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Kidney transplants in mice. An analysis of the immune status of mice bearing long-term, H-2 incompatible transplants.

Kidney transplants between strains of mice which are incompatible at either the K or the D end of the H-2 complex usually function for prolonged periods supporting the lives of nephrectomized recipients. This occurs with no recipient treatment. With multiple H-2 and non-H-2 determined incompatibilities, transplants may be rejected but more slowly than skin grafts. In the strain combination studied most extensively in these experiments (B10.D2 to B6AF(1)) in which the incompatibility was confined to the K end of the H-2 region, about 70 percent of recipients survived for many weeks with normal blood urea nitrogen levels. Skin grafts between untreated members of these strains were rejected promptly (mean survival time of 13.5 +/- 1.1 days) as were kidney transplants to recipients of prior skin grafts. Donor strain skin grafts to recipients of kidney transplants after kidney transplantation enjoyed greatly prolonged survival whereas skin grafts from a third party (A.SW) were rejected normally. If kidney tissue was transferred in the form of free grafts without primary vascular union, it was rejected promptly leaving its recipient highly immunized. Cellular and humoral immunity to donor antigens declined over the first few weeks after transplantation, and the spleens of long-term recipients contained no "killer cells." Recipient lymphoid cells could mount active graft versus host reactions to donor strain antigens on transfer to neonatal mice. Nevertheless, they were distinctly less able to respond specifically by the production of killer cells to donor strain antigens after sensitization in vitro. No evidence that this defect was associated with the presence of suppressor cells was forthcoming from several types of in vivo and in vitro tests.

Animals

Urine Proteomics as a Source of Biological Information and Outcome Predictor in Living Kidney Transplantation.

Kidney transplantation (KTx) is the preferred treatment for kidney failure. However, post-transplant management is challenging due to the limited lifespan of transplanted organs. Current methods for monitoring post-transplant complications are invasive and have limitations. Therefore, there is an urgent need for novel non-invasive biomarkers. This study investigates the proteomic composition of urine to understand renal biology during the process of transplantation and to identify potential markers for outcome prediction. Urine samples were collected from donors before transplantation and from recipients 4 weeks and 1 year after transplantation. Proteomic analysis was performed using mass spectrometry and label-free quantification. Statistical analyses included principal component analysis (PCA) and enrichment analysis. The resulting key findings were confirmed in an independent validation cohort. In addition, correlative regression models to evaluate the relationship between protein abundance and clinical outcomes in the further course after transplantation were performed. 106 urine samples in the setting of 70 kidney transplantations were analyzed. PCA revealed distinct clustering of donor and recipient samples, indicating significant proteomic changes after transplantation. Hierarchical clustering and gene ontology analysis identified molecular changes as a response to transplantation and showed an over-representation of relevant pathways related to inflammation, cell immune response and coagulation in both the original and validation cohorts. Multivariate regression analysis, including linear and logistic regression, identified 11 potential protein biomarkers, including ORM2, IL1RAP, APP, and FABP4 as predictors of eGFR 12 months after transplantation and 1 HP as a predictor of infections within the first year after transplantation, respectively. This study underscores the potential of non-invasive urine proteomics for identifying biological processes involved in kidney transplantation and for enhancing post-transplant monitoring and outcome prediction. We identified 12 potential biomarkers with added value to standard clinical parameters linked to transplant outcomes, which will be promising candidates for future outcome monitoring after KTx.

Humans

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

Humans

Atraumatic method of renal blood flow estimation by 133Xenoninhalation and its application to transplanted kidneys.

Non-invasive measurement of organ blood flow can be achieved by tracing the elimination patterns of 133Xe administered by inhalation. An adaption of the method for the estimation of renal blood flow was developed. The 133Xe is accumulated in the tissue by re-breathing for 1 min and the time course of its washout from the kidney is followed for 14 min thereafter. Normal values were determined in ten dogs and forty-five healthy human volunteers. In man they were similar to results obtained with 131I-hippuran clearance. When flow rates were between 250 and 600 ml/100 g/min the correlation coefficient was 0.84. Only in cases with high cortex flow rates (greater than 600 ml/100 g/min) did the inhalation method give values higher than those determined by the 131I-hippuran clearance. In dogs the results closely correlated with results obtained by direct intra arterial xenon injection (r = 0.96). The value of the inhalation method in routine examination of patients with kidney transplants and its suitability for the early detection of ongoing rejection is demonstrated.

