MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations.

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype-phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD.

A Descriptive, Correlational Study of Perceptions of Adult Kidney Transplant Recipients and Those Waiting for a Kidney Transplant About Managing Their Medications During a Pandemic.

Introduction: Little is known about COVID-19 impact on patient medication management. Research Question: The aim was to describe medication management, healthcare team interactions, and adherence during the COVID-19 pandemic in kidney transplant patients and those on the kidney transplant wait list. Design: Using a descriptive, correlational design 340 adults from a midwestern US transplant program were recruited. The Managing Medications in the Midst of a Pandemic Survey measured healthcare team encounters and medication management. The Basel assessment of adherence to medications scale measured medication adherence. Results: The response rate was 35% (119/340). During the pandemic, 88% had practiced/were currently practicing socially distancing, 85% had worn/were currently wearing a face mask in public, 18% had been/were currently diagnosed with COVID-19 and 82% received the vaccine. Medication management: 76% planned and organized their own medications. Healthcare team interactions: 89% met in the office, 20% via phone, 12% telehealth, and 13% delayed seeing a healthcare provider because of COVID-19 concerns. Pharmacy interactions: 11% changed their method of obtaining medications from pharmacy due to social distancing. Medication adherence implementation was problematic with 19% missing a dose; results from the binary logistic regression suggested that those with higher levels of education were more likely to report missing a dose. Conclusions: Patients acted to prevent COVID-19 but some still contracted the virus. The pandemic changed healthcare team medication management interactions. Adherence implementation problems were nearly 20%. Findings are relevant to the transplant healthcare team to understand the impact of a pandemic on patient/team interactions and medication adherence.

Novel role for the incretins in blood pressure regulation.

PURPOSE OF REVIEW: Incretin-based therapies are currently being used in the treatment of type 2 diabetes mellitus (T2DM). Apart from glycemic control, these agents have been shown to have multiple extra-pancreatic effects, including their role in blood pressure (BP) regulation. This article will review the origins of incretins, the incretin axis, possible mechanisms of antihypertensive effect of these agents, as well as the recent evidence. RECENT FINDINGS: Preclinical and clinical studies demonstrate the antihypertensive effects of glucagon-like peptide-1 (GLP-1) and its analogs in patients with T2DM and hypertension. This effect seems to be mediated through vasodilatation as well as modulation of renal sodium handling causing natriuresis, although the exact mechanisms are not fully known. SUMMARY: Incretin-based therapies are emerging as a novel class of hypoglycemic agents that display antihypertensive properties. Given the small decreases in BP, it is unlikely that these agents will be used as stand-alone antihypertensive agents, but they may be an attractive option in patients with T2DM and hypertension.

Health Facts Medication Adherence in Transplantation (H-MAT) Study: A Secondary Analysis of Determinants and Outcomes of Medication Nonadherence in Adult Kidney Transplant Recipients.

Aims: To explore the relationship between determinants and posttransplant medication nonadherence (MNA) in adult kidney transplant recipients, and to examine the relationship between posttransplant MNA and clinical outcomes. Methods: Using the World Health Organization's model, this retrospective, multicenter, correlational study examined the relationship between determinants, posttransplant MNA, and clinical outcomes in 16,671 adult kidney transplant recipients from the Cerner Health Facts national data warehouse. Results: With 12% MNA, those who were nonadherent were more likely to have the social/economic factors of being younger, single, Caucasian versus Hispanic race, have the condition-related factor of mental health/substance use disorder, and have the healthcare system-related factor of government/health maintenance organization/managed care insurance (p's < 0.05). Bivariate correlations indicated both age (OR = 1.006, p=0.01) and mental health or substance use disorder diagnosis (OR = 1.26, p=0.04) were significant predictors of MNA. Patients were 0.6% more likely to be medication adherent for each year they increased in age and 26% more likely to be MNA if they were diagnosed with a mental health/substance use disorder. Nonadherent patients were less likely to be readmitted, but more likely to have complications after transplant and medication side effects (p's < 0.01). Conclusions: Using one of the largest samples of adult kidney transplant patients, our findings support the WHO model and move the body of medication adherence intervention research forward by clarifying the importance of focusing interventions not only on the patient but on multilevel determinants. Consistent with previous studies, MNA negatively impacts transplant outcomes.

