Nephritic Syndrome - Renal - Medbullets Step 1

Snapshot

A 14-year-old boy presents with hematuria, problems with vision, and deafness. Approximately 2 weeks prior to symptom development, he recovered from a viral upper respiratory tract infection. Family history is significant for deafness and early initiation of lisinopril in his father. His temperature is 99°F (37.2°C), blood pressure is 140/90 mmHg, pulse is 75/min, and respirations are 18/min. Physical examination is signifcant for anterior lenticonus and sensorineural hearing loss. Urinalysis demonstrates dysmorphic red blood cells and red blood cell casts. (Alport syndrome)

Introduction

Clinical definition
- renal disease secondary to an inflammatory process injuring the glomerulus
  - this results in damage involving the
    - basement membrane
    - capillary endothelium
    - mesangium
Presentation
- symptoms
  - hypertension
  - hematuria
  - oliguria
  - headache
- physical exam
  - edema
    - can be peripheral and/or periorbital
Diagnosis
- studies
  - complete blood cell count
    - anemia may be noted
  - azotemia
  - complement levels
    - C3, C4, and CH50 should be obtained
  - urinalysis
    - dysmorphic red blood cells (RBCs)
      - suggests hematuria is of glomerular origin
    - RBC casts
    - subnephrotic range proteinuria (< 3.5 g/day)
      - if the nephritic syndrome is severe enough it can lead to nephrotic range proteinuria (> 3.5 g/day)
- renal biopsy
  - may be necessary to arrive to a definitive diagnosis and to determine prognosis

Nephritic Syndrome
Type	Pathophysiology	Renal Biopsy	Diagnostic Studies and Treatment
Acute poststreptococcal glomerulonephritis	Glomerulonephritis secondary to nephritogenic strains of streptococcus type III hypersensitivity reaction	Light microscopy glomerular hypercellularity e.g., polymorphonuclear leukocytes Immunofluorescence diffuse granular pattern on glomerular capillary walls and mesangium deposition of IgG, IgM, and C3 Electron microscopy electron-dense, glomerular subepithelial immune-complex deposits ("humps")	Streptococcus titers and serologies are positive ↓ serum C3 levels Typically self-resolves
Rapidly progressive glomerulonephritis	Goodpasture syndrome type II hypersensitivity anti-GBM antibodies against α3-chain of collagen type IV antibodies to the alveolar basement membrane result in hemoptysis and lung disease Pauci-immune processes granulomatosis with polyangiitis microscopic polyangiitis	Light microscopy and immunofluorescence crescent-shaped deposition of fibrin, C3b, glomerular parietal cells, monocytes, and macrophages	Granulomatosis with polyangiitis PR3-ANCA/c-ANCA positive Microscopic polyangiitis MPO-ANCA/p-ANCA Corticosteroids and cyclophosphamide
IgA nephropathy (Berger's disease)	IgA immune-complex deposition in glomerular mesangial cells that results in its proliferation patients present with hematuria and upper respiratory tract or gastrointestinal infection	Light microscopy mesangial proliferation Immunofluorescence IgA immune-complex deposition in the mesangium	ACE inhibitor or ARB for proteinuria and hypertension
Alport syndrome	Collagen type IV mutation that results in an abnormal basement membrane more commonly an X-linked dominant disorder characterized by renal involvement ocular involvement sensorineural hearing loss	Electron microscopy glomerular basement membrane lamellation "basket weave" appearance	No curative treatment
Membranoproliferative glomerulonephritis (MPGN)	Immune-complex and/or complement protein deposition in the mesangium and subendothelium of the capillaries this results in proliferation of the mesangium and remodeling of the capillary wall may be secondary to hepatitis C virus hepatitis B virus C3 nephritic factor MPGN type II	Light microscopy mesangial proliferation and thickening of the capillary wall Immunofluorescence "tram-track" appearance	↓ serum C3 and C4 levels Treat underlying disease in secondary causes e.g., control of hepatitis C virus infection
Diffuse proliferative glomerulonephritis (DPGN)	> 50% of glomeruli (thus diffuse) demonstrates an inflammatory process on histology Common in patients with systemic inflammatory diseases (e.g., systemic lupus erythematosus) can be secondary to membranoproliferative glomerulonephritis	Light microscopy capillary "wire-looping" Electron microscopy immune complex deposition affecting the subendothelial region maybe intramembranous Immunofluorescence granular appearance	Can lead to death in patients with systemic lupus erythematosus Aggressively treat with steroids

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²