Animals

Recurrence of dense deposits in transplanted kidney: II. Serum complement and nephritic factor profiles.

Dense deposit disease of the kidney is a rare form of chronic glomerulonephritis frequently associated with serum complement abnormalities (low C3 levels) and a circulating C3 convertase activator of the alternative pathway, the C3 nephritic factor (NF). Eleven patients with end-stage dense deposit disease underwent kidney transplantation. Of the 11, 7 had pretransplant low C3 and NF. In the posttransplant period, persisting low C3 levels were associated with persisting NF, although not quantitatively so. The original glomerular lesion recurred in the graft within 6 months in 9 of 11. Of these 9, 2 had no complement abnormalities either prior to or after transplantation. Pretransplant complement abnormalities were rapidly corrected in 4 of 7 patients whether or not recurrence of the original lesion occurred. Thus, serum complement profiles before and after transplantation are neither predictive nor indicative of recurrence.

Complement C3

Alternate day prednisone treatment may increase kidney transplant rejection.

A retrospective study has been done to determine whether alternate day prednisone and daily prednisone are equally safe. A statistically significant increase in the number of rejection episodes are measured by rises in serum creatinine occurred in the alternate day steroid group. The reasons for the difference may rest in the inherent mechanism of steroid action. The use of alternate day prednisone in transplantation should be reserved for the situations where the potential benefit clearly outweighs the risk of loss of the transplanted kidney.

Adult

Single-section multiplex spatial proteomics of immune microenvironments in kidney transplantation.

Characterizing kidney disease is challenged by marked cellular heterogeneity and limited tissue availability from renal biopsies. Conventional diagnostic workflows rely on multiple serial sections for parallel staining, increasing tissue consumption, sampling bias, and loss of spatial information, thereby constraining molecular characterization within intact tissue architecture. High-plex spatial proteomics may overcome these limitations by enabling comprehensive molecular profiling on a single section. Here, we present and evaluate a high-plex cyclic immunofluorescence imaging workflow (MACSima&#x2122;, Miltenyi Biotec) applied to kidney transplant biopsies, including BK virus nephropathy (BKVN) and focal segmental glomerulosclerosis (FSGS), to characterize spatial immune organization with a focus on complement system components. Feasibility and subcellular resolution were first assessed in a lupus nephritis section, demonstrating compatibility with diagnostic immune panels and preservation of tissue morphology. A 48-marker multiplex panel interrogating immunity, oxidative stress, senescence, and fibrosis was then applied to BKVN samples, including paired pre- and post-treatment biopsies, revealing distinct proteomic patterns and dynamic changes following therapy. In FSGS, a glomerulus-focused panel identified spatially resolved innate and adaptive immune signatures, including complement-related patterns supporting exploratory analysis of glomerular immune architecture. Structural, nuclear, membrane, and phosphorylated signaling markers enabled precise delineation of renal compartments and assessment of cellular states such as proliferation, DNA damage, and pathway activation. The workflow also supported detection of extracellular vesicles in cultured renal cells, highlighting its versatility. Overall, this approach provides a robust, tissue-sparing platform for integrated spatial and molecular profiling of renal biopsies, reducing sampling bias while enabling discovery-level phenotyping from a single section. This unified strategy is particularly suited to kidney transplantation, where diagnosis, therapeutic decision-making, and longitudinal monitoring are closely interconnected.

Kidney Transplantation

Simple cyst arising in a transplanted kidney: a case report.

