Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease.

Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978). Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

[Latest updates on immunotactoid glomerulopathy and fibrillary glomerulonephritis]. / Dernières nouveautés sur la glomérulopathie immunotactoïde et la glomérulonéphrite fibrillaire.

Various hematologic malignancies can lead to renal complications. The most common of these hemopathies to affect the kidney is multiple myeloma, however an increasing number of kidney diseases are associated with other monoclonal gammopathies. It is recognized that clones in small abundance can be responsible for severe organ damage, thus the concept of monoclonal gammopathy of renal significance (MGRS) has emerged. Although the hemopathy in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with multiple myeloma, the diagnosis of a renal complication changes the therapeutic management. Preservation and restoration of renal function is possible with treatment targeting the responsible clone. In this article, we take as an example immunotactoid and fibrillary glomerulopathies, two distinct entities with different etiologies and consequently different management. Immunotactoid glomerulopathy is most often associated with monoclonal gammopathy or chronic lymphocytic leukemia, the deposits on renal biopsy are monotypic, and treatment is therefore based on clone targeting. Fibrillary glomerulonephritis, on the other hand, is caused by autoimmune diseases or solid cancers. Deposits on renal biopsy are in the vast majority polyclonal. There is a specific immunohistochemical marker, DNAJB9, and treatment is less well established.

Onco-nephrology: Physicians' Expectations About a New Subspecialty.

INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.

Recurrence of IgA Nephropathy after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

[Renal failure and renal symptoms associated with molecular targeted therapies in oncology]. / Insuffisance rénale et symptômes rénaux associés aux thérapies moléculaires ciblées en oncologie.

"Targeted therapies and pathophysiological mechanisms of proteinuria Targeted therapy represents a promising therapeutic approach for patients with diverse cancers and has enabled significant development in medical oncology. This new class of anticancer drugs includes antibodies, fusion-proteins and receptor tyrosine kinase inhibitors among others. Depending on their molecular targeting, side effects can affect multiple organs, especially the kidney. Antiangiogenic agents inhibit the VEGF/VEGFR pathway resulting in reduction of nitric oxide production and alteration of podocytes function, which causes hypertension and proteinuria. EGFR inhibitors are responsible of electrolytic disorders. Hereby, we synthetized the current knowledge on renal toxicities on main molecular targeted therapies. Toxicities management is mainly based on clinical and biological monitoring, which can lead to drug withdrawing or dose adaptation."

"Thérapies ciblées et mécanismes physiopathologiques de la protéinurie Les thérapies ciblées occupent désormais une place majeure en oncologie médicale. Elles existent sous plusieurs formes d'administration, parentérale ou per os, et comportent entre autres des anticorps, des protéines de fusion et des inhibiteurs de récepteur des tyrosine kinases. Les effets indésirables liés à ces thérapies dépendent généralement de leur classe thérapeutique. Les antiangiogéniques, qui altèrent les podocytes et la production de monoxyde d'azote via l'inhibition de la voie VEGF/VEGFR, entraînent hypertension artérielle et protéinurie et sont parfois à l'origine de microangiopathies thrombotiques. Les inhibiteurs de l'EGFR entraînent principalement des troubles hydroélectrolytiques par inhibition de transporteurs rénaux. D'autres toxicités sont plus rares, comme les inhibiteurs de BRAF, parfois à l'origine d'insuffisances rénales aiguës immuno-allergiques. La prise en charge de ces toxicités repose généralement sur la surveillance clinique et biologique et peut conduire à la suspension des traitements ou à leur adaptation posologique."

Opioids and Kidney Transplantation.

The United States has faced an unprecedented opioid crisis in recent years, which has led to an increase in opioid overdose-related deaths and, consequently, an increase in the number of potential deceased donors available for transplantation. This new pool of potential organ donors is composed of younger donors with higher infectious disease transmission risk. The use of organs from these donors requires appropriate patient education, informed consent, and post-transplant monitoring practices. Prescription opioid use is also an important component of the evaluation of transplant and living donor candidates because it may impact outcomes and eligibility for the procedures. In kidney transplant recipients, prescription opioid use predicts a higher risk of mortality, graft loss, and post-transplant complications. These effects seem to be proportional to the levels of opioid use, and to parallel patterns in other transplant populations such as liver, heart and lung recipients. Among living kidney donors, predonation prescription opioid use is associated with an increased risk of re-admission after nephrectomy. Overall, the opioid epidemic creates educational needs for patients awaiting deceased donor transplant, and also impacts the evaluation and care of transplant candidates. Among transplant candidates and recipients, the identification of patients with chronic opioid use should prompt multidisciplinary evaluation and management strategies to minimize risks.

[Therapeutics for acute tubular necrosis in 2020]. / Prise en charge de la nécrose tubulaire aiguë en 2020.

Acute kidney injury is a major cause of in-hospital morbidity and mortality because of the serious nature of the underlying illnesses and the high incidence of complications. The two major causes of acute kidney injury that occur in the hospital are prerenal disease and acute tubular necrosis. Acute tubular necrosis has a histological definition, even if a kidney biopsy is rarely performed. Kidney injuries occurring during acute tubular necrosis are underlined by different pathophysiological mechanisms that emphasize the role of hypoxia on the tubular cells such as apoptosis, cytoskeleton disruption, mitochondrial function and the inflammation mediated by innate immune cells. The microcirculation and the endothelial cells are also the targets of hypoxia-mediated impairment. Repair mechanisms are sometimes inadequate because of pro-fibrotic factors that will lead to chronic kidney disease. Despite all the potential therapeutic targets highlighted by the pathophysiological knowledge, further works remain necessary to find a way to prevent these injuries.