Pediatric Renal Diseases Pediatric Renal Diseases

Developmental and Physiological Aspects 1. Urine volume: Newborns 1~3 ml/kg/h 3~10 d 100~300 ml/d ~2 m 250~400 ml/d ~1 y 400~500 ml/d

~3 y 500~600 ml/d ~5 y 600~800 ml/d ~8 y 600~1000 ml/d ~14 y 800~1400 ml/d >14 y 1000~1600 ml/d ~3 y 500~600 ml/d ~5 y 600~800 ml/d ~8 y 600~1000 ml/d ~14 y 800~1400 ml/d >14 y 1000~1600 ml/d

▲ Oliguria (low urine output): Newborns < 1ml/kg/h Infant & infancy <200ml/m 2 /d Pre-school age <300ml/m 2 /d School age <400ml/m 2 /d ▲ Anuria: < 50 ml/m 2 /d (newborns < 0.5 ml/kg/h)

2. Routine urine test 2.1. Urine color--normally yellow, color changes may be normal or abnormal 2.2. PH: normal range 5~ Specific gravity newborns – 1.006~1.008, >1 year old – 1.011~ Routine urine test 2.1. Urine color--normally yellow, color changes may be normal or abnormal 2.2. PH: normal range 5~ Specific gravity newborns – 1.006~1.008, >1 year old – 1.011~1.025

2.4. Urine analysis – freshly collected and centrifugal urine ● RBC < 3/hpf ● WBC < 5/hpf ● Casts–cellular ( RBC, WBC ) and granular casts are abnormal, hyaline casts can be normal

● Crystals – phosphate and ● Crystals – phosphate and urate crystals may be normal urate crystals may be normal ● Protein(Pro) – negative ● Protein(Pro) – negative ● Sugar (Glu) ● Sugar (Glu) ● Ketones (Ket) ● Ketones (Ket) ● Urobilinogen (Uro) ● Urobilinogen (Uro) ● Bilirubin (Bil) ● Bilirubin (Bil)

3. Addis count RBC < 50,0000, WBC <1,000,000, Casts < h total urinary protein less than 100 mg/m 2 /d, or <4 mg/m 2 /h, or <100 mg/L, or <150 mg/d 3. Addis count RBC < 50,0000, WBC <1,000,000, Casts < h total urinary protein less than 100 mg/m 2 /d, or <4 mg/m 2 /h, or <100 mg/L, or <150 mg/d

5. Renal function tests: BUN, Cr 6. Imaging procedures X-ray, Ultrasound, VCUG, Nuclear medicine ( 99m Tc DMSA, 99m Tc DTPA), IVP etc. 7. Renal Biopsy 5. Renal function tests: BUN, Cr 6. Imaging procedures X-ray, Ultrasound, VCUG, Nuclear medicine ( 99m Tc DMSA, 99m Tc DTPA), IVP etc. 7. Renal Biopsy

Glomerular Diseases Glomerular Diseases

Classify ▲ Clinical classify 1. Primary glomerular diseases 1.1. Glomerulonephritis (Nephritis) ﹉ Acute glomerulonephritis Classify ▲ Clinical classify 1. Primary glomerular diseases 1.1. Glomerulonephritis (Nephritis) ﹉ Acute glomerulonephritis

﹉ Rapidly progressive glomerulo- nephritis (RPGN) ﹉ Persistent glomerulonephritis ﹉ Chronic glomerulonephritis ﹉ Rapidly progressive glomerulo- nephritis (RPGN) ﹉ Persistent glomerulonephritis ﹉ Chronic glomerulonephritis

1.2. Nephrotic syndrome (NS) ﹉ Simple tape NS ﹉ Nephritic tape NS 1.2. Nephrotic syndrome (NS) ﹉ Simple tape NS ﹉ Nephritic tape NS

1.3. Asymptomatic (isolated) hematuria or proteinuria 1.4. Familial nephritis 2. Secondary glomerular diseases– it is part of mul- tisystem disorder, e.g. – 1.3. Asymptomatic (isolated) hematuria or proteinuria 1.4. Familial nephritis 2. Secondary glomerular diseases– it is part of mul- tisystem disorder, e.g. –

2.1. Hepatitis B virus related glomerulonephritis (HBV-GN) 2.2. Purpuric nephritis 2.3. Lupus nephritis (LN) ▲ Pathologic classify ▲ Immunopathology classify 2.1. Hepatitis B virus related glomerulonephritis (HBV-GN) 2.2. Purpuric nephritis 2.3. Lupus nephritis (LN) ▲ Pathologic classify ▲ Immunopathology classify