A 17-year-old girl was hospitalized for evaluation of gradually decreasing function of a kidney transplanted 8 years earlier. A plain film of the abdomen showed a possible renal calculus. Excretory urography proved that this calcification was slightly anterior to the kidney but in the upper pole a well rounded mass was discovered. An echogram confirmed the diagnosis of benign renal cyst. Malignant cystic lesions obviously must be differentiated from those that are benign. Patients on immunosuppressive therapy are known to have a higher incidence of malignancy than the general population. A malignant tumor may require withdrawal of immunosuppressive therapy and removal of the transplanted organ, whereas a benign cyst would require no therapy unless it becomes infected or produces obstruction.

Adolescent

Excretion of sodium and water by kidneys in situ and by transplanted kidneys following isotonic, hypotonic, iso-oncotic and hyperoncotic intravenous infusions in sodium-loaded and sodium-deprived dogs.

The excretion of sodium and water following isotonic, hypotonic, iso-oncotic and hyperoncotic intravenous infusions has been investigated in the kidneys in situ and in transplanted kidneys of narcotized dogs previously submitted to sodium-enriched or-deprived diets. The fractional excretion of sodium depended basically on the cumulative effect on the kidney of the changes in plasma oncotic pressure, plasma sodium concentration, and haematocrit. The differences in excretory responses of sodium-loaded or-deprived animals did not depend on differences in the distribution of infused fluids between intra- and extravascular compartments, but to the sensitivity of the kidney itself to the direct cumulative effect of these non-specific changes in blood composition.

Animals

Properties of guanylate cyclase from rat kidney cortex and transplantable kidney tumors.

The subcellular distribution and properties of guanylate cyclase was examined in preparations of normal rat renal cortex and Morris renal tumors MK2 and MK3. In normal kidney cortex about two-thirds of guanylate cyclase activity of homogenates was found in soluble fractions. With renal tumors the homogenate activity was less and the enzyme was equally divided between particulate and soluble fractions. The particulate enzyme in kidney cortex and tumors was associated with all particulate fractions. Triton X-100 increased the activity of all preparations. All preparations preferred Mn2+ as the sole cation. The stimulatory effects of Ca2+ on soluble enzyme and inhibitory effects on particulate activity were similar with preparations of renal cortex and tumors. ATP inhibited all preparations. Soluble and particulate guanylate cyclases from renal cortex were activated several-fold with 1 mM NaN3. Preparations of tumor enzymes did not respond to NaN3. Thus, compared to normal renal cortex the subcellular distribution of guanylate cyclase and some of its properties are altered in preparations of renal tumors.

Animals

[Preparation of the patient for kidney transplantation].

1. Before the kidney transplantation the renal insufficient patient should be tended in a chronic dialysis program, because only in this way all possibilities of the prolongation of his life are treated fully and favourable presuppositions can be provided for success of the transplantation. 2. The age of the patients above 50 years and a bad clinical condition are the most important risk factors for a kidney transplantation. Both of them must be avoided, if possible. 3. Part of the preparation of the transplantation is the rehabilitation of the patient. It has the following priorities in diagnostic and therapeutic relation: a) sanitation of the infection b) correction of complications of the terminal kidney insufficiency c) normalization of the function of the respiratory system and gastrointestinal tract and of the cardiovascular system.

Adult

[Possibilities and limits of kidney transplantation].

Chronic haemodialysis and renal transplantation are mutually supplementing methods for the treatment of patients with terminal renal lesion. The two methods have proved their worth in clinical practice. The expectance of life of patients with chronic renal insufficiency could essentially be improved during the last years. In last consequence the successes of the transplantation of kidneys depend on the solution of immunobiological problems, which are not yet cleared up nowadays. 1. In the determination of genotypical determinants possibly not all are known or recognizable. 2. The at present clinically usable examination methods do not yet allow to recognize rejections so early that by an aimed immunosuppressive treatment irreversible damages on the graft may be prevented. After a transplantation of kidneys of relatives a long survival time of transplanted patients is better than after a transplantation of kidneys taken from dead bodies. The rejection is still the main factor of the failure of the graft, the sepsis is the most frequent cause of death. It is neccessary, to develop less toxical remedies for the adaptation of the graft. Nevertheless, thousands of optimally transplanted patients prove the usefulness of the allogenic transplantation of the kidney.

