Reports show that AKI is a common complication of severe coronavirus disease 2019 (COVID-19) in hospitalized patients. Studies have also observed proteinuria and microscopic hematuria in such ...patients. Although a recent autopsy series of patients who died with severe COVID-19 in China found acute tubular necrosis in the kidney, a few patient reports have also described collapsing glomerulopathy in COVID-19.
We evaluated biopsied kidney samples from ten patients at our institution who had COVID-19 and clinical features of AKI, including proteinuria with or without hematuria. We documented clinical features, pathologic findings, and outcomes.
Our analysis included ten patients who underwent kidney biopsy (mean age: 65 years); five patients were black, three were Hispanic, and two were white. All patients had proteinuria. Eight patients had severe AKI, necessitating RRT. All biopsy samples showed varying degrees of acute tubular necrosis, and one patient had associated widespread myoglobin casts. In addition, two patients had findings of thrombotic microangiopathy, one had pauci-immune crescentic GN, and another had global as well as segmental glomerulosclerosis with features of healed collapsing glomerulopathy. Interestingly, although the patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RT-PCR, immunohistochemical staining of kidney biopsy samples for SARS-CoV-2 was negative in all ten patients. Also, ultrastructural examination by electron microscopy showed no evidence of viral particles in the biopsy samples.
The most common finding in our kidney biopsy samples from ten hospitalized patients with AKI and COVID-19 was acute tubular necrosis. There was no evidence of SARS-CoV-2 in the biopsied kidney tissue.
Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's ...own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers.
In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.
Thrombotic microangiopathy associated with hematopoietic stem cell transplantation (HSCT-TMA) is a well-recognized complication of HSCT that has a high risk for death. Even in patients who survive, ...HSCT-TMA is associated with long-term morbidity and chronic organ injury. HSCT-TMA is a multisystem disease that often affects the kidneys. Renal manifestations of HSCT-TMA include reduced glomerular filtration rate, proteinuria, and hypertension. Understanding of the pathophysiology of HSCT-TMA has expanded in the last decade. Endothelial injury plays a major role. Recent studies also suggest involvement of complement activation. HSCT-TMA has also been considered by some to be an endothelial variant of graft-versus-host disease. Understanding the pathophysiology of HSCT-TMA and its association with activation of the complement system may aid in developing novel therapeutic options. In this review, we summarize current knowledge focusing on epidemiology and prognosis, evidence of complement activation, and endothelial injury; the possible link to graft-versus-host disease; and treatment options for HSCT-TMA.
Immune checkpoint inhibitors (ICIs) are increasingly used to treat cancers. Kidney immune-related adverse events (IRAEs) are now well recognized, with the incidence of IRAEs ranging from 2% to 5%. ...Most of the initial data related to kidney IRAEs have focused on acute interstitial nephritis (AIN). There are minimal data on the types and relative frequencies of glomerular diseases associated with ICIs, their treatment, and outcomes.
We performed a systematic review and meta-analysis of all biopsy-proven published cases/series of glomerular pathology associated with ICIs. We searched the MEDLINE, EMBASE, and Cochrane databases from inception to February 2020. We abstracted patient-level data, including demographics, cancer and ICI therapy details, and characteristics of kidney injury.
After screening, 27 articles with 45 cases of biopsy-confirmed ICI-associated glomerular disease were identified. Several lesion types were observed, with the most frequent being pauci-immune glomerulonephritis (GN) and renal vasculitis (27%), podocytopathies (24%), and complement 3 GN (C3GN; 11%). Concomitant AIN was reported in 41%. Most patients had ICIs discontinued (88%), and nearly all received corticosteroid treatment (98%). Renal replacement therapy (RRT) was required in 25%. Most patients had full (31%) or partial (42%) recovery from acute kidney injury (AKI), although 19% remained dialysis-dependent, and approximately one-third died. Complete or partial remission of proteinuria was achieved in 45% and 38%, respectively.
Multiple forms of ICI-associated glomerular disease have been described. Pauci-immune GN, podocytopathies, and C3GN are the most frequently reported lesions. ICI-associated glomerular disease may be associated with poor kidney and mortality outcomes. Oncologists and nephrologists must be aware of glomerular pathologies associated with ICIs and consider obtaining a kidney biopsy specimen when features atypical for AIN are present.
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Selinexor for Refractory Multiple Myeloma Jhaveri, Kenar D; Wanchoo, Rimda; Chari, Ajai ...
