An observational cohort feasibility study to identify microvesicle and miRNA biomarkers of acute kidney injury following paediatric cardiac surgery

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Objectives: Micro-RNA, small noncoding RNA fragments involved in gene regulation, and microvesicles, membrane-bound particles less than 1 μm known to regulate cellular processes including responses to injury, may serve as disease-specific biomarkers of acute kidney injury. We evaluated the feasibility of measuring these signals as well as other known acute kidney injury biomarkers in a mixed pediatric cardiac surgery population. Design: Single center prospective cohort feasibility study. Setting: PICU. Patients: Twenty-four children (≤ 17 yr) undergoing cardiac surgery with cardiopulmonary bypass without preexisting inflammatory state, acute kidney injury, or extracorporeal life support. Interventions: None. Measurements and Main Results: Acute kidney injury was defined according to modified Kidney Diseases Improving Global Outcomes criteria. Blood and urine samples were collected preoperatively and at 6–12 and 24 hours. Microvesicles derivation was assessed using flow cytometry and NanoSight analysis. Micro-RNAs were isolated from plasma and analyzed by microarray and quantitative real-time polymerase chain reaction. Data completeness for the primary outcomes was 100%. Patients with acute kidney injury (n = 14/24) were younger, underwent longer cardiopulmonary bypass, and required greater inotrope support. Acute kidney injury subjects had different fractional content of platelets and endothelial-derived microvesicles before surgery. Platelets and endothelial microvesicles levels were higher in acute kidney injury patients. A number of micro-RNA species were differentially expressed in acute kidney injury patients. Pathway analysis of candidate target genes in the kidney suggested that the most often affected pathways were phosphatase and tensin homolog and signal transducer and activator of transcription 3 signaling. Conclusions: Microvesicles and micro-RNAs expression patterns in pediatric cardiac surgery patients can be measured in children and potentially serve as tools for stratification of patients at risk of acute kidney injury

Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease?

Type II diabetic kidney disease is devastating to patients and society alike. This review will evaluate bariatric surgery as a treatment for diabetic kidney disease primarily through its ability to induce and maintain regression of type II diabetes. The review begins by outlining the global challenge of diabetic kidney disease, its link to obesity, and the comparative benefits of bariatric surgery on weight and type II diabetes. It then surveys comprehensively the relevant literature, which reports that although bariatric surgery is associated with reductions in albuminuria, its effect on harder clinical end points like progression of diabetic kidney disease is not known. The review also includes a critical assessment of the risks and costs of bariatric surgery and concludes by acknowledging the major knowledge gaps in the field and providing research strategies to overcome them. Until these knowledge gaps are filled, clinicians will be forced to rely on their own subjective judgment in determining the benefit-risk ratio of bariatric surgery for patients with diabetic kidney disease

Francis Daniels Moore: one of the brightest minds in the surgical field.

Francis Daniels Moore was a pioneer ahead of his time who made numerous landmark contributions to the field of surgery, including the understanding of metabolic physiology during surgery, liver and kidney transplant, and the famous Study on Surgical Services of the United States (SOSSUS) report of 1975 that served for decades as a guideline for development of surgical residencies. He was the epitome of what a physician should be, a compassionate and dedicated surgeon, innovative scientist, and a medical professional dedicated to quality medical education across all specialties

Factors Associated with Unplanned Conversion to Open in Nephrectomy for Kidney Cancer

Minimally invasive surgery (MIS) has been adopted as an approach in kidney surgery. Laparoscopic kidney surgery has been introduced in the 1990s with robotics emerging a decade after. The minimally invasive approach has been technically feasible and has been shown to be noninferior with preserved oncology standards to open surgery. The ubiquitous use of MIS for kidney cancer has been standard of practice; however, unplanned conversion to open kidney surgery has been characterized at 4.9% for laparoscopic radical nephrectomy compared to 6.0% in robotic radical nephrectomy. Another analysis of 54,246 patients undergoing partial nephrectomy for kidney cancer observed an unplanned open conversion rate of 2.87% for cT1 renal masses. Furthermore, the unplanned conversion to open radical or partial nephrectomy after an attempted minimally invasive approach has been an independent predictor of increased risk of 30-day hospital readmission. Currently, the relative risk factors to predict unplanned conversion to open surgery has not been well characterized. Greater understanding of risk factors for unplanned open conversion has clinical implications to reduce intraoperative and postoperative outcomes. The early recognition of nationwide risk and predictors may aid in identifying patients for planned open kidney surgery. We aim to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify predictors and outcomes in a contemporary cohort

