The presentation, etiologies, pathophysiology, and treatment of pulmonary renal syndrome: A review of the literature.

Pulmonary renal syndrome (PRS) is a constellation of different disorders that cause both rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. While antineutrophil cytoplasmic antibody associated vasculitis and anti-glomerular basement membrane disease are the predominant causes of PRS, numerous other mechanisms have been shown to cause this syndrome, including thrombotic microangiopathies, drug exposures, and infections, among others. This syndrome has high morbidity and mortality, and early diagnosis and treatment is imperative to improve outcomes. Treatment generally involves glucocorticoids and immunosuppressive agents, but treatment targeted to the underlying disorder can improve outcomes and mitigate side effects. Familiarity with the wide range of possible causes of PRS can aid the clinician in workup, diagnosis and early initiation of treatment. This review provides a summary of the clinical presentation, etiologies, pathophysiology, and treatment of PRS.

The expanding role of primary care providers in care of individuals with kidney disease.

An estimated 37 million Americans have chronic kidney disease (CKD). Primary care providers (PCPs) have long played a critical role in detecting CKD and preventing disease progression, particularly in the early stages of the disease. With recent studies demonstrating substantial improvements in kidney outcomes with use of sodium glucose cotransporter 2 (SGLT2) inhibitors, PCPs have an even greater opportunity to improve care of individuals with CKD. Health disparities in nephrology have recently come to the forefront - again, PCPs will play a key role in efforts to reduce such disparities and ensure all patients receive high quality care. This review summarizes the latest guidelines for treatment of CKD and its complications, explores health disparities affecting patients with CKD, and highlights the role of the PCP in caring for this population.

Evaluation of cytomegalovirus "Blips" in high-risk kidney/kidney-pancreas transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality after solid organ transplantation. While guidelines suggest using highly sensitive QNAT assays for CMV detection, there is no defined viral load to guide initiation of preemptive therapy. This study evaluates the progression to quantifiable CMV (DNAemia) following a CMV "blip" in high-risk (D+/R) kidney/kidney-pancreas (KP) transplant recipients. METHODS: This is a single center, retrospective study. A CMV "blip" was defined as the first positive QNAT assay below the level of quantification (<1.37 × 102 IU/ml or <200 viral copies). Subsequent CMV QNAT assays were followed to assess the progression from blip to CMV DNAemia for 1 year following transplant. RESULTS: A total of 134 patients were included in the study. Fifty-three (39.6%) patients had their first positive CMV QNAT value below the level of quantification, a "CMV blip." Of these 53 patients, 69.8% (n = 37) progressed to DNAemia while 30.2% (n = 16) did not. The median time from transplant to the first CMV blip was 68 (46-97) days and most patients with viral blips (71.1%) were on prophylaxis. No differences in patient characteristics were found among those who progressed from blip to DNAemia and those who only had a blip. CONCLUSIONS: In CMV high-risk kidney/KP transplant recipients, CMV blips progressed to CMV DNAemia in the majority of cases. This progression typically occurred 2-3 weeks following the initial blip. CMV blips are common early posttransplant despite prophylaxis and likely represent an early marker of CMV infection.

Hepatitis C and Treatment in Patients with Chronic Kidney Disease.

Hepatitis C virus (HCV) is associated with increased mortality and morbidity in patients with chronic kidney disease (CKD). The early detection and treatment of Hepatitis C associated with kidney disease is paramount to preventing the progressive loss of kidney function. HCV treatment until the advent of direct acting anti-viral agents (DAAs) was limited to interferon and ribavirin. Interferon and ribavirin treatment resulted in only modest success but with frequent adverse events and poor tolerability. Furthermore, interferon and ribavirin could not be used in certain patient populations including those with advanced CKD, were on dialysis, or those who have received a kidney transplant. DAAs have now made treatment possible in these sub-groups with a sustained viral response (SVR) of 90-100% and minimal side effects. DAAs have helped increase transplant rates by allowing for the use of HCV positive kidneys in recipients who are HCV negative. Although the choice of DAAs should be carefully considered and based on patient characteristics, concomitant medications, and HCV genotype.

Survival benefit of renal transplantation in octogenarians.

