem caused by another condition such as →

Infections → Hep B/C, malaria, toxoplasmosis, syphilis, COVID-19

Drugs → NSAIDs, pamidronate, lithium, heroin

Malignancies → leukemia & lymphoma

Misc → Lupus, IgA, nephropathy, diabetes, MPGN

Pathophysiology of primary nephrotic syndrome?

Cause is not well understood

In minimal change disease (MCD), T-cell dysfunction is a proposed theory

T cells may release cytokines that injure podocytes and damage the charge barrier

This allows albumin to leak into urine → proteinuria

How is nephrotic syndrome diagnosed?

Edema → Periorbital, hands, and feet.

Proteinuria → Urinalysis 3+ protein; UPCR >2.

Hyperlipidemia

Hyponatremia

Hypoalbuminemia

Hypocalcemia

Goals of treatment for acute management of nephrotic syndrome?

Achieve remission of the disease by decreasing urinary protein spilling

Control symptoms arising from ongoing proteinuria and its complications

Treatment options for acute management of nephrotic syndrome?

Medications that modify the disease

Medications aimed at treating symptoms

What are the acute treatments for nephrotic syndrome?

Albumin 25%

Furosemide

Glucocorticoid

Low sodium diet

Albumin 25% for acute management of nephrotic syndrome?

0.5 g/kg q6-12 over 4h

Increase oncotic pressure → shift fluid intravascular

Furosemide for acute management of nephrotic syndrome?

1 mg/kg q6-12 (after albumin)

Remove excess interstitial fluid

When can you consider co-administration of albumin and furosemide for acute management?

If albumin < 2.5 g/dL

Glucocorticoid for acute management of nephrotic syndrome?

Prednisone, prednisolone or methylprednisolone

60 mg/m2 daily (max 60 mg)

Immunosuppression

Anti-inflammatory

Low sodium diet for acute management of nephrotic syndrome?

Decrease fluid retention

Nephrotic syndrome treatment?

Depends on exact disease → primary vs secondary, subset, and response to first line therapy

Meds used for disease control and remission →

Prednisone

Cyclophosphamide

Calcineurin inhibitors

Mycophenolate mofetil

Rituximab

Prednisone?

MOA → Broad immunosuppression; decreases IL-2, IFN-γ, and inflammatory cytokines and sequesters T cells in bone marrow

Initial episode → Treatment lasts 8–12 weeks

What is used in steroid sensitive nephrotic syndrome (SSNS)?

Steroid sparing therapies

1st line → Oral cyclophosphamide

Alternatives → Mycophenolate mofetil, Rituximab, Calcineurin inhibitors

Cyclophosphamide?

MOA → alkylating agent with non-specific immunosuppressive effects

Route → Oral recommended but can be given IV

Not recommended in SRNS, but 1st line for SSNs

Adverse effects of cyclophosphamide?

Fertility issues

Neutropenia

Alopecia

Amenorrhea

Infection risk

Hemorrhagic cystitis

Tacrolimus?

MOA → inhibits IL-2 mediated T-Cell activation

Route → oral

Monitor → dose based on goal levels (5-10ng/mL)

Clinical pearls for tacrolimus?

Often preferred over cyclosporine due to cosmetic side effects

Give at least for 12 months

Avoid grapefruit juice

Adverse effects of Tacrolimus?

Hypomagnesemia

Hypertension

Tremor

Hyperglycemia

Renal dysfunction

Cyclosporine?

MOA → Inhibits IL-2 mediated T cell activation

Route → Oral

Monitor → Adjust dose based on levels (60-150 ng/mL)

Adverse effects of cyclosporine?

Tremor

Gingival hyperplasia

Hypertrichosis

Hyperkalemia

Hypomagnesemia

Hypertension

Renal dysfunction

Clinical pearls for cyclosporine?

Stabilizes podocytes, helping reduce protein leakage

Give for at least 12 months

Mycophenolate Mofetil?

MOA → T and B lymphocyte inhibition

Route → Oral

Monitor → Target AUC > 50 mcg*h/mL

Adverse effects of mycophenolate mofetil?

Nausea/vomiting

Diarrhea

Pancreatitis

Bone marrow suppression

Decrease in effectiveness of oral contraceptives → REMs

Clinical pearls for Mycophenolate Mofetil?

Change to extended release formulation for GI side effects

Give for at least 12 months

Rituximab?

MOA → Targets CD20 on B lymphocytes

Route → IV

Monitor → CD20 levels, IgG levels screen for Tb and Hep B before administration

Adverse effects of Rituximab?

Infection

Infusion reactions

Bone marrow suppression

Hypogammaglobulinemia

Clinical pearls for Rituximab?

