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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 Foundation's 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.

Adolescent↗

[Renocortical oxygen supply after kidney transplantation. Renocortical oxygen supply and kidney circulation after autologous kidney transplantation in the dog; its value for human kidney transplantation].

Determination of the viability of a transplanted kidney is still an unsolved problem. Apart from immunological effects hemodynamic and microcirculatory changes in the kidney are important. Thus in 39 mongrel dogs renal floow flow (electromagnetic and local renocortical oxygen supply) and microcirculation (by meaning local tissue pO2) were determined before nephrectomy, immediately after revascularization and before sacrification in experiments with autologous transplantation. Whole kidney blood flow decreased by 30-40%. Measurements of tissue pO2 revealed distinct changes in renocortical oxygen supply. Graft function concomitantly was reduced. Hypotension during revascularization is followed by a strong decrease in renal blood flow and renocortical oxygen supply. Even short periods of hypotension should be avoided.

Animals↗

[Multicystic dysplastic kidney: natural history of the affected and the contralateral kidney compared to the normal and solitary kidney].

INTRODUCTION: Complications of multicystic dysplastic kidney are rare, but hypertension and malignant transformation represent real danger. PATIENTS/METHODS: In a 10-year period, 94 infants (60 boys, 34 girls) with multicystic dysplastic kidney were diagnosed. The data obtained from these patients were compared to 70 children with solitary kidney of which 36 were newborns. In 80 cases (85%) the diagnosis of multicystic dysplastic kidney was already suspected by prenatal sonography. RESULTS: Abnormalities of the contralateral kidney were found in 15 of the 94 patients (16%). Complete involution of the multicystic dysplastic kidney was observed in 19, and a decrease in size in 42%. In 37 children (39%) the dysplastic kidney has been removed at the age of about 1 year because of no involution. The length of the contralateral kidney, compared to the normal standard was already significantly larger at birth. In newborn babies with unilateral renal agenesia the solitary kidney was also significantly longer. CONCLUSIONS: Compensatory hypertrophy of single functioning kidneys occurs in utero both in patients with multicystic dysplastic kidney and in those with unilateral renal agenesia. Based on the results of these and previous studies, early nephrectomy cannot be recommended in the newborn period. Surgery remains an option for patients who have no involution at the time of about 1 year of age.

Female↗

Quantitative SPECT of technetium-99m-DMSA uptake in the kidneys of normal children and in kidneys with vesicoureteral reflux: detection of unilateral kidney disease.

UNLABELLED: Quantitative SPECT was used to evaluate renal functional volume (cc), percent of injected dose/cc (%ID/cc) and renal uptake (%) in 11 children with unilateral vesicoureteral reflux grade 3 or greater, and in 19 normal control children without reflux. METHODS: Studies were performed 4-6 hr after intravenous injection of 0.750-2 mCi of 99mTc-DMSA. RESULTS: Control kidneys (n = 38) had a volume of 99.7 +/- 29.5 cc. The %ID/cc was 0.27 +/- 0.08, and the uptake in one kidney was 24.8% +/- 3.9%. Global renal uptake (right plus left) was 49.6% +/- 7.3%. Functional volume of the control kidneys showed an increase with age, and the %ID/cc showed a steeper decrease with age, resulting in a trend of the kidney uptake to decrease with age. Kidneys with reflux had a decreased kidney uptake of 15.7% +/- 29.5%, compared to age- and sex-matched controls (t = 4.7, p < 0.001). The contralateral kidneys without reflux had a significantly increased total uptake of 33.4% +/- 6.8% as compared to controls (t = 3.44, p < 0.01). Global uptake by the kidneys was 49.2% +/- 8.6% and was not statistically different from controls (t = 1.0, ns). CONCLUSION: Our results suggest that SPECT quantitation of 99mTc-DMSA uptake in each kidney separately could be used as a noninvasive method to assess impairment and compensation of the function of the individual kidney in children with vesicoureteral reflux.