BACKGROUND: Elderly patients are the fastest growing population requiring renal replacement therapy. As previous studies have shown a survival benefit of kidney transplantation compared to dialysis for end-stage renal disease, we sought to evaluate if this survival benefit extends to octogenarians. METHODS: This was a single-center retrospective cohort study of renal allograft recipients ≥80 years transplanted from 1999 to 2014 who were compared to patients listed during the same period that did not proceed to transplantation. A secondary matched group was selected from the UNOS transplant waitlist database. The primary outcome was patient survival. Secondary outcomes included graft survival and rejection incidence. RESULTS: Thirty-three transplanted patients were compared to 71 patients waitlisted at our center and 66 patients from the UNOS database. Patients in the study group were transplanted 20.8 ± 16.1 months after listing. Patient survival was 87.8% at 6 months and 1 year and 71.4% at 3 years. Kidney transplantation was associated with a significant decrease in the risk of death after listing (HR: 0.22, CI: 0.11-0.45, P < .001). CONCLUSION: With escalating life expectancy, kidney transplantation is a suitable treatment option in eligible octogenarians.

COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care.

Coronavirus disease-2019 (COVID-19) has caused a pandemic that has affected millions of people worldwide. COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is spread by close contact and by respiratory droplets. It has also impacted different aspects of caring for people with kidney disease, including those with acute kidney injury (AKI), chronic kidney disease (CKD), those requiring kidney replacement therapy (KRT), and those with a kidney transplant. All of these patients are considered high risk. The lessons learned from the COVID-19 pandemic will hopefully serve to protect patients with kidney disease in a similar situation in the future.

Kidney transplantation for the primary care provider.

Advancement in kidney transplantation has led to prolonged survival in our population with kidney disease. Newer agents of immunosuppression have made this possible with less rejections and lesser opportunistic infections and transplant related deaths. Preventative care like timely vaccines, cancer screenings, aggressive blood pressure, blood sugar, lipid control, timely referral to consultants is required in these patient population to provide quality care and to prolong their survival. Primary care physicians are the best advocate for our transplant populations. To care for these complex transplant patients, it is vital for primary care physicians to be familiar with the overall approach on our patients.

The Evaluation and Therapeutic Management of Hypertension in the Transplant Patient.

Organ transplantation is the therapeutic option of choice in the appropriate patient with end-organ disease. A major comorbidity after the transplant is the development of hypertension which is a risk factor for cardiovascular disease. Cardiovascular disease is the most common cause of death in this population even when there is a functioning graft. It is essential to evaluate post-transplant hypertension not only in the office setting but at home and at night as well. Hence, the use of 24-h ambulatory blood pressure monitoring in both diagnosis and long-term care of this patient population is paramount. Factors involved in uncontrolled hypertension include the donor, recipient, and those specific to the transplant such as immunosuppressive drug exposure. The major offending immunosuppressive agents belong to the calcineurin inhibitor class. The therapy of post-transplant hypertension involves pharmaceutical and non-pharmaceutical interventions that should be tailored to the specific patient and type of transplant. There is clearly a need for more definitive data and quality studies in both the renal and non-renal transplant populations.

Prospective randomized controlled trial of rabbit antithymocyte globulin compared with IL-2 receptor antagonist induction therapy in kidney transplantation.

OBJECTIVE: The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression. BACKGROUND: The optimal induction therapy in patients at risk for rejection, particularly black recipients, in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear. METHODS: This was a prospective, risk-stratified, randomized, single-center, open-label study of 200 consecutively enrolled patients in a large academic teaching center. Patients were randomized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were stratified between groups to ensure equal numbers of black, retransplants, high panel reactive antibodies (PRAs) (>20%), and prolonged cold ischemic times (>24 hours) in each group. Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance. Patients were followed up for 12 months. Renal transplant recipients were included if they were adult (≥18 years old) and received an allograft from a deceased, living unrelated, or nonhuman leukocyte antigen identical living-related donor. RESULTS: A total of 200 patients (n = 98 in the interleukin-2 receptor antagonists, and n = 102 in the RATG) were enrolled from February 2009 through July 2011. One-year acute rejection rates were low and similar between groups (10% in the interleukin-2 receptor antagonist group vs 6% in the RATG group; P = 0.30). Creatinine clearance was also similar between groups (interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2; P = 0.73). Subanalysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection, without an increased risk of infection. Induction did not affect rejection rates according to recipient calculated PRAs; however, RATG was associated with an increased risk of BK virus in low-PRA patients. CONCLUSIONS AND RELEVANCE: RATG induction provides improved protection against early acute rejection in black renal transplant recipients, whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy. This study is registered at Clinicaltrials.gov (NCT00859131).

