Menopause in CKD.

Most women with dialysis-dependent chronic kidney disease (CKD) stage 5 (CKD stage 5D) are in the postmenopausal age group. Early menopause is reported for all CKD stages (stages 3-5D). The traditional definition of menopause is not applicable in CKD stage 5(D) because menses can resume with hormone replacement therapy or kidney transplantation. Treatment of vasomotor symptoms continues to be the primary indication for hormone replacement therapy, with no dosing studies done specifically for CKD or kidney transplantation populations. Similarly, the risk for cardiovascular disease and osteoporosis in menopause is well described in healthy women, but the role that menopause plays in accelerating the risk further in CKD/kidney transplantation is yet to be explored. Lack of data and specific guidance on management make the long-term effects of menopause one of the most under-recognized and neglected patient problems in clinical nephrology. The efficacy and side effects of widely available therapeutic options in healthy women for menopause-related clinical manifestations, be it hormone replacement therapy for vasomotor symptoms or antiresorptive agents for osteoporosis, are to be tested in kidney transplantation and CKD populations. Longitudinal clinical trials are in need to define menopause in CKD and determine the role that CKD plays in menopause transition and menopause on CKD manifestations.

Intensive hemodialysis associates with improved pregnancy outcomes: a Canadian and United States cohort comparison.

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.

Neurologic complications in renal transplantation.

Neurologic complications following kidney transplant are more common than in the general population with the reported incidence around 10-21%. Need for multiple drugs, decreased cellular immunity, accelerated atherosclerotic disease, and frequency of metabolic abnormalities are the most common predisposing factors for neurologic abnormalities. Neurologic side-effects of calcineurin inhibitors range from mild tremors to paraplegia or posterior reversible encephalopathy syndrome (PRES) and are generally reversible by lowering the dose or complete discontinuation of the drug when possible. Clinical presentation of central nervous system infection in transplant recipients can be different from the normal population as the anti-inflammatory effects of immunosuppressive therapy may obscure signs of meningeal inflammation and changes in the level of consciousness may be subtle. Bacterial infections remain the most common infections but unusual pathogens figure prominently in the differential diagnosis. The most frequent malignancies of the brain are lymphomas and metastatic tumors which are for the most part, de novo malignancies from immunosuppression. Decreasing immunosuppression is almost always a part of treating malignancy. The prevalence of stroke is reported to be around 8% with age>40 years, diabetic nephropathy as the underlying cause of end-stage kidney disease, and peripheral vascular disease being the strongest predictors.

Pregnancy in renal transplant recipients.

Fertility in women with kidney failure is restored by transplantation. It requires careful planning and is only advisable in women with good kidney function, controlled blood pressure, and general good health. Immunosuppressive drugs carry risks for the fetus, but the risks of prednisone, azathioprine, cyclosporine, and tacrolimus are surprisingly low. Mycophenolate is teratogenic. The success rate for pregnancy in kidney transplant recipients is lower than in the general population with 70% to 80% of pregnancies resulting in surviving infants. Prematurity, intrauterine growth restriction, and preeclampsia are all increased. Complications are higher and outcomes are worse for women with serum creatinine levels over 1.3 mg/dL. Ten to 15% of women have a temporary or permanent decline in kidney function, particularly if prepregnancy creatinine is high. Transplant-related infections can be serious for the mother and fetus. A multidisciplinary team should coordinate care.

Identifying potential kidney donors using social networking web sites.

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation.

A woman with GN presenting during pregnancy.

The combination of kidney disease and pregnancy has long been recognized as a high-risk situation. When renal disease is recognized for the first time during pregnancy, it presents unique problems for both the obstetric and the renal teams. Particularly difficult can be distinguishing preeclampsia from preexisting kidney disease in women presenting for the first time with hypertension, proteinuria, and reduced GFR during pregnancy. Decision-making regarding performing a kidney biopsy and treatment of glomerular disease during pregnancy is often much more complicated by safety concerns for both the mother and the developing fetus.