Acute Glomerulonephritis (AGN) Acute Glomerulonephritis (AGN)

Definition Glomerulonephritis is a various group of diseases– acute nephritic syndrome. ★ Acute poststreptococcal glomerulonephritis, APSGN (acute nephritis) Definition Glomerulonephritis is a various group of diseases– acute nephritic syndrome. ★ Acute poststreptococcal glomerulonephritis, APSGN (acute nephritis)

● Incidence age: in 5 ~14 years old ● peak age: 3~7 years old ● Boys > girls = 2:1 ● Incidence peak: Jan. Feb. Sep. and Oct. ● Incidence age: in 5 ~14 years old ● peak age: 3~7 years old ● Boys > girls = 2:1 ● Incidence peak: Jan. Feb. Sep. and Oct.

Etiology & Pathogenesis ● Bacterial: ▲ group Aβ- hemolytic streptococci, Staphylococci, Pneumococci, Gˉ bacilli Etiology & Pathogenesis ● Bacterial: ▲ group Aβ- hemolytic streptococci, Staphylococci, Pneumococci, Gˉ bacilli

● Viral: influenza virus, mumps virus, Coxsackie virus, ECHO virus and EBV ● Other pathogens fungi etc. ● Viral: influenza virus, mumps virus, Coxsackie virus, ECHO virus and EBV ● Other pathogens fungi etc.

The immunoreaction caused by group Aβ- hemolytic strep- tococci － nephritogenic strans The immunoreaction caused by group Aβ- hemolytic strep- tococci － nephritogenic strans

Circulating immunecomplexes (CIC) Antigens+antibodies In situ immunecomplexes Circulating immunecomplexes (CIC) Antigens+antibodies In situ immunecomplexes

→deposited on glomerular capillaries → complement system activated→ immune mediators and inflammatory mediators →deposited on glomerular capillaries → complement system activated→ immune mediators and inflammatory mediators

Pathology 1. The feature of pathological changes: Diffus, exudative and proliferative inflammation of the glomerulus Pathology 1. The feature of pathological changes: Diffus, exudative and proliferative inflammation of the glomerulus

2. Chief variety Endothelial and mesangial cells proliferation with leukocyte infiltration; immunofluorescence shows granular IgG & C 3 deposits

Electron microscopy ★ Hump-like electron dense deposits on epithelial side of GBM Pathophysiology (Figure) Electron microscopy ★ Hump-like electron dense deposits on epithelial side of GBM Pathophysiology (Figure)

Infection of streptococci Immune complexes Local immune inflammation in glomerular capillaries Stenosis of blood Glomerular filtration capillary cavity membrane injury GFR ↓ Hematuria Proteinuria Oliguria Cylindruria Blood volume↑ Venous pressure↑ Edema Circulatory load↑ Hypertension Infection of streptococci Immune complexes Local immune inflammation in glomerular capillaries Stenosis of blood Glomerular filtration capillary cavity membrane injury GFR ↓ Hematuria Proteinuria Oliguria Cylindruria Blood volume↑ Venous pressure↑ Edema Circulatory load↑ Hypertension

Clinical Manifestations ● Prodromal infections pharyngitis, scarlet fever, Angina, and pyoderma ● Incubation period: about 10 days for pharyngitis, 14~20 days for skin infection Clinical Manifestations ● Prodromal infections pharyngitis, scarlet fever, Angina, and pyoderma ● Incubation period: about 10 days for pharyngitis, 14~20 days for skin infection

1. Typical findings (general case) 1.1. Ordinary symptoms: low grade fever, nausea, debility, malaise, anorexia and vomiting, etc. 1. Typical findings (general case) 1.1. Ordinary symptoms: low grade fever, nausea, debility, malaise, anorexia and vomiting, etc.

1.2 Principal symptoms (nephric signs) a. Edema (nonpiting edema, nephritic edema) Edema is the most common initial sign– Periorbital edema Oliguria may be present 1.2 Principal symptoms (nephric signs) a. Edema (nonpiting edema, nephritic edema) Edema is the most common initial sign– Periorbital edema Oliguria may be present

b. Hematuria Microscopic ~ (most of cases) – >5/hpf, Gross~ (1/3~1/2 cases) – usually tea or cola colored (brownish) urine, continue 1~2 w b. Hematuria Microscopic ~ (most of cases) – >5/hpf, Gross~ (1/3~1/2 cases) – usually tea or cola colored (brownish) urine, continue 1~2 w

肉眼血尿

c.Hypertension: 1/3~2/3 cases Pre-school age>120/80mmHg School age>130/90 mmHg Headache may be present d. Proteinuria: 120/80mmHg School age>130/90 mmHg Headache may be present d. Proteinuria: <3+

