A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib.

BACKGROUND: Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy. CASE PRESENTATION: The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy. CONCLUSIONS: CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

Lung metabolomics after ischemic acute kidney injury reveals increased oxidative stress, altered energy production, and ATP depletion.

Acute kidney injury (AKI) is a complex disease associated with increased mortality that may be due to deleterious distant organ effects. AKI associated with respiratory complications, in particular, has a poor outcome. In murine models, AKI is characterized by increased circulating cytokines, lung chemokine upregulation, and neutrophilic infiltration, similar to other causes of indirect acute lung injury (ALI; e.g., sepsis). Many causes of lung inflammation are associated with a lung metabolic profile characterized by increased oxidative stress, a shift toward the use of other forms of energy production, and/or a depleted energy state. To our knowledge, there are no studies that have evaluated pulmonary energy production and metabolism after AKI. We hypothesized that based on the parallels between inflammatory acute lung injury and AKI-mediated lung injury, a similar metabolic profile would be observed. Lung metabolomics and ATP levels were assessed 4 h, 24 h, and 7 days after ischemic AKI in mice. Numerous novel findings regarding the effect of AKI on the lung were observed including 1) increased oxidative stress, 2) a shift toward alternate methods of energy production, and 3) depleted levels of ATP. The findings in this report bring to light novel characteristics of AKI-mediated lung injury and provide new leads into the mechanisms by which AKI in patients predisposes to pulmonary complications.

Prevention of Peritoneal Dialysis Drop-Out.

Compared with hemodialysis (HD), peritoneal dialysis (PD) is associated with reduced cost and improved quality of life. But despite those benefits, PD represents a small percentage of the renal replacement therapy performed. Although a number of factors contribute to that situation, peritoneal drop-out is a complex issue that leads to as much as a 35% annual transition from PD to in-center HD. The reasons for drop-out are multifaceted and include contributions from the patient or caregiver, health care regulatory systems, and factors intrinsic to the PD modality. In this review, we focus on specific causes of PD drop-out and on prevention and intervention strategies that can improve success and duration on PD.