Brent Alper

Respiratory complications of pregnancy

The pregnant woman is susceptible to a variety of respiratory complications. When a pregnant patient presents with an abnormal chest x-ray or a pulmonary complaint, an understanding of the pathophysiology of pregnancy will guide the clinician in establishing a diagnosis. Pregnancy brings about many changes to a woman’s body. One of the more intriguing is a decrease in the T helper cells, resulting in a state of relative immunosuppression. Despite this, the prevalence of infectious pneumonia is not increased in pregnancy. Complications from pneumonia, however, are increased in the pregnant host. Most notably are increases in both mortality related to influenza infection and the risk for dissemination of coccidioidomycosis. Other physiologic changes predispose the pregnant woman to certain disease processes. Hypercoagulability associated with pregnancy results in a marked increase in the incidence of thromboembolic disease. Although rare, pregnancy is also associated with other embolic phenomena including amniotic fluid embolism, air embolism, and trophoblastic embolism. Because of the increases in intravascular volume and cardiac output that occur in pregnancy, women with underlying structural heart disease will frequently present for the first time or have an exacerbation of their disease. This is especially true of mitral stenosis. Peripartum cardiomyopathy also can occur, and for the majority of patients, the heart remains damaged for life. Finally, although uncommon, lymphangioleiomyomatosis will often present or become exacerbated during pregnancy. Patients with this disorder need to be counseled concerning the increased risk associated with pregnancy. This paper reviews the various respiratory complications associated with pregnancy. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to review the changes in respiratory mechanics that occur during pregnancy, to list the various causes of pulmonary infections during pregnancy, and to describe the noninfectious causes of pulmonary complications during pregnancy.

Management of Metabolic Bone Disease in Kidney Transplant Recipients

Bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Hypovitaminosis D, hyperparathyroidism and hyperaluminemia may resolve after kidney transplant, but many patients have other risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism, poor allograft function, aging, and chronic diseases. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D analogues, bisphosphonates and calcitonin. Novel approaches to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fractures in kidney transplant recipients.

Living donor kidney transplantation: medical, legal, and ethical considerations.

The use of living donor kidneys has dramatically increased the number and success of kidney transplants across the world. But questions remain regarding the subjection of a healthy individual to surgery for the benefit of another. Donors do have medical and financial risks. The stigma of organ brokering remains today, with evidence of commercial transplantation in other countries. Here in the US, we are exposed to advertising for donors using the media. In the hope of increasing living donations, we run the risk of stretching altruism too far. In this manuscript, we highlight and discuss some of the current controversies surrounding living donor kidney transplantation across the world.

A Comparison of Long‐Term Survivals of Simultaneous Pancreas–Kidney Transplant between African American and Caucasian Recipients with Basiliximab Induction Therapy

African Americans (AA) have traditionally been thought to have higher immunologic risk than Caucasians (CA) for rejection and allograft loss. The impact of ethnicity on the outcome of simultaneous pancreas–kidney (SPK) transplant with basiliximab induction has not been reported. In this study, we retrospectively analyze the long‐term results of 36 AA and 55 CA recipients of primary SPK. The actual patient survival rates of AA and CA groups were 91.7% vs. 90.1% at 1 year, 93.3% vs. 88.1% at 3 years, and 94.4% vs. 83.3% at 5 years. The actual kidney survival of AA and CA were 91.7% vs. 89.1% at 1 year, 90% vs. 81% at 3 years, and 83.3% vs. 75% at 5 years. The actual pancreas survival of AA and CA were 88.9% vs. 85.5% at 1 year, 83.3% vs. 78.6% at 3 years and 72.2% vs. 70.8% at 5 years. Death‐censored analyses also found no difference in pancreas and kidney graft survival rates over 5 years. Higher rejection rate, but the same low CMV infection, and comparable quality of graft function were noted in AA group. AA may not have worse long‐term outcomes than CA recipients of SPK with basiliximab induction and tacrolimus (TAC), mycophenolate acid (MFA) and steroid maintenance immunotherapy.

