Pharmacotherapy considerations in pregnant patients on hemodialysis

Purpose

Successful pregnancy rates on dialysis are increasing with the advent of intensive hemodialysis and advances in medical management.

Summary

Data support the use of intensive hemodialysis in pregnant women with end-stage kidney disease (ESKD). This paper provides an overview of common pharmacotherapeutic changes in management when caring for a pregnant woman receiving intensive hemodialysis. Pregnant patients on peritoneal dialysis were excluded from this analysis due to insufficient data. Topics covered include those related to anemia (iron and erythropoietin stimulating agents), blood pressure agents, monitoring of phosphorus, as well as nutrition and anticoagulation.

Conclusion

When patients on hemodialysis become pregnant, medication adjustments are needed regarding antihypertensives, anemia management, and mineral-bone disease management as many agents require dose adjustment, switching agents due to teratogenicity, or cessation due to fetal complications. There are minimal data in this population; however, successful and healthy infants have been delivered in this patient population with the medication changes discussed.     

Sexual function in women receiving maintenance dialysis

While substantial attention has been paid to the issue of sexual dysfunction in men on chronic dialysis, less is known about this problem in women with end-stage renal disease. We sought to assess sexual dysfunction in women on chronic dialysis and determine whether patients discuss this problem with their providers and receive treatment. We prospectively enrolled women receiving chronic hemodialysis or peritoneal dialysis in Pittsburgh, PA. We asked patients to complete the 19-item Female Sexual Function Index (FSFI) to assess sexual function and a 5-item survey that assessed whether patients had discussed sexual dysfunction with their providers and/or received treatment for this problem in the past. We enrolled 66 patients; 59 (89%) on hemodialysis and 7 (11%) on peritoneal dialysis. All patients completed the FSFI, of whom 53 (80%) had FSFI scores <26.55, consistent with the presence of sexual dysfunction. Of 37 patients who were married or residing with a significant other, 27 (73%) had sexual dysfunction. Among 24 participants who reported having been sexually active over the previous 4 weeks, 11 (46%) had sexual dysfunction. Only 21% of patients with sexual dysfunction had discussed this problem with their gynecologist, renal or primary provider, and 3 (6%) reported having received treatment. Sexual dysfunction is common in women on dialysis, even among patients who are married or residing with a significant other and those who are sexually active. However, few women discuss this issue with their providers or receive treatment.     

Pregnancy in dialysis-dependent women--the importance of frequent dialysis and collaborative care: a case report

An increasing number of successful pregnancies have been reported among women on chronic hemodialysis. Even with reduced fertility and high risk of complications, women of childbearing age receiving hemodialysis, should not be discouraged from pregnancy. Practitioners should be familiar with the effects of renal disease on pregnancy, consult patients about the possibility of pregnancy and its hazards and provide, if necessary, prompt surveillance and treatment. This paper describes the case of an unplanned but successful pregnancy of a woman receiving hemodialysis, emphasizing pregnancy management, mother's response evaluation, and infant growth.     

Phosphorus-enriched hemodialysis during pregnancy: Two case reports

Successful pregnancy leading to delivery of a viable infant is an uncommon occurrence either in women with established renal disease or in those with renal failure requiring chronic dialytic treatment. The frequency of conception in patients with renal failure has increased, however, and the outcome of such pregnancies has improved over the past 32 years. Current guidelines for dialysis in pregnant women include prolonged dialysis times, generally 20 or more hours per week. This extensive dialysis regimen often results in a decrease in the serum inorganic phosphorus levels, with possible detrimental effects to the health of the mother and the unborn child. In this article, we report the successful multidisciplinary management of two pregnant women with end-stage renal disease, both of whom developed hypophosphatemia after initiation of intensive hemodialysis. Sodium phosphate salts were added to the dialysate of each patient and this addition successfully corrected the decrease in serum inorganic phosphate concentration. One patient was able to carry the pregnancy for 28 weeks with delivery of a healthy 1260-g infant. The pregnancy of the second patient ended at 25 weeks of gestation with delivery of a nonviable infant.     

Pregnancy in end-stage kidney disease: Great news that needs to be handled carefully

Compared to women with normal kidney function, women with end-stage kidney disease (ESKD) are much less likely to become pregnant, but more likely to have a complicated pregnancy. While renal transplantation remains the best option for women who desire to have a child, pregnancy on dialysis should be considered an option for those who may not receive a transplant during their reproductive years. Many physicians do not encounter a pregnant patient with ESKD during their nephrology training, and may not feel prepared to provide care for such patients in a busy practice. In this paper, we briefly provide an overview of the most significant practical points related to management of a pregnant patient with ESKD through a real-life case with twin pregnancy. The two key elements in management of these patients would be an intensified hemodialysis regimen and a multidisciplinary team that can provide frequent, regular, and multifaceted assessments.     

