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 glomerulonephritisGlomerulonephritis secondary to nephritogenic strains of streptococcustype III hypersensitivity reaction
Light microscopyglomerular hypercellularitye.g.,polymorphonuclear leukocytes
Immunofluorescencediffuse granular pattern on glomerular capillary walls and mesangiumdeposition of IgG, IgM, and C3
Electron microscopyelectron-dense, glomerular subepithelial immune-complex deposits ("humps")
Streptococcus titers and serologies are positive
↓ serum C3 levels
Typically self-resolves
Rapidly progressive glomerulonephritisGoodpasture syndrometype 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 processesgranulomatosis with polyangiitis
microscopic polyangiitis
Light microscopy and immunofluorescencecrescent-shaped deposition offibrin, C3b, glomerular parietal cells, monocytes, andmacrophages
Granulomatosis with polyangiitisPR3-ANCA/c-ANCA positive
Microscopic polyangiitisMPO-ANCA/p-ANCA
Corticosteroids and cyclophosphamide
IgA nephropathy (Berger's disease)IgA immune-complex deposition in glomerular mesangial cells that results in its proliferationpatients present with hematuria and upper respiratory tract or gastrointestinal infection
Light microscopymesangial proliferation
ImmunofluorescenceIgA immune-complex deposition in the mesangium
ACE inhibitor or ARB for proteinuria and hypertension
Alport syndromeCollagen type IV mutation that results in an abnormal basement membranemore commonly an X-linked dominant disorder
characterized by
renal involvement
ocular involvement
sensorineural hearing loss
Electron microscopyglomerular 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 capillariesthis results in proliferation of the mesangium and remodeling of the capillary wall
may be secondary tohepatitis C virus
hepatitis B virus
C3 nephritic factorMPGN type II
Light microscopymesangial proliferation and thickening of the capillary wall
Immunofluorescence"tram-track" appearance
↓ serum C3 and C4 levels
Treat underlying disease in secondary causese.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 tomembranoproliferative glomerulonephritis
Light microscopycapillary"wire-looping"
Electron microscopyimmune complex depositionaffecting thesubendothelial region
maybe intramembranous
Immunofluorescencegranularappearance
Can lead to death in patients with systemic lupus erythematosus
Aggressively treat with steroids

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 offibrin, C3b, glomerular parietal cells, monocytes, andmacrophages	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 tomembranoproliferative glomerulonephritis	Light microscopy capillary"wire-looping" Electron microscopy immune complex depositionaffecting the subendothelial region maybe intramembranous Immunofluorescence granularappearance	Can lead to death in patients with systemic lupus erythematosus Aggressively treat with steroids

Action	Numeric Key	Letter Key	Function Key
Show Bullets		S	Enter (frontside only)
20%	1	N
40%	2	H
60%	3	F	Enter (backside only)
80%	4	E
100%	5	M
Toss	0	T