Mobile Health Medication Adherence and Blood Pressure Control in Renal Transplant Recipients: A Proof-of-Concept Randomized Controlled Trial.

BACKGROUND: Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities (eg, hypertension, diabetes). These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients' physiological data. This technology is also relatively inexpensive, has an intuitive interface, and provides the capability for real-time personalized feedback to help motivate patient self-efficacy. Automated summary reports of patients' adherence and blood pressure can easily be uploaded to providers' networks helping reduce clinical inertia by reducing regimen alteration time. OBJECTIVE: The aim of this study was to assess the feasibility, acceptability, and preliminary outcomes of a prototype mobile health (mHealth) medication and blood pressure (BP) self-management system for kidney transplant patients with uncontrolled hypertension. METHODS: A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design. The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback. A 3-month proof-of-concept randomized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray. Participants randomized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging. Controls received standard of care and their adherence continued to be monitored with the medication tray reminders turned off. Providers received weekly summary reports of patient medication adherence and BP readings. RESULTS: Participation and retention rates were 41/55 (75%) and 31/34 (91%), respectively. The prototype system appears to be safe, highly acceptable, and useful to patients and providers. Compared to the standard care control group (SC), the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations. Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the standard care group (7 adjustments in 5 patients versus 3 adjustments in 3 patients) during the 3-month trial based on the information provided in the weekly reports. CONCLUSIONS: These data support the acceptability and feasibility of the prototype mHealth system. Further trials with larger sample sizes and additional biomarkers (eg, whole blood medication levels) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control after kidney transplantation over longer time periods. TRIAL REGISTRATION: Clinicaltrials.gov NCT01859273; http://clinicaltrials.gov/ct2/show/NCT01859273 (Archived by WebCite at http://www.webcitation.org/6IqfCa3A3).

Are thiazide diuretics safe and effective antihypertensive therapy in kidney transplant recipients?

BACKGROUND/AIMS: There are no published studies assessing the safety and efficacy of thiazides as antihypertensives in kidney transplantation (KTX). METHODS: This was a longitudinal retrospective cohort study conducted in adult KTX recipients. Patients were grouped based on receiving thiazides following KTX. Safety and efficacy comparisons were made between thiazide recipients and unexposed patients, as well as change in blood pressure (BP) within thiazide patients. RESULTS: 1,093 patients were included (thiazide group: 108, unexposed group: 985). Mean follow-up was 7.3 ± 4.5 years. Thiazide recipients were older (53 ± 11 vs. 48 ± 13 years, p < 0.001) and more likely to be female (52 vs. 41%, p = 0.023) and have pre-KTX hypertension (97 vs. 88%, p = 0.004) or diabetes (36 vs. 27%, p = 0.035). After controlling for baseline differences, safety analysis revealed thiazide recipients were not more likely to be readmitted to the hospital, but were at higher risk to develop hyperkalemia (56 vs. 38%, p < 0.001) or hypokalemia (28 vs. 18%, p = 0.010), with similar rates of hypotension, decreased estimated glomerular filtration rate, graft loss and death. Efficacy analysis demonstrated systolic (147 ± 17 to 139 ± 18 mm Hg, p < 0.001) and diastolic (79 ± 9 to 77 ± 11 mm Hg, p < 0.001) BPs were significantly reduced after thiazide initiation. Compared to unexposed patients, thiazide recipients had higher mean BPs during the entire follow-up (142/78 vs. 136/77, p < 0.001), with similar BPs while on thiazides and comparable rates of goal BPs (<130/80 mm Hg, 32 vs. 36%, p = 0.219). CONCLUSIONS: In KTX, based on long-term outcomes, thiazides appear to be safe and effective antihypertensives; in the short-term, thiazides may increase the risk of developing potassium disturbances.

Mediastinal mass and pericardial tamponade in a renal transplant recipient: A rare case of nocardia infection.