The New England journal of medicine,
11/2019, Letnik:
381, Številka:
20
Journal Article
Recenzirano
To the Editor:
In the article by Chari et al. (Aug. 22 issue)
1
on oral selinexor for multiple myeloma, we noticed that one of the most common grade 3 or 4 adverse events was hyponatremia (serum ...sodium level, <130 mmol per liter) (in 22% of the patients). This appears to be a class effect of selinexor, because other studies of this agent had similar incidences of hyponatremia, ranging from 7 to 26%.
2-5
The incidence of hyponatremia was higher in studies involving patients with multiple myeloma than in studies involving patients with solid tumors. No workup was performed or no cause . . .
Acute kidney injury (AKI) is common among hospitalized patients with coronavirus disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. An improved knowledge of the pathology ...of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who develop AKI during COVID-19. In this review, we summarize the published cases and case series of various kidney pathologies seen with COVID-19. Both live kidney biopsies and autopsy series suggest acute tubular injury as the most commonly encountered pathology. Collapsing glomerulopathy and thrombotic microangiopathy are other encountered pathologies noted in both live and autopsy tissues. Other rare findings such as anti-neutrophil cytoplasmic antibody vasculitis, anti-glomerular basement membrane disease and podocytopathies have been reported. Although direct viral infection of the kidney is possible, it is certainly not a common or even widespread finding reported at the time of this writing (November 2020).
Acute kidney injury (AKI) in the setting of hematopoietic stem cell transplantation (HSCT) is common in pediatric and adult patients. The incidence ranges from 12 to 66%, and development of AKI in ...the posttransplant course is independently associated with higher mortality.
Patients who undergo HSCT have many risk factors for developing AKI, including sepsis, use of nephrotoxic medications, graft versus host disease (GVHD), and veno-occlusive disease (VOD). In addition, engraftment syndrome/cytokine storm, transplant-associated thrombotic microangiopathy (TA-TMA), and less common infections with specific renal manifestations, such as BK and adenovirus nephritis, may lead to kidney injury. There has been significant advancement in the understanding of TA-TMA in particular, especially the role of the complement system in its pathophysiology. The role of early dialysis has been explored in the pediatric population, but not well studied in adult HSCT recipients SUMMARY: This review provides an update on the risk factors, causes, and treatment approaches to HSCT-associated AKI.
Left Ventricular Assist Devices and the Kidney Ross, Daniel W; Stevens, Gerin R; Wanchoo, Rimda ...
Clinical journal of the American Society of Nephrology,
02/2018, Letnik:
13, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Left ventricular assist devices (LVADs) are common and implantation carries risk of AKI. LVADs are used as a bridge to heart transplantation or as destination therapy. Patients with refractory heart ...failure that develop chronic cardiorenal syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility of CKD is hard to predict. After LVAD placement, significant GFR increases may be followed by a late return to near baseline GFR levels, and in some patients, a decline in GFR. In this review, we discuss changes in GFR after LVAD placement, the incidence of AKI and associated mortality after LVAD placement, the management of AKI requiring RRT, and lastly, we review salient features about cardiorenal syndrome learned from the LVAD experience. In light of the growing number of patients using LVADs as a destination therapy, it is important to understand the effect of these devices on the kidney. Additional research and long-term data are required to better understand the relationship between the LVAD and the kidney.
Lorlatinib induced proteinuria: A case report Lee, Chung-Shien; Wanchoo, Rimda; Seetharamu, Nagashree
Journal of oncology pharmacy practice,
06/2021, Letnik:
27, Številka:
4
Journal Article
Recenzirano
Introduction
Lorlatinib is an oral anaplastic lymphoma kinase (ALK) and C-ros oncogene (ROS1) tyrosine kinase inhibitor with excellent central nervous system (CNS) penetrability. It is currently ...approved for use as second line therapy for those with ALK positive non-small cell lung cancer (NSCLC). Given its CNS penetrating effects, lorlatinib has shown to cause CNS adverse events such as seizures, hallucinations, and changes in cognitive function. To our knowledge proteinuria has not been previously described with this medication.
Case Report
We report a case lorlatinib induced proteinuria in a patient receiving lorlatinib as second line treatment for ROS1 rearranged NSCLC.
Management & Outcome: The patient’s dose was reduced from 100 mg to 75 mg and further down to to 50 mg daily. At that point the proteinuria improved. Other adverse events attributable to the medication, specifically hallucinations and peripheral neuropathy also improved.
Discussion
Our case demonstrates objective evidence for proteinuria induced by lorlatinib, which may also be dose dependent.
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