Kdigo CMKD CC Speakers Guide v4 July 17 Final

KDIGO 2016 Controversies Conference
ATYPICAL HEMOLYTIC
UREMIC SYNDROME
AND
C3 GLOMERULOPATHY
This presentation is based on: Goodship T. et al., Kidney Intl (2017) 91:539-551.
SUPPORTED BY
The content of this presentation reflects the position of the authors of the original
paper. It does not reflect the official opinion of Alexion or Achillion and should not be
viewed as a position endorsed by them. Responsibility for the information and views
expressed in this presentation lies entirely with the authors.
Disclaimer: Eculizumab is not currently approved for the treatment of C3G.
Kidney Disease: Improving Global Outcomes

PART 1:
INTRODUCTION

THE ROLES OF COMPLEMENT
Ricklin D, et al. Nat Rev Nephrol 12: 383-401, 2016.

ATYPICAL HEMOLYTIC UREMIC
SYNDROME (aHUS)
• Ultra-rare disease characterized by acute kidney injury (AKI),
thrombocytopenia, and microangiopathic hemolytic anemia.
• At least 50% of aHUS patients have an underlying inherited
and/or acquired complement abnormality.
• Eculizumab, a humanized mAb against C5, makes it possible to
control aHUS and prevent development of ESRD in the
majority of patients.

C3 GLOMERULOPATHY (C3G)
• C3G comprises a group of kidney diseases driven by
uncontrolled activation of the complement cascade that leads
to C3 deposition within the glomerulus.
• The dysregulation of C3 convertase is driven by genetic and/or
acquired defects.
• A biopsy is required to make the diagnosis.
• Two major subtypes are recognized: dense deposit disease
(DDD) and C3 glomerulonephritis (C3GN).

COMPLEMENT DYSREGULATION IN
C3G & aHUS
Mastellos DC, et al. Trends in Immunology 38: 383-394, 2017

SECTION A
Atypical Hemolytic Uremic

Syndrome (aHUS)

PART 2:
RENAL PATHOLOGY: aHUS

aHUS PATHOLOGY
• aHUS is a thrombotic microangiopathy (TMA).
• Pathology resembles tissue responses to endothelial injury.
• The presence of C5b-9 staining is not a reliable indicator of
aHUS.
• In general, it is not possible to determine etiology from
morphology.

MORPHOLOGICAL FEATURES IN
MICROANGIOPATHY
Active Lesions Chronic Lesions
Glomeruli Glomeruli
 Thrombi  Double contours of peripheral capillary walls by
 Endothelial swelling or denudation LM, with variable mesangial interposition
 Fragmented red blood cells  New subendothelial basement membrane by EM
 Subendothelial flocculent material by EM  Widening of the subendothelial zone by EM
 Mesangiolysis
 Microaneurysms
Arterioles Arterioles
 Thrombi  Hyaline deposits
 Endothelial swelling or denudation
 Intramural fibrin
 Fragmented red blood cells
 Intimal swelling
 Myocyte necrosis
Arteries Arteries
 Thrombi  Fibrous intimal thickening with concentric
 Myxoid intimal swelling lamination (onion skin)
 Intramural fibrin
 Fragmented red blood cells


aHUS CASE STUDY
• 30-y.o. male, 2-week history of general malaise, presented with AKI
(plasma creatinine (Cr) 250 µmol/L) and microangiopathic hemolytic
anemia (hemoglobin (Hb) 9.5 g/dL and fragmented cells on a peripheral
blood film).
• Platelet count 130 x 109/L.
• Renal biopsy showed endothelial swelling and denudation,
mesangiolysis, double contours of the glomerular basement membrane
and subendothelial accumulation of electron-lucent, flocculent material.
• No evidence of intraluminal thrombus.
• Patient’s maternal grandmother had developed kidney failure after the
delivery of her second child.

aHUS CASE STUDY
Which of the following are correct?
A. The renal biopsy appearances are not compatible with a
diagnosis of aHUS.
B. Screening for secondary causes of a renal thrombotic
microangiopathy should be undertaken.
C. Genetic screening for inherited complement abnormalities
should be undertaken.
D. The family history is not relevant.
E. Treatment with high-dose steroids should be commenced.
F. Both B and C.
G. Both D and E.