Aging↗

Kidney-specific allo- and autoantibodies in the alloantibody response to rat kidney: the use of kidney homogenate as a target for serological analysis.

LEW anti-DA kidney and DA anti-LEW kidney sera were assayed using an indirect 125I anti-immunoglobulin-binding assay with kidney homogenate as target. This allowed the full spectrum of antibodies to be analysed since the tissue used for immunization was the same as that used as the target in the serological analysis. It was found that around 80% of the LEW anti-DA kidney serum was directed at kidney-specific antigens, approximately half at a kidney-specific alloantigen, and half at a kidney-specific autoantigen. Only a small component, around 20% of the antibodies, was directed at major histocompatibility complex (MHC) antigens. In contrast, the DA anti-LEW kidney serum, which was much weaker, was directed entirely at autoantigens, and was more complex in that at least two autoantigens were involved. None of the DA and LEW kidney autoantibodies reacted with lymphocytes. The potential of this assay system for the study of tissue-specific antibodies, especially autoantibodies in man, is discussed.

Animals↗

Expression of fetal kidney growth factors in a kidney tumor line: role of FGF2 in kidney development.

To identify growth factors which may play a role in kidney organogenesis, we have analyzed culture supernatants from the pediatric kidney tumor cell line G401. G401 cells were found to secrete fibroblast growth factor 2 (FGF2), a potent mitogen for mesenchymal cells, OP-1/BMP7, an epithelial cell growth inhibitor, and midkine (MK). Northern blotting confirmed expression of FGF2, OP-1/BMP7 and MK mRNA, as well as Wnt5A mRNA in G401 cells. In situ hybridization and immunocytochemistry on human fetal kidney demonstrated FGF2 expression in epithelial cells of the branching ureteric bud epithelium, nephron precursors ("S-shaped bodies"), proximal tubule epithelium and the parietal epithelium of the glomerulus. FGF2 protein in condensed "caps" of induced mesenchymal cells was also detected by immunocytochemistry. FGF2 protein was found to be concentrated in nuclei, particularly in proximal tubule epithelial cells. Recombinant FGF2 was found to act as a mitogen on primary mouse fetal kidney cell cultures. The results demonstrate G401 cells secrete a variety of fetal kidney growth factors and that FGF2 may act as a mitogen for fetal kidney cells and thus could play a role in the morphogenesis of the kidney.

Animals↗

Blood group A glycolipid antigen expression in kidney, ureter, kidney artery, and kidney vein from a blood group A1Le(a-b+) human individual. Evidence for a novel blood group A heptaglycosylceramide based on a type 3 carbohydrate chain.

Kidney, ureter, kidney artery, and kidney vein tissue were obtained from a single human transplant specimen. The donors erythrocyte blood group phenotype was A1Le(a-b+). Total non-acid glycolipid fractions were isolated and individual glycolipid components were identified by immunostaining thin layer plates with a panel of monoclonal antibodies and by mass spectrometry of the permethylated and permethylated-reduced total glycolipid fractions. The dominating glycolipids in all tissues were mono- to tetraglycosylceramides. In the kidney, ureter, and artery tissue less than 1% of the glycolipids were of blood group type, having more than 4 sugar residues. In contrast, 14% of the vein glycolipids were of blood group type, and the dominating components were type 1 chain blood group H pentaglycosylceramides and A hexaglycosylceramides. Trace amounts of structurally different blood group A glycolipids (type 1 to 4 core saccharide chains) with up to 10 sugar residues were found in the kidney, ureter, and vein tissues, including evidence for a novel blood group A heptaglycosylceramide based on the type 3 chain in the vein. The only detected A glycolipid antigen in the artery tissue was the blood group A difucosyl type 1 chain heptaglycosylceramide (ALeb) structure. Blood group Lewis and related antigens (Lea, Leb, and ALeb) were expressed in the kidney, ureter, and artery, but were completely lacking in the vein, indicating that the Le gene-coded alpha 1-4-fucosyltransferase was not expressed in this tissue. The X and Y antigens (type 2 chain isomers of the Lea and Leb antigens) were detected only in the kidney tissue.