Insights into nephrologist training, clinical practice, and dialysis choice

There is variable emphasis on dialysis-specific training among US nephrology fellowship programs. Our study objective was to determine the association between nephrology training experience and subsequent clinical practice. We conducted a national survey of clinical nephrologists using a fax-back survey distributed between March 8, 2010 and April 30, 2010 (N = 629). The survey assessed the time distribution of clinical practice, self-assessment of preparedness to provide care for dialysis patients at the time of certification examination, distribution of dialysis modality among patients, and nephrologists' choice of dialysis modality for themselves if their kidneys failed. While respondents spent 28% of their time caring for dialysis patients, 38% recalled not feeling very well prepared to care for dialysis patients when taking the nephrology certification examination. Sixteen percent obtained additional dialysis training after fellowship completion. Only 8% of US dialysis patients use home dialysis; physicians very well prepared to care for dialysis patients at the time of certification or who obtained additional dialysis training were significantly more likely to provide care to home peritoneal dialysis patients. Even though 92% of US dialysis patients receive thrice weekly in-center hemodialysis, only 6% of nephrologists selected this for themselves; selection of therapy for self was associated with dialysis modalities used by their patients. Nephrology training programs need to ensure that all trainees are very well prepared to care for dialysis patients, as this is central to nephrology practice. Utilization of dialysis therapies other than standard hemodialysis is dependent, in part, on training experience.     

Gustatory sweating recurring on peritoneal dialysis but resolving during periods of hemodialysis

Gustatory sweating is a rare disorder characterized by profuse sweating on the forehead, face, scalp, and neck occurring soon after ingesting food, which has been reported in diabetic patients. The mechanism is thought to be triggered by taste buds and not gastric stimulation. We report a case where gustatory sweating repeatedly developed on peritoneal dialysis that resolved on periods of hemodialysis. A 32-year-old woman with diabetic end-stage renal disease developed gustatory sweating shortly after beginning continuous ambulatory peritoneal dialysis despite excellent clearances. After 5 months, she changed to hemodialysis for 2 months and noticed complete resolution of her gustatory sweating; however, after her return to peritoneal dialysis 2 months later, her gustatory sweating recurred. While on peritoneal dialysis, she was treated with clonidine, which resulted in improvement but not resolution of her symptoms as had occurred on hemodialysis. Another period on hemodialysis resulted in the resolution of her symptoms that returned again after restarting peritoneal dialysis. Clonidine provided incomplete relief while topical glycopyrrolate was effective and without complications. We report recurrent gustatory sweating on peritoneal dialysis that resolved with hemodialysis. We have no data to suggest that intra-abdominal stimulation played a role, but rather that despite excellent clearances neuropathy may have played a role. Treatment with topical glycopyrrolate may be safe and effective given every third day if clonidine is ineffective.     

What Went Wrong with Home Hemodialysis in the United States and What Can Be Done Now?

In 1973, almost 40% of the more than 10 000 dialysis patients were treated by home hemodialysis. Today, with more than a quarter of a million dialysis patients in the United States, fewer than 2000 are on home hemodialysis. A number of factors have contributed to this change. First, many nephrologists and administrators who were developing new dialysis units had little or no practical experience with dialysis for chronic renal failure. Second, more elderly and diabetic patients were admitted to treatment. Home hemodialysis was more difficult for such patients, and often their helpers were themselves were elderly. Third, hemodialysis machines were difficult to learn and operate. Fourth, following publication of the results of the National Cooperative Dialysis Study, there developed the erroneous concept that a Kt/V equal to 1.0 was “adequate dialysis.” As bigger dialyzers became available, there was a widespread shortening of dialysis time. This decrease in time was embraced by for‐profit dialysis facilities and inadequately educated patients, and assembly‐line dialysis became generally accepted. Finally, continuous ambulatory peritoneal dialysis, with its simplicity and short training time, began to fill the need of many patients for home dialysis and independence, at least temporarily. Fortunately, the trend is now reversing. Two developments clearly have benefits for home hemodialysis. The first is an increasing interest in the use of more frequent dialysis. The second is the development of new equipment designed specifically for use by the patient, and requiring a minimum of effort on the patient's part.     

Portable and wearable dialysis: where are we now?

