scholarly journals Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
G. Guzzo ◽  
S. Kissling ◽  
G. Pantaleo ◽  
M. Pascual ◽  
S. Sadallah ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Complement Activation ◽  
Thrombotic Microangiopathy ◽  
Clinical Picture ◽  
Post Partum ◽  
Kidney Injury ◽  
Pressure Control ◽  
Oocyte Donation ◽  
Renal Prognosis ◽  
Post Partum Haemorrhage

Abstract Background Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. Case presentation A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. Conclusions We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

scholarly journals Plasma exchange for thrombotic microangiopathy secondary to dermatomyositis associated with acute kidney injury and complement activation: a case report with literature review

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Norifumi Hayashi ◽  
Keiichirou Okada ◽  
Yuko Tsuruyama ◽  
Yu Kagaya ◽  
Sho Kumano ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Intensive Care ◽  
Case Report ◽  
Plasma Exchange ◽  
Complement Activation ◽  
Thrombotic Microangiopathy ◽  
Kidney Injury ◽  
Ivig Therapy ◽  
Case Presentation ◽  
Life Threatening

Abstract Background Thrombotic microangiopathy (TMA) in patients with connective tissue disease is rare but life-threatening. In particular, the survival rate of patients with dermatomyositis (DM) that develop TMA is low. The effectiveness of plasma exchange (PEX) therapy is unclear for the treatment of TMA secondary to DM. Case presentation We describe a case of a 28-year-old woman who developed severe DM complicated by aspiration pneumonia from dysphagia and acute kidney injury. The patient was unresponsive to corticosteroids and intravenous immunoglobulin (IVIG) therapy and developed TMA. In this case, immunofluorescence of skin biopsy revealed that complement activation was involved in the pathogenesis of DM. After 6 PEX therapies, thrombocytopenia improved. She was successfully treated by intensive care and PEX therapy. Conclusions PEX therapy was effective to treat TMA secondary to DM associated with complement activation.

Postpartum atypical hemolytic uremic syndrome: Evaluating thrombotic microangiopathy in the pregnant woman

2020 ◽  
pp. 1753495X2092604
Author(s):  
S So ◽  
E Fischer ◽  
M Gangadharan Komala ◽  
B Bose
Keyword(s):  
Acute Kidney Injury ◽  
Pregnant Woman ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Post Partum ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Uremic Syndrome ◽  
In Pregnancy

Acute kidney injury in women during pregnancy and the puerperium is often ascribed to hypertensive complications of pregnancy, especially pre-eclampsia. However, rarer causes, including atypical hemolytic uremic syndrome (aHUS) can be triggered by pregnancy. We present a case of a woman with post-partum acute kidney injury due to aHUS, which was successfully treated with the C5a inhibitor eculizumab. We also present a summary of the evaluation and management of thrombotic microangiopathy in pregnancy.

scholarly journals A rare case of posterior reversible encephalopathy syndrome in a patient with severe leptospirosis complicated with rhabdomyolysis and acute kidney injury; a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jayawardane Pathiranage Roneesha Lakmali ◽  
Kanapathipillei Thirumavalavan ◽  
Danapala Dissanayake
Keyword(s):  
Blood Pressure ◽  
Acute Kidney Injury ◽  
Blood Pressure Control ◽  
Posterior Reversible Encephalopathy Syndrome ◽  
Vision Loss ◽  
Kidney Injury ◽  
Pressure Control ◽  
Posterior Reversible Encephalopathy ◽  
Peripheral Nerve Involvement ◽  
Reversible Encephalopathy

Abstract Background Leptospirosis is a zoonotic spirochetal disease caused by Leptospira interrogans. The clinical presentation ranges from an asymptomatic state to a fatal multiorgan dysfunction. Neurological manifestations including aseptic meningitis, spinal cord and peripheral nerve involvement, cranial neuropathies and cerebellar syndrome are well recognized with varying frequencies among patients with this disease. Posterior reversible encephalopathy syndrome is a very rare occurrence in leptospirosis and only two cases are reported in the medical literature up to now. We report a case of posterior reversible encephalopathy syndrome in a patient with leptospirosis with rhabdomyolysis and acute kidney injury. Case presentation A 21 year-old male presented with fever and oliguric acute kidney injury with rhabdomyolysis. A diagnosis of leptospirosis was made and he was being managed according to the standard practice together with regular hemodialysis. The clinical condition was improving gradually. On day 8 of the illness, he developed headache and sudden painless complete bilateral vision loss followed by several brief generalized tonic clonic seizure attacks. Examination was significant for a Glasgow Coma Scale of 14/15, blood pressure of 150/90 mmHg and complete bilateral blindness. The findings of magnetic resonance imaging of the brain were compatible with posterior reversible encephalopathy syndrome. He was managed with blood pressure control and antiepileptics with supportive measures and standard treatment for leptospirosis and made a complete recovery. Conclusion Posterior reversible encephalopathy syndrome, though very rare with leptospirosis, should be considered as a differential diagnosis in a patient with new onset visual symptoms and seizures, especially during the immune phase. Optimal supportive care together with careful blood pressure control and seizure management would yield a favourable outcome in this reversible entity.

