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)

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

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

Autoimmunity results from loss of mechanisms controlling self-reactivity. Autoimmune disorders play an increasingly important role and CD40-CD40 ligand (CD40L) interaction on immunocompentent cells is able to break established immunotolerance. To study the effects of the calcineurin-inhibitor FK506 on CD40L-induced systemic autoimmunity, CD40L transgenic (tg) mice, which spontaneously develop a mixed connective tissue-like disease, were treated with FK506 after onset of overt autoimmunity. Interestingly, FK506-treated CD40L tg mice showed significantly reduced autoimmune dermatitis scores and markedly decreased numbers of lesional infiltrating leukocytes. This finding was associated with diminished lymphadenopathy induced by FK506 treatment. Furthermore, FK506 suppressed the development of cytotoxic/autoreactive CD8(+) T cells as evidenced by the reduced expression of T cell activation markers in treated CD40L tg mice. Importantly, FK506 induced a significant reduction in autoantibody titers in the serum of CD40L tg animals. As CD40L tg mice develop nephritis leading to loss of renal function proteinuria was determined after FK506 injections. Notably, FK506 treatment re-established renal function as indicated by significantly reduced uric protein concentrations of treated CD40L tg mice. Together, these findings show the beneficial therapeutic effects of FK506 for the treatment of CD40L-induced autoimmunity. Additionally, these results demonstrate that FK506 is able to suppress ongoing severe autoimmune responses.
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PMID:FK506 controls CD40L-induced systemic autoimmunity in mice. 1670 68

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

We investigate the effect of conversion from a cyclosporine (CsA) based-regimen to a tacrolimus (FK506)-based regimen with respect to graft renal function induced by chronic allograft nephropathy (CAN). Thirty-one patients with a histological diagnosis of CAN were included after other causes of chronic graft dysfunction had been excluded. Conversion to FK506 was undertaken at an initial dose of 0.15 mg/kg/d, which was subsequently adjusted to maintain FK506 whole blood trough levels between 5 and 10 mug/L. The rate of decline of renal function before and after the FK506 conversion was represented by regression lines (slope) of the reciprocal of serum creatinine versus time. To evaluate the effect of conversion on allograft function, we gathered data on serum lipids, blood glucose, proteinuria, and hypertension. When postconversion slopes were compared to preconversion slopes for each patient, 20 patients (64.5%) showed positive regression lines and four patients (12.9%), less negative. Seven patients (22.6%) displayed an increased rate of decline in renal function with regression lines becoming more negative. FK506 was associated with a significant decrease in lipid levels, proteinuria, and hypertension. No patient returned to dialysis at the end of the 36-month follow-up. Conversion from a CsA-based regimen to a tacrolimus-based regimen was an effective alterative for salvage of patients with abnormal graft renal function induced by CAN.
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PMID:Conversion from cyclosporine to tacrolimus for chronic allograft nephropathy. 1758 Jan 48

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


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