Nephritic Syndrome

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
Total (recumbent)	6.0-7.8 g/dL
Albumin	3.5-5.5 g/dL
Globulin	2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma	.5-5.0 μU/mL
Thyroidal iodine (¹²³I) uptake	8%-30% of administered dose/24h
Thyroxine (T4), serum	5-12 μg/dL
Triglycerides, serum	35-160 mg/dL
Triiodothyronine (T3), serum (RIA)	115-190 ng/dL
Triiodothyronine (T3) resin uptake	25%-35%
Urea nitrogen, serum	7-18 mg/dL
Uric acid, serum	3.0-8.2 mg/dL

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

(M1.RL.85) Three weeks after recovering from pharyngitis, a nine-year-old girl presents with periorbital edema and dark brown urine. An image of the kidney biopsy is shown in Figure A. What is responsible for these changes? Review Topic

QID: 101039

FIGURES:

Glomerular basement membrane lamellation

(1/11)

IgA deposition and subsequent mesangial proliferation

(1/11)

Neutrophil infiltration in response to immune complex deposition along the glomerulus basement membrane and mesangium

82%

(9/11)

Loss of negative charge on the glomerular basement membrane

(0/11)

Widespread intermembraneous deposits due to an autoantibody against C3 convertase

(0/11)

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PREFERRED RESPONSE 3

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(M1.RL.32) A 9-year-old Caucasian girl presents to your office with hematuria. An electron micrograph of her renal biopsy is shown below in Figure A. Which of the following is the most likely composition of the structures marked by the white arrows? Review Topic

QID: 100986

FIGURES:

Albumin

(2/80)

Non-enzymatic glycosylation

(1/80)

IgA

10%

(8/80)

IgG

(6/80)

IgG, IgM, C3

75%

(60/80)

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(M1.RL.4671) A 62-year-old man presents to his primary care doctor complaining of recent-onset hemoptysis. He has not had any fevers, night sweats, or weight loss. He recently traveled to Italy with his wife. He has a 5 pack-year smoking history. On review of systems, he reports that his urine has been “red-tinged” for several months. Urinalysis reveals the findings shown in Figure A. He is referred to a nephrologist and undergoes a renal biopsy. Immunofluorescence staining of the biopsy is shown in Figure B. Which of the following is the most likely underlying pathogenesis of his disease? Review Topic

QID: 107162

FIGURES:

Type III hypersensitivity reaction

12%

(8/64)

Antibodies to collagen type IV

69%

(44/64)

Presence of C-ANCA

16%

(10/64)

Mycobacterial infection

(0/64)

Metastatic malignancy

(0/64)

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PREFERRED RESPONSE 2

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(M1.RL.67) A 21-year-old male presents to your office with hematuria 3 days after the onset of a productive cough and fever. Following renal biopsy, immunofluorescence shows granular IgA deposits in the glomerular mesangium. Which of the following do you suspect in this patient? Review Topic

QID: 101021

Lipoid nephrosis

(1/15)

Berger’s disease

93%

(14/15)

Poststreptococcal glomerulonephritis

(0/15)

Systemic lupus erythematosus

(0/15)

HIV infection

(0/15)

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PREFERRED RESPONSE 2

(M1.RL.11) Multiple patients present to your office with hematuria following an outbreak of Group A Streptococcus. Biopsy reveals that all of the patients have the same disease, characterized by large, hypercellular glomeruli with neutrophil infiltration. Which patient has the best prognosis? Review Topic

QID: 100965

65-year-old nulliparous woman

(1/95)

50-year-old man with a history of strep infection

(6/95)

8-year-old boy who undergoes no treatment

74%

(70/95)

38-year-old man with sickle cell trait

(3/95)

18-year-old man treated with corticosteroids

12%

(11/95)

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PREFERRED RESPONSE 3

(M1.RL.35) A 6-year-old boy presents to your office with hematuria. Two weeks ago the patient had symptoms of a sore throat and fever. Although physical exam is unremarkable, laboratory results show a decreased serum C3 level and an elevated anti-DNAse B titer. Which of the following would you most expect to see on renal biopsy? Review Topic

QID: 100989

Large, hypercellular glomeruli on light microscopy

76%

(13/17)

Polyclonal IgA deposition on immunofluorescence

(1/17)

Immune complex deposits with a "spike and dome" appearance on electron microscopy

(0/17)

Wirelooping and hyaline thrombi on light microscopy

(0/17)

Antibodies to GBM resulting in a linear immunofluorescence pattern

(1/17)

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PREFERRED RESPONSE 1

(M1.RL.86) A 37-year-old man presents with significant hematuria and hemoptysis. The results of the immunoflouresence are shown in Figure A. What pathologic changes would be expected under light microscopy? Review Topic

QID: 101040

FIGURES:

"Wire looping" of the capillaries

(1/16)

Hypercellular glomeruli

(0/16)

Crescentic glomerulonephritis

88%

(14/16)

Focal proliferative glomerulonephritis

(1/16)

Normal glomeruli

(0/16)

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PREFERRED RESPONSE 3

(M1.RL.73) A 25-year-old male visits his primary care physician with complaints of hemoptysis and dysuria. Serum blood urea nitrogen and creatinine are elevated, blood pressure is 160/100 mm Hg, and urinalysis shows hematuria and RBC casts. A 24-hour urine excretion yields 1 gm/day protein. A kidney biopsy is obtained, and immunofluorescence shows linear IgG staining in the glomeruli. Which of the following antibodies is likely pathogenic for this patient’s disease? Review Topic

QID: 101027

Anti-DNA antibody

(0/13)

Anti-neutrophil cytoplasmic antibody (C-ANCA)

15%

(2/13)

Anti-neutrophil perinuclear antibody (P-ANCA)

(0/13)

Anti-glomerular basement membrane antibody (Anti-GBM)

69%

(9/13)

Anti-phospholipid antibody

(0/13)

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Alport Syndrome

Nephritic vs Nephrotic Syndrome

Rapidly Progressive Glomerulonephritis