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)

Tacrolimus has proven to be superior to cyclosporine-Sandimmune with regard to the prevention of acute rejections, but data comparing tacrolimus with Neoral are scarce. A total of 128 consecutive renal transplant recipients was studied. The patients were treated with Neoral-based (n = 74) or tacrolimus-based (n = 54) immunosuppressive regimens. Survival analyses (Cox regression analysis) were performed on an intention-to-treat basis. Renal function and cardiovascular risk profile were analyzed by means of a repeated-measures analysis of variance (ANOVA) up to 12 months after transplantation. Immunological features were less favorable in the tacrolimus group. Two-year patient and graft survival were comparable. Acute-rejection-free survival was 82 % in the tacrolimus group versus 40 % in the Neoral group (P < 0.0001). The severity of the rejections (1997 Banff classification) was comparable (P = 0.43). Immunological graft loss (3.7 % vs. 12.2 %, P = 0.02) and conversion because of rejection (0 % vs. 28.4 %, P < 0.001) were less in the tacrolimus group. A higher proportion (68.5 % vs. 14.9 %, P < 0.001) was successfully put on monotherapy. Creatinine clearance, proteinuria, and fractional uric acid clearance were similar. In the tacrolimus group mean blood pressure was comparable, but patients needed less anti-hypertensive drugs (P < 0.001) and, even with fewer patients on lipid-lowering drugs, total cholesterol was lower (5.2 vs. 6.0 mmol/l, P = 0.003). Treatment for post-transplant diabetes mellitus was 18.5 % versus 10.8 % (P = 0.22). In both groups, antidiabetic medication could be withdrawn for most patients. This study indicates that tacrolimus is superior to cyclosporine-Neoral in preventing acute rejection with comparable patient and graft survival rates. Because of a lower need for treatment of hypertension and hypercholesterolemia, the cardiovascular risk profile is more favorable. A considerable proportion of patients can be successfully weaned off co-medication and treated with tacrolimus monotherapy.
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PMID:Single-center experience with tacrolimus versus cyclosporine-Neoral in renal transplant recipients. 1179 34

Tacrolimus (Tac) is the most frequently used base inmunosuppressant for transplantation in Spain and the United States. However, long-term data on its use in renal transplant patients are lacking. The aim of this study was to analyze the 10-year outcome of patients from our institution treated with Tac or cyclosporine (CsA) who were included in the European Multicenter Study of kidney transplantation (1993 to 1994). This trial compared the efficacy and safety of steroids + Tac + azathioprine versus steroids + CsA + azathioprine at 1 year, showing a significantly lower acute rejection rate in Tac patients, with no differences in graft or patient survival. In our long-term analysis, we included patients with a functioning graft after the first year: 15 patients on Tac and 11 on CsA. In the "intent-to-treat" (ITT) analysis, patient survival was 14/15 (93%) versus 9/11 (82%) and death noncensored graft survival was 10/15 (67%) versus 8/11 (73%) in Tac and CsA, respectively. Analyzing patients "into treatment" (TT), death/noncensored graft survival was 11/16 (69%) versus 6/9 (67%), respectively. Serum creatinine tended to be lower in Tac group (ITT 1.26 +/- 0.42 vs 1.63 +/- 1.16 mg/dL, P = NS; TT 1.23 +/- 0.4 vs 1.86 +/- 1.28 mg/dL, P = NS). However, in the TT analysis, Tac patients exhibited a significantly better creatinine clearance (89.3 +/- 40 vs 46.8 +/- 21 mL/min, P = .037) and lower systolic blood pressure (125 +/- 5 vs 140 +/- 12 mm Hg, P = .007) at 10 years. No other significant differences were observed in blood pressure, lipid profile, or glucose metabolism. Outstandingly, Tac monotherapy was the most frequently used regimen after 10 years: ITT 6/9 (67%) versus 1/8 (12.5%), P = .05, TT 7/10 (70%) versus 0/6 (0%), P = .011. Patients under Tac monotherapy exhibited an excellent graft function (serum creatinine 1.08 +/- 0.14 mg/dL) and negative proteinuria, with Tac trough levels of 7.9 +/- 1.3 ng/mL. In summary, our results suggest that Tac-based immunosuppression provides an excellent kidney function 10 years after transplantation and allows monotherapy in a high percentage of kidney transplant patients.
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PMID:Ten years of treatment with tacrolimus is related to an excellent renal function, allowing monotherapy in a large proportion of cases: unicentric results of the tacrolimus versus cyclosporine A European Multicentric Study in kidney transplant patients. 1638 23

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.
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PMID:Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial. 1709 29

Persistent proteinuria in patients with quiescent lupus can result from membranous lupus nephritis and/or glomerular scarring following previous flares. This pilot study examined the effects of tacrolimus over two years in six patients with membranous/inactive lupus nephritis and persistent proteinuria despite angiotensin inhibition/blockade. Tacrolimus treatment reduced proteinuria and increased serum albumin (time effect, P = 0.047 and 0.032 respectively). Compared with baseline levels, proteinuria improved by more than 50% in five patients (83.3%) and hypoalbuminaemia was corrected in four patients. The efficacy was most prominent in four patients with biopsy-proven membranous lupus nephritis, whose protienuria improved by over 80%. One patient developed biopsy-proven chronic nephrotoxicity after 10 months of tacrolimus treatment, despite non-excessive blood levels. These data suggest that tacrolimus is an effective treatment for proteinuria due to membranous lupus nephritis, but should probably be reserved for patients who are refractory to other non-nephrotoxic treatments, in view of the potential risk of subclinical nephrotoxicity.
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PMID:A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade. 1728 85

An eight-yr-old combined liver and kidney transplant recipient for hyperoxaluria type I developed significant proteinuria and hypertension after conversion of a Tacrolimus, MMF, and corticosteroids-based immunosuppression to Sirolimus, low-dose Tacrolimus, and corticosteroids six and a half yr after the transplant for chronic allograft nephropathy. There was only one class I HLA match and the recipient had multiple blood exposures prior to transplantation. The patient was treated with combined hemodialysis and peritoneal dialysis while awaiting transplantation to reduce the oxalate load. A renal biopsy revealed a de novo transplant glomerulopathy that was associated with specific HLA antibodies unrelated to the donor (HLA DR 17 and 18). After reintroduction of MMF, these antibodies became undetectable and the proteinuria completely resolved. We hypothesize that HLA antibodies may cause transplant glomerulopathy even if they are not donor-specific. Their production appears more susceptible to MMF therapy. A thorough work-up of new-onset proteinuria after conversion to Sirolimus should be performed, including an immunological work-up and a renal biopsy.
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PMID:Sirolimus is not always responsible for new-onset proteinuria after conversion for chronic allograft nephropathy. 1743 Apr 94

Arterial hypertension develops in up to 80% of renal transplant recipients. Uncontrolled hypertension induces left ventricular hypertrophy, heart failure and death, but also promotes deterioration of allograft function. Cadaveric transplantation, delayed graft function, renal artery stenosis, presence of native kidneys, increased body weight and therapy with calcineurin inhibitors and steroids have been associated with an increased incidence of hypertension after kidney transplantation. Cyclosporine increases both systemic and renal vascular resistance, enhances sympathetic activation, endothelin production and, possibly, decreases vascular relaxation by decreasing the generation of nitric oxide. Tacrolimus has less pronounced prohypertensive role after renal transplantation. Corticosteroids contribute to the development of hypertension, since their withdrawal results in a significant decrease of blood pressure in the majority of patients. Renal artery stenosis occurs in almost 12% of hypertensive renal transplant recipients. It is a correctable cause of hypertension, and for this reason should be investigated in all suspected patients. Doppler ultrasonography is used as the screening method that is highly sensitive and specific in the hands of a well-experienced investigator. However, dependence of the method on the experience of the investigator is its major drawback. Magnetic resonance angiography and spinal computed tomography angiography are useful noninvasive methods, but arteriography remains a method for establishing the definitive diagnosis. Percutaneous balloon angioplasty, with or without placement of the stent, is successful in the majority of patients, but with a high incidence of restenoses (20%). Surgery is indicated for stenoses that cannot be treated with angioplasty or that recur. Auto-transplantation of the kidney with complex stenoses of graft arteries is useful in selected cases. Posttransplant hypertension should be aggressively treated to prevent the development of end-organ damage. Every effort should be invested in reducing immunosuppression when appropriate, together with salt restriction and weight reduction. Calcium channel blockers have good antihypertensive properties accompanied with minimization of cyclosporine-induced renal vasoconstriction. Angiotensin-converting enzyme inhibitors (ACEi) should be used in patients with proteinuria. Renal function should be carefully monitored after their introduction since they may cause transitory deterioration of glomerular filtration and/or hyperkaliemia. ACEi can induce anemia in renal transplant recipients, side effect that is often used in the treatment of posttransplant erythrocytosis. All other antihypertensive drugs could be used, with minoxidil being the most potent one. Patients with resistant hypertension should be investigated for the presence of renal artery stenosis. After exclusion of rejection, renal artery stenosis and recurrent disease, in cases of severe hypertension, native kidneys laparoscopic nephrectomy should be considered.
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PMID:[Arterial hypertension in renal transplant recipients]. 1836 9

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts. We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Caucasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years). The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25-3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32-3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07-3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03-1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12-1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg. Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.
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PMID:Early pulse pressure and low-grade proteinuria as independent long-term risk factors for new-onset diabetes mellitus after kidney transplantation. 1869 75

Results at 1 year of a pilot randomized trial with 87 kidney graft recipients, comparing the maintenance treatment with sirolimus, tacrolimus and steroids (group I) versus tacrolimus withdrawal since the third month onward, followed by maintenance with SRL and steroids (group II) have shown that early elimination of tacrolimus may result in improved renal function and blood pressure control. At 2 years, 26 and 25 patients in groups I and II, respectively, were analyzed in an on-therapy and an ITT analysis. In the on-therapy analysis, group II showed lower serum creatinine (1.3+/-0.2 vs. 1.6+/-0.6 mg/dL) and lower diastolic blood pressure (74+/-9 vs. 80+/-11 mm Hg). No acute rejections occurred during the second year of follow-up. In more than 90% of patients, proteinuria was less than 1 g/d, and in 50% it was negative. In the ITT analysis, differences were found only in diastolic blood pressure (80+/-10 vs. 74+/-8 mm Hg in groups I and II respectively, P=0.009). Tacrolimus withdrawal from a combination of sirolimus and tacrolimus, in selected patients, may be observed at 2 years by an improvement in renal function and blood pressure without a higher incidence of proteinuria.
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PMID:Improved renal function, with similar proteinuria, after two years of early tacrolimus withdrawal from a regimen of sirolimus plus tacrolimus. 1872 34

Since most lupus nephritis patients have an incomplete response to mycophenolate mofetil, combination regimens may improve outcomes. Tacrolimus (FK506) has shown some benefit in lupus nephritis in small trials, and combined with mycophenolate mofetil is standard immunosuppression in transplant patients. We investigate the addition of FK506 to mycophenolate mofetil, in patients who were mycophenolate mofetil failures. All patients were part of a prospective cohort, but evaluated retrospectively. Seven lupus nephritis patients (mean age 27.1, 100% female, 42% Caucasian and 42% African American) were evaluated. Three patients had combined ISN class III and V, two ISN class IV, one ISN class V and II and one ISN class IV and V. Six were taking an ACE-inhibitor or angiotensin receptor blocker, 6 hydroxychloroquine and 5 prednisone (mean dose 11.5 mg; range 0-30 mg). Mean mycophenolate mofetil dose at time of tacrolimus addition was 2.8 g (range 2-3 g). Mean tacrolimus dose was 3.4 mg (range 2-8 mg) titrated to a mean level of 4.67 ng/dl (range 2.2-11.8 ng/dl) for a mean of duration of 16 months (range 2-54 months). Two patients continued both therapies, while five discontinued therapy. One patient achieved a complete renal remission, while three achieved partial remission with 82.9%, 77.1%, 55.3% reductions in proteinuria. Toxicity limited the use of combination therapy: diabetic ketoacidosis (one patient), pneumonia (two) and muscle pain (two). These data suggest that adding tacrolimus in patients refractory to mycophenolate mofetil might have some benefit, although complete responses were rare. Unfortunately, tacrolimus toxicity appeared to be prevalent in these systemic lupus erythematosus patients, limiting its long term use.
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PMID:Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis. 2038 22

We conducted an open-labeled, prospective study to determine the efficacy and safety of tacrolimus as an alternative therapeutic option for those patients with refractory lupus nephritis. The study population comprised one male and eight female patients with diffuse proliferative lupus nephritis. All patients had failed to respond to sufficient intravenous cyclophosphamide therapy with proteinuria of >or=1 g/day and active urinary sediments. Tacrolimus (0.1 mg/kg/day) was administered for 1 year with adjusting drug level (4-10 microg/l). The mean serum creatinine level and spot urine protein creatinine ratio (UPCR) at baseline were 1.39 mg/dl and 2.27, respectively. After the treatment, proteinuria reduced significantly from median UPCR value of 2.19 (range, 1.19-3.34) to 0.44 (range, 0.12-2.13) (p < 0.05). Seven (78%) of the nine patients showed a complete clinical response, which was defined as stabilization in the disease-activity markers and serum creatinine level with reduction of >or=50% in UPCR; two patients showed complete remission with UPCR <0.2. One patient showed treatment failure because of the disease progression. No serious adverse effects were observed during the study. This study demonstrates that tacrolimus can show a significant therapeutic response in cases that are refractory to the standard regimen for diffuse proliferative lupus nephritis.
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PMID:Tacrolimus is an alternative therapeutic option for the treatment of refractory lupus nephritis. 2058 Oct 20


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