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Abstract Background Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant. recipients (KTR). Methods We analysed the epidemiology of adjudicated TMA in consecutive KTR during the. 2009–2021 period. Results TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1–8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5–6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9–15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features. Conclusions TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.

Background: Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant. recipients (KTR). Methods: We analysed the epidemiology of adjudicated TMA in consecutive KTR during the. 2009–2021 period. Results: TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1–8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5–6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9–15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features. Conclusions: TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis. [ABSTRACT FROM AUTHOR]

Background: Malignant hypertension is a condition characterized by severe hypertension and multi-organ ischemic complications. Albeit mortality and renal survival have improved with antihypertensive therapy, progression to end-stage renal disease remains a significant cause of morbidity and mortality. The underlying cause of malignant hypertension, which can be primary or secondary hypertension, is often difficult to identify and this can substantially affect the treatment outcomes, as we report here.Case Presentation: A 33-year-old woman presented with severe hypertension and acute renal failure. Initial evaluation demonstrated hyperreninemia with hyperaldosteronism and a possible renal artery stenosis at the contrast-enhanced CT scan. Although this data suggested the presence of a secondary form of hypertension, further exams excluded our first diagnosis of renal artery stenosis. Consequently, the patient did not undergo renal angiography (and the contrast media infusion associated with it), but she continued to be medically treated to achieve a tight blood pressure control. Our conservative approach was successful to induce renal function recovery over 2 years of follow-up.Conclusion: This case highlights the difficulty in differentiating between primary and secondary forms of malignant hypertension, particularly when the patient presents with acute renal failure. Clinicians should consider renal artery ultrasound as a first level diagnostic technique, given that the presentation of primary malignant hypertension can often mimic a renal artery stenosis. Secondly, adequate control of blood pressure is essential for kidney function recovery, although this may require a long time. [ABSTRACT FROM AUTHOR]

Background: Proteasome inhibitors are a relatively new class of chemotherapeutic agents. Bortezomib is the first agent of this class and is currently being used for the treatment of multiple myeloma. However, recent reports have linked exposure to bortezomib with the development of thrombotic microangiopathy. A new agent in this class, carfilzomib, has been recently introduced as alternative therapy for relapsing and refractory multiple myeloma. We report a case of renal thrombotic microangiopathy associated with the use of carfilzomib in a patient with refractory multiple myeloma. Case presentation: A 62 year-old Caucasian man with hypertension and a 4-year history of multiple myeloma, had been previously treated with lenalidomide, bortezomib and two autologous hematopoietic stem cell transplants. After the second hematopoietic stem cell transplant, he developed acute kidney injury secondary to septic shock and required dialysis for 4 weeks. Subsequently, his serum creatinine stabilized at 2.1 mg/dL (185.64 µmol/L). Seventeen months after the second hematopoietic stem cell transplant, he was initiated on carfilzomib for relapse of multiple myeloma. Six weeks later, he developed abrupt worsening of lower extremity edema and hypertension, and new onset proteinuria. His kidney function remained stable. Kidney biopsy findings were consistent with thrombotic microangiopathy. Eight weeks after discontinuation of carfilzomib, proteinuria and hypertension improved. Due to progression of multiple myeloma, he died a few months later. Conclusion: In view of the previously reported association of bortezomib with thrombotic microangiopathy, the temporal association of the clinical picture with the initiation of carfilzomib, and the partial resolution of symptoms after discontinuation of the drug, we conclude that carfilzomib may have precipitated a case of clinically evident renal thrombotic microangiopathy in our patient. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein glomerulopathy (LPG) is a rare inherited renal disease characterized by intraglomerular lipoprotein within the lumina of severely dilated glomerular capillaries. The common clinical presentation of LPG includes proteinuria or nephrotic syndrome. Hypertension and anemia were thought to be mild in LPG. Thrombotic microangiopathy (TMA) in LPG has not been previously reported. In this report, we present a patient with LPG that developed TMA. To the best of our knowledge, this is the first report of TMA in LPG. Case presentation: Four years ago (2005), a 19-year-old Chinese woman was diagnosed with nephrotic syndrome and provided prednisone treatment. A combination of prednisone and cyclophosphamide did not have any effect and was discontinued after six months. Although she was steroid-resistant, over the next subsequent three years, she maintained normal renal function without anemia and thrombocytopenia. In February 2009, she had a severe headache and blurry vision and presented at a local hospital with severe hypertension. Blood pressure was 220/ 160 mmHg. Laboratory data showed hemoglobin 3.8 g/dL; platelet counts 29×109/L; urinary protein 7.90 g/d; total bilirubin 29.9 umol/L; indirect bilirubin 28.2 umol/L; LDH 1172 U/L; ALB 2.66 g/dL; urea nitrogen 52 mg/dL; serum creatinine 3.2 mg/dL; triglyceride 253 mg/dL; total cholesterol 273 mg/dL. ANA, ds-DNA, ANCA, anti-GBM antibody and anticardiolipin were all negative. A renal biopsy revealed LPG with TMA. Genetic evaluation showed the patient carried the APOE Kyoto mutation. Adequate control of blood pressure improved microangiopathic anemia and thrombocytopenia, however, renal function did not improve and she eventually developed uremia and became hemodialysis dependent. Conclusion: We report on a rare case of TMA probably due to malignant hypertension in LPG. Early lipid-lowering and antihypertensive treatment may improve outcome. The pathophysiologic relationship between LPG and TMA should be investigated further. [ABSTRACT FROM AUTHOR]

Background: Malignant hypertension is frequently complicated by renal insufficiency. Although the survival of this hypertensive emergency has improved, recent data on renal outcome and its predictors are lacking. We assessed renal outcome and its predictors in patients with malignant hypertension.Methods: Retrospective analysis of patients admitted with malignant hypertension in Amsterdam, the Netherlands between August 1992-January 2010. Follow-up data on vital status, renal function and blood pressure (BP) were obtained from the outpatient department and from general practitioners. The primary composite endpoint was end-stage renal disease (ESRD) defined as the start of kidney replacement therapy (KRT) or ? 50% decline of estimated glomerular filtration rate (eGFR). The secondary endpoint was all cause mortality.Results: A total of 120 patients admitted with malignant hypertension were included. After a median follow-up period of 67 months (IQR 28 to 108 months) the primary endpoint was reached by 37 (31%) patients, whereas 18patients (15%) reached the secondary endpoint. Twenty-nine (24%) patients started KRT and 8 patients (7%) had an eGFR decline ? 50%. After the acute phase (> 3 months after admission), initial serum creatinine and follow-up BP were the main predictors of future ESRD with hazard ratios of 6.1 (95% CI, 2.2-17) for patients with initial serum creatine ? 175 ?mol /L and 4.3 (95% CI, 1.4-14) for patients with uncontrolled hypertension.Conclusions: Progressive renal function decline leading to ESRD remains a major threat to patients with malignanthypertension. BP control during follow-up was an important modifiable predictor of renal outcome. [ABSTRACT FROM AUTHOR]