2. Severe findings (Severe case) Appear the following symp- toms within 2 w of the onset.

a. Circulatory congestion RR↑, HR↑, fidget, hepa- tomegaly→→dyspnea, jugular phlebectasia, pulmonary edema, gallop rhythm and cardiac dilation a. Circulatory congestion RR↑, HR↑, fidget, hepa- tomegaly→→dyspnea, jugular phlebectasia, pulmonary edema, gallop rhythm and cardiac dilation

Chest X-ray: Enlarged cardiac silhouette, lung markings coarsen (pulmonary vascular congestion)

b. Hypertensive encepha- lopathy BP↑→brain hypoxia and edema b. Hypertensive encepha- lopathy BP↑→brain hypoxia and edema

Smart headache, nausea, vomiting and diplopia or transient blindness → convulsion, coma ● Hypertensive crisis

c. Acute renal insufficiency Severe oliguria or anuria→ temporary azotemia, distur- bance of electrolytes and metabolic acidosis c. Acute renal insufficiency Severe oliguria or anuria→ temporary azotemia, distur- bance of electrolytes and metabolic acidosis

3. Atypical findings (Atypical case) ▲ Extrarenal symptomatic nephritis ▲ Acute nephritis with neph- rotic manifestation ▲ Asymptomatic AGN 3. Atypical findings (Atypical case) ▲ Extrarenal symptomatic nephritis ▲ Acute nephritis with neph- rotic manifestation ▲ Asymptomatic AGN

Laboratory investigations 1. Routine urinalysis RBC↑, 2 + ~ 3 +, > 5/hpf, protein 1 + ~ 3 +, may occur hyaline (or granular or red cell) casts, +/- WBC Laboratory investigations 1. Routine urinalysis RBC↑, 2 + ~ 3 +, > 5/hpf, protein 1 + ~ 3 +, may occur hyaline (or granular or red cell) casts, +/- WBC

2. Blood exam 2.1. Hemogram: initial mild anemia ( due to hemodilution), WBC↑ or normal 2.2. ESR↑ 3. Renal functions: BUN and Cr are normal or slight increase 2. Blood exam 2.1. Hemogram: initial mild anemia ( due to hemodilution), WBC↑ or normal 2.2. ESR↑ 3. Renal functions: BUN and Cr are normal or slight increase

4. Immunologic exam Evidence of recent streptococcal infection— 4.1. ASO↑: 70%~80% of patients, 10~14 days after infected, incidence peak at 3~5w, normal after 3~6 m 4. Immunologic exam Evidence of recent streptococcal infection— 4.1. ASO↑: 70%~80% of patients, 10~14 days after infected, incidence peak at 3~5w, normal after 3~6 m

4.2. ADNase-B: positive rate is high (more than 90% cases ) 4.3. ADPNase 4.4. Ahase 4.2. ADNase-B: positive rate is high (more than 90% cases ) 4.3. ADPNase 4.4. Ahase

5. Serum complement 80%~90% cases– low CH 50 and low C 3 (within 2 w of the onset), normalized in 6~8 w ● If C 3 still low after 8 w — other etiology? 5. Serum complement 80%~90% cases– low CH 50 and low C 3 (within 2 w of the onset), normalized in 6~8 w ● If C 3 still low after 8 w — other etiology?

Course & Prognosis ▲ Course: About 2 w ▲ Routine urine test: returns to normal within 4~6 w ▲ ESR: returns to normal Course & Prognosis ▲ Course: About 2 w ▲ Routine urine test: returns to normal within 4~6 w ▲ ESR: returns to normal within 2~3 m within 2~3 m

▲ Addis count: 4~8 m ▲ Microscopic hematuria may persist for 6 m~ 1 y ▲ Prognosis: most children ( 95 %)have a complete recover, recurrences are rare ▲ Addis count: 4~8 m ▲ Microscopic hematuria may persist for 6 m~ 1 y ▲ Prognosis: most children ( 95 %)have a complete recover, recurrences are rare

Diagnosis Clinical diagnosis —Acute Nephritic Syndrome ▲ Diagnostic point 1. Prodromal infections, evidence of streptococcal infection Diagnosis Clinical diagnosis —Acute Nephritic Syndrome ▲ Diagnostic point 1. Prodromal infections, evidence of streptococcal infection

