Hypertension in Women and Pregnancy.

Hypertension has been shown to have long-term cardiovascular effects if left untreated. Hypertension also has been shown to affect women during pregnancy, which can be detrimental not only to the patient but also to the fetus. Early identification and treatment are paramount to prevent adverse outcomes. This article details the epidemiology, clinical presentation, diagnosis, and treatment of essential hypertension in women, gestational hypertension, preeclampsia, and eclampsia.

Clinical Evaluation of Dapagliflozin in the Management of CKD: Focus on Patient Selection and Clinical Perspectives.

Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that was recently approved in the USA and the EU for the treatment of adults with chronic kidney disease (CKD) with or without diabetes mellitus (DM). The DAPA-CKD trial showed a 39% decline in the risk of worsening kidney function, onset of end-stage kidney disease, or kidney failure-related death. Patients with lower levels of eGFR and higher levels of albuminuria are among those who stand to gain the greatest absolute benefits. These benefits were similar in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related nephrotoxicity. Suggested mechanisms for renal protection include hemodynamic effects; BP reduction and improving salt sensitivities and metabolic effects; and glucose, uric acid and triglycerides (TG)-lowering effects. There have been already many excellent reviews on dapagliflozin and CKD management. Most of them cover both efficacy and safety. This review will focus on clinical perspectives and patient selection for the practicing clinician.

Acute Renal Failure and Its Complications, Indications for Emergent Dialysis, and Dialysis Modalities.

Acute kidney injury or acute renal failure is commonly observed in the critically ill patient with hemodynamic compromise. Dialysis is frequently used in the intensive care units as part of the critical care management of metabolic derangements fluid status and electrolyte issues. It is imperative that the bedside critical care nurse is able to identify acute kidney injury and is familiar with the modalities used to manage the metabolic consequences of renal failure, particularly important as the bedside nurse is operating the continuous renal replacement machine at the bedside. This article will review the common risks and causes of acute kidney injury in the critically ill patient, indications for conservative management versus initiation of renal replacement therapy, prevention of acute kidney injury, and important consequences of renal failure such as electrolyte disturbances and uremia. We will also briefly touch on specific conditions where acute kidney injury is common such as hepatorenal syndrome, cardiorenal syndrome, rhabdomyolysis, and tumor lysis syndrome.

Donor Ethnicity and Kidney Transplant Outcomes in African Americans.

BACKGROUND: Transplantation of African American (AA) compared to non-AA donor kidneys is generally associated with inferior outcomes. It is unclear whether enhanced genetic risk associated with AA donor kidneys would be counterbalanced by favorable immunologic matching when AA donor kidneys are transplanted into AA recipients. We aimed to compare the outcomes of AA vs non-AA deceased-donor kidneys (DDKs) stratified by kidney donor profile index (KDPI) that were transplanted into AA recipients. METHODS: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified AA DDK recipients from 2000 to 2015 who received peri-operative induction followed by calcineurin inhibitor/mycophenolate mofetil maintenance. These patients were divided into 4 KDPI groups (0%-20%, 21%-50%, 51%-85%, and 86%-100%). Adjusted long-term graft and patient outcomes were compared between AA recipients of kidneys from AA vs non-AA donors in each KDPI category using a multivariable Cox model. RESULTS: Among a total of 17,516 AA DDK transplant recipients, 3303 were in KDPI 0%-20% (AA donor = 239; non-AA donor = 3064), 5821 in KDPI 21%-50% (AA donor = 1414; non-AA donor = 4407), 6364 in KDPI 51%-85% (AA donor = 1619; non-AA donor = 4745), and 2028 in KDPI 86%-100% (AA donor = 932; non-AA donor = 1096) groups. Adjusted overall graft, death-censored graft, and patient survival were similar between AA recipients of AA vs non-AA donor kidneys across all KDPI groups. DISCUSSION: Our study showed similar outcomes for transplanting AA vs non-AA deceased-donor kidneys into AA recipients despite the generally observed inferior outcomes associated with AA donor kidney transplantation.

Update on kidney transplantation in human immunodeficiency virus infected recipients.

Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV(+) donors to HIV(+) recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV(+) to HIV(+) kidney transplant in the United States and the first HIV(+) to HIV(+) liver transplant in the world were recently performed at the Johns Hopkins University Medical Center.

Outcomes of Early Steroid Withdrawal in Recipients of Deceased-Donor Expanded Criteria Kidney Transplants in the Era of Induction Therapy.

