Acute Thrombotic Microangiopathy Research Articles

De novo normotensive scleroderma renal crisis six years after living-donor renal transplantation in a patient with overlapping systemic sclerosis/systemic lupus erythematosus syndrome: a case report

BackgroundScleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists.Case presentationWe report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction.ConclusionsSRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.

Drug-induced thrombotic microangiopathy

Abstract Introduction/Objective Drug-induced thrombotic microangiopathy is observed in the patient on the new cancer therapy. It shares similar pathologic changes, as seen in conventional thrombotic microangiopathy, and is characterized by a pentad of hemolytic anemia, thrombocytopenia, renal dysfunction, fever, and neurological dysfunction. However, some patients may not have full scope of the pentad. Instead, only “diad” (hemolytic anemia and thrombopenia) exists, which could be mistakenly attributed to the drug side effect of bone marrow suppression. Methods/Case Report A 71-year-old white male with a history of multiple myeloma (MM) and cardiomyopathy presented with nausea and vomiting following the second round of carfilzomib and pomalidomide chemotherapy. Laboratory tests showed anemia, thrombocytopenia, and peripheral blood abnormalities such as normocytic erythrocytes with occasional schistocytes, slight left shift in leukocytes, and decreased platelet count. Results (if a Case Study enter NA) The biopsy shows diffuse closure of glomerular capillaries, occasional microthrombi and fragmented red cells in glomerular capillaries. Under electron microscope, there are subendothelial space widening, mesangial interposition and wrinkling of glomerular basement membranes. These changes are consistent with acute or subacute thrombotic microangiopathy (TMA). Conclusion With the frequent use of advanced chemotherapy drugs, awareness of the drug-induced TMA should be emphasized. Early recognition is important to avoid development of more permanent kidney damage.

A Case of Antiphospholipid Syndrome Nephropathy with Acute Thrombotic Microangiopathy After Renal Transplantation.

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

#4808 DIFFERENTIATING POSTPARTUM HELLP SYNDROME FROM ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims HELLP (hemolysis, elevated liver enzymes, low platelets) is a severe variant of preeclampsia whose pathogenesis remains unknown but likely involves abnormal placentation, endothelial dysfunction and release of vasoactive substances. Complement dysregulation is implicated in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and there is growing evidence to support its role in HELLP syndrome. Here we present a case of postpartum thrombotic microangiopathy (TMA) in the setting of HELLP syndrome. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 22 year old G1P1 Caucasian woman presents at 37 weeks gestation with abdominal pain and severe hypertension. Labs demonstrated TMA including hemoglobin 95, platelets 30, LDH 2597, and schistocytes. She had severe transaminitis with AST 1845 and ALT 830, and proteinuric acute kidney injury. She was diagnosed with HELLP syndrome and treated with anti-hypertensives and emergency Caesarean section. Unfortunately, the infant did not survive, and there was no placental abruption. Platelets recovered by day 5 postpartum, LDH by day 7. However, renal function worsened and by day 6 postpartum, she required hemodialysis. A renal biopsy revealed acute and chronic TMA. She did not have cortical necrosis. Further workup revealed normal C3, C4 and ADAMTS13 levels. Dialysis was stopped after two weeks. By 6 months, her renal function and proteinuria returned to normal. Complement function testing revealed negative complement factor H autoantibody, but elevated soluble C5b-9 (sC5b-9) level (0.42 mg/L, normal <0.3). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed both on resting (182%, normal <150%) and on ADP-activated endothelial cells (273%, normal <150%). This test was repeated 6 months postpartum when renal function had normalized, and results were persistently abnormal both on resting (215%, normal <150%) and on ADP-activated endothelial cells (282%, normal <150%). aHUS genetic testing was negative. Conclusion Results from Burwick et al suggest that this patient had a very high likelihood of clinical aHUS in association with HELLP syndrome (elevated LDH >1832 U/L and creatinine >1.9 mg/dL) [1]. Identifiable aHUS genetic mutations only occur in 50% of aHUS patients. Complement function testing is not routinely assessed for postpartum HELLP; however, the severity of her HELLP syndrome prompted further investigation (C5b-9 deposition testing). The persistence of increased C5b-9 deposition 6 months postpartum for this patient mimics the findings of patients who have confirmed aHUS [2]. Our patient's unique results suggest the patient may be at risk for recurrent TMA/aHUS in her lifetime, particularly if another pregnancy is being considered. Future research should explore which pregnancy associated TMA patients may benefit from anti-complement therapy.