2. Urine exam: RBC, protein and casts 3. Low C 3 2. Urine exam: RBC, protein and casts 3. Low C 3

Differential Diagnosis 1.Other AGN: e.g. MPGN, IgA nephropathy ( IgAN) 2. Acute exacerbation of chronic nephritis Differential Diagnosis 1.Other AGN: e.g. MPGN, IgA nephropathy ( IgAN) 2. Acute exacerbation of chronic nephritis

3. Rapidly progressive GN 4. Nephrotic syndrome 5. Secondary GN, e.g. HSP nephritis 3. Rapidly progressive GN 4. Nephrotic syndrome 5. Secondary GN, e.g. HSP nephritis

Therapy There is no specific treatment for typical cases. 1. General measures 1.1. Frequent measurement of BP Therapy There is no specific treatment for typical cases. 1. General measures 1.1. Frequent measurement of BP

1.2. Rest treatment Bed rest: within 2 w of onset Slight activities: edema sub- sided, BP be normal and gross hematuria disappeared

Continue to attend school: ESR returns to normal Normal activities: 3 m after the routine urine test be normal Continue to attend school: ESR returns to normal Normal activities: 3 m after the routine urine test be normal

1.3. Diet ★ Edema, hypertension– re- strict sodium – low salt diet (sodium chloride 60 mg/kg/d ), or salt-free diet 1.3. Diet ★ Edema, hypertension– re- strict sodium – low salt diet (sodium chloride 60 mg/kg/d ), or salt-free diet

★ Azotemia: proteins 0.5 g/ kg/d ★ Severe oliguria, BP↑or circulatory congestion: re- stricting fluid intake, chart to record intake and output ★ Azotemia: proteins 0.5 g/ kg/d ★ Severe oliguria, BP↑or circulatory congestion: re- stricting fluid intake, chart to record intake and output

2. Antibiotics Object : to eradicate remnant bacteria in the focuses, but does not alter natural history of AGN PG im, for 10 ~14 days 2. Antibiotics Object : to eradicate remnant bacteria in the focuses, but does not alter natural history of AGN PG im, for 10 ~14 days

3. Symptomatic treatment 3.1. Diuretics HCT 1~2 mg/kg/d, Lasix 1~2 mg/kg/time, q6~8 h (prn) 3. Symptomatic treatment 3.1. Diuretics HCT 1~2 mg/kg/d, Lasix 1~2 mg/kg/time, q6~8 h (prn)

3.2. Antihypertensive medica -tion Systolic pressure>140 mmHg Diastolic pressure>90 mmHg ★ Nifedipine 0.2~0.3 mg/kg/d (Max. 1 mg/kg/d ), bid~tid, po/sublingual 3.2. Antihypertensive medica -tion Systolic pressure>140 mmHg Diastolic pressure>90 mmHg ★ Nifedipine 0.2~0.3 mg/kg/d (Max. 1 mg/kg/d ), bid~tid, po/sublingual

★ Reserpine 0.07 mg/kg/time, po/im, (Max. 1.5 ～ 2 mg/time) →0.02 mg/kg/d, po ★ Captopril 0.3~0.5 mg/kg/d, po, (Max. 5~6 mg/kg/d), bid or tid ★ Reserpine 0.07 mg/kg/time, po/im, (Max. 1.5 ～ 2 mg/time) →0.02 mg/kg/d, po ★ Captopril 0.3~0.5 mg/kg/d, po, (Max. 5~6 mg/kg/d), bid or tid

4. Deal with serious symptoms 4.1. Hypertensive encephalo- pathy ▲ Treatment must be given promptly

Use sodium nitroprusside infusion － 5~10 mg+10%GS 100ml(50~100 ug/ml), 1ug/ kg/min, ≯ 8 ug/kg/min Attention: Survey BP Use sodium nitroprusside infusion － 5~10 mg+10%GS 100ml(50~100 ug/ml), 1ug/ kg/min, ≯ 8 ug/kg/min Attention: Survey BP

4.2. Serious circulatory congestion a. Restrict the intake of water and sodium b. Treatment of hypertension c. Diuretics 4.2. Serious circulatory congestion a. Restrict the intake of water and sodium b. Treatment of hypertension c. Diuretics

4.3. Acute renal insufficiency Lasix 5 mg/kg/time, Fluid 400ml/m 2 /24h, Dialytic treatment 5. Follow-up: measure BP, blood test (C 3, BUN, Cr), urine test 4.3. Acute renal insufficiency Lasix 5 mg/kg/time, Fluid 400ml/m 2 /24h, Dialytic treatment 5. Follow-up: measure BP, blood test (C 3, BUN, Cr), urine test

Prevention Proper treatment of pharyngitis and skin infections; less crowded living conditions. Prevention Proper treatment of pharyngitis and skin infections; less crowded living conditions.

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