Although dialysis is a life-saving treatment for patients with acute and chronic kidney disease, mortality remains high, with the survival of patients treated by regular hemodialysis similar to that of some solid organ tumors. Recent reports have suggested that a major increase in the dose of dialysis, delivered by frequent nocturnal dialysis, may improve survival. Unfortunately, only a minority of centers can offer this type of therapy, and only to a minority of their patients. Thus, to improve access to dialysis as well as increase the delivered dose of dialysis, a major change in the current paradigm of dialysis delivery is required. For many years, the "holy grail" of dialysis has been to develop a wearable or portable system, allowing patients to be treated while performing their normal activities of daily living. It is only recently with the advances in technology that such dialysis devices have been possible. Prototype devices for both hemodialysis and peritoneal dialysis have been studied with favorable results. Typically, these have been short-term studies, and longer term trials are eagerly awaited, to determine whether the current generation of wearable continuous dialysis devices cannot only remove waste products of metabolism and control volume but also maintain acid-base and electrolyte homeostasis and actually improve outcomes. In addition, a novel generation of dialysis devices based on nanotechnologies are being developed. Hopefully, these wearable continuous devices will be available as an option for routine clinical practice in the not-too-distant future.     

The epidemiology of pregnancy-associated emergency department injury visits and their impact on birth outcomes

OBJECTIVE: Describe the demographics, injury types, mechanisms, and intents of emergency department (ED) injury visits by pregnant women and to quantify their risk of adverse birth outcomes. METHODS: Through a retrospective cohort study design, Utah ED, birth, and fetal death records were probabilistically linked to identify women seen in an ED with an injury during pregnancy among births and fetal deaths from 1999 to 2002. Logistic regression was used to assess the effect of having an injury-related ED visit on various adverse pregnancy outcomes. RESULTS: 7350 (3.9%) women experienced an injury-related ED visit during pregnancy. Motor vehicle occupant injuries were the leading mechanism of ED injury visits (22.4%). Controlling for known risks, pregnant women with an injury-related ED visit were more likely than non-injured pregnant women to experience preterm labor (OR=1.22, 95% CI=1.12-1.34), placental abruption (OR=1.33, 95% CI=1.08-1.65), and cesarean delivery (OR=1.27, 95% CI=1.19-1.36). Infants born to women who were injured during pregnancy were more likely to be born preterm (OR=1.23, 95% CI=1.12-1.34) and have low birth weight (OR=1.22, 95% CI=1.1-1.35). CONCLUSIONS: Most injured pregnant women are treated and released from the ED; however, significant increased risks remain for several maternal complications and birth outcomes.     

Hemodialysis for infants,children, and adolescents

Children with chronic kidney disease stage 5 requiring dialysis can be treated by peritoneal or hemodialysis. In the United Kingdom nearly twice as many children receive peritoneal dialysis compared with hemodialysis. Technical aspects of pediatric hemodialysis are challenging and include the relative size of extracorporeal circuit and child's blood volume, assessment of adequacy,technical and complications of vascular access. Alternatives to standard hospital‐based hemodialysis are also increasingly available. Optimizing nutritional status with the support of specialist pediatric dietitians is key to the management of children receiving hemodialysis. The effects of chronic illness on growth and school achievement, as well as the psychological, emotional, and social development of the child should not be underestimated. This review focuses on the above elements and highlights common pediatric practice in the United Kingdom.     

Sleep apnea and dialysis therapies: Things that go bump in the night?

Sleep apnea has been linked to excessive daytime sleepiness, depressed mood, hypertension, and cardiovascular disease in the general population. The prevalence of severe sleep apnea in the conventional thrice-weekly hemodialysis population has been estimated to be more than 50%. Sleep apnea leads to repetitive episodes of hypoxemia, hypercapnia, sleep disruption, and activation of the sympathetic nervous system. The hypoxemia, arousals, and intrathoracic pressure changes associated with sleep apnea lead to sympathetic activation, endothelial dysfunction, oxidative stress, and inflammation. Because sleep apnea has been shown to be widespread in the conventional dialysis population, it may be that sleep apnea contributes substantially to the sleepiness, poor quality of life, and cardiovascular disease found in this population. The causal links between conventional dialysis and sleep apnea remain speculative, but there are likely multiple factors related to volume status and azotemia that contribute to the high rate of severe sleep apnea in dialysis patients. Both nocturnal automated peritoneal dialysis and nocturnal hemodialysis have been associated with reduced severity of sleep apnea. Nocturnal dialysis modalities may provide tools to increase our understanding of the uremic sleep apnea and may also provide therapeutic alternatives for end-stage renal disease patients with severe sleep apnea. In conclusion, sleep apnea is an important, but overlooked, public health problem for the dialysis population. The impact of sleep apnea treatment in this high-risk population may include reduced sleepiness, better mood and blood pressure, and lowered risk of cardiovascular disease.     

