Burden of Kidney Disease in an Aging Population Living with HIV in the United States.

Antiretroviral therapy (ART) has significantly improved mortality rates for individuals living with HIV, but kidney disease remains prevalent, especially among older adults. Our study analyzed the burden of kidney disease in individuals aged 65 and older at The Miriam Hospital Immunology Center in Rhode Island. We calculated estimated glomerular filtration rates using the last creatinine values from 2019 and identified chronic kidney disease (CKD) stages.

SET8 inhibition preserves PTEN to attenuate kidney cell apoptosis in cisplatin nephrotoxicity.

The aberrant expression of SET8, a histone methyltransferase that mediates H4 lysine 20 mono-methylation (H4K20me1), is implicated in the pathogenesis of various tumors, however, its role in acute kidney injury (AKI) is unknown. Here we showed that SET8 and H4K20me1 were upregulated in the murine kidney with AKI induced by cisplatin, along with increased renal tubular cell injury and apoptosis and decreased expression of E-cadherin and Phosphatase and Tensin Homolog (PTEN). Suppression of SET8 by UNC0379 improved renal function, attenuated tubule damage, and restored expression of PTEN, but not E-cadherin.

Unexpected Medical Conditions Discovered During Live Donor Kidney Evaluation: Single Center Study.

Objectives: Living donor kidney transplantation (LDKT) is the preferred method of treatment for patients with end-stage kidney disease. Potential living kidney donors (PLKD) are evaluated through a thorough medical, psychological and surgical work-up to ensure successful transplantation with minimal risks to all parties involved. The transplant center at Rhode Island Hospital has noticed an increasing number of PLKDs excluded from donation due to conditions newly diagnosed during the screening process.

Obstructive Uropathy due to Bilateral Sliding Hernia in a Renal Transplant Patient with Incidental RCC in Native Kidney.

Background: Ureteral obstruction is a common complication after kidney transplantation. Ureteral obstruction caused by inguinal hernia, however, is a rare complication of transplantation and requires urgent surgical repair to prevent allograft loss.  Case presentation: A 58-year-old man presented with allograft dysfunction 18-years after renal transplant.

Sleep duration and cognitive function among older adults with chronic kidney disease: results from the National Health and Nutrition Examination Survey (2011-2014).

Background: Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the chronic kidney disease (CKD) population, we tested whether the association between sleep duration and cognitive function differed between older adults with and without CKD.

Methods: This was a study of 3215 older adults (age ≥60 years) enrolled in the National Health and Nutrition Examination Survey (2011-14) evaluating sleep duration, cognitive function (immediate recall, delayed recall, verbal fluency, executive function and processing speed and global cognition) and kidney function.

Inhibition of MLL1-menin interaction attenuates renal fibrosis in obstructive nephropathy.

Mixed lineage leukemia 1 (MLL1), a histone H3 lysine 4 (H3K4) methyltransferase, exerts its enzymatic activity by interacting with menin and other proteins. It is unclear whether inhibition of the MLL1-menin interaction influences epithelial-mesenchymal transition (EMT), renal fibroblast activation, and renal fibrosis. In this study, we investigated the effect of disrupting MLL1-menin interaction on those events and mechanisms involved in a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO), in cultured mouse proximal tubular cells and renal interstitial fibroblasts.

Practical ethical concerns in allocation of pig kidneys to humans.

The fundamental ethical question of whether pig organs should be transplanted into humans has been settled, as recent surgeries demonstrating proof of concept demonstrate. Other issues need to be considered and reconciled before xenotransplantation of pig kidneys becomes a solution to the organ shortage for people waiting for a kidney transplant or as a viable alternative to the deceased donor or living donor human kidneys. Human trials will be needed beyond brain-dead individuals to show that xenotransplantation is safe from immunologic and infectious standpoints.

The Diabetic Cardiorenal Nexus.

The end-stage of the clinical combination of heart failure and kidney disease has become known as cardiorenal syndrome. Adverse consequences related to diabetes, hyperlipidemia, obesity, hypertension and renal impairment on cardiovascular function, morbidity and mortality are well known. Guidelines for the treatment of these risk factors have led to the improved prognosis of patients with coronary artery disease and reduced ejection fraction.

Inhibition of polycomb repressive complex 2 by targeting EED protects against cisplatin-induced acute kidney injury.

Polycomb repressive complex 2 (PRC2) is a multicomponent complex with methyltransferase activity that catalyzes trimethylation of histone H3 at lysine 27 (H3K27me3). Interaction of the epigenetic reader protein EED with EZH2, a catalytic unit of PRC, allosterically stimulates PRC2 activity. In this study, we investigated the role and underlying mechanism of the PRC2 in acute kidney injury (AKI) by using EED226, a highly selective PRC2 inhibitor, to target EED.

Efficacy of remdesivir for hospitalized COVID-19 patients with end stage renal disease.

Background: Since the beginning of corona virus disease 2019 (COVID-19) pandemic, there has been a widespread use of remdesivir in adults and children. There is little known information about its outcomes in patients with end stage renal disease who are on dialysis.

Aim: To assess the clinical outcomes with use of remdesivir in adult patients with end stage kidney failure on hemodialysis.

Ethical analysis examining the prioritisation of living donor transplantation in times of healthcare rationing.

The transplant community has faced unprecedented challenges balancing risks of performing living donor transplants during the COVID-19 pandemic with harms of temporarily suspending these procedures. Decisions regarding postponement of living donation stem from its designation as an elective procedure, this despite that the Centers for Medicare and Medicaid Services categorise transplant procedures as tier 3b (high medical urgency-do not postpone). In times of severe resource constraints, health systems may be operating under crisis or contingency standards of care.