Home Dialysis in the Coronavirus Disease 2019 Era.

The coronavirus disease 2019 pandemic has had a significant impact on patients with end-stage kidney disease and their care, especially given the potential for severe coronavirus disease 2019 in those with a depressed immune status. Patients receiving in-center hemodialysis have been particularly affected by this pandemic because of their need to travel multiple times a week to receive treatment. Although patients on home dialysis are able to avoid such exposure, they face their own unique challenges. In this review, we will discuss the challenges posed by the coronavirus disease 2019 pandemic for patients on home dialysis, the impact of coronavirus disease 2019 on various aspects of their care, and the resultant rapid adaptations in policy/health-care delivery mechanisms with implications for the future care of patients on home dialysis.

Calciphylaxis: An Analysis of Concomitant Factors, Treatment Effectiveness and Prognosis in 30 Patients.

BACKGROUND: Calciphylaxis is a rare but severe complication mostly affecting patients with end-stage renal disease (ESRD) and is associated with high morbidity and mortality. The natural history, concomitant factors, pathogenesis, and treatment for calciphylaxis remain equivocal. METHODS: We conducted a retrospective study on patients diagnosed with calciphylaxis in a tertiary care center between January 1, 2012, and December 31, 2017. We describe demographics, co-morbidities, laboratory parameters, effectiveness of sodium thiosulfate treatment and outcomes. RESULTS: Of the 30 patients (age 65.6 ± 12.79 years, male:female = 8:22), 23 (76.67%) had ESRD and were either on hemodialysis (15 [65.22%], median duration 22.5 months [range 0.2-96 months]) or peritoneal dialysis (8 [34.78%], duration 29±10 months). Predisposing home medications: 8 (28%) had calcium supplements, 10 (36%) had warfarin, 16 (57%) had vitamin D and 5 (18%) had iron supplements. The median parathyroid hormone (PTH) level was 239.8 pg/mL (range 4.7-2922). Calciphylaxis was found on extremities in 21 (70%) and on torso in 6 (20%) patients. Sodium thiosulfate (STS) was given for treatment in 20 (67%) patients and 3 were cured in <2.25 months. One-year survival for all patients with calciphylaxis was 26% (29% for STS group and 20% for those that did not receive STS) and following any surgical treatment regardless of STS use was 14%. LIMITATIONS: Retrospective design, absence of a control group and low power. CONCLUSION: Calciphylaxis was more common among females with a predilection for extremities over the torso. Elevations in PTH and inflammatory markers were common. Treatment with STS did not show a statistically significant improvement in survival. Those who were cured, were treated with STS up to three months.

A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient.

Detection of donor-specific antibodies (DSA) is an essential part of diagnosing antibody-mediated renal allograft rejection (ABMR). The role of solitary preformed, or post-transplant HLA-C antigens in solid organ transplantation is unclear, due to the less sensitive nature of the historical assays, lack of data, low expression level on the cell surface, and their co-existence with other anti-HLA DSA. Herein, we present the case of a 39-year-old African American man, without prior history of pre-transplant sensitization that was diagnosed with biopsy-proven ABMR due to de novo donor-specific anti-HLA-C antibodies. This case report illustrates the role of HLA-C antibodies in causing ABMR if generated toward immunogenic-shared epitopes and demonstrates the need for their recognition in the pre- and post-transplant period. Another interesting aspect of this case is the incidental finding of Fabry-like zebra bodies, which we eventually determined to be of unclear etiology.

Plasmapheresis and corticosteroids in infective endocarditis-related crescentic glomerulonephritis.