PART 3:
CLINICAL PHENOTYPE AND
ASSESSMENT: aHUS

aHUS: PRESENTATION
• Current classifications of aHUS reflect a better understanding of
disease mechanisms, including the impact of genetic background
and etiologic triggers.
• Precipitating factors include autoimmune conditions, transplants,
pregnancy, infections, drugs, and metabolic conditions.
• The time course and persistence of an aHUS episode are not well
understood.
• Many patients appear to be at life-long risk for the recurrent
acute presentation of aHUS.
• Disease penetrance for an acute episode of aHUS in carriers of
known pathogenic mutations increases with age.

aHUS: EXTRARENAL MANIFESTATIONS
• Extrarenal manifestations are reported in up to 20% of
patients.
• It is unclear whether these manifestations are a direct
consequence of complement activation, TMA, or other factors
such as severe hypertension and uremia. (Suppl Table 1)

aHUS: EXTRARENAL MANIFESTATIONS
• Digital gangrene, skin
• Cerebral artery thrombosis/stenosis
• Extracerebral artery stenosis
• Cardiac involvement/myocardial infarction
• Ocular involvement
• Neurologic involvement
• Pancreatic, gastrointestinal involvement
• Pulmonary involvement
• Intestinal involvement

aHUS: LABORATORY ANALYSIS
• Investigations should focus on determining the underlying
etiology and excluding other diagnoses.
• Measure ADAMTS13 activity to diagnose or exclude
thrombotic thrombocytopenic purpura (TTP).
o Because the incidence of TTP is much lower in children than in adults,
expert opinion recommends that in children, treatment with
eculizumab should not be delayed while ADAMTS13 activity is being
determined; however, signs of nonresponse should be carefully
monitored.
• Investigation for STEC-HUS should be routine in all patients
with presumed aHUS.

aHUS: LABORATORY ANALYSIS
• Serum/plasma levels of complement proteins should be
measured in all patients with primary aHUS prior to plasma
therapy.
o C3 levels will be low in 30-50% of aHUS cases.
o Low C3 levels are also noted in acute STEC-aHUS and pneumococcal
aHUS.
• Complement split products and assays of complement
function can also be obtained, although the significance of
some of these assays requires further study.

aHUS CASE STUDY
24-y.o. female presented with:
• AKI (Cr 500 µmol/L)
• thrombocytopenia (platelet count 50 x 109/L); and
• a microangiopathic haemolytic anaemia, following a 2-week
history of intermittent diarrhea.

aHUS CASE STUDY
Which of the following investigations should be undertaken to
elucidate the cause of illness?
A. Measure serum levels of C3 and C4.
B. Measure ADAMTS13 activity.
C. Screen for STEC infection.
D. Screen for factor H autoantibodies.
E. Screen for anticardiolipin antibodies.
F. All of the above.
G. None of the above.

PART 4:
GENETIC AND ACQUIRED
DRIVERS OF DISEASE: aHUS

aHUS: GENETIC DRIVERS OF DISEASE
• Studies of hundreds of aHUS patients have provided an
excellent understanding of genetic drivers of disease, leading
to the development of individualized care.
• Genetic screening and molecular diagnostics, with expert
interpretation of the results, should inform therapeutic
decisions.

aHUS: GENETIC TESTING
• The minimum set of genes that should be screened includes
CFH, CD46, CFI, C3, CFB, THBD, CFHR1, CFHR5, and DGKE.
• Genetic testing should also include the risk haplotypes CFH-
CFHR3 and MCPggaac as they modify disease penetrance and
severity.
o Delays in obtaining results from genetic or molecular diagnostic studies
should not prevent a clinical diagnosis or postpone treatment, as early
anticomplement treatment is crucial to preserve renal function and
avoid irreversible sequelae.
• Technologies to detect copy number variation, hybrid genes and
other complex genomic rearrangements in the CFH/CFHRs
genomic region must be included in the genetic testing.

aHUS: GENETIC TESTING
• Genetic analysis is essential in living-related kidney donor
transplantation.
o Transplantation from living-related kidney donors should only be
considered if causative genetic or acquired factors are clearly
identified in the recipient and the related donor is free of these
factors.
• Genetic testing is recommended for patients in whom
discontinuation of eculizumab is being considered.

