Epidemiology of Cancer in Kidney Transplant Recipients.

Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.

The Intersection of SGLT2 Inhibitors, Cognitive Impairment, and CKD.

Impairment in cognition and decline in kidney function often converge in the aging individual with chronic kidney disease (CKD). Cognitive impairment (CI) may be preventable through modification of health behaviors and risk factors that contribute to the vascular disease burden. CKD patients often have multiple coexisting comorbid conditions contributing to vascular risk. These comorbidities include hypertension, diabetes, cerebrovascular disease, and cardiovascular disease. Emerging evidence suggests that the management and prevention of vascular risk factors and cardiovascular diseases may indirectly contribute to the prevention of CI in CKD. Sodium glucose transport protein 2 inhibitors (SGLT2i) are emerging as the standard of care for selected individuals with CKD, type 2 diabetes (T2DM), and heart failure with rapidly expanding indications being actively investigated. In this narrative review, we examine the intriguing hypothesis that SGLT2i demonstrate potential disease modifying properties in CI among individuals with CKD.

Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age.

Importance: Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use. Objective: To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age. Design, Setting, and Participants: Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level. Exposure: Dispensed sodium polystyrene sulfonate in an outpatient setting. Main Outcomes and Measures: The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription. Results: From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury. Conclusions and Relevance: The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

Heme Oxygenase-1 Induction Prevents Autoimmune Diabetes in Association With Pancreatic Recruitment of M2-Like Macrophages, Mesenchymal Cells, and Fibrocytes.

Immunoregulatory and regenerative processes are activated in the pancreas during the development of type 1 diabetes (T1D) but are insufficient to prevent the disease. We hypothesized that the induction of cytoprotective heme oxygenase-1 (HO-1) by cobalt protophoryrin (CoPP) would prevent T1D by promoting anti-inflammatory and pro-repair processes. Diabetes-prone BioBreeding rats received ip CoPP or saline twice per week for 3 weeks, starting at 30 days and were monitored for T1D. Immunohistochemistry, confocal microscopy, quantitative RT-PCR, and microarrays were used to evaluate postinjection pancreatic changes at 51 days, when islet inflammation is first visible. T1D was prevented in CoPP-treated rats (29% vs 73%). Pancreatic Hmox1 was up-regulated along with islet-associated CD68(+)HO-1(+) cells, which were also observed in a striking peri-lobular interstitial infiltrate. Most interstitial cells expressed the mesenchymal marker vimentin and the hematopoietic marker CD34. Spindle-shaped, CD34(+)vimentin(+) cells coexpressed collagen V, characteristic of fibrocytes. M2 macrophage factors Krüppel-like factor 4, CD163, and CD206 were expressed by interstitial cells, consistent with pancreatic upregulation of several M2-associated genes. CoPP upregulated islet-regenerating REG genes and increased neogenic REG3ß(+) and insulin(+) clusters. Thus, short-term induction of HO-1 promoted a protective M2-like milieu in the pancreas and recruited mesenchymal cells, M2 macrophages, and fibrocytes that imparted immunoregulatory and pro-repair effects, preventing T1D.

Gut immune deficits in LEW.1AR1-iddm rats partially overcome by feeding a diabetes-protective diet.

The gut immune system and its modification by diet have been implicated in the pathogenesis of type 1 diabetes (T1D). Therefore, we investigated gut immune status in non-diabetes-prone LEW.1AR1 and diabetes-prone LEW.1AR1-iddm rats and evaluated the effect of a low antigen, hydrolysed casein (HC)-based diet on gut immunity and T1D. Rats were weaned onto a cereal-based or HC-based diet and monitored for T1D. Strain and dietary effects on immune homeostasis were assessed in non-diabetic rats (50-60 days old) and rats with recent-onset diabetes using flow cytometry and immunohistochemistry. Immune gene expression was analysed in mesenteric lymph nodes (MLN) and jejunum using quantitative RT-PCR and PCR arrays. T1D was prevented in LEW.1AR1-iddm rats by feeding an HC diet. Diabetic LEW.1AR1-iddm rats had fewer lymphoid tissue T cells compared with LEW.1AR1 rats. The percentage of CD4(+)  Foxp3(+) regulatory T (Treg) cells was decreased in pancreatic lymph nodes (PLN) of diabetic rats. The jejunum of 50-day LEW.1AR1-iddm rats contained fewer CD3(+) T cells, CD163(+) M2 macrophages and Foxp3(+) Treg cells. Ifng expression was increased in MLN and Foxp3 expression was decreased in the jejunum of LEW.1AR1-iddm rats; Ifng/Il4 was decreased in jejunum of LEW.1AR1-iddm rats fed HC. PCR arrays revealed decreased expression of M2-associated macrophage factors in 50-day LEW.1AR1-iddm rats. Wheat peptides stimulated T-cell proliferation and activation in MLN and PLN cells from diabetic LEW.1AR1-iddm rats. LEW.1AR1-iddm rats displayed gut immune cell deficits and decreased immunoregulatory capacity, which were partially corrected in animals fed a low antigen, protective HC diet consistent with other models of T1D.