Individual- and Community-Level Socioeconomic Status and Deceased Donor Renal Transplant Outcomes.

BACKGROUND: This study examined the relationship between socioeconomic status (SES), race, and ethnicity and clinical outcomes following deceased donor kidney transplant (DDKT) at a high-volume transplant center. METHODS: This retrospective cohort study used regression models and survival analyses to examine the relationship between individual- and community-level SES, race, and ethnicity and DDKT outcomes (i.e., delayed graft function, graft failure, mortality) adjusting for potential confounders. RESULTS: The analytic sample included 3366 patients; 40.7% (n = 1370) were female, the mean age was 54.7 (SD = 13.3) years, 49.3% were non-Hispanic White, and the median follow-up time was 39.5 months (IQR = 24.2-68.1). Patients living in the most disadvantaged communities (using the US Census data) had a higher likelihood of delayed graft function (adjusted relative risk [RR] = 1.12, p = 0.042) and a higher hazard of mortality (adjusted hazard ratio [HR] = 1.32, p = 0.025) compared to patients living in the least disadvantaged communities. Patients without a high school diploma had a higher risk of delayed graft function compared to patients with an associate degree or more (RR = 1.37, p < 0.001). Patients with public insurance coverage had a higher risk of delayed graft function (RR = 1.24, p < 0.001) and a higher hazard of mortality (HR = 1.37, p < 0.001) and graft failure (HR = 1.71, p < 0.001) compared to patients without public insurance. There were no differences in graft failure or mortality by race and ethnicity. CONCLUSIONS: SES was not consistently associated with outcomes following DDKT; however, many of the predictors were associated with delayed graft function. With a large and diverse sample size, these findings further the heterogeneity of the present renal transplant research suggesting the need for further investigation to guide implementation of innovative strategies and interventions.

Case report: JC polyomavirus nephropathy in simultaneous heart-kidney transplantation: the role of viral-specific in situ hybridization staining.

Introduction: JC polyomavirus (JCPyV) is a ubiquitous virus that can be latent in the brain and the kidney. It is the etiologic agent responsible for progressive multifocal leukoencephalopathy, a fatal, demyelinating disease of the central nervous system, and rarely causes polyomavirus nephropathy in immunocompromised kidney transplant recipients. Case description: We present the first case of JCPyV nephropathy in a simultaneous heart-kidney transplant patient, where viral-specific in situ hybridization staining of the kidney tissue was utilized to confirm the diagnosis. The patient was diagnosed 6 years after simultaneous heart-kidney transplantation and was treated with immunosuppression reduction and intravenous immunoglobulin. Discussion: JCPyV nephropathy should be considered in the differential diagnosis of kidney allograft injury, particularly, with suggestive light microscopy histologic features in the absence of BK polyomavirus viremia and/or viruria. In addition to obtaining JCPyV PCR in the blood, in situ hybridization staining may have a utility in confirming the diagnosis. To date, we lack effective JCPyV-specific therapies, and prompt initiation of immunosuppression reduction remains the mainstay of treatment.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

The Value of Pharmacogenomics for White and Indigenous Americans after Kidney Transplantation.

BACKGROUND: There is a paucity of evidence to inform the value of pharmacogenomic (PGx) results in patients after kidney transplant and how these results differ between Indigenous Americans and Whites. This study aims to identify the frequency of recommended medication changes based on PGx results and compare the pharmacogenomic (PGx) results and patients' perceptions of the findings between a cohort of Indigenous American and White kidney transplant recipients. METHODS: Thirty-one Indigenous Americans and fifty White kidney transplant recipients were studied prospectively. Genetic variants were identified using the OneOme RightMed PGx test of 27 genes. PGx pharmacist generated a report of the genetic variation and recommended changes. Pre- and post-qualitative patient surveys were obtained. RESULTS: White and Indigenous American subjects had a similar mean number of medications at the time of PGx testing (mean 13 (SD 4.5)). In the entire cohort, 53% received beta blockers, 30% received antidepressants, 16% anticoagulation, 47% pain medication, and 25% statin therapy. Drug-gene interactions that warranted a clinical action were present in 21.5% of patients. In 12.7%, monitoring was recommended. Compared to the Whites, the Indigenous American patients had more normal CYP2C19 (p = 0.012) and CYP2D6 (p = 0.012) activities. The Indigenous American patients had more normal CYP4F2 (p = 0.004) and lower VKORC (p = 0.041) activities, phenotypes for warfarin drug dosing, and efficacy compared to the Whites. SLC6A4, which affects antidepressant metabolism, showed statistical differences between the two cohorts (p = 0.017); specifically, SLC6A4 had reduced expression in 45% of the Indigenous American patients compared to 20% of the White patients. There was no significant difference in patient perception before and after PGx. CONCLUSIONS: Kidney transplant recipients had several drug-gene interactions that were clinically actionable; over one-third of patients were likely to benefit from changes in medications or drug doses based on the PGx results. The Indigenous American patients differed in the expression of drug-metabolizing enzymes and drug transporters from the White patients.