UNDERSTANDING GENETIC VARIANTS
• Genetic variants should be classified as “benign,” “likely
benign,” “variant of uncertain significance (VUS),” “likely
pathogenic,” or “pathogenic,” following international
guidelines.
• Pathogenic variants compromise protection of host
endothelial cells and platelets from complement
damage/activation.

aHUS: ACQUIRED DRIVERS OF DISEASE
• Acquired drivers of disease are autoantibodies to complement
proteins or protein complexes that impair normal function.
• The best-studied acquired drivers are FH autoantibodies,
which are usually seen in association with deletion of the
CFHR3 and CFHR1 genes.
o The deletion of CFHR3 and CFHR1 is a common copy number variation
that can be identified on genetic testing.
o The finding of FH autoantibodies should be confirmed in a second
sample at least 4 weeks after the initial sample.

aHUS: ACQUIRED DRIVERS OF DISEASE
• Testing should also be performed in the pre-renal transplant
period.
• In pediatric patients, FH autoantibody assays should be
performed following consensus guidelines: at diagnosis and if
positive, at day 7, 14, 28, monthly and one year.
• Relapses of anti-FH associated HUS occur in about 20-25%
patients.

aHUS CASE STUDY
• 35-y.o. female presented with AKI, thrombocytopenia, and a
microangiopathic hemolytic anemia.
• Treated with eculizumab and made a full recovery.
• On genetic screening, she was found to carry a heterozygous
CFH/CFHR1 hybrid gene.
• Family history:
 Both parents alive.
 Two brothers and 3 sisters.
 Two children aged 6 and 2.

aHUS CASE STUDY
A. Other members of the family are not at risk of developing aHUS.
B. There is no need to offer screening to other family members for
the CFH/CFHR1 hybrid gene.
C. The finding of the CFH/CFHR1 hybrid gene in an unaffected family
member has no implications for that individual.
D. Family members should be offered genetic counselling.
E. aHUS can present at any age in unaffected carriers of the
CFH/CFHR1 hybrid gene.
F. Both A and C.
G. Both D and E.

PART 5:
TREATMENT STRATEGIES:
aHUS

aHUS: TREATMENT
• All patients with a clinical diagnosis of primary aHUS are
eligible for treatment with eculizumab.
o The dosing schedule reported in the trials that led to the approval of
eculizumab should be followed.
• Treatment duration is controversial as there is no evidence to
support life-long therapy in all aHUS patients.

aHUS: TREATMENT
• Two options for long-term dosing have been considered:
o The minimal dose required to achieve complement blockade.
o A discontinuation dosing schedule.
• No data exist to support either option, and both require

monitoring of complement activity.
• There are no data to inform the frequency of testing
• Dose reduction or discontinuation require ongoing monitoring of
complement activity.
• In patients who have undergone transplant, especially patients
who have lost previous allografts, discontinuation is not
recommended.

aHUS: TREATMENT
• If access to eculizumab is unavailable, plasma therapy can be
used.
• The use of plasma exchange when eculizumab is available
may be associated with some improvement, but delaying use
of eculizumab may lead to a suboptimal therapeutic outcome.
• Eculizumab increases the risk of meningococcal infection.
o Patients should receive vaccination against meningococcus (including
Type B); however, vaccination should not delay the start of eculizumab
therapy.
o Antibiotic prophylaxis is mandated during the first 2 weeks.

aHUS TREATMENT: TRANSPLANT
• Kidney transplantation should be delayed for at least 6
months after the start of dialysis as limited renal recovery is
possible several months after starting eculizumab.
• Living-related kidney donation carries a risk for recurrence in
the recipient and a risk of de novo disease in the donor should
the donor carry an at-risk genetic variant.
• Liver transplant remains an option in patients with liver-
derived complement protein abnormalities, in particular for
renal transplant recipients with uncontrolled disease activity
despite eculizumab therapy.