Used after oral options fail or are inadequate to induce remission

What is used for steroid resistant nephrotic syndrome (SRNs)?

Steroid sparing therapies

1st → Calcineurin inhibitors

Alternatives → Mycophenolate mofetil, Rituximab

Cyclophosphamide is NOT recommended for SRNs

Consider renal biopsy if they have 2 or more of:

Age ≥ 12 years

Macroscopic hematuria

Renal sufficiency

Low serum C3 complement

Severe hypotension

When else can you consider a renal biopsy?

Steroid failure → if they have persistent proteinuria after 1 month of daily steroids (after initial biopsy or follow up)

How is hypertension treated in nephrotic syndrome?

First line → ACEIs (enalapril) / ARBs (losartan)

BP goal → Below the 90th percentile for age, sex, and height

How is dyslipidemia managed in nephrotic syndrome?

First line → Low-fat diet

Statins → Consider if fasting LDL-C is consistently >160–190 mg/dL

What immunizations are recommended in nephrotic syndrome?

Recommended → Pneumococcal and influenza vaccines

Live vaccines → Contraindicated while receiving corticosteroid-sparing immunosuppressants

When to defer live vaccines → Until prednisone is below 1 mg/kg/day or 2 mg/kg every other day

Hydronephrosis?

Swelling of the kidney due to build up of urine → causes renal pelvis to become enlarged

Urine cannot drain normally due to an obstruction or reversal of flow / reflux from the bladder

Increased ureteral pressure changes GFR, tubular function, and renal blood flow

What is the epidemiology of hydronephrosis?

Incidence: 2–9 per 1,000

Found in 1–5% of pregnancies; one of the most common findings

Transient hydronephrosis?

Temporary kidney dilation that resolves without chronic issues

Incidence → 41–88% of children with antenatal renal pelvis dilation resolve spontaneously

Ureteropelvic junction (UPJ) obstruction?

Incidence: 5–64% of hydronephrosis cases

Increased risk of other urologic abnormalities

How common is vesicoureteric reflux (VUR) in children with antenatal hydronephrosis?

Occurs in 10–20% of children

VUR → Urine flows backward from the bladder toward the kidneys

What causes hydronephrosis?

Kidney stone

Congenital blockage

Blood clot

Scar tissue

Malignancy

Urinary tract infection

Symptoms of Hydronephrosis?

Flank, abdominal, or groin pain

Pain during urination

Urinary frequency

Incomplete urination

Incontinence

Fever

How is hydronephrosis diagnosised?

Renal ultrasound

Voiding cystourethrography (VCUG) is considered

Severity: Mild, moderate, or severe; grades I–V

Grade I: Least severe

Grade V: Most severe

Risk of hydronephrosis?

Antenatal hydronephrosis increases the risk to have pyelonephritis-related hospitalizations during 1st year of life → 12x more likely

Antibiotic prophylaxis is controversial

Treatment of hydronephrosis?

Amoxicillin

Cephalexin

Nitrofurantoin

Bactrim → do not use before 2 months of life

What defines hypertension in pediatric patients?

Children under 13 → BP ≥95th percentile for age, sex, and height

Age 13 and older → BP ≥130/80 mmHg

Confirm with repeated measurements

How do you determine a child's 90th percentile BP?

Use a BP table based on age, sex, and height percentile.

• Measure and record systolic and diastolic BP

• Find the child's age in the table

• Follow the age row to the child's height percentile

• Read the 90th percentile BP for comparison

Management of elevated BP in pediatric hypertension?

Lifestyle interventions → diet, sleep, physical activity

Repeat BP in 6 months

Management of stage 1 or 2 hypertension and asymptomatic?

Lifestyle interventions

Start treatment

Management of stage 2 and symptomatic or >30mmHg above the 95th percentile?

Emergency department

What is the BP treatment goal for children with hypertension and special conditions?

Diabetes → Target BP below the 90th percentile for age, sex, and height

What is the treatment goal for pediatric hypertension?

Reduce SBP and DBP to below the 90th percentile

Adolescents ≥13 years: goal below 130/80 mmHg

What medications treat pediatric hypertension?

First-line options → ACEI, ARB, long-acting CCB, or thiazide diuretic

Beta blockers → Not recommended as initial treatment

CKD, proteinuria, or diabetes → ACEI or ARB preferred

Which BP medications are preferred for African American children?

Thiazide diuretics or long-acting CCBs

What are examples of medications used to treat pediatric hypertension?

CCBs → Amlodipine, isradipine

ACE inhibitors → Enalapril, lisinopril

Thiazides → Chlorothiazide, hydrochlorothiazide