OBJECTIVES: This study explored the safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants. MATERIALS AND METHODS: Using the Organ Procurement and Transplant Network-United Network of Organ Sharing database, we identified patients who underwent expanded criteria deceased-donor kidney transplant between January 2000 and December 2008 after receiving induction with rabbit-antithymocyte globulin (n = 3717), alemtuzumab (n = 763), or interleukin 2 blocking agent (n = 2600) followed by calcineurin inhibitor and mycophenolate mofetil-based maintenance with and without steroid therapy. RESULTS: Adjusted overall graft survival (hazard ratio 1.32; 95% confidence interval, 1.1-1.56; P = .002) and patient survival (hazard ratio 1.46, 95% confidence interval, 1.16-1.83, P = .001) were inferior, whereas death-censored graft survival (hazard ratio 1.13; 95% confidence interval, 0.87-1.47; P = .35) was similar for chronic steroid maintenance versus early steroid withdrawal groups in rabbit-antithymocyte globulin-induced patients. Graft and patient outcomes were similar for chronic steroid maintenance versus early steroid withdrawal groups among alemtuzumab and interleukin 2 blocking agent-induced patients. Among rabbit-antithymocyte globulin-induced patients, adjusted overall graft survival (hazard ratio 1.57; 95% confidence interval, 1.2-2.0; P < .001) and patient survival (hazard ratio 1.5; 95% CI, 1.15-2.1; P = .004) were inferior, whereas death-censored graft survival (hazard ratio 1.5; 95% confidence interval, 0.97-2.43; P = .07) trended inferior for chronic steroid maintenance versus early steroid withdrawal groups in recipients > 60 years old (n = 1729). CONCLUSIONS: Our study showed safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants who underwent perioperative induction followed by calcineurin inhibitor and mycophenolate mofetil maintenance. Among rabbit-antithymocyte globulin-induced patients, chronic steroid maintenance was associated with inferior graft and patient outcomes, an effect limited to older recipients.

Use of Extracorporeal Techniques in the Removal of Dabigatran.

Dabigatran is a novel direct thrombin inhibitor that has proven effective in the prevention of vascular events in patients with nonvalvular atrial fibrillation. Not much is known about the clearance capability with extracorporeal techniques of dabigatran. This review showcases the pharmacokinetics and a perusal of the current literature regarding cases that involved the clearance of the drug in patients with normal renal function and end-stage renal disease. Renal replacement therapy represents a therapeutic option to eliminate dabigatran and decreased the risk of bleeding in patients undergoing emergent surgical procedures on dabigatran.

Impact of steroid maintenance on the outcomes in first-time deceased donor kidney transplant recipients: Analysis by induction type.

AIM: To analyze the impact of steroid maintenance on the outcomes in kidney transplant recipients stratified by induction agent received. METHODS: Patients who underwent first-time deceased donor kidney transplantation between 2000 and 2008 after receiving induction therapy with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an interleukin-2 receptor blocker (IL-2B) and discharged on a calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)-regimen along with or without steroids were identified from the Organ Procurement and Transplant Network/United Network of Organ Sharing database. For each induction type, adjusted overall and death-censored graft as well as patient survivals were compared between patients discharged on steroid vs no steroid. Among r-ATG induced patients, analysis was repeated after splitting the group into low and high immune risk groups. RESULTS: Among the 37217 patients included in the analysis, 17863 received r-ATG (steroid = 13001, no-steroid = 4862), 3028 alemtuzumab (steroid = 852, no-steroid = 2176) and 16326 IL-2B (steroid = 15008, no-steroid = 1318). Adjusted overall graft survival was inferior (HR = 1.16, 95%CI: 1.06-1.27, P = 0.002) with similar death-censored graft survival (HR = 0.99, 95%CI: 0.86-1.14, P = 0.86) for steroid vs no-steroid groups in r-ATG induced patients. Both adjusted overall and death-censored graft survivals for steroid vs no-steroid groups were similar in alemtuzumab (HR = 0.92, 95%CI: 0.73-1.15, P = 0.47 and HR = 0.87, 95%CI: 0.62-1.22, P = 0.43 respectively) and IL-2B (HR = 1.05, 95%CI: 0.91-1.21, P = 0.48 and HR = 0.94, 95%CI: 0.75-1.18, P = 0.60 respectively) induced groups. Adjusted patient survivals were inferior for steroid vs no-steroid groups in r-ATG induced (HR = 1.31, 95%CI: 1.15-1.49, P < 0.001) but similar in alemtuzumab (HR = 1.02, 95%CI: 0.75-1.38, P = 0.92) and IL-2B (HR = 1.17, 95%CI: 0.97-1.40, P = 0.10) induced patients. Among the r-ATG induced group there were 4346 patients in the low immune risk and 13517 patients in the high immune risk group. Adjusted overall graft survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.34, 95%CI: 1.09-1.64, P = 0.001) and high immune (HR = 1.18, 95%CI: 1.07-1.30, P = 0.005) risk groups. Adjusted death-censored graft survivals for steroid vs no steroid groups were similar in both low (HR = 1.06, 95%CI: 0.78-1.45, P = 0.70) and high (HR = 1.04, 95%CI: 0.98-1.20, P = 0.60) immune risk groups. Adjusted patient survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.54, 95%CI: 1.18-2.02, P < 0.001) and high immune (HR = 1.32, 95%CI: 1.16-1.51, P = 0.002) risk groups. Overall, there were significantly higher deaths from infections and cardiovascular causes in patients maintained on steroids. CONCLUSION: Our study showed an association between steroid addition to a CNI/MMF-maintenance regimen and increased death with functioning graft in patients receiving r-ATG induction for first-time deceased donor kidney transplantation.