Clinical diagnosis
of
aHUS
High titer
FH autoantibody11
Plasma therapy22 Eculizumab

aHUS CASE STUDY
• 44-y.o. male on hemodialysis for 15 years.
• Primary renal disease is aHUS.
• Received two cadaver renal transplants, both of which were lost
within 3 months of transplantation to recurrent disease despite
treatment with plasma exchange.
• Genetic screening showed a heterozygous mutation in factor H,
which has been reported previously in six other patients with
aHUS.
• Being considered for a third transplant.

aHUS CASE STUDY
A. Prophylactic use of eculizumab immediately before and then
long-term after the transplant is unlikely to prevent disease
recurrence in the transplanted kidney.
B. Prophylactic plasma exchange immediately before and then
long-term after the transplant is highly likely to prevent disease
recurrence after the transplant.
C. A living-related transplant should not be considered under any
circumstances.
D. If he receives prophylactic eculizumab, he should be vaccinated
against meningococcus.

aHUS RESEARCH RECOMMENDATIONS:
o A comparative study ofSUMMARY
biopsies from patients with well-documented
malignant hypertension and patients with well-documented
alternative complement pathway disease.
o A longitudinal study of patients with features of chronic
microangiopathy on biopsy but without a history of acute
presentation.
• Clinical studies
o Define how complement biomarkers correlate with current or
impending aHUS relapse and/or renal involvement.
o Identify risk factors for relapse upon cessation of anti-complement
therapy.
o Identify alternative anti-complement therapeutics.

SECTION B
C3 Glomerulopathy (C3G)

PART 2:
RENAL PATHOLOGY: C3G

C3G PATHOLOGY
• The C3G disease spectrum is caused by abnormal control of
complement activation, deposition or degradation that results
in predominant glomerular C3 fragment deposition.
• A renal biopsy using immunofluorescence (IF) is required to
diagnose C3G.
• Electron microscopy (EM) is used to sub-classify C3G as DDD
or C3GN.

MORPHOLOGICAL FEATURES
Light Microscopy
Active lesions
• Mesangial expansion with or without hypercellularity
• Endocapillary hypercellularity including monocytes and/or neutrophils
• Capillary wall thickening with double contours (the combination of capillary wall thickening and
mesangial increase is referred to as a membranoproliferative pattern)
• Necrosis
• Cellular/fibrocellular crescents

Chronic lesions
• Segmental or global glomerulosclerosis
• Fibrous crescents
Immunofluorescence Microscopy
• Typically dominant C3 staining
Electron Microscopy
• DDD: Dense osmiophilic mesangial and intramembranous electron dense deposits
• C3GN: Amorphous mesangial with or without capillary wall deposits including subendothelial,
intramembranous and subepithelial electron dense deposits
• Sub-epithelial ‘humps’ may be seen in both DDD and C3GN

C3G PATHOLOGY: CONTROVERSIES
• Correlations between renal biopsy appearances, etiology, and
clinical outcome are ill-defined.
• IF staining is subjective and semiquantitative.
o Well-defined for dense deposit disease (DDD).
o Not clear if characteristic for C3 glomerulonephritis (C3GN).
• Distinguishing DDD and C3GN by EM can be difficult.

C3G CASE STUDY
• 7-y.o.male with 3-day h/o macroscopic hematuria 4-wk after
being culture-positive for Group A β-hemolytic Strep pharyngitis.
• Normal blood pressure and urine output, no edema.

• Urinalysis: numerous RBCs; RBC casts; 4+ protein; negative
leukocytes and nitrites.
• Serum Cr 1.0 mg/dL (normal 0.2-0.6 mg/dL); normal electrolytes
and albumin.
• ASO elevated (1240 IM/mL [normal <150 IU/mL]); ANA negative;
C3 39 mg/dL (normal 87-181 mg/dL).
• FH: negative for renal disease.

C3G CASE STUDY
• Diagnosed with APSGN and monitored as an outpatient. One
month later, creatinine has improved to 0.7 mg/dL, UPC ratio is
0.7 (normal <0.2), and C3 is 22 mg/dL.
What would you do now?
A. Get a renal biopsy.
B. Continue to monitor and get a renal biopsy 3 months after
onset if C3 has not improved.
C. Start an oral course of prednisone at 2 mg/kg/day.
D. Get genetic testing.
E. Get comprehensive complement studies.

PART 3:
CLINICAL PHENOTYPE AND
ASSESSMENT: C3G

C3G: PRESENTATION
• C3G generally follows a chronic, indolent course with
persistent AP activation resulting in a 10-year renal survival of
approximately 50%.
• There are, however, cases of C3G that present as a rapidly
progressive GN.

C3G: EXTRARENAL MANIFESTATIONS
• Acquired partial lipodystrophy (APL) and retinal drusen are
reported and appear to be direct consequences of
complement activation.