Effectiveness of education and attitudes toward different types of deceased donor kidneys: Survey analysis of single-center experience.

Background: We lack data on the effectiveness of education and the patient's attitude toward different deceased donor kidney types. A prospective study was performed to evaluate patient attitudes, baseline knowledge, and effectiveness of our kidney transplant education process. We also analyzed the knowledge retention of our waitlist patients. Design: We prospectively surveyed a patient cohort using a paired analysis pre and post education with initial evaluation visit. Knowledge retention among waitlist patients was assessed with annual waitlist visit. Results: One hundred four patients received paired surveys to assess the baseline knowledge and effectiveness of education. Forty-three patients received a single survey with their annual waitlist evaluation to assess knowledge retention. Paired survey showed mixed results, with no statistically significant improvement in the kidney donor profile index domain. Significant improvement was seen in the hepatitis C virus-positive donor domain and the Public Health Service (PHS) increased-risk donor domain. For the waitlist cohort, overall knowledge retention ranged from excellent to fair, with a decline in knowledge for the PHS increased-risk donor domain. Conclusion: Our study suggests that the education intervention regarding different deceased donor kidney types is effective overall and transplant candidates retain the knowledge while waiting for transplant.

Impact of Glomerulitis on Long-term Outcomes After Kidney Transplantation.

The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods: A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results: We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]' respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion: Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.

Sodium-glucose cotransporter 2 inhibitors for treatment of diabetes mellitus after kidney transplantation.

INTRODUCTION: Diabetes mellitus in kidney transplant recipients is a risk factor for cardiovascular events and premature death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in nontransplant populations to improve diabetes control and cardiovascular and renal benefits. Limited literature exists regarding the safety and efficacy of these agents in renal transplant recipients. METHODS: We retrospectively reviewed all kidney transplant recipients within our health system who were prescribed a SGLT2i after transplantation for diabetes. The safety, tolerability, and effectiveness of SGLT2i were analyzed. RESULTS: Thirty-nine kidney transplant recipients were initiated on SGLT2i therapy, twenty-seven of which remained on therapy for at least 1 year. Ten (25%) patients experienced an adverse event while on a SGLT2i, with urinary tract infections (UTI) being the most common. Seventeen patients (43%) discontinued the SGLT2i at the time of chart review, most commonly due to cost and kidney function decline. The median [IQR] hemoglobin A1c (HbA1c) at SGLT2i initiation of 8.4% [7.8-9.2] decreased to 7.5% [6.8-8.0%] after 3 months and 7.5% [6.5-7.9] after 12 months. No meaningful change in kidney function or tacrolimus exposure was observed. CONCLUSION: SGLT2i may be a safe and effective treatment for diabetes in kidney transplant recipients. Cost is a barrier to SGLT2i therapy, and UTIs were the most frequently encountered adverse events in this cohort. More studies are needed to understand the safety profile and determine the effect of SGLT2i on diabetes-related comorbidities among kidney transplant recipients.

Kidney donor profile index and post-transplant health care utilization: Implications for value of transplant care delivery.

BACKGROUND: Centers discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization. METHODS: We conducted a retrospective cohort study from a high-volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n = 652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long-term graft function and patient survival. RESULTS: High (n = 107) and low KDPI (n = 545) KTRs had similar length of stay (median = 3 days, P = .66), and readmission rates at 7, 30, and 90 days after surgery (all, P > .05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P > .05). Low KDPI KTRs had significantly better eGFR at 2 years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P < .001), but similar 3-year patient and graft survival (both, P > .09). CONCLUSIONS: High and low KDPI KTRs demonstrated similar 90-day risk-adjusted health care utilization, which should encourage use of high KDPI kidneys.

Solid Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients: A Single-center Experience.

BACKGROUND: The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. METHODS: Abdominal solid organs from SARS-CoV-2-infected donors were transplanted into uninfected recipients. RESULTS: Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2-infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. CONCLUSIONS: Transplanting nonlung organs from SARS-CoV-2-infected donors into uninfected recipients demonstrated no evidence of virus transmission.