Genetic, clinical, and pathological study of patients with severe hypertension-associated renal microangiopathy.

Severe hypertension may be a prominent manifestation of complement-mediated thrombotic microangiopathy. Furthermore, patients with severe hypertension-associated thrombotic microangiopathy may present with concurrent hematologic abnormalities that mimic complement-mediated thrombotic microangiopathy. Whether or not severe hypertension-associated thrombotic microangiopathy is associated with genetic susceptibility in complement- and/or coagulation-pathway genes remains unclear, and there is thus a need to identify clinicopathological clues to distinguish between these entities. Forty-five patients with concomitant severe hypertension and thrombotic microangiopathy on kidney biopsy were identified retrospectively. Whole-exome sequencing was performed to identify rare variants in 29 complement- and coagulation-cascade genes. Clinicopathological features were compared between patients with severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension. Three patients with pathogenic variants diagnostic of complement-mediated thrombotic microangiopathy and two with anti-factor H antibody positivity were diagnosed with complement-mediated thrombotic microangiopathy with severe hypertension. Among the 40 patients with severe hypertension-associated thrombotic microangiopathy, 53 rare variants of uncertain significance were found in the analyzed genes in 34 (34/40, 85%) patients, of whom 12 patients harbored two or more variants. Compared with complement-mediated thrombotic microangiopathy patients with severe hypertension, patients with severe hypertension-associated thrombotic microangiopathy were more likely to have left ventricular wall thickening (p < 0.001), less-severe acute glomerular thrombotic microangiopathy lesions including mesangiolysis and subendothelial space widening (both p < 0.001), and less arteriolar thrombosis formation (p < 0.001). Rare genetic variants involving complement and coagulation pathways can be found in patients with severe hypertension-associated thrombotic microangiopathy; their role needs further investigation. Cardiac remodeling and acute glomerular TMA lesions may help to differentiate between severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median=86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Sustained Response to Eculizumab in a Patient With COVID-19–Associated Acute Thrombotic Microangiopathy of the Allograft Kidney: A Case Report

Acute thrombotic microangiopathy (TMA) developing in association with SARS-CoV-2 infection is a rare but recognized phenomenon in native kidneys. In the allograft kidney, a diagnosis of TMA has a broad etiologic differential, including antibody-mediated rejection and recurrent and de novo causes of TMA that affect the native kidney. Prior case reports have described plasma exchange or eculizumab use in patients with COVID-19-associated TMA. Herein, we describe the course of a kidney transplant patient with COVID-19-associated TMA with response to eculizumab that was sustained after medication withdrawal and review the literature on COVID-19-associated TMA of the allograft kidney.

Oxalate Nephropathy.

Oxalate Nephropathy.