Sirolimus and nefazodone interaction in a renal transplant patient

Background and Objectives: Our case demonstrates the first report of aninteraction with sirolimus and nefazodone in a stable renal transplant patient. Nefazodonecan inhibit cytochrome P450 3A4 and may result in elevated concentrations of sirolimussince sirolimus is metabolized by cytochrome P450 3A4. Methods: A 44-year-old patient was taking nefazodone pre-transplant and post-transplant. When nefazodone was discontinued the sirolimus level was undetectable. Results: This drug interaction was not suspected because the patient was on nefazodonepre-transplant. Conclusions: It is very important to monitor the sirolimus trough level when nefazodoneis initiated, discontinued, or the dose is adjusted to prevent sirolimus subtherapeuticor supratherapeutic trough levels (AU)

Living donor kidney transplantation in the United States--looking back, looking forward.

There is a desperate need for kidney donors. Twenty-five years ago, we urged more widespread acceptance of unrelated living donors for kidney transplantation. Since then, 2 of us have donated a kidney to an unrelated recipient. In our view, the major challenges for living donor transplantation today are to improve access to this extraordinary gift of life and ensure its safety. Our perspective is that altruism is the motivation for most living kidney donors and the decision to donate represents a shared responsibility among the donor, the donor's physician, and the team of professionals at the transplant center. Thus, sound knowledge of the benefits and risks to donors and recipients is required for informed decisions, and all parties share in the responsibility for the outcomes after living kidney donation. We encourage our colleagues and agencies within the US Department of Health and Human Services to accept the responsibility to do their utmost to provide access to this life-enhancing procedure and systematically evaluate the safety of kidney donation as it evolves to meet the needs of more of our patients.

Transplant tourism--a dangerous journey?

INTRODUCTION: While the ethical aspects of transplant tourism have received much attention recently, less has been written about the medical safety of this practice. We retrospectively evaluated the outcomes of patients who purchased organs internationally and presented to our center for follow-up care. METHODS: Baseline demographic characteristics were recorded. Post-operative outcomes including patient survival, graft survival, five-yr graft function, and complications were assessed. RESULTS: Eight patients who purchased international organs for transplant were identified. The country of transplant was China (n = 3), Pakistan (n = 3), India (n = 1), and the Philippines (n = 1). All patients were born in either Asia or the Middle East and traveled to the region of their ethnicity for transplantation. The mean time to presentation was 49 d post-operatively. The overall one- and two-yr patient survival rates were 87% and 75%, respectively. One patient died of miliary tuberculosis and another of Acinetobacter baumanii sepsis. There was one case of newly acquired hepatitis B infection. At last follow-up, all six surviving patients had functioning grafts with a mean creatinine level of 1.26 mg/dL at five yr. CONCLUSION: Although intermediate-term graft function is acceptable, the early morbidity and mortality among transplant tourists is high. These results suggest that the associated risks may not justify the trip.

Beta HCG levels in a pregnant dialysis patient: a cautionary tale.

Conception is rare in patients on chronic dialysis and diagnosis is often delayed as it is least expected. Serum beta HCG levels are elevated in both pregnant and non-pregnant dialysis patients, and pregnant dialysis patients have slightly higher beta HCG levels when compared with normal pregnancy. This can be erroneously interpreted as non-viable pregnancy and so results should be viewed with caution. Serial beta HCG levels must be followed when non-viable pregnancy is suspected in a dialysis patient before contemplating termination of pregnancy as described in our case.

Obesity in kidney transplant recipients and candidates.