C3G: LABORATORY ANALYSIS
• Serum/plasma levels of complement proteins should be
measured in all patients with C3G prior to plasma therapy.
o C3 levels will be low in 30-50% of aHUS cases and up to 75% of C3G
cases.
• Complement split products and assays of complement
function can also be obtained, although the significance of
some of these assays requires further study.

C3G CASE STUDY
• 33-y.o.female with a diagnosis of DDD.
• Ophthalmologic examination showed drusen.
• Complement labs showed:
 C3, <0.15 g/L (normal 0.9-1.8g/L); C3c, 3.3mg/L (normal <2.0 mg/L)
 B, 23.9 mg/L (normal 22-50 mg/dL); Bb, 2.3 mg/L (normal <2.2mg/L)
 C5, 12 mg/dL (normal 10-21 mg/dL); soluble C5b-9, 0.25mg/L (normal
<0.3mg/L)
 CH50, <5 U/ml (normal 30-90 U/ml); alternative pathway functional assay
(APFA) 0% (normal 50-130%)

C3G CASE STUDY
What do these results mean?
A. There is no ongoing complement activity.
B. The ongoing complement activity is primarily at the level of the
alternative pathway.
C. The ongoing complement activity is primarily at the level of the
classical pathway.
D. The ongoing complement activity is primarily at the level of the
terminal pathway.

PART 4:
GENETIC AND ACQUIRED
DRIVERS OF DISEASE: C3G

C3G: GENETIC DRIVERS OF DISEASE
• Understanding of the genetics of C3G is not yet comparable to
that of aHUS.
• There is no clear benefit to performing genetic analysis in all
cases of C3G.

C3G: GENETIC TESTING
• The minimum set of genes that should be screened includes
CFH, CD46, CFI, C3, CFB, THBD, CFHR1, CFHR5, and DGKE.
• Technologies to detect copy-number variation, hybrid genes,
and other complex genomic rearrangements in the
CFH/CFHRs genomic region must be included in the genetic
testing.

C3G: GENETIC TESTING
• Genetic analysis is essential in living-related kidney donor
transplantation.
o All planned recipients of a living-related kidney should be screened. If
a genetic abnormality is found, the donor should be tested to exclude
that genetic abnormality.

UNDERSTANDING GENETIC VARIANTS
• Genetic variants should be classified as “benign,” “likely
benign,” “variant of uncertain significance (VUS),” “likely
pathogenic,” or “pathogenic,” following international
guidelines.
• C3G appears mechanistically more complex than aHUS.
o There is limited information about genotype/phenotype correlations
to distinguish different C3G subtypes, inform prognosis and/or
recommend treatment.

C3G: ACQUIRED DRIVERS OF DISEASE
• Acquired drivers of disease are autoantibodies to complement
proteins or protein complexes that impair normal function.
• In C3G, the most common autoantibodies are to C3
convertase, a serine protease formed from C3b and Bb.
o These autoantibodies are called C3Nefs.
o They stabilize C3 convertase and prolong its half-life.
• Other antibodies in C3G include FH autoantibodies, C4Nefs

and C5Nefs.
• In older adults, serum free light chains (FLC) should be
assayed.

C3G CASE STUDY
• 24-y.o.male with a diagnosis of DDD on hemodialysis.
• Planning living-related donor transplant from sibling.
• Family history: Cousin also on dialysis.
• Genetic testing identified:
 An ultra-rare variant in the complement factor H gene, CFH c.3229T>C,
which substitutes Cys at position 1077 for Arg (p.Cys1077Arg); this is
classified as a VUS (variant of uncertain significance).
 A common copy-number variant (CNV) in which one copy of the
complement factor H–related 3 and –related 1 genes are deleted
(delCFHR3-CFHR1).

C3G CASE STUDY
What do these results mean and what would you do?
A. These results can be dismissed.
B. He should not receive a kidney transplant because factor H is
synthesized by the liver, and his disease will recur.
C. The donor sibling should be screened for the complement
factor H gene variant and, if found, he should be excluded from
donating.
D. The donor sibling should be screened for the complement
factor H gene variant and, if found, he should be cleared to
donate.