PS-R05-6: A CASE OF ACUTE KIDNEY INJURY WITH THROMBOTIC MICROANGIOPATHY CAUSED BY MALIGNANT HYPERTENSION

A 31-year-old man was transferred to our hospital because of severe hypertension, acute kidney injury (AKI) and thrombotic microangiopathy (TMA). A month earlier, the patient sought medical attention for epigastric pain. Upper gastrointestinal endoscopy revealed hemorrhagic gastric ulcer, and hemostasis was performed. At that time, his was found to have severe high blood pressure (200/140 mmHg), together with low levels of hemoglobin (Hb) (10.5 g/dL) and platelet (Plt) count (107 x 109/L). One week later, gastric ulcer tended to improve, but the blood pressure was still high (192/122 mmHg), along with severe abnormalities in creatinine (Cr) (10.7 mg/dL), Hb (6.6 g/dL) and Plt levels (139 x 109/L). On the following day, the serum Cr level increased to 13.7 mg/dL, while Hb and Plt levels decreased to 6.3 g/dL and 111 x 109/L, respectively. He was referred and admitted to a local affiliated hospital. Because the patient was considered as AKI due to dehydration and anemia, fluid replacement and blood transfusion were performed. However, his renal function was worsened further and pulmonary congestion appeared, which required initiation of hemodialysis therapy. Because low platelet counts, high LDH levels and schistocytes in peripheral blood were observed, he was diagnosed with TMA and transferred to our hospital. Laboratory data on admission revealed as follows: the plasma renin activity (PRA), 7.8 ng/ml/h, plasma aldosterone concentration (PAC), 443 pg/mL, plasma adrenaline, 12 pg/mL, noradrenaline, 172 pg/ml, ACTH, 17.3 pg/mL, cortisol, 6.9 g/dL, and TSH, 1.71 IU/mL. Renal artery stenosis was not observed by renal artery ultrasound. Echocardiography showed hypertrophy of the left ventricle. Funduscopic examination showed retinal hemorrhages. Renal biopsy revealed a large number of collapsed glomeruli, onion skin lesions in the arterioles and interlobular arteries, luminal narrowing due to thrombosis, and fibrin accumulation on the blood vessel walls, which lead to histological diagnosis of malignant nephrosclerosis and TMA. Intensive treatment with a calcium channel blocker, an ACE inhibitor, and other antihypertensive agents resulted in improved hypertension, and normalized platelet count and LDH levels, together with reduced PRA (3.2 ng/ml/h) and PAC (208 pg/mL). However, withdrawal from hemodialysis was not achieved. We consider that in this case TMA was caused by malignant hypertension due to essential hypertension. We conclude that early detection and intervention for hypertension are mandatory to prevent the progression of malignant hypertension and related organ damages.

Acute and chronic histopathological findings in renal biopsies in COVID-19.

The dominant ICU admission diagnosis of COVID-19 patients is respiratory insufficiency, but 32-57% of hospitalized COVID-19 patients develop acute kidney injury (COVID-AKI). The renal histopathological changes accompanying COVID-AKI are not yet fully described. To obtain a detailed insight into renal histopathological features of COVID-19, we conducted a review including all studies reporting histopathological findings of diagnostic and postmortem kidney biopsies from patients with COVID-19 published between January 1, 2020, and January 31, 2021. A total of 89 diagnostic and 194 postmortem renal biopsies from individual patients in 39 published studies were investigated and were included in the analysis. In the diagnostic biopsy group, mean age was 56years and AKI incidence was 96%. In the postmortem biopsy group, mean age was 69years and AKI incidence was 80%. In the diagnostic biopsy group, the prevalence of acute glomerular diseases was 74%. The most common glomerular lesions were collapsing focal segmental glomerulosclerosis (c-FSGS) in 54% and thrombotic microangiopathy (TMA) in 9% of patients. TMA was also found in 10% of patients in the postmortem biopsy group. The most common acute tubular lesions was acute tubular necrosis (ATN) which was present in 87% of patients in the diagnostic and in 77% of patients in the postmortem biopsy group. Additionally, we observed a high prevalence of preexisting chronic lesions in both groups such as atherosclerosis and glomerulosclerosis. Histopathological changes in renal biopsies of COVID-19 patients show a heterogeneous picture with acute glomerular lesions, predominantly c-FSGS and TMA, and acute tubular lesions, predominantly ATN. In many patients, these lesions were present on a background of chronic renal injury.

Rapid Diagnosis of Acute Thrombotic Thrombocytopenic Purpura (TTP) Using a New Fully Automated Chemiluminescent Assay for Adamts-13 Activity. Clinical Performance and Cost-Effectiveness Analysis