Female

[Effect of high-dosage prednisolone administration on interstitial transplantation edema following allogeneic kidney transplantation in rats].

To measure subcapsular pressure of rat kidneys and kidney allografts, microcatheters were implanted in the subcapsular space and the pressure was continuously recorded with a transducer. Subcapsular pressure was found to increase significantly during allograft rejection. After single bolus injection of prednisolone 300 mg/kg on the day of transplantation or on the fourth postoperative day, considerably lower subcapsular pressures were recorded. This steroid effect together with other immunosuppressive measures could have an important influence on graft function and prognosis.

Animals

[Urological treatments before and after kidney transplantations].

The repair of pre-existing bladder sphincter lesions in patients excluded from kidney transplant programs, and the recovery of grafts threatened by ureteral complications, are favourable influences in establishing equilibrium between dialysis and transplantation. In a series of 74 kidney transplants, two patients were able to receive grafts: one after the reconstruction of an ileal tube and the other after bladder diverticulectomy and resection of the bladder neck. Two other grafts, complicated by ureteral necrosis, were able to be conserved following a uretero-ureterostomy in the first case, and a psoic bladder in the second. These repair operations are discussed from three points of view: incidence, procedures, and complications. Advances made in transplanting kidneys encourage its use in patients who were previously excluded from receiving transplants because of bladder sphincter lesions. These lesions can be the cause of a renal insufficiency, or those associated with the original kidney disease. This group of patients represents 3 to 5% of the population of patients on permanent dialysis who respond to the other criteria for inclusion in the lists of potential receivers of kidney transplants: some of them could benefit from the graft if their lesions were treated by the standard urological methods. Furthermore, 5 to 8% of those with kidney transplants could lose the grafted kidney, which is immunologically tolerated, because of urological complications. As with patients in the first category, they also could obtain benefit from repair procedures on the urinary tract. A total of 74 kidney grafts were performed in the Sheba medical Center between March 1971 and July 1977: two patients were able to benefit from preventive urological procedures before transplantation: two others with grafts developed ureteral complications and were benefited by therapeutic procedures rarely used in kidney transplantation cases.

Adult

Delayed hyperacute rejection in recipients of kidney transplants from HLA identical sibling donors.

Delayed hyperacute rejection, with its characteristic clinical course and histopathologic findings, occurred within one month after transplantation in five recipients of kidney transplants from HLA-A, B and D identical sibling donors. In all cases, unidirectional mixed lymphocyte cultures and immunologic studies to detect cytotoxic antibodies in the recipients against their respective donors, before kidney transplantation and after transplant nephrectomy, were unresponsive or negative. Onset of delayed hyperacute rejection was preceded by bacteremia in two of these patients. Two of these received second kidney transplants, three to six months later, from HLA-A, B and D identical sibling donors again. Although both have had an episode of acute rejection in the early postoperative period, the grafts have maintained excellent function for 21 and 25 months, respectively. Irreversible forms of transplant rejection, such as delayed hyperacute rejection, do occur even in recipients of kidney transplants from HLA-A, B and D identical sibling pairs, indicating that genetic determinants other than HLA-A, B and D loci, and perhaps other nongenetic immune mechanisms, play an important role in the ultimate results of kidney transplantation.

Adult

Hypertensive crisis, erythrocytosis, and uraemia due to renal-artery stenosis of kidney transplants.

Two patients with kidney transplants had hypertensive encephalopathy and rapidly progressive kidney failure 10 weeks and 18 months postoperatively. In one patient renal failure was associated with erythrocytosis. Absence of proteinuria, despite progressive renal insufficiency in both patients, suggested that these abnormalities were not due to rejection episodes. Subsequently, angiography proved that each of these patients had renal-artery stenosis. Surgical repair of this lesion increased creatinine clearance at least threefold, and the hypertension and erythrocytosis disappeared. Apparent "rejection" episodes in which there is no proteinuria should alert clinicians to the possiblity of renal-artery stenosis of the graft. Restoration of kidney function and amelioration of hypertension may follow revascularisation, even after many months of renal ischaemia producing severe uraemia.

Adult