Infant mortality review as a vehicle for quality improvement in a local health department

BACKGROUND: Many communities across the United States have established fetal and infant mortality review (FIMR) programs as a way of gaining insight into the causes of such deaths and of devising and implementing ways to improve the health of pregnant women and their infants. IMR PROCESS: The IMR process in the Jefferson County Department of Health in Birmingham, Alabama, evolved in a somewhat different fashion than that in other communities. A technical review team reviews all the infant deaths in the county, with particular attention to each woman's pregnancy history. A community review team reviews composite cases that illustrate some particular problem that might lead to infant mortality, such as teenage pregnancy or short intervals between pregnancies. This team provides insights into cultural patterns and a community perspective on the problems. Recommendations from the two teams are acted on by the health department, with the assistance of other agencies as needed. IMPACT OF THE IMR PROCESS: The IMR process has been used to increase community agency participation in health department activities, improve health department procedures, increase health department staff acceptance of a new and controversial program (Healthy Start), and offer services to women who need them. CONCLUSIONS: IMR has become a mechanism for CQI in the health department, embodying many of the principles of CQI, including the use of teams, focus on a team mission, and examination of processes, not individuals. The program offers a model of how to reduce rates of fetal and infant mortality.     

Dialysis education and options for late presenters—An ongoing dilemma

Pre-dialysis education forms a crucial part of dialysis preparation. Acute start dialysis patients often commence and remain on in-center hemodialysis (ICHD) without the benefit of an informed decision making process for kidney replacement therapy options. The aim of this review is to evaluate the evidence surrounding methods of education provision to the acute dialysis start population and their associated outcomes. Publications have described a holistic education pathway with multimedia provision of information and interactive experiences. One or more trained specialist nurses provided information over 3–5 sessions. Formal education was mostly initiated as an inpatient. 86%–100% of acute start dialysis patients are initiated and remain on ICHD. Following formal education, 21%–58% of patients chose peritoneal dialysis (PD), 10%–24% home hemodialysis, 33%–58% ICHD. This brings the number of patients maintained on an independent form of dialysis similar to the planned dialysis start population. Patients commenced on PD without needing temporary hemodialysis, hence avoided complications associated with such. Patients aged under 75 (p < 0.0001) and males (p = 0.006) were more likely to be influenced by education to select PD. The adjusted 5 year survival rates among discharged patients were similar between home and ICHD groups (73% vs. 71% respectively), with a comparable age of death. A targeted education program in the acute dialysis start population has proven to be feasible. Adaptations are likely required for each center; however, various methods have been shown to be effective, with an increased number of patients choosing an independent dialysis modality when given the choice.     

Modality options for renal replacement therapy: the integrated care concept revisited

As the End-stage renal disease population continues to grow, innovative strategies that optimize patient outcomes while capitalizing on the relative strengths of the existing modalities must be sought. Renal transplantation remains the preferred form of renal replacement therapy, but given the limited supply of donor organs, dialytic therapies will continue to constitute a large part of the modality mix. Matching patients to the most suitable modalities requires that a number of factors be considered. These include the patient's autonomy, medical and social factors, system-related issues, patient outcomes, and finances. While peritoneal dialysis and hemodialysis (HD) have traditionally been viewed as competing modalities, we propose that they, along with home and frequent HD regimens, may be used in a complementary manner, which is based on current evidence, and may provide optimal outcomes while containing treatment costs. In this review, we attempt to synthesize the current literature describing the various issues that affect modality selection, and offer an approach to achieving a balance between these many competing factors.     

The relationship between symptoms and blood pressure during maintenance hemodialysis