Infective endocarditis (IE)-related glomerulonephritis (GN) typically resolves with the treatment of IE. A 59-year-old woman with a baseline creatinine of 0.7 mg/dL presented with rash on her legs, night sweats and weight loss for 3 weeks. Further evaluation revealed IE. Her blood cultures grew gamma-haemolytic streptococcus, which subsequently cleared on appropriate antibiotic therapy. Her creatinine, however, progressively worsened requiring haemodialysis. Kidney biopsy showed immune complex-mediated necrotising and crescentic GN. She was started on plasmapheresis (PE) and high-dose steroids with rapid taper, with subsequent improvement in her creatinine to 0.8 mg/dL. She subsequently had aortic valve replacement and ventricular septal defect closure. She did not improve as expected with antibiotic therapy but turned around dramatically with steroids and PE. Our case supports the possible beneficial role of PE and steroids in IE-related crescentic GN that worsens despite appropriate antibiotic therapy, although the risks of immunosuppression and aggravating endocarditis need to be considered.

Refractory orthostatic hypotension after creation of a brachio-basilic arteriovenous fistula.

Arteriovenous fistulas (AVFs) are preferred vascular access in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). However, AVFs, can occasionally lead to clinically significant complications. Of these, cardiovascular complications have been well described in the literature. In this report, we describe a case of a 78-year-old Caucasian male with ESRD who presented with severe debilitating dizziness and orthostatic hypotension that started soon after the creation of left brachiobasilic AVF. The patient had no significant cardiovascular history apart from essential hypertension. His symptoms persisted despite extensive evaluation and interventions, and abated only after banding of the AVF. This report describes the timeline of the patient's clinical course beginning from the day of creation of his AVF, through the course of his hospitalization leading to AVF banding and ending with postoperative recovery phase with resolution of symptoms. We will also review the pathophysiologic effects of AVF on cardiovascular system, as well as the potential causes of our patient's clinical presentation.

A 9-year survival analysis of the presternal Missouri swan-neck catheter.

Peritoneal dialysis (PD) catheter survival is challenging because of infection and malfunction. The swan-neck presternal catheter has a coiled intra-abdominal segment with a bead and a flanged cuff at the peritoneum; a titanium adapter joins the abdominal segment to the upper segment. The upper segment has two cuffs, one on either side of the presternal swan-neck segment. The present study evaluated the survival of Missouri presternal swan-neck PD catheters implanted at the University of Missouri--Columbia and followed at Dialysis Clinics, Inc., through 2006. Catheter type and insertion date were prospectively recorded. Survival was defined as the interval from insertion date to date of removal, censoring, or analysis. Catheters were censored for transplant, death, or transfer to another unit. A total of 131 presternal catheters were implanted in 129 patients. Mean patient age was 60.9 +/- 16.3 years. No catheters were removed during the first 3 months for either infection or technical problems. One catheter was removed at 6 months for malposition and another at 2 years for an external leak; all other catheter losses were attributable to peritonitis. Cumulative catheter survival was 93.5%, 82.5%, 63.9%, and 60.0% at 1, 2, 3, and 4 years respectively. The mean observation period was 19. 7 +/- 17.8 months, and the longest catheter survival was 87.5 months. New episodes of peritonitis were 91 in number, a rate of 1 episode per 28 patient-months. Although catheter survival exceeded the recommendation of better than 80% at 1 year, we noted a trend toward lower catheter survival and a higher peritonitis rate than were reported earlier in this series with a smaller number of catheters. That trend is partly explained by repeated episodes of peritonitis in 11 catheters; 8.5% of the patients experienced 40% of the peritonitis episodes.

A case of hypothermia on CRRT.

A 64-year-old Asian man, with past medical history of hypertension, hypothyroidism, and hyperlipidemia, presented with 3 days history of fever associated with cough and worsening shortness of breath. Subsequent clinical course was complicated by acute lung injury leading to acute respiratory distress syndrome requiring positive pressure ventilation, septic shock requiring inotropic support, and acute kidney injury requiring continuous renal replacement therapy (CRRT). On day 3 of CRRT, the patient developed significant hypothermia (temporal temperature 27.5°C), which was successfully managed. Continuous renal replacement therapy was subsequently discontinued as renal function recovered and the patient was discharged home after a prolonged hospital stay. He currently remains off dialysis and is being followed as an outpatient for chronic kidney disease. In this article, we examine various aspects of pathophysiology and management of hypothermia on CRRT and review relevant literature in this field.

Calcific uremic arteriolopathy in end stage renal disease: pathophysiology and management.