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats

Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats

Those who Give: Art and Gail Pasquarella Support Jefferson Transplant Institute

Art Pasquarella is a donor in every sense of the word. He gave a kidney as a living donor to one of his brothers. He gives his time as a volunteer for the National Kidney Foundation. And he and his wife, Gail, have made a very generous gift to support the vision for the Jefferson Transplant Institute. As Art explains, the Pasquarellas had more than one reason to support transplant services at Jefferson. The first reason was a kidney transplant for Art’s late father, Valentino H. Pasquarella, Sr., in the mid-1990s. “Jefferson did a fabulous job for my father,” Art recalls, “That started our family’s affinity toward Jefferson.” Some 15 years later, Art’s oldest brother, Valentino H. Pasquarella, Jr., was suffering from another type of kidney disease, which had developed from an illness during infancy. Art and his other brother, Joe, underwent the battery of tests to determine compatibility. After discovering that he was a 100 percent match, Art signed on to be a living donor. In November 2010, Adam Frank, MD, FACS, and Carlo Gerardo Ramirez, MD, FACS, operated on Art and Val, respectively. The operations were both successful, and today the Pasquarella family continues to enjoy spending time together. Art is thankful that his big brother still joins him at the table: “Val has one heck of a sense of humor,” Art laughs. “He’s the ‘entertainer’ at our family dinners, and my daughters and nephews are quick to indicate their disappointment if their Uncle Val is going to miss a family dinner.” When he isn’t enjoying time with his family, Art works as executive vice president and chief operating officer of Equus Capital Partners, Ltd., in Center City. Since 2006, he has also been active with the National Kidney Foundation. For two years, he served as chair of the Delaware Valley Board of the National Kidney Foundation. In 2011, he joined the National Board of the National Kidney Foundation and will soon become chair of the National Board’s Development Committee. “It’s one thing to support a charity by writing checks and soliciting for donations,” he says. “Being a living donor has brought it all really close to home. You realize you have the opportunity to actually change someone’s life.” With their generous donation, the Pasquarellas hope to change more lives by supporting Cataldo Doria, MD, PhD, FACS, the Nicoletti Family Professor of Transplant Surgery and Director, Division of Transplant Surgery, in developing and implementing the Transplant Institute. As Dr. Doria explains, the Transplant Institute represents a multi-institutional alignment of the transplant programs within the Jefferson Health System: “Our goal is for participating hospitals to collaborate on strategic, clinical, quality and financial initiatives – thereby strengthening our collective performance,” he says. “The Institute will work to promote standardized clinical pathways and protocols and to deliver a streamlined experience for the patient.” For information about planned giving, or to make a contribution to the Department of Surgery, please contact Lara Goldstein in the Jefferson Foundation at 215-955-8797 or Email Lara Goldstei

Prevention of acute kidney injury and protection of renal function in the intensive care unit : update 2017

Background: Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity. Objectives: To determine and update previous recommendations for the prevention of AKI, specifically the role of fluids, diuretics, inotropes, vasopressors/vasodilators, hormonal and nutritional interventions, sedatives, statins, remote ischaemic preconditioning and care bundles. Method: A systematic search of the literature was performed for studies published between 1966 and March 2017 using these potential protective strategies in adult patients at risk of AKI. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, exposure to potentially nephrotoxic drugs and radiocontrast. Clinical endpoints included incidence or grade of AKI, the need for renal replacement therapy and mortality. Studies were graded according to the international GRADE system. Results: We formulated 12 recommendations, 13 suggestions and seven best practice statements. The few strong recommendations with high-level evidence are mostly against the intervention in question (starches, low-dose dopamine, statins in cardiac surgery). Strong recommendations with lower-level evidence include controlled fluid resuscitation with crystalloids, avoiding fluid overload, titration of norepinephrine to a target MAP of 65-70 mmHg (unless chronic hypertension) and not using diuretics or levosimendan for kidney protection solely. Conclusion: The results of recent randomised controlled trials have allowed the formulation of new recommendations and/or increase the strength of previous recommendations. On the other hand, in many domains the available evidence remains insufficient, resulting from the limited quality of the clinical trials and the poor reporting of kidney outcomes

Tissue oxygenation and vascular reactivity as measured with Near-Infrared Spectroscopy in (perioperative) patients

Many processes surrounding surgery can influence the oxygen supply or consumption of organs. This thesis aimed to gain insight into a measurement method that can non-invasively measure oxygen levels in tissue: near-infrared spectroscopy (NIRS). Early detection of oxygen deficiency in the kidney or brain of patients during surgery might prevent damage to these organs.In literature, lower kidney NIRS values were associated with kidney damage after surgery in approximately 63% of the cases. Unfortunately, we cannot recommend kidney NIRS measurements for evaluating the oxygen content in the kidney, as we discovered in healthy volunteers that kidney NIRS measurements underestimate the directly measured oxygen content in the kidney's blood vessels. We found that lower brain NIRS values (72 hours after cooling) in children born with oxygen deprivation are associated with adverse neurological development later in life. Low brain NIRS values directly after intubation in pediatric cardiac surgery are associated with increased mortality 30 days after surgery.The dynamics of small blood vessels influence the oxygen supply to the organs and can be objectified by adding a short blood vessel occlusion test to the NIRS measurements. Literature has described that the dynamics of small blood vessels decrease during surgery, possibly due to the (sterile) inflammatory reaction. Different oxygen or carbon dioxide concentrations in the inhaled air in healthy volunteers did not influence these dynamics

Robot-assisted surgery in horseshoe kidneys: A safety and feasibility multi-centre case series

OBJECTIVE: We assessed the safety and feasibility of minimally invasive robot-assisted surgery for horseshoe kidney (HSK). METHOD: A prospectively maintained data set for consecutive patients undergoing robotic kidney surgery was reviewed for patients with HSK. Cases were performed by experienced robotic surgeons, across two high-volume centres between 2016 and 2020. RESULTS: A prospectively maintained data set for consecutive patients undergoing robotic kidney surgery was reviewed for patients with HSK. Cases were performed by experienced robotic surgeons, across two high-volume centres between 2016 and 2020. CONCLUSION: We report one the largest series of robot-assisted surgery on HSK. Robotic surgery is safe and feasible for HSK in centralised high-volume centres with acceptable perioperative outcomes. Established benefits of minimally invasive surgery, such as reduced LOS and low complication rates, were demonstrated. LEVEL OF EVIDENCE: 4