The impact of COVID-19 on kidney transplant care.

The SARS-CoV-2 virus precipitated the coronavirus 2019 (COVID-19) pandemic, which placed considerable strain on healthcare systems and necessitated immediate and rapid alterations in the delivery of healthcare. In the transplant population, COVID-19 directly impacts an inherently vulnerable population in the setting of immunosuppression and co-morbidities, but also further complicates the clinical evaluation and management of kidney transplant candidates and recipients in a strained healthcare environment being challenged by the pandemic. Many transplant centers around the world saw mortality rate spikes in organ recipients related to COVID-19, and changes in care delivery abound. This review evaluates the care of the kidney transplant patient through all phases of the process including pre-operative evaluations, perioperative care, post-transplantation considerations, and how the global pandemic has changed the way we care for our patients.

Screening coronary angiography in patients with long-standing diabetes mellitus undergoing kidney transplant evaluation.

BACKGROUND: The utility of coronary angiography in patients with diabetes mellitus undergoing kidney transplant evaluation is unclear. Predictors of critical angiography lesions in these patients will aid in appropriate use of angiography. METHODS: Single-center study of 80 patients with ≥15 years of diabetes mellitus who underwent a screening coronary angiography despite a negative cardiac stress test. Risk factors for needing coronary intervention (CI) (percutaneous or bypass grafting) were analyzed. RESULTS: Eighteen patients (23%) had a ≥70% occlusion in one or more major coronary vessel(s), with right coronary artery being the most commonly involved (71%). Fifteen patients (19%) underwent coronary intervention: ten percutaneously and five with bypass surgery. Risk factors for needing CI were not being on statin (OR 3.54, P = 0.047) and history of stroke or peripheral vascular disease (PVD; OR 3.5, P = 0.034). A model that included statin use, stroke/PVD history, and glycosylated hemoglobin had a receiver operating characteristic curve area under the curve of 0.8 to predict CI. CONCLUSION: Despite a negative stress test, the prevalence of critical coronary lesions was high among kidney transplant candidates with long-standing diabetes. Risk factors for needing coronary intervention were absence of statin use and a history of stroke or peripheral vascular disease.

Cardiorespiratory Fitness (Peak Oxygen Uptake): Safe and Effective Measure for Cardiovascular Screening Before Kidney Transplant.

BACKGROUND: Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. METHODS AND RESULTS: We outlined a pre-renal transplant screening algorithm to incorporate VO2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. CONCLUSIONS: We conclude that incorporating an objective measure of cardiorespiratory fitness with VO2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Cytomegalovirus infection in high-risk kidney transplant recipients receiving thymoglobulin induction-a single-center experience.

BACKGROUND: The burden of cytomegalovirus infection in CMV high-risk (donor positive to recipient negative) kidney transplant recipients getting thymoglobulin induction and six months of valganciclovir is not well characterized. Additionally, the role of post-prophylaxis surveillance remains unclear. METHODS: One-year observational study of forty-eight high-risk CMV kidney transplant recipients transplanted under thymoglobulin between January 2013 and July 2014. All received valganciclovir for six months, followed by monthly CMV PCR for three months. RESULTS: CMV infection defined as viremia with or without symptoms occurred in 40% (19/48). Of these, 47% (9/19) occurred during prophylaxis, 32% (6/19) during surveillance and 21% (4/19) during post-surveillance period (9-12 months). Among breakthrough infections, suboptimal valganciclovir dosing was present in 55% (5/9). With routine surveillance, there was a trend toward lower CMV-related hospitalization (17% vs 56% and 75% during prophylaxis and post-surveillance, respectively [P=.23]) and lower mean peak viral loads (19 432 copies/mL vs 97 925 copies/mL and 536 021 copies/mL during prophylaxis and post-surveillance, respectively [P=.07]). CONCLUSION: CMV infection remains a significant problem with thymoglobulin induction despite six months of valganciclovir. Suboptimal valganciclovir dosing was common among breakthrough infections. Monthly surveillance post-prophylaxis appears to detect early CMV infection with lower degree of viremias requiring fewer hospitalizations.

Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment.

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.

Bridging Translation by Improving Preclinical Study Design in AKI.

Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.

Neurologic Complications After Kidney Transplantation.

The clinical focus after kidney transplantation often is centered on graft function. However, neurologic complications are a common, significant, and under-recognized contributor to patient morbidity and mortality. Neurologic syndromes can arise through exacerbation of pre-existing conditions or can be newly acquired in the setting of increased risk of infection and drug toxicity after transplantation. We present a comprehensive review of neurologic complications after kidney transplantation.