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) that can be caused by congenital or acquired severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), an enzyme that cleaves von Willebrand factor (VWF). ADAMTS-13 deficiency leads to the accumulation of ultra-large VWF multimers, leading to platelet aggregation and microthrombi formation. Aside clinical symptoms, the diagnosis of TTP is based on laboratory parameters such as thrombocytopenia, hemolytic anemia with the presence of schistocytes, and severely reduced activity of ADAMTS-13 (<10%). As TTP is a life-threatening condition characterized by microvascular thrombosis, it is of great importance to shorten the time to the treatment, and according to the French recommendations, patients with suspected TTP must be treated with the triplet therapy including plasma exchange (PEX), rituximab, and caplacizumab, plus corticosteroids until the results of ADAMTS-13 was obtained. As this therapy must be pursued only in the case of deficiency, a rapid ADAMTS-13 testing is critical for early diagnosis and optimal management of acute TTP. Design and aims of the study: We first retrospectively compared the performance of a rapid fully automated chemiluminescent assay (HemosIL AcuStar ADAMTS-13) to those of the FRETS-VWF73 assay in the diagnosis of TTP. Then, we compared the cost-effectiveness of a strategy based on the on-site measurement of ADAMTS-13 activity using the AcuStar assay vs. its centralized measurement in a reference laboratory, as it is currently the case at our institution. For that purpose, we created two scenarios based on either the local measurement of ADAMTS-13 activity with a maximum time-to-result of 16 hours (assay performed during daytime, 7/7) or its centralized measurement with a median time-to-result of 4 days (range: 2-8), as demonstrated from the 2018-2021 estimates. The triplet therapy was hypothesized to be started on admission and stopped if ADAMTS-13 activity was >10%. In case of ADAMTS-13 activity <10%, an inhibitor screening would be performed at the reference laboratory, as this assay was not expected to be locally implemented. For the calculation, we considered the costs of reagent, shipping/handling of the samples to the reference laboratory, laboratory staff workload, reimbursement rates, and treatments administered in patients with suspected TTP until availability of the ADAMTS-13 result. Results: In the plasma from 56 patients with acute TMA, ADAMTS-13 activity was not significantly different when evaluated using the HemosIL AcuStar ADAMTS-13 and the FRETS-VWF73 assays [median=72.6% (range: 0.2-126) vs. 79% (range: 5-150); p=0.08]. The concordance of test results as whether ADAMTS-13 activity was below (n=5) or above the threshold of 10% using the 2 assays was excellent (kappa=1.00), allowing an accurate diagnosis of the 5 patients with confirmed TTP. Based on the local activity between 2018 and 2021, there was a mean of 60 prescriptions of ADAMTS-13 activity per year. Most were for the follow-up of TTP patients and for patients with non-TTP TMA, whereas 7 were for the diagnosis of acute TTP, as suggested by the French score, which was confirmed in 4 cases (mean values). As shown in the Table, the local measurement of ADAMTS-13 activity was found to be cost-effective with a 16%-reduction of the costs compared to its centralized measurement in the 7 patients with suspected TTP during the first 4 days. This equates to 4,508 € saved per patient with suspected acute TTP. Conclusions: Together with its short turnaround time (33 min) and its full automation, our results suggest that the HemosIL AcuStar ADAMTS-13 activity assay could be an assay of choice to rapidly measure ADAMTS-13 activity in the plasma and thus to establish the diagnosis of acute TTP in emergency settings. Considering the local costs, using the strategy based on the local evaluation of ADAMTS-13 activity led to a 16%-reduction of the overall costs during the first 4 days after admission of the 7 patients with suspected acute TTP. Moreover, by dramatically decreasing the time-to-result (<1 day vs. 4 days), unnecessary potentially harmful and expensive treatments could be withheld earlier in patients in whom the diagnosis of TTP was ruled out based on an ADAMTS-13 activity >10%. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ACUTE KIDNEY INJURY IN PATIENTS WITH ACUTE LEUKEMIA AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: A SERIES OF CLINICAL CASES

Relevance: Acute renal kidney injury is a severe complication in patients with acute leukemia who underwent hematopoietic stem cell&#x0D; transplantation (HSCT). According to statistics, acute renal dysfunction often occurs in the first 100 days after HSCT.&#x0D; This study aimed to evaluate kidney function in patients with acute leukemia after hematopoietic stem cell transplantation.&#x0D; Methods: The article presents clinical cases of patients with acute lymphoblastic leukemia who developed acute renal failure after&#x0D; HSCT. The dynamics of the functional state of kidneys in patients with acute lymphoblastic leukemia after HSCT are described.&#x0D; Results: The acute kidney disorder in the studied patients was mainly caused by HSCT complications. We have identified renal kidney&#x0D; damage in the form of acute tumor lysis and thrombotic microangiopathy.&#x0D; Conclusion: Patients with acute lymphoblastic leukemia risk developing acute kidney disorder during HSCT, which requires careful&#x0D; monitoring of kidney function, especially in the early post-transplant period

ACUTE RENAL DISORDER IN PATIENTS WITH ACUTE LEUKEMIA&#x0D; AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION:&#x0D; A SERIES OF CLINICAL CASES