PART 5:
TREATMENT STRATEGIES: C3G

C3G TREATMENT: ALL PATIENTS
All Patients • Optimal blood pressure control (suggested blood pressure below the 90% in children and ≤120/80 in adults)
o Priority agents include angiotensin converting enzyme inhibitors and angiotensin receptor blockers
 Optimal nutrition for both normal growth in children, healthy weight in adults
 Lipid control
Moderate Disease Description
 Urine protein over 500 mg/24 hours despite supportive therapy
OR
 Moderate inflammation on renal biopsy
OR
 Recent increase in serum creatinine suggesting risk for progressive disease

Recommendation
 Prednisone
 Mycophenolate mofetil
Severe Disease Description
 Urine protein over 2000 mg/24 hours despite immunosuppression and supportive therapy
OR
 Severe inflammation represented by marked endo- or extracapillary proliferation with or without crescent formation
despite immunosuppression and supportive therapy
OR
 Increased serum creatinine suggesting risk for progressive disease at onset despite immunosuppression and supportive
therapy

Recommendation
 Methylprednisolone pulse dosing as well as other anti-cellular immune suppressants have had limited success in rapidly
progressive disease
 Data are insufficient to recommend eculizumab as a first-line agent for the treatment of rapidly progressive disease

C3G: TREATMENT
• A retrospective study supports the effectiveness of
mycophenolate mofetil in C3GN patients.
• No specific recommendation can be made for plasma therapy
or rituximab (an anti-CD20 antibody).
• Since the pathogenesis of C3G is due to dysregulation and
hyperactivity of the alternative pathway of complement,
eculizumab has been tried in a limited number of patients
with varied results.

C3G TREATMENT: TRANSPLANT
• No specific data are available to inform decisions surrounding
transplantation in C3G.
• Recommendations reflect expert opinion and limited case
reports.
• C3G recurs in allografts at a high rate, leading to graft loss in
~50% of patients.

C3G CASE STUDY
• 32-y.o. male with C3GN diagnosed 2 years ago.
• On ACEs and ARBs with good control of HTN but increasing
proteinuria and decreasing renal function.
 CKD G3 with eGFR 45 mL/min/1.73 m2
• Complement studies:
 No rare genetic variants identified in CFH, CD46, CFI, C3, CFB, THBD,
CFHR1, CFHR5, and DGKE
 C3, <0.55g/L (normal 0.9-1.8 g/L; C3c, 2.2mg/L (normal <2.0 mg/L); C5,
8.5 mg/dL (normal 10-21 mg/dL); soluble C5b-9, 5.45 mg/L (normal
<0.3 mg/L); CH50, <26 U/mL (normal 30-90 U/mL); APFA (alternative
pathway functional assay 3% (normal 50-130%)
 C3Nef +2; C5Nef +4

C3G CASE STUDY
What would you do next?
A. Add rituximab.
B. Begin plasma exchange.
C. Add mycophenolate mofetil.
D. Add eculizumab.

C3G RESEARCH RECOMMENDATIONS:
• SUMMARY
A multicenter study analyzing biopsies to define the
relationship of morphology to etiology, clinical course, and
response to therapy.
• Comprehensive genetic testing to fill the knowledge gap in
establishing robust phenotype-genotype correlations.
• Clinical studies
o Assess the value of proximal (at the level of the AP) anti-complement
therapy.
 Development and trial of novel complement inhibitors.
o Determine value of complement biomarkers to inform clinical
outcome in C3G patients and stratify them into targeted treatment
groups.

CONCLUSIONS
• While there are knowledge gaps in both aHUS and C3G, the
evidence base for the management of patients with C3G lags
behind that of aHUS; addressing this disparity should be a
priority.
• Although these two diseases are presented as distinct entities,
there is substantial overlap in their pathogenesis and clinical
presentation.

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KDIGO 2016 Controversies Conference

Disclaimer: Eculizumab is not currently approved for the treatment of C3G.

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Ricklin D, et al. Nat Rev Nephrol 12: 383-401, 2016.

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Mastellos DC, et al. Trends in Immunology 38: 383-394, 2017

Kidney Disease: Improving Global Outcomes

Atypical Hemolytic Uremic

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

• No data exist to support either option, and both require

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Plasma therapy22 Eculizumab

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

• Distinguishing DDD and C3GN by EM can be difficult.

Kidney Disease: Improving Global Outcomes

• Normal blood pressure and urine output, no edema.

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes

Kidney Disease: Improving Global Outcomes