ABO Blood-Group System↗

Simultaneous kidney-pancreas transplantation versus kidney transplantation alone: patient survival, kidney graft survival, and post-transplant hospitalization.

This study compared patient survival, kidney graft survival, and post-transplant hospitalization between patients who received simultaneous kidney and pancreas (SKP) transplants and those who received a kidney transplant alone (KTA). A total of 3,168 diabetic end-stage renal disease (ESRD) patients, ages 18-45, who began their first ESRD treatment between 1981 and 1989 and received their first cadaveric kidney transplant between 1986 and 1989 were selected for study; patient and kidney graft survival were followed until 1 March 1990. Twelve percent (380) of these patients received SKP transplants. No statistically significant difference in patient survival was found between SKP and KTA patients (p = 0.86). Kidney graft survival was statistically significantly higher for SKP patients than KTA patients (p = 0.008). Post-transplant hospitalization rates were statistically significantly higher for SKP patients (p < 0.001), indicating potentially higher post-transplant morbidity among this group.

Adolescent↗

The liver neither protects the kidney from rejection nor improves kidney graft survival after combined liver and kidney transplantation from the same donor.

It has been proposed that the liver protects a simultaneously transplanted kidney from acute rejection. Using the United Network for Organ Sharing database, we compared the kidney allograft data from 248 combined liver and kidney transplants (LKT) with a control group comprising 206 contralateral kidney alone transplants (KAT) from the same donor. The LKT and KAT groups were identical with respect to most baseline parameters, save a greater degree of HLA matching in the KAT group. The overall 3-year graft survival rate was higher in the KAT group compared with the LKT group (80% vs 68%, P < 0.01). When these data were censored to remove death as a cause of graft loss and to minimize the matching effect, the 3-year survival rates were not statistically different (78% for KAT and 81% for LKT, P = NS). We conclude that the liver neither protects the kidney from rejection nor improves kidney allograft function or survival after LKT.

Adult↗

Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation.

BACKGROUND: Combined liver-kidney transplantation (LKT) is the accepted treatment for patients with liver failure and irreversible renal insufficiency. Controversy exists as to whether simultaneous LKT with organs from the same donor confers immunologic and graft survival benefit to the kidney allograft. This study compares the outcomes of simultaneous LKT with the contralateral kidneys used for kidney alone transplantation (KAT) or combined pancreas-kidney transplantation (PKT) to understand the factors that account for the differences in survival. METHODS: From October 1987 to October 2001, LKTs with organs from 899 cadaver donors were reported to the United Network for Organ Sharing; 800 contralateral kidneys from these donors were used in 628 KAT and 172 PKT recipients. These 800 paired control patients were the basis of this analysis. RESULTS: Graft and patient survival rates were lower among LKT recipients compared with KAT (P<0.001) and PKT recipients (P<0.001), because of a higher patient mortality rate during the first 3 months posttransplant. Among human leukocyte antigen-mismatched transplants, LKT recipients demonstrated the highest 1-year rejection-free survival rate (LKT 70%, KAT 61%, and PKT 57% ) (P=0.005 vs. KAT, P=0.005 vs. PKT). There was a lower incidence of renal graft loss resulting from chronic rejection among LKT recipients (LKT 2% vs. KAT 8% vs. PKT 6%, P<0.0001). CONCLUSIONS: Patients undergoing LKT exhibit a higher rate of mortality during the first year posttransplant compared with patients undergoing KAT and KPT. Analysis of the data indicates an allograft-enhancing effect of liver transplantation on the renal allograft.

Adult↗

The grafted kidney takes over: disappearance of the nephrotic syndrome after preemptive pancreas-kidney and kidney transplantation in diabetic nephropathy.