Relevance: Acute renal kidney disorder is a serious complication in patients with acute leukemia who underwent hematopoietic stem cell&#x0D; transplantation (HSCT). According to statistics, acute renal dysfunction often occurs in the first 100 days after HSCT.&#x0D; This study aimed to evaluate kidney function in patients with acute leukemia after hematopoietic stem cell transplantation.&#x0D; Methods: The article presents clinical cases of patients with acute lymphoblastic leukemia who developed acute renal failure after HSCT. The&#x0D; dynamics of the functional state of kidneys in patients with acute lymphoblastic leukemia after HSCT are described.&#x0D; Results: The acute kidney disorder in the studied patients was mainly caused by HSCT complications. We have identified renal kidney damage&#x0D; in the form of acute tumor lysis and thrombotic microangiopathy.&#x0D; Conclusion: Patients with acute lymphoblastic leukemia risk developing acute kidney disorder during HSCT, which requires careful monitoring of kidney function, especially in the early post-transplant period.

Early graft loss due to acute thrombotic microangiopathy accompanied by complement gene variants in living-related kidney transplantation: case series report

BackgroundRecently, early graft loss has become very rare in living-related kidney transplantation (LKT) as a result of decreased risk of hyperacute rejection and improvements in immunosuppressive regimens. Post-transplant acute thrombotic microangiopathy (TMA) is a rare, multi-factorial disease that often occurs shortly after kidney transplantation and is usually resistant to treatment with dismal renal outcomes. The complement genetic variants may accelerate the development of TMA. However, the complement genetic test was seldom performed in unknown native kidney disease recipients scheduled for LKT.Case presentationWe reported three cases of unknown native kidney diseases who had fulminant TMA in the allograft shortly after LKT. Both the donors and the recipients were noted to carry complement genetic variants, which were identified by genetic testing after transplantation. However, all recipients were refractory to treatment and had allograft loss within 3 months after LKT.ConclusionThis case series highlights the suggestion to screen complement gene variants in both the donors and the recipients with unknown native kidney diseases scheduled for LKT.

Lombardy diagnostic and therapeutic network of thrombotic microangiopathy

BackgroundThrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region.MethodsWe perfomed a cohort study in the frame of the project “Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis”, including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h.ResultsForty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs ≥ 10%: median difference of -27 × 109/l, 95% CI − 37 to − 3). PEX treatment was initiated in all patients, but soon discontinued in cases without severe ADAMTS13 deficiency. In this group, the mortality rate was higher and no episode exacerbations or relapses within 6 months occured. The estimated average annual incidence of acute acquired TTP events was 1.17 [0.78–1.55] per million people.ConclusionsSevere ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.

Immunotherapy and the Spectrum of Kidney Disease: Should We Individualize the Treatment?

The new targeted cancer therapies including immune checkpoint inhibitors (ICIs) have been demonstrated to improve the survival of oncological patients, even in cases of metastatic cancer. In the past 5 years, several studies have revealed that ICI can produce several immune-mediated toxicities involving different organs, such as the skin, the gastrointestinal tract, the liver, and, of course, the kidney. The most frequent lesion of immunotoxicity in the kidney is acute interstitial nephritis (AIN), although other nephropathies have also been described as a consequence of the use of ICI, such as glomerulonephritis and acute thrombotic microangiopathy, among others. In addition, kidney rejection has also been reported in kidney transplant patients treated with ICI. Normally randomized clinical trials with ICI exclude patients with end-stage kidney disease, namely, patients undergoing dialysis and kidney transplant patients. Several important questions need to be addressed in relation to immunotherapy and patients with kidney disease: (a) when to start corticosteroid therapy in a patient with suspected acute kidney injury (AKI) related to ICI, (b) the moment of nephrologist referral and kidney biopsy indication, (c) management of ICI in patients undergoing dialysis, and (d) the effect of ICI in kidney transplantation, immunosuppressive personalized treatment, and risk of allograft rejection in kidney transplant patients. The objective of this review was to summarize the recently published literature on a wide spectrum of kidney disease patients with cancer and ICI. This review will address three main important groups of individuals with kidney disease and cancer immunotherapy, AKI associated with ICI, patients undergoing dialysis, and kidney transplant recipients. We believe that the information provided in this review will enlighten the personalized ICI treatment in individuals with a broader spectrum of kidney diseases.