Outpatient Dialysis for Patients with AKI: A Policy Approach to Improving Care.

The rate of AKI requiring dialysis has increased significantly over the past decade in the United States. At the same time, survival from AKI seems to be improving, and thus, more patients with AKI are surviving to discharge while still requiring dialysis. Currently, the options for providing outpatient dialysis in patients with AKI are limited, particularly after a 2012 revised interpretation of the Centers for Medicare and Medicaid Services guidelines, which prohibited Medicare reimbursement for acute dialysis at ESRD facilities. This article provides a historical perspective on outpatient dialysis management of patients with AKI, reviews the current clinical landscape of care for these patients, and highlights key areas of knowledge deficit. Lastly, policy changes that have the opportunity to significantly improve the care of this at-risk population are suggested.

Severe sepsis and septic shock in patients with pre-existing non-cardiac pulmonary hypertension: contemporary management and outcomes.

OBJECTIVE: To review treatment and outcomes of septic shock in patients with pulmonary hypertension (PH) managed at a tertiary care institution. DESIGN, SETTING AND PATIENTS: We identified consecutive patients with non-cardiac PH (non-Group 2 in the World Health Organization classification) who were treated for septic shock in four intensive care units at a tertiary care institution between July 2004 and July 2007. Patients with a left ventricular ejection fraction < 50%, diastolic dysfunction, pericardial effusion or significant valve disease were excluded. Descriptive statistics were used to analyse the data. MAIN OUTCOME MEASURES: Hospital mortality, duration of vasopressor and ventilatory support, length of hospital and ICU stay. RESULTS: The final group for analysis comprised 82 patients. The major causes of PH were chronic obstructive pulmonary disease, interstitial lung disease and portopulmonary hypertension. PH was mild in 46 patients (56%), moderate in 21 (26%) and severe in 15 (18%). Vasopressor treatment was initiated in 69 patients (84%) within the first 48 hours: noradrenaline was most commonly used (53 patients, 65%), and 51 patients (62%) were treated with more than one agent. Sixty-seven patients (82%) were mechanically ventilated, and 33 (40%) required renal replacement therapy. Fortythree patients (52%) survived to hospital discharge; 23 (28%) remained alive at 1 year. Hospital mortality increased with severity of PH: 28% in mild, 67% in moderate and 80% in severe PH. Nonsurvivors were more likely to have plateau pressures beyond 30 cm H(2)O while mechanically ventilated within the first 48 hours in the ICU (56% v 29%, P = 0.03), to develop atrial fibrillation (AF) (46% v 12%, P < 0.001), and to require longer vasopressor support (mean, 5.3 v 2.6 days, P = 0.003). In a multivariate logistic regression analysis, severity of PH (odds ratio [OR], 1.55; 95% CI, 1.04-2.46; P = 0.04), new-onset AF (OR, 6.51; 95% CI, 2.24-22.07; P < 0.001) and longer duration of vasopressor support (OR, 1.15; 95% CI, 1.03-1.34; P = 0.04) were associated with increased hospital mortality. CONCLUSIONS: The severity of PH, new-onset AF, and longer vasopressor support were associated with poor outcomes in patients with PH who developed severe sepsis and septic shock.

Arterial pulmonary hypertension in noncardiac intensive care unit.

Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response.

Acute renal dysfunction in acetaminophen poisoning.

Although acetaminophen (APAP)-associated liver injury is well recognized, there are few reports describing APAP nephrotoxicity, and most of them are single cases. It has also been suggested that N-acetylcysteine (NAC), used to treat the hepatotoxicity, may be harmful to the kidneys. To examine this contention and to determine whether renal involvement in APAP poisoning is at all common, we analyzed the incidence and outcome of acute renal dysfunction in patients hospitalized for APAP overdose reported to our regional poison center over a year. Eleven APAP-poisoned patients had elevated liver function tests; nine of them had azotemia. Those with higher AST levels tended to be younger and to have lower APAP levels on admission. Two patients with acute renal injury died after admission. The other seven patients with renal dysfunction recovered in 2 to 7 days. Six of these received NAC; their mean serum creatinine fell from 3.2 +/- 2.0 versus 1.7 +/- 0.9 mg/dL (p < 0.05). We conclude that acute renal failure is not uncommon in APAP poisoning and appears to be unrelated to the degree of liver injury. NAC therapy did not seem to worsen nephrotoxicity.