Relationship between chronic kidney disease and metabolic syndrome: current perspectives.

Both metabolic syndrome (MetS) and chronic kidney disease (CKD) are increasing in incidence and lead to significant cardiovascular morbidity and mortality. The relationship between these two entities is complex. Individual components of the MetS are known risk factors for incident kidney disease, but it is not clear how the clustering of these components is linked to the development and progression of kidney disease. Cross-sectional studies show an association of the MetS and prevalent CKD; however, one cannot draw conclusions as to which came first - the MetS or the kidney disease. Observational studies suggest a relationship between MetS and incident CKD, but they also demonstrate the development of MetS in patients with established CKD. These observations suggest a bidirectional relationship. A better understanding of the relationship between components of the MetS and whether and how these components contribute to progression of CKD and incident cardiovascular disease could inform more effective prevention strategies.

Steroid maintenance in repeat kidney transplantation: influence of induction agents on outcomes.

The influence of steroid maintenance on the outcomes of repeat kidney transplant (RKT) recipients with respect to induction type is unclear. Using the Organ Procurement and Transplant Network/United Network of Organ Sharing (OPTN/UNOS) database, we identified patients (≥ 18 years) who underwent deceased donor RKT from January 2000 to December 2008 after receiving induction with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an IL-2 receptor blocker (IL-2B) and were discharged on a calcineurin inhibitor/mycophenolate mofetil regimen with or without steroids. Of 5634 patients, 3643 received r-ATG (steroid = 3157, no-steroid = 486), 448 alemtuzumab (steroid = 196, no-steroid = 252) and 1543 an IL-2B (steroid = 1465, no-steroid = 78). Unadjusted graft survivals were similar for the no-steroid versus steroid groups for induction with r-ATG [hazard ratio (HR) 0.85 and 95% confidence interval (95% CI) 0.70-1.03, P = 0.10], alemtuzumab (HR 0.76, 95% CI 0.51-1.14, P = 0.18) and IL-2B (HR 0.77, 95% CI 0.56-1.70, P = 0.23). In the adjusted model, steroid use improved graft survival in alemtuzumab (HR 0.44, 95% CI 0.25-0.76, P = 0.003) but not in the r-ATG (HR 0.86, 95% CI 0.68-1.09, P = 0.21) or IL-2B (HR 0.98, 95% CI 0.56-1.70, P = 0.94) groups. Steroid use was associated with inferior patient survival in unadjusted (HR 1.30, 95% CI 1.17-1.44, P <0.001) and adjusted (HR 1.29, 95% CI 1.14-1.45, P <0.001) models for r-ATG induction, whereas this was not observed with alemtuzumab (unadjusted HR 1.11, 95% CI 0.89-1.37, P = 0.36; adjusted HR 0.90, 95% CI 0.68-1.20, P = 0.49) or IL-2B (unadjusted HR 1.01, 95% CI 0.87-1.18, P = 0.87; adjusted HR 1.15, 95% CI 0.97-1.38, P = 0.12) inductions. Our study showed a graft survival benefit in the alemtuzumab- and patient death risk in the r-ATG-induced RKT recipients discharged on steroids.

Effect of allopurinol on slowing allograft functional decline in kidney transplant recipients.

OBJECTIVES: Hyperuricemia may be a risk factor for graft loss in kidney transplant recipients. The purpose of this study was to evaluate the effects of allopurinol in kidney transplant recipients. MATERIALS AND METHODS: A single center retrospective case-control study was performed with kidney transplant recipients who were treated with allopurinol (54 patients) and a control group matched for time of transplant (± 3 months) and estimated glomerular filtration rate (54 patients). We evaluated the relation between allopurinol use and estimated glomerular filtration rate, graft survival, blood pressure, and number of anti-hypertensive drugs used. RESULTS: At the start of allopurinol therapy, mean serum uric acid level was greater in the allopurinol (476 ± 119 µmol/L) than control group (404 ± 125 µmol/L; P ≤ .001) and estimated glomerular filtration rate was similar between the 2 groups (allopurinol, 39 ± 16 mL/min; control, 38 ± 16 mL/min; not significant). At 1 year, mean estimated glomerular filtration rate was greater in the allopurinol than control group (allopurinol, 41 ± 15 mL/min; control, 36 ± 13 mL/min; P ≤ .04). At 2 years, mean serum uric acid level was significantly lower in the allopurinol (399 ± 101 µmol/L) than control group (452 ± 95 µmol/L; P ≤ .02). Graft survival, blood pressure, and antihypertensive requirements were similar between the groups. CONCLUSIONS: Allopurinol use is associated with preservation of estimated glomerular filtration rate in kidney transplant recipients. There may be potential benefit in treating asymptomatic hyperuricemia in kidney transplant recipients.