POS-044 ECULIZUMAB INTERRUPTION IN KIDNEY TRANSPLANT RECIPIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME: ANALYSIS OF A BRAZILIAN SHORTAGE

IntroductionAfter a period of eculizumab shortage in Brazil, an interruption of therapy in Atypical Hemolytic Uremic Syndrome (aHUS) patients brought about high relapse rate. This study aimed to analyze the aHUS relapse rate in kidney transplant recipients who had eculizumab therapy interrupted.MethodsWe screened 800 Brazilian centers of dialysis, transplantation and nephrology throughout Brazil, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included kidney transplant recipients with aHUS who underwent interruption of eculizumab therapy for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy in a renal graft biopsy.ResultsWe analyzed 9 patients and 9 episodes of exposure to risk of relapse. Median age was 34 (27 - 36) years, 5 (55%) patients were female, 8 (88%) had genetic study performed and 5 (55%) had any complement variant identified, among them, one (11%) had CFH variant found. Four patients (44%) had relapse after eculizumab withdrawal. Genetic characteristics related to relapses were: one patient did not have genetic study performed, one did not have pathogenic variants in complement genes identified, one had pathogenic variants found in CFI and CFB and one, in C3, CFI and CFHR1-CFHR3. The cumulative incidence of aHUS relapse at one year was 60%.ConclusionsThis study showed a high cumulative incidence of relapse (60%) at one year when eculizumab therapy in kidney transplant recipients was interrupted after a shortage in Brazil.No conflict of interest IntroductionAfter a period of eculizumab shortage in Brazil, an interruption of therapy in Atypical Hemolytic Uremic Syndrome (aHUS) patients brought about high relapse rate. This study aimed to analyze the aHUS relapse rate in kidney transplant recipients who had eculizumab therapy interrupted. After a period of eculizumab shortage in Brazil, an interruption of therapy in Atypical Hemolytic Uremic Syndrome (aHUS) patients brought about high relapse rate. This study aimed to analyze the aHUS relapse rate in kidney transplant recipients who had eculizumab therapy interrupted. MethodsWe screened 800 Brazilian centers of dialysis, transplantation and nephrology throughout Brazil, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included kidney transplant recipients with aHUS who underwent interruption of eculizumab therapy for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy in a renal graft biopsy. We screened 800 Brazilian centers of dialysis, transplantation and nephrology throughout Brazil, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included kidney transplant recipients with aHUS who underwent interruption of eculizumab therapy for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy in a renal graft biopsy. ResultsWe analyzed 9 patients and 9 episodes of exposure to risk of relapse. Median age was 34 (27 - 36) years, 5 (55%) patients were female, 8 (88%) had genetic study performed and 5 (55%) had any complement variant identified, among them, one (11%) had CFH variant found. Four patients (44%) had relapse after eculizumab withdrawal. Genetic characteristics related to relapses were: one patient did not have genetic study performed, one did not have pathogenic variants in complement genes identified, one had pathogenic variants found in CFI and CFB and one, in C3, CFI and CFHR1-CFHR3. The cumulative incidence of aHUS relapse at one year was 60%. We analyzed 9 patients and 9 episodes of exposure to risk of relapse. Median age was 34 (27 - 36) years, 5 (55%) patients were female, 8 (88%) had genetic study performed and 5 (55%) had any complement variant identified, among them, one (11%) had CFH variant found. Four patients (44%) had relapse after eculizumab withdrawal. Genetic characteristics related to relapses were: one patient did not have genetic study performed, one did not have pathogenic variants in complement genes identified, one had pathogenic variants found in CFI and CFB and one, in C3, CFI and CFHR1-CFHR3. The cumulative incidence of aHUS relapse at one year was 60%. ConclusionsThis study showed a high cumulative incidence of relapse (60%) at one year when eculizumab therapy in kidney transplant recipients was interrupted after a shortage in Brazil.No conflict of interest This study showed a high cumulative incidence of relapse (60%) at one year when eculizumab therapy in kidney transplant recipients was interrupted after a shortage in Brazil.

