Impact of gender and gender disparities in patients with kidney disease.

PURPOSE OF REVIEW: Despite evidence of gender-specific differences in epidemiology and outcomes in all stages of chronic kidney disease (CKD), most studies ignore the issue of gender. This review addresses this knowledge gap by evaluating data on gender disparity in this population. RECENT FINDINGS: Population-based studies indicate a higher prevalence of CKD in women; however, there are fewer women on renal replacement therapy than men. Men may progress to end-stage kidney disease more rapidly. Gender differences in rates of CKD progression may be influenced by potential antifibrotic and antiapoptotic effects of estrogen or proinflammatory deleterious effects of testosterone. Women are referred later for kidney replacement therapy and receive fewer arteriovenous fistulas than men receive, irrespective of race. Women are also less likely to receive kidney transplants as compared with men but are more likely to donate a kidney. SUMMARY: Recommendations for medical management of CKD patients are currently made in a gender-blind manner, despite the fact that women have differing underlying physiology. Addressing gender differences and disparities is an important and overlooked area in the care of patients with kidney disease.

Complementary and integrative medicine in kidney transplantation.

PURPOSE OF REVIEW: Complementary and integrative medicine (CIM) use is widely prevalent in kidney transplant recipients but studies of efficacy or potential harm are sparse. This review examines prevalence of use of CIM and discusses potential beneficial and harmful aspects of CIM in renal transplant recipients. RECENT FINDINGS: The prevalence of CIM use in kidney transplant patients varies from 12 to 45%. There is a knowledge gap regarding CIM modalities among healthcare professionals that may contribute to reluctance to discuss CIM use with patients. Patients often do not spontaneously disclose its use, and those that use it may be more likely to be nonadherent to allopathic therapies. Herbal supplements may be nephrotoxic or interact with pharmaceutical agents, including calcineurin inhibitors. More data are needed to assess the potential benefits of other modalities of CIM, including yoga, Tai Chi or meditation, as these modalities have been beneficial for people with diabetes or hypertension, both of which are common in the posttransplant period. SUMMARY: Despite a high prevalence of CIM use in kidney transplant recipients, data are limited regarding risks and benefits. Education of healthcare providers who care for kidney transplant recipients should be encouraged. Intervention studies should be designed to investigate the CIM modalities, including yoga, meditation and Tai Chi that have been shown to be beneficial in other chronic diseases.

Mortality after Renal Allograft Failure and Return to Dialysis.

INTRODUCTION: The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. METHODS: We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. RESULTS: We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m2 at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. CONCLUSIONS: Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes.

Management of glycemia in diabetic patients with stage IV and V chronic kidney disease.

Diabetic kidney disease is a leading cause of end-stage kidney disease worldwide. Data suggest that prevention of progression to end-stage may lie in excellent blood glucose control; however, as kidney disease progresses, the risk of hypoglycemia increases, due to unpredictable insulin kinetics and altered pharmacokinetics of hypoglycemic agents. In addition, whole classes of hypoglycemic agents become contraindicated and regimens must be adjusted for declining kidney function. There is no consensus regarding the best therapy for the patient with advanced chronic kidney disease. In the best of circumstances, the care of these patients will involve intensive monitoring, with the input of a team of health care providers creating a coordinated care plan, including dietary advice and a drug regimen tailored to the specific issues faced by the individual patient. An open dialogue is necessary at all times, as patients may become frustrated and attempt self-treatment using over the counter alternatives.

Use of Repository Corticotropin Gel (Acthar) in Progressive Nephrotic Syndrome Secondary to Transplant Glomerulopathy: A Report of Three Cases.

Transplant glomerulopathy is a feared complication of kidney transplantation, often resulting in rapid loss of kidney function and ultimate graft failure. The underlying cause is unclear, with both antibody and cell-mediated immune mechanisms postulated, as well as intrinsic glomerular factors. At the present time, there is no known therapy. We report here 3 cases in which corticotropin gel (Acthar) was used with varying response of proteinuria and stabilization of graft function with continued graft survival as long as 10 years following the diagnosis. Future randomized controlled trials are warranted to examine the efficacy and safety of ACTH gel therapy in nephrotic patients with transplant glomerulopathy.

Complementary Medicine Use, Symptom Burden and Non-Adherence in Kidney Transplant Recipients.