Intradialytic hypotension (IDH) is a detrimental complication of maintenance hemodialysis, but how it is defined and reported varies widely in the literature. European Best Practice Guideline and Kidney Disease Outcomes Quality Initiative guidelines require symptoms and a mitigating intervention to fulfill the diagnosis, but morbidity and mortality outcomes are largely based on blood pressure alone. Furthermore, little is known about the incidence of asymptomatic hypotension, which may be an important cause of hypoperfusion injury and impaired outcome. Seventy‐seven patients were studied over 456 dialysis sessions. Blood pressure was measured at 15‐minute intervals throughout the session and compared with post‐dialysis symptom questionnaire results using mixed modeling to adjust for repeated measures in the same patient. The frequency of asymptomatic hypotension was estimated by logistic regression using a variety of commonly cited blood pressure metrics that describe IDH. In 113 sessions (25%) where symptoms were recorded on the questionnaire, these appear not to have been reported to dialysis staff. When symptoms were reported (293 sessions [64%]), an intervention invariably followed. Dizziness and cramp were strongly associated with changes in systolic blood pressure (SBP), but not diastolic blood pressure. Nausea occurred more frequently in younger patients but was not associated with falls in blood pressure. Thresholds that maximized the probability of an intervention rather than a session remaining asymptomatic were SBP <100 mmHg or a 20% reduction in SBP from baseline. The probability of SBP falling to <100 mmHg in an asymptomatic session was 0.23. Symptoms are frequently not reported by patients who are hypotensive during hemodialysis, which leads to an underestimation of IDH if symptom‐based definitions are used. A revised definition of IDH excluding patient‐reported symptoms would be in line with literature reporting morbidity and mortality outcomes and include sessions in which potentially detrimental asymptomatic hypotension occurs.     

The Decline in Residual Renal Function in Hemodialysis Is Slow and Age Dependent

Background: Persons on peritoneal dialysis and hemodialysis with preserved residual renal function experience lower mortality rates than those without. Previous studies have shown slower rates of decline of residual renal function for peritoneal dialysis (PD)(2 to 3% decrease/month), compared with hemodialysis (HD)(6 to 7% decrease/month). However, our clinical observations suggested a lower rate of decline in hemodialysis patients. Methods: We evaluated data in 174 hemodialysis patients cared for from January 2000 through October 2001. Eighty‐seven (50%) patients had at least two timed quarterly urine collections to estimate the rate of change of residual renal function over time (urea clearance, or KrU). All patients underwent thrice‐weekly hemodialysis using polysulfone dialyzers with formaldehyde reprocessing. The rate of decline of residual renal function and the effect of KrU on laboratory variables were estimated using a random effects (MIXED) model, adjusting for the effects of age, sex, race, diabetes, and dialysis vintage. Results: The mean KrU at baseline was 3.5 mL/min. Men (P < 0.001) and persons of shorter vintage (P < 0.0001) had more residual renal function at baseline. The estimated rate of decline of residual renal function was ? 0.07 mL/min/month (? 1.9% decrease/month). The rate of decline in residual renal function was unaffected by sex, race, diabetes, or vintage, although the rate of decline was significantly attenuated among older individuals (age x time interaction, P = 0.01). Serum phosphorus (P = 0.03) and the calcium x phosphorus product (P = 0.009) increased over time and were influenced by the level of residual renal function (P = 0.06 and P = 0.006, respectively). Residual renal function did not influence the rate of change of other laboratory variables. Conclusions: In an ethnically diverse cohort of hemodialysis patients, the rate of decline of residual renal function was relatively slow and age dependent, as well as consistent with values others have reported for patients on peritoneal dialysis. Universal use of biocompatible dialyzers and bicarbonate dialysate may have contributed to differences discussed in prior reports. Residual renal function attenuated the increase in calcium–phosphorus product over time. A better understanding of the determinants of the rate of decline in residual renal function, and the specific benefits afforded to patients via maintenance of residual renal function, would help to inform the debates on timing of initiation and various dosing strategies in hemodialysis.     

Understanding barriers to home‐based and self‐care in‐center hemodialysis

Despite superior outcomes and lower associated costs, relatively few patients with end‐stage renal disease undergo self‐care or home hemodialysis. Few studies have examined patient‐ and physician‐specific barriers to self‐care and home hemodialysis in the modern era. The degree to which innovative technology might facilitate the adoption of these modalities is unknown. We surveyed 250 patients receiving in‐center hemodialysis and 51 board‐certified nephrologists to identify key barriers to adoption of self‐care and home hemodialysis. Overall, 172 (69%) patients reported that they were “likely” or “very likely” to consider self‐care hemodialysis if they were properly trained on a new hemodialysis system designed for self‐care or home use. Nephrologists believed that patients were capable of performing many dialysis‐relevant tasks, including: weighing themselves (98%), wiping down the chair and machine (84%), clearing alarms during treatment (53%), taking vital signs (46%), and cannulating vascular access (41%), but thought that patients would be willing to do the same in only 69%, 34%, 31%, 29%, and 16%, respectively. Reasons that nephrologists believe patients are hesitant to pursue self‐care or home hemodialysis do not correspond in parallel or by priority to reasons reported by patients. Self‐care and home hemodialysis offer several advantages to patients and dialysis providers. Overcoming real and perceived barriers with new technology, education and coordinated care will be required for these modalities to gain traction in the coming years.