This report describes the rapid and complete reversal of proteinuria after preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6 mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria 0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2 diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1 month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria pattern changed (pre: glomerular nonselective, tubular complete; post: physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of the native kidneys, despite high pretransplant clearance (> 50 mL/min). The effect was not linked to euglycemia or readily explainable by pharmacologic effects (no difference in renal parameters after pancreas transplantation with the same protocols). These data confirm the efficacy of preemptive kidney and kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that a regulatory hemodynamic effect should be investigated.

Adult↗

Combined liver-spleen-kidney scintigraphy and subsequent subtraction of the kidney scintiphotograph in the evaluation of displaced kidney.

The displacement of kidney was studied by using the combined liver-spleen-kidney scintigraphy and the subsequent subtraction of the kidney scintiphotograph to leave the liver-spleen scintiphotograph alone. A suprarenal mass was shown as cold spot between the liver and right kidney on the combined study. When the liver scintiphotograph and kidney scintiphotograph were over-lapped and the differential diagnosis was difficult, the subsequent subtraction of the kidney scintiphotograph was useful in the diagnosis of the enlarged liver.

Adrenal Gland Neoplasms↗

The organization of Kidney Transplantation Services at Ramathibodi Hospital: fourteen years experience on waiting list, kidney donors and kidney transplantation.

The Kidney Transplantation Program at Ramathibodi Hospital was established in 1985. By the end of 1998, there were 1,614 patients on the cumulative waiting list. The first kidney transplantation (KT) was started in 1986 by using kidney from living-related donor (LD) while cadaveric KT (CD-KT) was started in 1987. A total of 528 KT were done, 278 cases (52.7%) were CD-KT and 250 cases (47.3%) were LD-KT. Six patients had two kidney transplants. 278 kidneys were donated from 189 cadaveric donors. Fifty cadaveric donors (26.4%) were from Ramathibodi Hospital while the rest were from other hospitals and the Organ Donation Center, Thai Red Cross Society. For LD, 233 out of 250 (93.2%) were from living-related, more than 50 per cent of these donors were from siblings. 17 spousal donors have been accepted for KT at Ramathibodi Hospital since 1997. Concerning the recipient pools, 522 patients (32.3%) were transplanted, 123 patients (7.6%) died without KT, 111 patients (6.9%) underwent KT at other hospitals, and 78 patients (4.8%) changed to waiting lists at other hospitals. The rest were lost to follow-up. At present, only 265 patients are still actively waiting (send serum every month). The number of KT and living donors has gradually increased, whereas, the number of cadaveric donors has decreased. However, cooperation with the "Organ Donation Center" has improved the number of cadaveric donation in the last two years. Sufficient organ donations and an active working team will provide a good kidney transplant service for the patients.

Adolescent↗

National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification.

OBJECTIVES: A series of new guidelines has been developed by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative to improve the detection and management of chronic kidney disease (CKD). In most instances of CKD, the earliest manifestations of the disorder may be identified by relatively simple tests. Unfortunately, CKD is often "underdiagnosed," in part because of the absence of a common definition of CKD and a classification of the stages in its progression. The Kidney Disease Outcomes Quality Initiative clinical practice guidelines for CKD evaluation, classification, and stratification provide a basis to remedy these deficits. The specific goals of the guidelines described in this review are to provide: 1) an overview of the clinical practice guidelines as they pertain to children and adolescents, 2) a simple classification of the stages of CKD, and 3) a practical approach to the laboratory assessment of kidney disease in children and adolescents. METHODS: The guidelines were developed as part of an evidence-based evaluation of CKD and its consequences in patients of all ages. The data that were used to generate the guidelines in this article were extracted from a structured analysis of articles that reported on children with CKD. RESULTS AND CONCLUSIONS: This review presents the definition and 5-stage classification system of CKD developed by the work group assigned to develop the guidelines, and summarizes the major recommendations regarding the early detection of CKD. Major emphasis is placed on the identification of children and adolescents with CKD by measuring the protein-to-creatinine ratio in spot urine specimens and by estimating the glomerular filtration rate from serum creatinine using prediction equations.

