Current concepts in C3 glomerulopathy

Thomas, Sajan; Ranganathan, Dwarakanathan; Francis, Leo; Madhan, K.; John, George T.

doi:10.4103/0971-4065.134089

Cited by 17 publications

(11 citation statements)

References 61 publications

(85 reference statements)

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“…C3 glomerulopathy (C3G) is an emerging kidney disease caused by dysregulation of the alternative complement pathway [ 1 – 5 ]. The characteristic pathology of this disease is glomerular depositions of dominant C3 with absent or weak immunoglobulins [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Given that C3G is defined by predominant glomerular C3 deposition (two orders greater than immunoglobulins), other glomerulonephritis types, particularly those that are immune complex-mediated, occasionally fit this criterion, too. Table 1 summarizes the clinical and histopathological features of DDD [ 5 , 32 , 46 , 52 – 56 ], C3GN [ 5 , 32 , 46 , 52 , 57 ], and PIGN [ 52 , 58 – 61 ].…”

Section: Introductionmentioning

confidence: 99%

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C3 glomerulopathy and current dilemmas

2016

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C3 glomerulopathy (C3G) is a recently identified disease entity caused by dysregulation of the alternative complement pathway, and dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory detection of complement dysregulation is still uncommon in practice, “dominant C3 deposition by two orders greater than that of immunoglobulins in the glomeruli by immunofluorescence”, as stated in the consensus report, defines C3G. However, this morphological definition possibly includes the cases with glomerular diseases of different mechanisms such as post-infectious glomerulonephritis. In addition, the differential diagnosis between DDD and C3GN is often difficult because the distinction between these two diseases is based solely on electron microscopic features. Recent molecular and genetic advances provide information to characterize C3G. Some C3G cases are found with genetic abnormalities in complement regulatory factors, but majority of cases seem to be associated with acquired factors that dysregulate the alternative complement pathway. Because clinical courses and prognoses among glomerular diseases with dominant C3 deposition differ, further understanding the background mechanism, particularly complement dysregulation in C3G, is needed. This may resolve current dilemmas in practice and shed light on novel targeted therapies to remedy the dysregulated alternative complement pathway in C3G.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C3 glomerulopathy and current dilemmas

2016

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“…The time to allograft recurrence in the two reported patients varies widely (in patient C3GN1 disease repalsed after 3 years, and in patient C3GN3 after 3 months), which is in line with previous reports [ 12 ]. Rituximab has been discussed as a treatment option in autoantibody positive transplant recurrent C3G [ 46 ]. In our study (patient C3GN1 ), it did not affect disease progression and a previous report showed poor outcome [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Treating C3 glomerulopathy with eculizumab

et al. 2018

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BackgroundC3 glomerulopathy (C3G) is a rare, but severe glomerular disease with grim prognosis. The complex pathogenesis is just unfolding, and involves acquired as well as inherited dysregulation of the alternative pathway of the complement cascade. Currently, there is no established therapy. Treatment with the C5 complement inhibitor eculizumab may be a therapeutic option. However, due to rarity of the disease, parameters predicting treatment response remain largely unknown.MethodsSeven patients with C3G (five with C3 glomerulonephritis and two with dense deposit disease) were treated with eculizumab. Subjects underwent biopsy before enrollment. The histopathology, clinical data, and response to eculizumab treatment were analyzed. The key parameters to determine outcome were changes of serum creatinine and urinary protein over time.ResultsAfter treatment with eculizumab, four subjects showed significantly improved or stable renal function and urinary protein. A positive response occurred between 2 weeks and 6 months after therapy initiation. One subject (with allograft recurrent C3 glomerulonephritis) initially showed a positive response, but relapsed when eculizumab was discontinued, and did not respond after re-initiation of treatment. Two subjects showed impaired renal function and increasing urinary protein despite therapy with eculizumab.ConclusionsEculizumab may be a therapeutic option for a subset of C3G patients. The response to eculizumab is heterogeneous, and early as well as continuous treatment may be necessary to prevent disease progression. These findings emphasize the need for studies identifying genetic and functional complement abnormalities that may help to guide eculizumab treatment and predict response.Electronic supplementary materialThe online version of this article (10.1186/s12882-017-0802-4) contains supplementary material, which is available to authorized users.

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“…C3NeF is prevalent in 50%-80% C3G patients[ 27 ]. Other autoantibodies have also been found ( e.g ., autoantibodies against factor B[ 28 ], CFH[ 29 , 30 ] and C3 convertase)[ 28 ].…”

Section: Clinical Presentationmentioning

confidence: 99%

“…There is no documented relation between mode of presentation, C3 serum levels, or C3NeF levels and C3GN recurrence[ 48 ]. The only trustworthy risk factor correlated with C3 recurrence is the presence of heavy proteinuria, with two thirds of C3 patients showing vulnerability to recurrence and a high incidence of graft loss[ 5 , 7 , 27 ]. All the available data about recurrence are based on case series, with the largest by Zand et al[ 7 ] that failed to reveal robust evidence of recurrence risk.…”

Section: Clinical Presentationmentioning

confidence: 99%

Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options in de novo and recurrent diseases

Abbas¹,

Kossi

Kim

et al. 2018

WJT

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For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy (a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases. Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.

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Current concepts in C3 glomerulopathy

Cited by 17 publications

References 61 publications

C3 glomerulopathy and current dilemmas

C3 glomerulopathy and current dilemmas

Treating C3 glomerulopathy with eculizumab

Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options in de novo and recurrent diseases

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