The prevalence of obesity in dialysis patients is increasing, and as a result, more obese dialysis patients are being evaluated for kidney transplant. Despite several limitations associated with the use of body mass index (BMI), BMI is commonly used to define obesity, with many transplant centers using BMI of 30-35 kg/m(2) as a limit for transplant eligibility. This limit evolved from the belief that obese patients have more complications and shorter transplant and patient survival than ideal-weight patients. Data for obesity and posttransplant complications are conflicting, with the exception of increased risk of postoperative wound complications, and there are no large trials showing a benefit of weight loss before transplant on subsequent patient or transplant survival. In our opinion, patient death and transplant failure rates in patients with BMI of 30-35 kg/m(2) are low enough that these individuals should not be excluded from transplant. Weight gain posttransplant is relatively common, and although sustained weight loss through conservative intervention is difficult to achieve, prevention of weight gain is a more feasible goal that should be addressed routinely. Although obesity is a complex and often multifactorial clinical condition that includes nonmodifiable factors, obese individuals often are viewed as being solely responsible for their obesity. Accordingly, in addition to encouragement of lifestyle modification, available pharmacologic and surgical options should be reviewed in appropriate patients. After pharmacologic and/or surgical interventions, close monitoring of immunosuppressive medications is necessary because of variability in drug absorption.

Treatment of idiopathic membranous nephropathy with the herb Astragalus membranaceus.

A 77-year-old woman with nephrotic syndrome secondary to idiopathic membranous nephropathy was treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, cyclosporine A, and mycophenolate mofetil, without response. After more than 2 years of unremitting nephrosis, she began therapy with the herb Astragalus membranaceus, used by traditional Chinese physicians to treat various immune disorders, including glomerulonephritis. After institution of Astragalus at a dose of 15 g/d, there was a marked decrease in proteinuria. Nephrotic syndrome recurred after temporary cessation of Astragalus therapy, with complete remission of nephrosis observed after its reintroduction. The clinical course of this patient suggests that Astragalus may have beneficial effects in patients with idiopathic membranous nephropathy.

Historical perspective of pregnancy in chronic kidney disease.

Preeclampsia was first recognized as a cause of proteinuria unique to pregnancy in 1843 and the risk of pregnancy in women with preexisting renal disease was noted in the 1930s. Since then, we have recognized that the majority of women with kidney disease who become pregnant have surviving infants. The exception is women on dialysis whose pregnancies result in only 50% to 75% of infant survival. All women with renal disease are at increased risk for hypertension during pregnancy, but the risk of more rapid than expected progression of renal disease generally occurs in women with serum creatinines greater than 1.4 mg/dL, with an even higher risk in women with serum creatinines greater than 2 mg/dL. Dialysis patients conceive infrequently and have a high frequency of fetal loss and neonatal death. Fertility is restored by renal transplant and guidelines are being developed regarding the ideal timing of pregnancy, the kidney function required for a safe pregnancy, and the use of immunosuppressive drugs in pregnancy.

Increasing body mass index and obesity in the incident ESRD population.

An increase in obesity prevalence among patients who initiate dialysis may influence the growth of the total ESRD population as a result of improved survival and decreased likelihood for transplantation. Temporal trends in mean body mass index (BMI) and obesity prevalence were examined among incident patients with ESRD by year of dialysis initiation between 1995 and 2002, and these trends were compared with those in the US population during this same period. Among incident dialysis patients, BMI was calculated with the height and estimated dry weight collected from the Centers for Medicare and Medicaid Services End-Stage Renal Disease Medical Evidence Form. In the US population, self-reported height and weight were used. Prevalence of total obesity and obesity stage > or =2 were defined as a BMI > or =30 and > or =35 kg/m(2), respectively. Among incident patients with ESRD, mean BMI increased from 25.7 to 27.5 kg/m(2), and total obesity and obesity stage > or =2 increased by 33 and 63%, respectively, among incident patients with ESRD (P < 0.0001 for obesity trends). BMI slope was approximately two-fold higher in the incident ESRD population compared with the US population for all age groups. However, temporal increases in obesity prevalence were similar between the two populations. As a result of the survival advantage associated with obesity and decreased likelihood for transplantation, these trends most likely will influence the total number of patients who receive dialysis in the next decade.

Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.

It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.