Long-term outcome of highly sensitized African American patients transplanted with deceased donor kidneys

Undertaking transplantation in highly sensitized African American (AA) patients as transplant recipients represents a unique challenge. We retrospectively compared the outcomes of AA with non‐African American (NAA) patients who had panel reactive antibody >80% and received deceased donor (DD) kidneys by virtual crossmatch. Immunosuppressive regimen included basiliximab induction and tacrolimus, mycophenolate acid and steroids maintenance. Among 835 consecutive transplants from 1998 to 2007, 142 (17%) were sensitized patients including 89 (16.6%) AA and 53 (17.7%) NAA patients. The AA group had similar 5‐year incidence of acute rejection as NAA group (21.4% vs. 26.4%, P = 0.25). Kaplan–Meier estimated graft survival at 1, 3 and 5 years were 91%, 85% and 82% in AA group, and 94%, 79% and 71% in NAA group (P = 0.08). The death‐censored graft survival at 1, 3, and 5 years were 93%, 86% and 84% in AA group, and 96%, 83% and 78% in NAA group (P = 0.11). The 1, 3, and 5 years patient survivals were 93%, 88% and 85% in AA group, and 96%, 96% and 94% in NAA group (P = 0.17). Highly sensitized AA patients could be transplanted with DD kidneys at a similar rate as NAA patients, and they may not have a higher incidence of rejection or an inferior graft survival than NAA patients.

The Effects of Body Mass Index on Graft Survival in Adult Recipients Transplanted with Single Pediatric Kidneys

Background: There is insufficient data on the impact of recipient body mass index (BMI) on the long-term graft survival of adult patients transplanted with single pediatric kidneys. Methods: We performed a retrospective analysis of adult patients transplanted with single pediatric kidneys at our center. The recipients were classified into 2 groups: group 1 (BMI ≥30) and group 2 (BMI <30). Donor/recipient demographics, postoperative outcomes and survival rates were compared between the 2 groups. Results: There was no significant difference in donor/recipient demographics between the 2 groups. In group 1, the death-censored graft survival (DCGS) at 1, 3 and 5 years was 90% at all 3 time points, and in group 2 it was 86, 68 and 60%, respectively (p = 0.05). The mean glomerular filtration rate (with standard deviation in parentheses) at 1, 3 and 5 years was, respectively, 55 (15), 59 (19) and 55 (28) ml/min for group 1, compared to 65 (28), 69 (23) and 67 (20) ml/min in group 2 (p = NS). Multivariate analysis revealed a hazard ratio of 5.12 (95% confidence interval 1.06–24.7; p = 0.04) for graft loss in nonobese patients when compared to obese patients. Obese patients had an increased risk for acute rejections within the first month of transplant (p = 0.02). Conclusion: Patients with a BMI ≥30 transplanted with single pediatric kidneys have better DCGS rates when compared to nonobese patients.

Early inhibition of the renin‐angiotensin system improves the long‐term graft survival of single pediatric donor kidneys transplanted in adult recipients

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin‐angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996–2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan–Meier estimated death‐censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33–5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18–0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long‐term graft survival among adults transplanted with single pediatric donor kidneys.

Respiratory Bronchiolitis: An Unusual Cause of Pulmonary Infiltrates in a Pregnant Woman

Numerous mechanical, biochemical, and immunologic changes occur during pregnancy. Because of these changes, pregnant women are more susceptible to infection, thromboembolic disease, exacerbation of underlying immunologic disease, and heart failure than women who are not pregnant. The differential diagnosis of diffuse pulmonary infiltrates in a pregnant woman is broad; thus, the work-up can be very challenging. If the patient fails to respond to conservative measures, such as antibiotics, the cause of the infiltrate must be aggressively evaluated because the treatment may be essential for the survival of the mother and fetus. We report a case of a pregnant woman who presented with diffuse bilateral infiltrates. After video-assisted thoracoscopic lung biopsy, this patient was found to have respiratory bronchiolitis, a disease not previously reported during pregnancy. Treatment with glucocorticoids resulted in a prompt improvement in symptoms.

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients.

AIM To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients. METHODS From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2(nd) month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041). CONCLUSION Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.