BACKGROUND: Complementary Medicine (CAM) is often used by patients with chronic illness and may not be disclosed to health care providers without prompting. In other populations, patients who use CAM were more likely to alter medications without discussing it with their provider. This study examined the relationship between self-reported use of CAM, attitudes toward care, and adherence to medical therapy in a population of inner-City kidney transplant recipients. METHODS: Cross-sectional observational analysis in a random convenience sample from the outpatient transplant clinic. Data were obtained via face-to-face structured closed-ended interview using validated survey instruments. RESULTS: 45% of patients reported using CAM. Of the study participants who used CAM, 39.1% reported non-adherence to immunosuppressant medications within the past three months, while among the non-CAM users, 17.9% reported non-adherence (p value=0.084). Adherence to hypoglycemic medication was significantly lower CAM users,(p=0.029). Patients who reported having somatic symptoms were more likely to use CAM. Symptom sum was significantly associated with CAM use, p=0.030, with 47.8% CAM users reporting skin problems vs. 10.7% non-CAM users,p=0.003 and 17.4% CAM users noting loss of appetite, compared to 3.5% of non-CAM users,p=0.002 In a random subgroup of 26 patients, 15% who did not use CAM reported medication side effects, while 53% of CAM users reported them, p =0.039. CONCLUSIONS: Use of CAM was common in our kidney transplant population. Patients who use CAM reported more somatic symptoms, more medication side effects and were more likely to be non-adherent to non-immunosuppressant medications. Positive response to questions about CAM use may be a surrogate marker for high symptom burden and risk of non-adherence to non-immunosuppresion medications in kidney transplant recipients.

Gender disparity in fistula use at initiation of hemodialysis varies markedly across ESRD networks-Analysis of USRDS data.

BACKGROUND: Gender disparities had been noted in the care of women with end stage renal disease (ESRD) in the early 2000's, including less frequent initiation of hemodialysis utilizing a fistula but more recent data have not been examined and underlying factors have not been extensively studied. STUDY DESIGN: Data from the United States Renal Data System (USRDS) were examined, including 202,999 hemodialysis patients. Only those who had received prior nephrology care were included. Multiple logistic regression was used, adjusted for possible confounders, including age, race, cause of ESRD, BMI, height, history of alcohol or drug abuse, medical comorbidities, ability to ambulate, time of nephrology care, type of insurance, and ESRD network. RESULTS: The odds of arteriovenous fistula (AVF) use at initiation of hemodialysis were significantly lower in women compared to men (OR = 0.69, 95% CI 0.67-0.71, P < 0.0001). The gender gap in AVF use at initiation was highest in New York and the upper Midwest (networks 2 and12) and smallest for Southern California and the Pacific Northwest and Alaska (18 and 16). Gender disparity was more pronounced for black women, with odds ratios for AVF use at initiation of dialysis (OR = 0.66, 95% CI 0.62-0.69), P < 0.0001 as compared to non-black (OR 0.70, 95% CI 0.68-0.73), P ≤ 0.0001. LIMITATIONS: Limitations include use of USRDS data. Data misclassification or errors in data reporting may exist and certain comorbid conditions may be underreported. Data regarding rate of primary fistula non-function are also not available. CONCLUSION: Adjusted odds ratio for AVF use was significantly lower in women compared to men, independent of time of nephrology care and other predictors. The gender disparity was most pronounced for black women and also varied from 20% to 46% lower odds for AVF use in women for different ESRD networks, after controlling for possible confounding variables, suggesting that practice based factors may be of importance in explaining this important finding.

Potential benefits of complementary medicine modalities in patients with chronic kidney disease.

Use of complementary and alternative medicine (CAM) by the general population is common, and, although potential for harm exists, evidence is accumulating that several modalities, including acupuncture, massage, relaxation response/guided or integrative imagery, meditation, and herbal supplements, have actions that are beneficial for patients with chronic illness. Potential areas in which CAM might benefit patients with kidney disease include prolonging time of progression to kidney failure as well as treatment of concomitant problems, including arthritides, pruritus, cardiovascular risk factors, anxiety, depression, and fatigue, as well as hepatoprotection and treatment of uremic bruising. Although no systematic survey of prevalence of use has been performed in patients with chronic kidney disease and much research remains to be done so that safety and efficacy issues can be resolved, it is likely that many patients are using the services of CAM providers without the knowledge of their nephrologists. Thus, it behooves us to become conversant in these therapies so that we may hold open dialogues with our patients, discouraging potentially harmful treatments, suggesting potentially helpful ones, and monitoring them for effects, both beneficial and harmful.

New-onset diabetes mellitus in transplant patients: pathogenesis, complications, and management.