Low-Dose Valganciclovir Prophylaxis Is Safe and Cost-Saving in CMV-Seropositive Kidney Transplant Recipients.

Observational studies suggest that low-dose valganciclovir prophylaxis (450 mg daily for normal renal function) is as effective as and perhaps safer than standard-dose valganciclovir (900 mg daily) in preventing CMV infection among kidney transplant recipients. However, this practice is not supported by current guidelines due to concerns for breakthrough infection from resistant CMV, mainly in high-risk CMV donor-seropositive/recipient-seronegative kidney transplant recipients. Standard-dose valganciclovir is costly and possibly associated with higher incidence of neutropenia and BKV DNAemia.

New Insights Into the Effects of Individual Chinese Herbal Medicines on Chronic Kidney Disease.

The clinical and experimental study into the effects of Chinese herbal medicines on chronic kidney disease has evolved over the past 40 years with new insight into their mechanism and evidence of their clinical effects. Among the many traditional Chinese herbs examined in chronic renal disease, five were found to have evidence of sufficient clinical efficacy, high frequency of use, and well-studied mechanism. They are: and , and its components (tanshinone II A, salvianolic acid A and B); and its monomer ; and its components (triptolide, tripterygium glycosides); Kudzu root and its monomer .

Critical roles of SMYD2 lysine methyltransferase in mediating renal fibroblast activation and kidney fibrosis.

SET and MYND domain protein 2 (SMYD2) is a lysine methyltransferase that mediates histone H3 lysine 36 trimethylation (H3K36me3) and acts as a regulator of tumorgenesis and cystic growth. However, its role in renal fibrosis remains unknown. In this study, we found that SMYD2 was highly expressed in the murine kidney of renal fibrosis induced by unilateral ureteral obstruction, and primarily located in interstitial fibroblasts and renal tubular epithelial cells.

Kidney Disease among People Who Are Incarcerated.

CKD affects 15% of US adults and is associated with higher morbidity and mortality. CKD disproportionately affects certain populations, including racial and ethnic minorities and individuals from disadvantaged socioeconomic backgrounds. These groups are also disproportionately affected by incarceration and barriers to accessing health services.

Nephrotoxicity of immune checkpoint inhibitor therapy: a pharmacovigilance study.

Background: Immune checkpoint inhibitor (ICI) therapy has demonstrated impressive clinical benefits across cancers. However, adverse drug reactions (ADRs) occur in every organ system, often due to autoimmune syndromes. We sought to investigate the association between ICI therapy and nephrotoxicity using a pharmacovigilance database, hypothesizing that inflammatory nephrotoxic syndromes would be reported more frequently in association with ICIs.

Porcine models of acute kidney injury.

Pigs represent a potentially attractive model for medical research. Similar body size and physiological patterns of kidney injury that more closely mimic those described in humans make larger animals attractive for experimentation. Using larger animals, including pigs, to investigate the pathogenesis of acute kidney injury (AKI) also serves as an experimental bridge, narrowing the gap between clinical disease and preclinical discoveries.

Epidermal Growth Factor Receptor: A Potential Therapeutic Target for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease worldwide and the major cause of renal failure among patients on hemodialysis. Numerous studies have demonstrated that transient activation of epidermal growth factor receptor (EGFR) pathway is required for promoting kidney recovery from acute injury whereas its persistent activation is involved in the progression of various chronic kidney diseases including DKD. EGFR-mediated pathogenesis of DKD is involved in hemodynamic alteration, metabolic disturbance, inflammatory response and parenchymal cellular dysfunction.

Coronavirus Disease 2019 in Kidney Transplant Recipients: Single-Center Experience and Case-Control Study.

Background: Kidney transplant recipients (KTR) are considered high-risk for morbidity and mortality from coronavirus disease 2019 (COVID-19). However, some studies did not show worse outcomes compared to non-transplant patients and there is little data about immunosuppressant drug levels and secondary infections in KTR with COVID-19. Herein, we describe our single-center experience with COVID-19 in KTR.

Frailty and Kidney Transplantation.

Two significant policy changes, one in the way people are put forward for kidney transplants and the other in the way in which kidneys are distributed to people on the waiting list, make the question of whether someone is too frail to receive a transplant all the more relevant, particularly in Rhode Island. An executive order signed by President Donald Trump1 stresses that efforts to treat kidney disease need to concentrate on providing more people with kidney transplants and increasing the number of organs transplanted rather than discarded. An effort to decrease waiting times for kidneys in large metropolitan areas2 potentially means that younger, more desirable kidneys will be shipped out of New England, leaving longer waiting times and less desirable organs for transplantation in our region.

Histone demethylase JMJD3 protects against renal fibrosis by suppressing TGFβ and Notch signaling and preserving PTEN expression.

The Jumonji domain containing-3 (JMJD3), a specific histone demethylase for trimethylation on histone H3 lysine 27 (H3K27me3), is associated with the pathogenesis of many diseases, but its role in renal fibrosis remains unexplored. Here we examined the role of JMJD3 and mechanisms involved in the activation of renal fibroblasts and development of renal fibrosis. Murine models of 5/6 surgical nephrectomy (SNx) and ureteral unilateral obstruction (UUO) were used to assess the effect of a specific JMJD3 inhibitor, GSKJ4, and genetic deletion of JMJD3 from FOXD1 stroma-derived renal interstitial cells on the development of renal fibrosis and activation of renal interstitial fibroblasts.