BACKGROUND: Calcific uremic arteriolopathy (CUA), a debilitating condition with high morbidity and mortality, is most commonly seen in patients with kidney disease. The pathophysiology of CUA is multifactorial, leading to a disruption in the balance between factors that promote and those that inhibit calcification, although the exact pathophysiological mechanisms of CUA remain to be elucidated. METHODS: This review provides an overview of the pathophysiology, clinical presentation and diagnosis, and treatment of CUA. RESULTS: Diagnosis of CUA requires a high degree of suspicion; skin biopsy with histological examination remains the gold standard to confirm the diagnosis. Treatment of CUA requires a multidisciplinary approach. CONCLUSION: With a high degree of clinical suspicion and early diagnosis, an aggressive multifactorial treatment approach involving optimal wound management, minimization/avoidance of risk factors and precipitating causes, and correction of calcium-phosphorus abnormalities can significantly improve patient outcomes.

Fluid overload and acute kidney injury.

Acute kidney injury is commonly encountered in critically ill patients, and is associated with worse outcomes. Fluid therapy is a key component in the management of these patients, often leading to fluid overload, especially in the setting of septic acute kidney injury. Emerging data overwhelmingly suggest that fluid overload in these patients may be associated with adverse outcomes. Management of such patients should include a strategy of early guided resuscitation, followed by careful assessment of fluid status, and early initiation of renal replacement therapy as soon as it is deemed safe, aiming for a neutral or negative fluid balance. This review will focus on the pathophysiological link between fluid overload and acute kidney injury, mechanisms of organ dysfunction in fluid overload, and strategies for management.

Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure--role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate.

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NSF) is an emerging scleromyxedema-like cutaneous disorder of unknown cause that is seen in patients with renal failure, and the number of reported cases has grown significantly since its first recognition. Recent case reports associated the use of gadolinium (Gd3+)-based contrast agents with the development of NSF. Herein is reported an additional patient who had NSF and had multiple previous exposures to Gd3+-based magnetic resonance imaging studies and had marked improvement in pain and skin changes after a trial of intravenous sodium thiosulfate. Discussed are the possible association of Gd3+-based contrast media with the development of NSF and potential for the use of sodium thiosulfate in the treatment of NSF.

Understanding essential hypertension from the perspective of the cardiometabolic syndrome.

Hypertension (HTN) is an important modifiable risk factor for major health problems such as coronary heart disease, stroke, congestive heart failure, end-stage renal disease, and peripheral vascular disease. Because of the associated morbidity and mortality, and the cost to society, HTN is an important public health challenge. HTN is frequently associated with other cardiovascular disease risk factors constituting the cardiometabolic syndrome, which individually and synergistically influence the pathophysiology of HTN, and the resultant increased redox stress contributes to the remodeling changes in key organs such as the heart and kidney. Remodeling at the subcellular level, and extracellular matrix in the heart and kidney of the hypertensive Ren2 transgenic rat model of tissue angiotensin II overexpression (TG(mREN-2)27), compared with the Sprague Dawley control rat model, has been observed by light and electron microscopy and are discussed. A better understanding of the pathophysiology of HTN may provide clinician and researcher, tools to effectively investigate and manage this complicated disease process.

Chronic kidney disease and cardiovascular risk.

Chronic kidney disease (CKD) is a global public health concern, and there is emerging a strong relationship between CKD and increased cardiovascular disease (CVD) risk. CKD in the presence of other co-morbidities such as type 2 diabetes mellitus (T2DM) and hypertension (HTN) can lead to early progression to end-stage renal disease (ESRD/stage V CKD) and confer a greater risk for CVD morbidity and mortality. CVD events are the leading cause of premature death in patients with CKD, even before their progression to ESRD, with the rate of CVD progression being twice as common compared with the general population. The higher mortality from CVD persists even after adjusting for most of the traditional risk factors, suggesting the possible contributions of uremia-related, nontraditional risk factors. This has led to the current understanding that the pathophysiology of CVD in CKD involves a complex interplay of both the traditional as well as nontraditional, uremia-related risk factors. This review will elaborate on the pathophysiology of CVD in CKD and will discuss the role of microalbuminuria (MAU)-proteinuria as a potential diagnostic and prognostic tool for CVD in CKD risk assessment.