Blanche M. Chavers

20 years or more of follow-up of living kidney donors

The perioperative and long-term risks for living kidney donors are of concern. We have studied donors at the University of Minnesota 20 years or more (mean 23.7) after donation by comparing renal function, blood pressure, and proteinuria in donors with siblings. In 57 donors (mean age 61 [SE 1]), mean serum creatinine is 1.1 (0.01) mg/dl, blood urea nitrogen 17 (0.5) mg/dl, creatinine clearance 82 (2) ml/min, and blood pressure 134 (2)/80 (1) mm Hg. 32% of the donors are taking antihypertensive drugs and 23% have proteinuria. The 65 siblings (mean age 58 [1.3]) do not significantly differ from the donors in any of these variables: 1.1 (0.03) mg/dl, 17 (1.2) mg/dl, 89 (3.3) ml/min, and 130 (3)/80 (1.5) mm Hg, respectively. 44% of the siblings are taking antihypertensives and 22% have proteinuria. To assess perioperative mortality, we surveyed all members of the American Society of Transplant Surgeons about donor mortality at their institutions. We documented 17 perioperative deaths in the USA and Canada after living donation, and estimate mortality to be 0.03%. We conclude that perioperative mortality in the USA and Canada after living-donor nephrectomy is low. In long-term follow-up of our living donors, we found no evidence of progressive renal deterioration or other serious disorders.

Mesangial Expansion as a Central Mechanism for Loss of Kidney Function in Diabetic Patients

Diabetic nephropathy leading to kidney failure is a major complication of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus, and glomerular structural lesions (especially expansion of the mesangium) may constitute the principal cause of decline in kidney function experienced by a significant fraction of diabetic patients. Although the biochemical bases of these mesangial abnormalities remain unknown, an understanding of the natural history of diabetic nephropathy from a combined structural and functional approach can lead to greater pathophysiological insight. Work in animals has supported the concept that the metabolic disturbances of diabetes mellitus cause diabetic nephropathy, with structural and functional lesions prevented or reversed with improved or normalized glycemie control. Additional research must address this fundamental issue in humans, especially the response of advancing mesangial lesions to improved glycemie control. Factors not directly related to the metabolic perturbations of diabetes may serve to accelerate or diminish the pathophysiological processes of diabetic nephropathy. The elucidation and management of these factors, when coupled with improved glycemie control, may moderate the development or progression of diabetic kidney lesions in humans.

Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10‐year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundations Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1–3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4–5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.

Excerpts From the US Renal Data System 2009 Annual Data Report

This 21st US Renal Data System Annual Data Report covers data through 2007, and again includes a section on chronic kidney disease (CKD) in the United States. Using NHANES and employer group health plan data, we estimate the relationship between kidney disease markers and mortality risk and the likelihood of blood pressure and lipid control by CKD stage; illustrate use of the new ICD-9-CM CKD diagnosis codes; and report on morbidity, mortality, care and costs during the transition to ESRD. New chapters address CKD patient care, the transition to ESRD, and acute kidney injury. In 2007, 111,000 patients started end-stage renal disease (ESRD) therapy, and the prevalent population reached 527,283 (including 368,544 dialysis patients); 17,513 transplants were performed, and 158,739 patients had a functioning graft at year’s end. Program expenditures reached

United States Renal Data System 2008 Annual Data Report Abstract

35.3 billion, with

PRETRANSPLANT DIALYSIS STATUS AND OUTCOME OF RENAL TRANSPLANTATION IN NORTH AMERICAN CHILDREN: A NAPRTC STUDY. NORTH AMERICAN PEDIATRIC RENAL TRANSPLANT COOPERATIVE STUDY

23.9 billion from Medicare (accounting for 5.8% of total Medicare expenditures). The incident rate fell 2.1%, to 354 per million. Fistula use in prevalent patients declined 2.6 percent; catheter use continues to be a concern. The percentage of patients with hemoglobin levels above 13 g/dl has fallen since 2006, but levels in the incident population frequently exceed 12. First-year mortality and morbidity among hemodialysis patients—particularly the increasing rate of hospitalizations due to infections—continue to be major concerns, and pediatric patient survival has not improved. The public health impact of kidney disease is larger than previously appreciated, and early detection, education, intervention, and risk factor control need to address the heavy burden of cardiovascular disease and adverse events in this vulnerable population.

Relationship Between Retinal and Glomerular Lesions in IDDM Patients

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Long-term quality of life after kidney transplantation in childhood.