Adolescent↗

Differential effects of IFN-gamma on kidney cell expression of MHC class II molecules, kidney cell associated molecules and their stimulatory capacity in mixed lymphocyte kidney cell culture.

Mixed cell co-cultures of lymphocytes responding to kidney cells (MLKC), islets of Langerhans (MLIC) and mixed lymphocyte culture (MLC), were used to clarify mechanisms in allogeneic and autoimmune (tissue-associated) antigen presentation. Fresh kidney cortical tubular cells (KC), Madin-Darby canine kidney (MDCK), and dog kidney (6247) (DK) cell lines were used in MLKC reactions, and islets of Langerhans were used in the MLIC as putative antigen presenting cells (APC). The stimulating cells were treated with purified or recombinant dog interferon-gamma (IFN-gamma), and the detection of class II MHC molecule expression was assessed by a moneclonal antibody (mAb) (B1F6). Transcription of MHC class II mRNA and IFN-gamma mRNA was measured by semiquantitative polymerase chain reaction, and detection of a kidney cell (tissue-associated) antigen molecule was assessed by the mAb I1F6 that recognizes 72 and 150 kDa tubular cell protein(s) (KT1). The MDCK cell line constitutively expressed low levels of MHC class II molecules and KT1. The steady-state level of the MHC class II mRNA transcription was virtually unaltered by treatment with IFN-gamma (400 units) for 48 hours; however, the MHC cell surface protein expression was enhanced. The KC and DK cell lines constitutively expressed KT1, but not MHC class II molecules; these cells required a minimum of 4000 units, and a 62-hour incubation with IFN-gamma was needed to upregulate both surface MHC class II molecules and the transcription of corresponding specific mRNA. In the MLKC reaction both the MDCK and DK cell lines, as well as fresh KC cells, could serve as lymphocyte activators. This could be amplified by exogenous IFN-gamma. The removal of APC from the responding T cell population did not reduce the IFN-gamma effect. This indicates that IFN-gamma treatment allows for the expression of all of the co-stimulating factors and/or adhesion molecules necessary for these cells to serve as (surrogate) APC (direct as opposed to indirect antigen presentation). The requirements for purified IFN-gamma to increase this amplification was greater in the MLKC reactions with kidney cells than in the MLC reactions. The mAbs anti-IFN-gamma and I1F6 differed in their ability to inhibit lymphocyte proliferation depending on the different cell types involved. The I1F6 inhibited the MDCK and DK cell-driven MLKC (in the absence of exogenous IFN-gamma).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Influence of the kidney histology at the time of donation on long term kidney function in living kidney donors.

Living donation is the best choice for kidney transplantation, obtaining long-lasting good results for the recipient. Some concern still remains regarding the donor's long-term health. Kidney biopsy was routinely performed in our donor population at the time of donation many years ago. We found the existence of morphological kidney disease in those samples, in spite of normal clinical evaluations before donation. We attempted to correlate those abnormalities with long-term clinical outcomes. Donors were at least 10 years after surgery. A medical interview, including the SF-36 Health Survey, laboratory evaluation, and ambulatory blood pressure monitoring was performed on 27 donors meeting the inclusion criteria. Two donors had died after donation from unrelated causes with no known nephropathy. Histological analysis showed abnormalities in 16 of 29 donors. We found an increased prevalence of hypertension compared to the general population. Interestingly, there was no proteinuria in the donor population, and none developed clinical nephropathy. All subjects felt emotionally rewarded with donation, stating that their lives had no limitations. Our results suggest that kidney biopsy is neither necessary nor useful prior to donation because, although many donors had morphological kidney disease, none developed clinical nephropathy in the long term.

Blood Pressure Monitoring, Ambulatory↗