PATIENT: Female, 30 FINAL DIAGNOSIS: Nocardiosis Symptoms: Cardiac tamponade • cough • dyspnea • hoarseness • mediastinal mass • pericardial effusion • short of breath MEDICATION: - Clinical Procedure: - Specialty: Transplantology. OBJECTIVE: Rare disease. BACKGROUND: Nocardia infections can complicate solid organ transplantation. The usual clinical presentations include pulmonary infiltrates with or without cavitation and subcutaneous and brain abscesses. We report an unusual case of nocardia infection in a kidney transplant recipient that presented as mediastinal mass and was associated with pericardial tamponade. CASE REPORT: A 30 year old African American renal transplant recipient presented with cough, hoarseness and shortness of breath nine months after kidney transplantation. She received basiliximab perioperatively and her maintenance immunosuppression included tacrolimus, mycophenolate mofetil and prednisone. Computed tomography (CT) showed a large mediastinal mass with a large pericardial effusion. An echocardiogram revealed collapse of the right ventricle consistent with tamponade. We performed emergent pericardiocentesis to treat the tamponade. A mediastinoscopic biopsy of the mediastinal mass was done to establish a diagnosis. The mediastinal biopsy confirmed the growth of Nocardia. After 2 weeks of imipenem and 6 weeks of linezolid, there was marked radiographic improvement in the size of the mediastinal mass. CONCLUSIONS: We report a rare case of a large mediastinal mass associated with pericardial tamponade from nocardia infection in a renal transplant recipient. An invasive approach may be necessary to obtain tissue diagnosis to direct treatment in these cases. Prompt and appropriate medical therapy leads to marked radiographic improvement.

Hypertension after kidney transplantation: a pathophysiologic approach.

Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.

BK virus in the kidney transplant patient.

BK virus, a member of the polyomavirus family, is a well-recognized cause of irreversible graft failure after kidney transplantation. Awareness of the relationship between BK infection and immunosuppression along with better understanding of its pathogenesis has contributed to increasing rates of its diagnosis. Current therapies are aimed at early diagnosis, limiting inflammation caused by the virus and elimination of the virus through different strategies. The epidemiology, pathogenesis and the different modalities of therapy available are discussed in this review along with the approach to retransplantation in the setting of graft failure from BK infection.

Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection.

BACKGROUND AND OBJECTIVES: BK virus is an infection in kidney transplantation patients jeopardizing graft survival. Unfortunately, there is no consensus on treatment of BK viremia and nephropathy. Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring. This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study was a retrospective, single-center, longitudinal analysis of patients identified with BK viremia with or without nephropathy. Patients were grouped according to whether they received leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to determine pharmacodynamics, and were correlated with clinical outcomes. RESULTS: Of 76 patients identified, 52 received leflunomide therapy and 24 did not. Patients who received leflunomide were further analyzed according to A77 1726 concentrations and BK clearance; there was no difference in BK clearance. There was a lack of correlation between A77 1726 concentrations and log change in BK viral PCR concentration. Multivariate analysis demonstrated that mycophenolate mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load were significantly associated with BK viral clearance; leflunomide use lacked this association. CONCLUSIONS: Pharmacodynamic analysis revealed no association between A77 1726 concentrations and BK viral PCR reductions. Multivariate analysis demonstrated that leflunomide therapy was not associated with BK viral clearance. Randomized studies are needed to determine the utility of leflunomide for BK viremia and nephropathy.

Allograft dysfunction in a patient with an odd-looking kidney: case of renal lipomatosis and review of literature.

Renal lipomatosis was diagnosed in a kidney transplant recipient who presented with acute kidney injury (AKI) several years after transplantation. The patient had an odd-looking kidney transplant on ultrasound and computed tomography (CT) scan, showing a medullary mass with resultant compression of the surrounding renal parenchyma. A biopsy of the renal medulla confirmed fatty infiltration of the renal parenchyma. The patient underwent percutaneous nephrostomy and AKI resolved with relief of the obstruction. Renal lipomatosis is a rare condition that should be differentiated from other neoplasms of the kidney. When it occurs in a functioning transplant kidney, the treatment approach proves to be very challenging.

Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer.

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab) (Genetech, Inc. 2008). This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG) and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical) atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.

Mechanics and hemodynamics of esophageal varices during peristaltic contraction.

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.

Evaluation of the upper esophageal sphincter (UES) using simultaneous high-resolution endoluminal sonography (HRES) and manometry.

The aim of this study was to characterize the motion, morphology, and pressure of the upper esophageal sphincter (UES). The UES and its surrounding structures were evaluated in seven normal subjects and four human cadavers, using simultaneous high-resolution endoluminal sonography and manometry. The UES musculature on ultrasound is a C-shaped structure with an angle of 107 +/- 19 degrees. The mean peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA) of 0.87 +/- 0.33 cm2. During swallowing, the UES moved in an orad direction. Localizing the UES sonographically, the peak UES pressure in the cadavers was 19.7 +/- 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than the upper esophageal body. In the cadaver studies, the UES was imaged in conjunction with a significant increase in pressure, indicating that the pressure is due to passive mechanical conformational changes.