Hyperuricemia and the progression of chronic kidney disease: is uric acid a marker or an independent risk factor?

Hyperuricemia is seen when kidney function declines. Whether elevated uric acid (UA) levels play a role in the initiation and progression of kidney disease is a subject of a great debate. Animal studies demonstrate that elevated UA level is a risk factor for kidney disease. In humans, the relationship between UA and kidney disease is more complicated. Cross-sectional studies show an association of hyperuricemia with the presence of CKD; however, from cross-sectional studies, one cannot determine which came first-the elevated UA level or the kidney disease. UA levels are also associated with other risk factors for kidney disease, including hypertension, metabolic syndrome, and microalbuminuria, but it is not clear whether these are mediators or confounders of a relationship. Observational studies suggest a relationship of UA level with incident CKD, but studies evaluating the relationship with decline in kidney function in established CKD are conflicting. Finally, small clinical trials using allopurinol to lower UA levels provide weak, but potentially promising, evidence that lowering UA levels may retard the progression of CKD. In this article, we will review the evidence of the association of hyperuricemia and CKD.

Angiotensin receptor blockade improves arterial distensibility and reduces exercise-induced pressor responses in obese hypertensive patients with the metabolic syndrome.

Patients with the metabolic syndrome have three or more of five cardiovascular risk factors and increased oxidative stress, arterial stiffness and pressor responses to exercise, which may contribute to their threefold greater risk for coronary heart disease. In addition to lowering basal blood pressure (BP), angiotensin receptor blockers (ARBs) may benefit metabolic syndrome patients by reducing oxidative stress, arterial stiffness, and pressor responses to exercise. Twelve patients, 7 women and 5 men, with the metabolic syndrome (aged 45 +/- 2 years, BP 145 +/- 5/85 +/- 2 mm Hg, waist girth 110 +/- 3 cm, triglycerides 186 +/- 23 mg/dL, HDL cholesterol 44 +/- 2 mg/dL, glucose 99 +/- 3 mg/dL) were studied off medications, while on modest sodium restriction ( approximately 100 mmol/d). Patients were randomized to the ARB losartan or placebo for 3 weeks then crossed over to the complement for 3 weeks. Studies were performed at the end of each phase following an overnight fast. Serum lipids and biomarkers of oxidative stress (F2-isoprostanes, thiobarbituric acid reacting substances) were unchanged by losartan, whereas large artery elasticity at rest, measured with the HDI PulseWave, increased from 13.6 +/- 0.7 on placebo to 16.2 +/- 1.1 mL/mm Hg on losartan, P <.05. Losartan lowered systolic BP pre-exercise from 142 +/- 3 to 131 +/- 3 mm Hg (P <.001) and systolic BP after 6 min of treadmill exercise from 192 +/- 6 to 169 +/- 5 mm Hg (P <.001). Losartan lowered systolic BP (-23 +/- 3 v -11 +/- 2 mm Hg, P <.05) and pulse pressure (-4 +/- 1 v -15 +/- 2 mm Hg, P <.05) more during exercise than rest. Losartan reduces the pressor response to exercise, perhaps by enhancing arterial compliance. In addition to lowering basal BP, angiotensin receptor blockade in patients with metabolic syndrome improves arterial compliance and reduces pressor reactivity to exercise.

DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity.

Evidence suggests that obesity may raise blood pressure (BP) through oxidative stress-sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet (DASH-CD) may decrease BP by enhancing antioxidant capacity. To address this question, 12 obese patients with high-normal-to-stage 1 hypertension (hypertensives) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in random sequence for 4 weeks each. Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin. Ferric-reducing activity of plasma (FRAP) and plasma F2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress, respectively. BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets (-8.1+/-1.5/-7.4+/-1.6 mm Hg, P<0.05). BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet. FRAP on usual diets was higher in lean subjects than in obese subjects. FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet, and the group difference disappeared. F2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD. Among free-living obese hypertensives, the DASH-CD raises antioxidant capacity, lowers BP, and reduces oxidative stress induced by acute hyperlipidemia. The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD.