Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased (Na+/K+)-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and (Na+/K+)-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2 nephropathy. The roles of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-ATPase. It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.
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PMID:Collecting duct (Na+/K+)-ATPase activity is correlated with urinary sodium excretion in rat nephrotic syndromes. 1075 19

Renal transplants may undergo changes secondary to the decrease of the renal mass, the effects of rejection, and various other risk factors that contribute to the progression of renal insufficiency. We have performed a prospective study of 285 cadaveric renal transplants recipients, that were receiving various maintenance immunosuppressives regimens, to study the evolution of their renal function and to evaluate the influence of various factors in the progression of renal insufficiency. All variables were analysed in a regression model of multivariate analysis. We found a progressive increase of the serum creatinine in the studied population. The mean initial creatinine was 1.70 +/- 0.84 mg/dl and final creatinine in the study 2.17 +/- 2.06 mg/dl, difference statistically significant (p = 0.000). We calculated the increase of creatinine in each patient. We observed that 113 patients (42.2%), had stable serum creatinine but the remaining 155 patients (57.8%) had a mean increase of 0.04 +/- 0.8 mg/dl/month. We analysed the patients according to various variables. Although in most the final creatinine is significantly greater than the initial, this increase of creatinine level was not present in patients with delayed graft function, in patients with no acute rejection, in the extreme age groups, in the grafts from younger donors and in those patients without initial proteinuria. The patients transplanted from younger donor had the best renal function, without any decrease in their function during the study. The advanced age of the donor has a great negative impact in the evolution of the renal transplant. According to our study, proteinuria and its quantity is a major predictor of progressive renal insufficiency. The multivariate analysis confirms that the age of the donor and initial proteinuria predict decrease of renal function. It is important to identify the factors that they could predict a greater progression to the failure of the graft. We have the possibility of acting on them, establishing immunosuppressive strategies that reduce the deleterious effects of the calcineurin inhibitors in the recipients of grafts from older donors' and to encourage the use of drugs which reduce proteinuria.
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PMID:[Changes in renal function in renal transplantation. Predictive factors for functional deterioration]. 1147 10

DE NOVO DIABETES AND CARDIOVASCULAR RISK: Certain kidney transplant recipients who develop de novo diabetes have an unfavorable cardiovascular risk profile, comparable to patients with type 2 diabetes mellitus, with advanced age, dyslipidemia, obesity and high blood pressure. MYOCARDIAL INFARCTION IN THE PERIOPERATIVE PERIOD: Among kidney transplant recipients, those whose risk factors include male gender diabetes, age over 50 years and prior revascularization procedure for coronary artery disease have a higher risk for myocardial infarction in the perioperative period. The usefulness of anticoagulant or beta-blockers as preventive treatment for these high-risk patients remains to be determined. HYPERLIPIDEMIA: A retrospective analysis of 530 kidney transplant recipients demonstrated that a very significant proportion of those with dyslipidemia are not receiving appropriate care although their lipid profile is indicative of a high or very high cardiovascular risk. MASSIVE PROTEINURIA: An angiotensin II inhibitor, losartan, has been found to be effective against massive proteinuria (> 3.5 g/l) occurring after kidney transplantation. CALCINEURIN-INHIBITOR-INDUCED HEMOLYTIC UREMIA SYNDROME: Five to ten percent of patients given calcineurin inhibitors develop a hemolytic uremia syndrome. Sirolimus appears to be a very interesting alternative for immunoprophylaxys against acute rejection.
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PMID:[Complications in kidney transplantation]. 1157 77

Sirolimus, being nonnephrotoxic, is a viable alternative in patients who develop renal insufficiency caused by calcineurin inhibitors (CIs). The aim of this study is to determine whether there is improvement in renal function in liver transplant recipients after switching to sirolimus-based immunosuppression. In this retrospective review, patients who were more than 3 years posttransplantation were selected. Patients who had proteinuria (protein > 300 mg/24 hr), those administered any other nephrotoxic agents, and those with a creatinine clearance (CCr) less than 20 mL/min were excluded. Renal insufficiency was defined as mild (CCr > 70 mL/min), moderate (CCr, 40 to 70 mL/min), or severe (CCr, 20 to 40 mL/min). In the 16 patients studied; there was significant improvement in serum blood urea nitrogen (36 mg/dL; range, 19 to 53 mg/dL; to 25 mg/dL; range, 10 to 37 mg/dL; P =.002) and serum creatinine levels (median, 1.95 mg/dL; range, 1.3 to 2.8 mg/dL; to 1.5 mg/dL; range, 1.0 to 2.4 mg/dL; P =.001) 6 months after switching to sirolimus therapy. There also was a trend in improvement in CCr from 43 mL min (range, 24 to 68 mL/min) to 49 mL/min (range, 22 to 152 mL/min). Among 9 patients with moderate renal insufficiency, 2 patients improved to mild renal insufficiency, 4 patients remained unchanged, and 3 patients deteriorated to severe renal insufficiency. Among 7 patients with severe renal insufficiency, 1 patient improved to mild renal insufficiency, 4 patients improved to moderate renal insufficiency, and 2 patients remained unchanged. No patient developed cellular rejection or other graft-related complications. In liver transplant recipients with chronic renal insufficiency, conversion to sirolimus-based immunosuppression allows complete withdrawal of CIs, leading to some improvement in renal function.
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PMID:Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients. 1254 5

Rapamycin is a new immunosuppressive agent approved for maintenance therapy after kidney transplantation. It may allow calcineurin-inhibitor-free, non-nephrotoxic immunosuppression. We report, however, on four kidney-transplant recipients who developed post-transplantation glomerulonephritis after conversion from a calcineurin-inhibitor-based immunosuppression to rapamycin. In all four patients nephrotic-range proteinuria occurred 2-9 months after conversion to rapamycin. Renal biopsy confirmed membrano-proliferative glomerulonephritis type 1 in one case, membranous glomerulonephritis in another and IgA-nephropathy in two cases, respectively. Calcineurin-inhibitor-based immunosuppression was reintroduced and resulted in complete remission of proteinuria and in stabilised renal function in all patients. We conclude that in the case of rapamycin-associated post-transplantation glomerulonephritis an attempt should be made to replace rapamycin by a calcineurin inhibitor.
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PMID:Rapamycin-associated post-transplantation glomerulonephritis and its remission after reintroduction of calcineurin-inhibitor therapy. 1511 32

We reviewed the outcome of three methods employed for living-related renal transplantation (RTx) in our institution to assess triple immunosuppressive regimens. Between January 1989 and July 2003, a total of 35 living-related RTxs were performed at our institution. The immunosuppressive regimen given to 16 patients (group A) was cyclosporine (CsA), steroid and azathoprine (AZ) that given to 9 patients (group B) was tacrolimus (TAC), steroid and AZ and that given 9 patients (group C) was TAC, steroid and mycophenolate mofetil (MMF). Graft survival rate, serum creatinine, proteinuria, acute rejection, chronic allograft nephropathy (CAN), cytomegalovirus (CMV) infection and drug-induced nephropathy were investigated. There was no significant difference in graft survival rate among the three groups. Although serum creatinine levels (mg/dl) at 3 months post-transplant were 1.22+/-0.37 in group A, 1.43+/-0.14 in group B, 1.30+/-0.34 in group C, respectively (p<0.05; A vs. B), there was no significant difference at 1 year post-transplant. Frequency of proteinuria in groups A, B and C was 75.0, 50.0, 25.0%, respectively (p<0.05; A vs. C). The incidences of acute rejection and CAN within 1 year post-transplant were, respectively, 56.3% and 43.8% in group A, 37.5% and 37.5% in group B; and, 25.0% and 12.5% in group C (NS). The incidence of drug-induced nephrotoxicity was 12.5, 50.0% and 37.5% in groups A, B and C, respectively (p<0.05; A vs. B). The triple immunosuppressive therapy including calcineurin inhibitors, especially the regime of TAC, MMF, and steroids decreased the frequencies of proteinuria and rejections, which deteriorated the long-term outcome in living-related RTxs.
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PMID:[Clinical results of immunosuppressive triple therapies in living-related renal transplantation--a single center experience]. 1551 24

In spite of considerable progress in immunosuppressive and supportive treatment, numerous problems persist which interfere with the success of renal transplantation. Before transplantation has been performed, factors impacting on outcome include the donor (living vs cadaver, age and HLA system) as well as the recipient (age, immunological reactivity, potential sensitization and duration of dialysis). These are the main factors that affect the outcome of the transplant, particularly in the long-term. After transplantation a number of events may put graft function at risk: potential recurrence of the primary renal disease in the allograft; 'de novo' renal disease triggered by infections, drugs or autoimmunity; and non-specific progression promoters, such as diabetes, hypertension, proteinuria, nephrotoxic agents and/or viral infections. The two most frequent causes of chronic allograft dysfunction are (i) chronic rejection (often triggered by preceding acute rejection, delayed graft function or poor compliance) and (ii) calcineurin-inhibitor nephrotoxicity (more likely to develop in kidneys of older donors or in marginal kidneys). The differential diagnosis between these two entities is generally difficult, but some histological clues (reduplication of glomerular basement membrane, obliterating vasculopathy and C4d deposits) as well as the demonstration of humoral antibodies are pointers suggesting rejection. Treatment of chronic graft dysfunction is difficult, whatever the cause, particularly in cases with advanced renal lesions. Therefore, early diagnosis is of paramount importance. In this regard, graft biopsy can be of great help. In spite of many problems and complications, not only short-term but also long-term results of renal transplantation are improving progressively, as documented by CTS data showing that in Europe for transplants performed between 1982 and 1984 the mean graft half-life was 7 years, while for transplants performed between 1997 and 1999 it was 20 years.
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PMID:Renal transplantation 2004: where do we stand today? 1557 92

Chronic allograft nephropathy (CAN) is an anatomical and clinical alteration, characterized by proteinuria, hypertension and a progressive decline in kidney function, which begins at variable times (months, years) and can lead to the loss of the transplanted organ. CAN pathogenesis, which remains to be fully clarified, involves both immunological (early acute rejection, hyperimmunization, HLA-mismatches between donor and recipient, suboptimal immunosuppression, etc) and non-immunological factors (ischemia/reperfusion injury, reduced nephron mass, age differences between donor and recipient, dialysis time, hypertension, dislipidemia, proteinuria, etc). The possible prevention strategies for CAN consist of procedures aimed at the reduction of some potential risk factors: optimization of the conditions for organ explantation, diminution of ischemia/reperfusion injury, aggressive pharmacological treatment of acute rejection episodes, routine utilization of anti-hypertensive and hypolipidemic agents, and appropriate and rational immunosuppressive regimen. Moreover, some categories of immunosuppressive drugs, such as calcineurin inhibitors, can have a nephrotoxic effect, often regardless of therapeutic dosage. The introduction in clinical practice of novel immunosuppressive drugs with no nephrotoxicity, like mycophenolate mofetil and rapamycin, makes therapeutical strategies able to reduce the incidence of CAN feasible.
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PMID:[Therapy strategies in the prevention of chronic allograft nephropathy]. 1578

Liver transplant recipients are at risk of chronic renal failure (CRF), customarily considered to be secondary to CsA/FK506 nephrotoxicity. We have examined renal biopsies from 26 liver transplant recipients with CRF. Before OLT, 5 patients had CRF, 8 were diabetic and 9 hypertensive. Renal biopsies were performed at a mean of 5 years after liver transplantation. Mean SCr was then 212 micromol/L, proteinuria was 1 g/24 h. Twelve patients were diabetic and 25 hypertensive. Histology revealed impressive renal destruction, with a mean of 45% interstitial fibrosis and 45% glomerular sclerosis. All biopsies showed severe arteriosclerosis. CRF can be attributed to four associated primary lesions: (i) specific chronic CsA/FK506 arteriolopathy; (ii) typical diabetic nephropathy; (iii) acute or chronic thrombotic microangiopathy attributed to CsA/FK506 or alpha-IFN and (iv) tubular changes related to administration of hydroxyethylstarch. At the end of the follow-up, after a mean of 6.4 years, 12 patients required dialysis, 13 had CRF and only 1 had normal renal function. Thus, CRF in OLT recipients is more complex than originally thought and should not be classified as anti-calcineurin nephrotoxicity without further investigations, including renal histology. These investigations have therapeutic potential, that is, they may lead to a more aggressive treatment of hypertension and/or diabetes.
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PMID:Renal histopathological lesions after orthotopic liver transplantation (OLT). 1581 74

Side effects of calcineurin inhibitors (CNIs) include nephrotoxicity and hypertension. Moreover, children have a higher risk of infections and posttransplantation lymphoproliferative disorders. We retrospectively evaluated the efficacy and safety of Sirolimus (SRL) in 18 patients, who were 10.52 +/- 5.03 years at time of transplantation and received a CNI as the core immunosuppression. The most common indications for starting SRL therapy were chronic allograft nephropathy, Epstein-Barr virus-associated neoplasia, and thrombotic microangiopathy. The patients were converted to SRL at 49.14 +/- 45.9 months posttransplantation. Mean follow-up after the switch to SRL was 13.83 +/- 7.24 months. All patients who began SRL therapy remained on that medication. We observed a significant improvement (P < .05) in glomerular filtration rate assessed using the Schwartz formula at 3 months, which was sustained thereafter. There were no changes in proteinuria, plasma lipids, and platelet number. Although the prevalence of hypertensive patients decreased during follow-up, it was not significant. There was one steroid-sensitive, acute rejection episode. Serious adverse events included 1 death due to a relapse of B lymphoma, 1 sepsis, and 1 pancreatic pseudo-cyst. Adverse events were present in 17% of patients: 3 Herpes Simplex infections, and 1 dose-related lymphedema. Further studies are necessary to assess the impact of adverse events in the pediatric transplant population receiving SRL as immunosuppression.
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PMID:Sirolimus in pediatric renal transplantation. 1584


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