POS-036 A YOUNG FEMALE WITH RENAL CORTICAL NECROSIS TREATED WITH INTRAVENOUS IMMUNOGLOBULIN IN A RESOURCE POOR SETTING: CASE REPORT

Renal cortical necrosis is a rare cause of acute kidney injury (AKI) characterized by diffuse or patchy ischemic coagulation necrosis of the cortex. One of the important causes is acute Thrombotic Microangiopathy (TMA).Thrombotic microangiopathy (TMA) is one of the most important causes of Renal cortical necrosis and Rapidly progressive renal failure (RPRF). It can be classified into Primary (hereditary or acquired) & secondary TMA. It is very crucial to diagnose & treat Renal cortical necrosis & TMA early to avoid morbidity & mortality.

Treatment of catastrophic antiphospholipid syndrome to pregnant woman

The research aimed to study and analyze the life-threatening complication of antiphospholipid syndrome by acute thrombotic microangiopathy, which can lead to multiorgan damage. The progression of catastrophic antiphospholipid syndrome during pregnancy creates a lot of problems in diagnostic due to its extended clinical manifestations and coincidence with additional obstetric intricacies and microangiopathic diseases. Early diagnosis and aggressive treatment (anticoagulants, glucocorticoids, and plasma metabolism (or intravenous immunoglobulins) remain key factors for favorable. In cases of refractory CAPS, cyclophosphamide or monoclonal antibodies (rituximab, eculizumab) should be considered.

Outcomes Following Intolerance to Tacrolimus/Sirolimus Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis regimen following allogeneic hematopoietic cell transplantation (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. This study was conducted to assess the outcomes of patients with TAC/SIR intolerance and guide their subsequent management. We retrospectively analyzed transplantation outcomes of consecutive adult patients at Moffitt Cancer Center who underwent allogeneic HCT with TAC/SIR as GVHD prophylaxis between 2009 and 2018. TAC/SIR intolerance was defined as discontinuation of either TAC or SIR due to toxicity before post-transplantation day +100. A total of 777 patients met the inclusion criteria. The median duration of follow-up was 22 months (range, 0.2 to 125 months). Intolerance occurred in 13% (n = 104) of the patients at a median of 30 days (range, 5 to 90 days). The most common causes of intolerance were acute kidney injury (n = 53; 51%), thrombotic microangiopathy (n = 31; 28%), and veno-occlusive disease (n = 23; 22%). The cumulative incidence of grade II-IV acute GVHD at 100 days was 50% (95% CI, 39% to 64%) in the TAC/SIR-intolerant patients and 25% (95% CI, 22% to 29%) in patients tolerant to this regimen (P < .0001). In multivariate analyses, the incidence of grade II-IV 4 acute GVHD was significantly higher in the TAC/SIR-intolerant patients (hazard ratio [HR], 2.40; 95% CI, 1.59 to 3.61; P < .0001). Similarly, in multivariate analyses, the TAC/SIR-intolerant patients had a higher incidence of chronic GVHD (HR, 1.48; 95% CI, 1.03 to 2.12; P = .03). The nonrelapse mortality (NRM) at 1 year was 47% (95% CI, 38% to 59%) in the TAC/SIR-intolerant patients and 12% (95% CI, 10% to 15%) in those tolerant to the regimen (P < .0001). The 2-year relapse-free survival was 35% (95% CI, 25% to 44%) in the TAC/SIR-intolerant patients and 60% (95% CI, 57% to 65%) in the TAC/SIR-tolerant patients (HR, 2.30; 95% CI, 1.61 to 3.28; P < .0001). Intolerance stratified by early (≤30 days) versus late (31 to 100 days) significantly affected the cumulative incidence of acute GVHD at 75% (early; 95% CI, 59% to 94%) versus 33% (late; 95% CI, 21% to 50%) (P = .001), as well as the cumulative incidence of NRM at 61% (early; 95% CI, 48% to 77%) versus 35% (late; 95% CI, 24% to 51%) (P = .006). Most patients who developed TAC/SIR intolerance were switched to an alternative 2-drug regimen (71 of 104; 68%), most commonly mycophenolate mofetil in addition to continuing TAC or SIR (68 of 71; 96%). Overall, TAC/SIR intolerance was associated with poorer outcomes. Early intolerance contributed to a higher risk of acute GVHD, increased NRM, and inferior survival. Patients with early intolerance were often switched to an alternative agent, and patients with late intolerance tended to be continued on single-drug therapy without substitution. The use of single-drug versus 2-drug regimens after intolerance did not appear to affect outcomes. Management strategies to mitigate the risks of intolerance are warranted.