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

2021 ◽  
Vol 118 (37) ◽  
pp. e2104347118
Author(s):  
Ravi Shankar Keshari ◽  
Narcis Ioan Popescu ◽  
Robert Silasi ◽  
Girija Regmi ◽  
Cristina Lupu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Anemia ◽  
Complement Activation ◽  
Inflammatory Responses ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Immune Recognition ◽  
Gram Positive ◽  
Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

scholarly journals Acute Kidney Injury Relevant to Tubulointerstitial Nephritis with Late-Onset Uveitis Superimposed by Thrombotic Microangiopathy: A Case Report and Review of the Literature

2020 ◽  
Vol 6 (6) ◽  
pp. 414-421
Author(s):  
Youlu Zhao ◽  
Junwen Huang ◽  
Tao Su ◽  
Zhikai Yang ◽  
Xizi Zheng ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Thrombotic Microangiopathy ◽  
Tubulointerstitial Nephritis ◽  
Late Onset ◽  
Drug Hypersensitivity ◽  
Oral Prednisone ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Renal Recovery

<b><i>Background:</i></b> The syndrome of tubulointerstitial nephritis and uveitis (TINU) is an uncommon and multisystemic autoimmune disorder. This review reports a rare case of TINU being superimposed on thrombotic microangiopathy (TMA) and, by comparing with the available literature, also summarizes the clinical features, associated conditions, treatment, and outcome of patients with TINU. <b><i>Summary:</i></b> Herein, we report the case of a 37-year-old male patient with acute kidney injury (AKI) clinicopathologically identified as malignant hypertension-induced TMA superimposed by acute tubulointerstitial nephritis, which was suspected to be related to drug hypersensitivity. After treatment with oral prednisone combined with a renin-angiotensin system inhibitor, the patient achieved partial renal recovery and was withdrawn from hemodialysis. Recurrent AKI concomitant with new-onset asymptomatic uveitis was detected during routine clinical follow-up after cessation of prednisone. TINU was then diagnosed, and prednisone followed by cyclophosphamide was prescribed. The patient achieved better renal recovery than in the first round of treatment and maintained stable renal function afterward. By reviewing the literature, 36 cases were reported as TINU superimposed on other conditions, including thyroiditis, osteoarthropathy, and sarcoid-like noncaseating granulomas. <b><i>Key messages:</i></b> TINU could be complicated by many other conditions, among which TMA is very rare. When presented as AKI, kidney biopsy is important for differential diagnosis. The case also shows that recurrent AKI with concomitant uveitis after prednisone withdrawal strongly suggested the need for long-term follow-up and elongated prednisone therapy for TINU syndrome.

scholarly journals A case of acute kidney injury associated with anti-glomerular basement membrane antibody disease and thrombotic microangiopathy

2012 ◽  
Vol 45 (10) ◽  
pp. 973-978
Author(s):  
Aiko Ookubo ◽  
Yuka Shimizu ◽  
Taisuke Irifuku ◽  
Takayuki Naito ◽  
Takahiko Ogawa ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Thrombotic Microangiopathy ◽  
Kidney Injury

Haemolytic uraemic syndrome

2020 ◽  
pp. 5027-5032
Author(s):  
Edwin K.S. Wong ◽  
David Kavanagh
Keyword(s):  
Escherichia Coli ◽  
Acute Kidney Injury ◽  
Complement System ◽  
Shiga Toxin ◽  
Thrombotic Microangiopathy ◽  
Initial Treatment ◽  
Haemolytic Uraemic Syndrome ◽  
Kidney Injury ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy characterized by the triad of thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. It is most often caused by Shiga toxin-producing Escherichia coli (STEC-HUS), and any HUS not caused by this is often termed atypical HUS (aHUS). aHUS may be caused by an underlying complement system abnormality (primary aHUS) or by a range of precipitating events, such as infections or drugs (secondary aHUS). Management of STEC-HUS is supportive. In aHUS, plasma exchange is the initial treatment of choice until ADAMTS13 activity is available to exclude thrombotic thrombocytopenic purpura as a diagnosis. Once this has been done, eculizumab should be instigated as soon as possible.