BACKGROUND There are no large studies of the effect of pretransplant dialysis status on the outcome of renal transplantation (Tx) in children. This study evaluated the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry data for the outcome of Tx in pediatric patients who either (1) received their transplants preemptively or (2) were maintained on dialysis before receiving their transplants. METHODS We compared graft survival and patient survival rates, incidence of acute tubular necrosis (ATN), acute rejection episodes, and causes of graft failure in peritoneal dialysis (PD) patients with those maintained on hemodialysis (HD) and those undergoing preemptive Tx (PTx). RESULTS Primary Tx was performed in 2495 children (59% male; 61% Caucasian; 1090 PD, 780 HD, 625 PTx) between 1/1/1992 and 12/31/1996. The overall graft survival rates of the PD and HD groups were similar, but were less than that of the PTx group (3-year: 82% PD and HD, 89% PTx, overall P = 0.0003). Improved graft survival in the PTx group was present only in recipients of grafts from living donors. There was no difference in the overall patient survival rate at 3 years, or in time to first acute-rejection episodes in the three groups. The incidence of ATN in the first 7 days post-Tx was higher in PD and HD patients than in PTx patients (11% PD and 12% HD vs. 2% PTx, P<0.001; HD vs. PD, P = NS). The major single cause of graft failure in each group was: PD, vascular thrombosis (200%); HD, chronic rejection (27%); PTx, acute and chronic rejection (21% each). CONCLUSION NAPRTCS data show that graft survival is improved in patients receiving PTx, compared with those receiving PD and HD. Graft loss resulting from vascular thrombosis is more common in children who receive PD than in those receiving HD.

Renal transplantation in infants.

Current knowledge regarding the concordance and discordance of the eye and kidney complications of diabetes is based on observations by ophthalmoscopy of retinal structural changes, which may be present at early stages of the disorder, and renal functional changes, which only become apparent at the later stages of the disease. For this reason we investigated the relationship between retinal structural lesions and quantitative measures of glomerular structure in patients with insulin-dependent diabetes mellitus (IDDM). Renal biopsies were evaluated using morphometric techniques, and retinopathy classification was determined by retinal fundus photography in 86 patients with IDDM: age 30.4 ± 7.3 years and duration of IDDM 18.9 ± 6.3 years (mean ± SD). Retinopathy score correlated with glomerular basement membrane width (r = 0.39, P = 0.0002), mesangial volume fraction (VvMes/Glom) (r = 0.35, P = 0.0009), surface density of the peripheral capillary wall (SvPGBM/Glom) (r = 0.34, P = 0.0013), and index of arteriolar hyalinosis (r = 0.36, P = 0.0008). Abnormalities in VvMes/Glom and SvPGBM/Glom were more pronounced in patients with both retinopathy and hypertension. Four of the 15 patients (27%) with either normal urinary albumin excretion (UAE) or low-level microalbuminuria had advanced retinopathy but normal VvMes/Glom. In conclusion, the presence of advanced retinal disease with or without hypertension in patients with IDDM indicates a greater likelihood of advanced nephropathy as evidenced by increased VvMes/Glom and decreased SvPGBM/Glom. However, marked discordance between retinopathy and nephropathy occurs, as illustrated by patients with normal UAE or low-level microalbuminuria, normal glomerular structural measures, and advanced retinopathy.

The use of mycophenolate mofetil suspension in pediatric renal allograft recipients.

Transplantation is the treatment of choice for children with end-stage renal disease. However, the long-term quality of life and socioprofessional outcome for those with successful transplants have not previously been reported. We studied these factors in patients transplanted when<18 years old who currently have ≥10 years of graft function. A total of 57 questionnaires were sent out; 57 (100%) responded [24 female and 33 male patients; average (±SD) age at tx = 10±5 years (0.9–17.7); average f/u = 15.6±3 years (10–26); current age = 26±5 years (12–38); 26 had < 1 transplant]. Of the 57 respondents, 9 are<18 (all are in school); 48 are ≥18 (7 in school, 37 employed, 4 unemployed); 12 are married, 1 engaged, and 2 divorced; and 9 have children. While in school, 43 (75%) had participated in sports, 37 (65%) in other extracurricular activities; 7 (12%) were A and 33 (58%) B students; 15 (26%) received awards or scholarships. For those working, the range of occupations is broad (average work week = 41±5 hr). Health-related absence from work has been nonexistent for 93%. Health is rated as good to excellent by 91% and fair by 9%. The future is regarded as hopeful or promising by 80%. Similarly, 89% are satisfied with life in general; 95% said health never or seldom interferes with family life; 95% feel health and drug side effects are of no or minor concern in sexual relationships. Only 3% feel health is a problem in maintaining a sexual relationship (41% are not sexually active). Only 4% stated that health often interferes with social life; 98% meet with friends on a regular basis; 76% are satisfied with personal relationships and 8% dissatisfied; 91% are satisfied with their ability to perform at work or school and 5% dissatisfied. Of note, 32% are dissatisfied with body appearance. Major concerns are short stature and brittle bones. Major suggestions include education/support groups to deal with teasing at school and peer problems. We conclude that transplanted children with long-term graft function have a favorable social and professional outcome. Overall, quality of life seems excellent.