New-onset diabetes mellitus after transplantation is characterized by decreased insulin secretion and increased insulin resistance secondary to the effects of immunosuppression. Although impaired beta cell function appears to be the primary mechanism of calcineurin inhibitor-induced new-onset diabetes, impaired peripheral glucose utilization also appears to contribute to insulin resistance and abnormal glucose metabolism. Because transplant recipients who develop new-onset diabetes mellitus after transplantation are at increased risk for infections, cardiovascular disease, and poor patient and graft survival, all patients should undergo careful assessment of risk for diabetes prior to transplantation and regular screening for the development of hyperglycemia thereafter. For patients in high-risk groups, including certain ethnic backgrounds, older adults, and the very young, and patients with hepatitis C, consideration should be given to initiating immunosuppressive therapy with agents that are less diabetogenic. Recent guidelines include more stringent criteria for diagnosis and stress the importance of strict glycemic control. Diet, exercise, and weight management are core components of treatment with addition of oral hypoglycemic agents and/or insulin as needed to achieve control. Concomitant measures include aggressive control of lipids and blood pressure to reduce the risk of cardiovascular disease. New-onset diabetes after transplantation is a serious issue affecting patient and graft outcomes and warrants the attention of all health care professionals involved in assessing and managing the transplant recipient.

Management of the well renal transplant recipient: outpatient surveillance and treatment recommendations.

Although renal transplantation offers survival and quality of life advantages as a renal replacement therapy, a substantial proportion of transplant recipients develop worsening of preexisting medical diseases or new complications, including sequelae of rejection, new onset diabetes after transplantation (NODAT), hyperlipidemia, opportunistic infections, cancer, and other systemic diseases secondary to immunosuppression. Management of these problems can be a complex endeavor due to medication interactions that often affect immunosuppression levels. However, successful management of the chronic medical problems associated with renal transplantation can prolong the life span of the graft and the patient.

Guidelines for the treatment and management of new-onset diabetes after transplantation.

Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new-onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss. In 2003, International Consensus Guidelines on New-onset Diabetes after Transplantation were published, which aimed to establish a precise definition and diagnosis of the condition and recommend management strategies to reduce its occurrence and impact. These updated 2004 guidelines, developed in consultation with the International Diabetes Federation (IDF), extend the recommendations of the previous guidelines and encompass new-onset diabetes after kidney, liver and heart transplantation. It is hoped that adoption of these management approaches pre- and post-transplant will reduce individuals' risk of developing new-onset diabetes after transplantation as well as ameliorating the long-term impact of this serious complication.

Allograft diabetic nephropathy may progress to end-stage renal disease.

Mesangial expansion and glomerular basement membrane thickening characteristic of diabetic nephropathy recur in diabetic recipients of renal allografts from non-diabetic donors but progression to renal failure is minimally documented. Three female renal allograft recipients (aged 40, 62 and 73 yr), who developed end-stage renal disease (ESRD) due to recurrent diabetic nephropathy (two patients) and de novo diabetes (one patient) are reported. Onset of proteinuria, uncontrolled hypertension, azotemia, renal allograft pathologic findings and the need for hemodialysis were analyzed. None of the kidney donors (one cadaver, two living related) had known diabetes or perturbed glucose metabolism pre-transplantation. The three patients presented had different varieties of diabetes; type 1, type 2 and new onset diabetes after transplantation (NODAT). In each subject, proteinuria was detected by dipstick at a mean of 8.3 yr (range 8-9) post-transplantation and increased to the nephrotic range (3.7-4.8 g/day) inducing hypoalbuminemia and azotemia. A histopathologic diagnosis of allograft diabetic nephropathy was made in a mean of 11.7 yr (range 10-14), based on glomerular basement membrane thickening, nodular and diffuse intercapillary glomerulosclerosis, arteriolosclerosis, and tubular atrophy with marked tubular basement membrane thickening characteristic of advanced diabetic nephropathy. All three patients manifested uremia and resumed hemodialysis. Two patients died from sepsis within 2 months and one patient died 2.5 yr later after resumption of maintenance hemodialysis. We infer that recurrent or de novo diabetic nephropathy in renal allografts follows a clinical decade-long course irrespective of diabetes. Reports of ESRD due to allograft diabetic nephropathy (ADN) have been limited because of shorter survival of diabetic transplant recipients and few kidney biopsies performed in patients with chronic allograft dysfunction. The occurrence of allograft diabetic nephropathy in some, but not all patients, however, suggests that individual genetic variability modulates disease expression.

Successful treatment of post-renal transplant Kaposi's sarcoma with paclitaxel.

Kaposi's sarcoma (KS) is a complication of immunosuppressive therapy for renal transplant recipients. Treatment is usually withdrawal of immunosuppression; nonresponders often receive chemotherapy. Successful treatment with single agent paclitaxel (PTX) has been documented in only one patient. We report two patients with generalized cutaneous, and visceral KS, which progressed despite withdrawal of immunosuppressive therapy, and were treated with weekly PTX. Both patients' KS regressed completely after four courses of PTX, and remained in remission for > 1 year. PTX may be important in the treatment of post-transplant KS resistant to withdrawal of immunosuppressive therapy.