scholarly journals P0531CONTINUOUS HEMODIAFILTRATION WITH PMMA HEMOFILTER MODULATED COMPLEMENT ACTIVATION AND RENAL DYSFUNCTION IN A SWINE MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alessandra Stasi ◽  
ROSSANA FRANZIN ◽  
Fabio Sallustio ◽  
Chiara Divella ◽  
Claudia Curci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Complement Activation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Kidney Injury ◽  
Swine Model ◽  
Complement Factor ◽  
Factor B ◽  
Renal Biopsies

Abstract Background and Aims Sepsis-induced acute kidney injury (AKI) is a growing health care problem, refractory to conventional treatments. This disease is characterized by an overwhelmed immune response against a primary insult that become responsible for renal dysfunction and poor outcome. Therapeutic strategies based on blood purification have been developed for the treatment of this disease. The use of polymethyl methacrylate (PMMA) membrane hemofilter in continuous hemodiafiltration (CHDF) modality showed better hemodynamic stability and efficient renal support in chronic dialysis maintenance. Here we investigated the efficacy of Hemofeel PMMA membrane (TORAY, Japan) in interfering with Complement activation and renal damage in a swine model of sepsis-induced AKI. Method After 3 hours from LPS infusion, 7 hours of PMMA-CVVH treatment or 7 hours of polysulfone (PSF)-CVVH were performed. Animals were sacrificed after 24h from LPS infusion. Histologic and renal function parameters were analyzed in all pigs. Pentraxin-3 (PTX3) and C5b-9 deposits were assessed on renal biopsies. Systemic Complement activation was evaluated by Wieslab kit. Gene expression profile was obtained from isolated PBMCs by Agilent SurePrint G3 Porcine Gene Expression Microarrays. Genespring and R software were used for the analysis. Results were validated by Real-time PCR. Results Analysis of renal biopsies from septic pigs presented increased interstitial leucocyte infiltrate, extensive collagen deposition and diffuse glomerular thrombi compared to healthy pigs (p&lt;0.05). Confocal analysis showed extensive PTX-3 and C5-b9 deposits at tubulo-interstitial level associated with significant activation of systemic complement classical and alternative pathways (p&lt;0.05). Interestingly, PMMA-CVVH treatment significantly reduced local and systemic complement activation, leucocyte infiltrate and tubule-interstitial fibrosis (p&lt;0.05). On the contrary, no significant improvement was observed by PSF-CVVH treatment. Then, we compared the whole-genome gene expression profiles of swine PBMC. We identified 711 differentially expressed genes comparing PBMC before LPS infusion (LPS T0) and after 24 hours from LPS infusion (LPS T24) and 913 genes comparing gene expression profiles of LPS T24 group with that of septic pigs treated with PMMA-CVVH (PMMA T24 group) (fold change &gt;2 ; false discovery rate &lt;0.05). The most modulated genes were Granzime B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, SERPINB-1 and TIMP-2 that were closely related to sepsis-induced immunological process. Finally, quantitative PCR confirmed the microarray data indicating that Granzime B and Complement Factor B upregulation in PBMC was significantly hampered by PMMA treatment. Conclusion Our data suggest that LPS induced AKI is characterized by activation of Classical and alternative Complement pathways resulting in significant renal tissue damage. By interfering with complement activation and inflammatory response, PMMA membrane might prevent dysfunctional activation of resident renal cells with prevention of sepsis-induced AKI.

scholarly journals Eculizumab, a novel potential treatment for acute kidney injury associated with preeclampsia/HELLP syndrome

2019 ◽  
Vol 12 (9) ◽  
pp. e228709 ◽  
Author(s):  
Hatem Elabd ◽  
Mennallah Elkholi ◽  
Lewis Steinberg ◽  
Anjali Acharya
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Complement Activation ◽  
Hellp Syndrome ◽  
Kidney Injury ◽  
Complement Protein ◽  
Igg Antibody ◽  
Elevated Liver Enzymes

The kidney is one of the major organs affected in preeclampsia. There is evidence suggesting a role for excessive complement activation in the pathogenesis of preeclampsia. We describe a case of preeclampsia with severe features, including HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and acute kidney injury (AKI) that developed following caesarian section. The patient required renal replacement therapy. A trial of daily plasma exchange was not effective. The patient received a single dose of eculizumab, a humanised monoclonal IgG antibody that binds to complement protein C5. One week post administration of eculizumab, there was significant improvement in haematologic, hepatic and renal function. Blood pressure had normalised and renal replacement therapy was discontinued. The use of eculizumab may have contributed to recovery of kidney function further supporting the role of complement activation in the pathogenesis of preeclampsia and associated AKI.

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