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)

Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end-stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high-dose steroids, high-dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8-12 week course of 1-2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89-1.75 mg/kg/day. All patients tolerated CTX well. After 8-12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow-up at 8, 38, and 125 months post-transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post-transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis post-renal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well-tolerated treatment for recurrent FSGS in children.
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PMID:Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide. 786 17

Clinical studies of treatment with angiotensin converting enzyme (ACE) inhibitors in patients with glomerular disease have shown the clinical efficacy of these agents. Fifteen renal transplant hypertensive and proteinuric patients on triple drug treatment with cyclosporin (CSA), azathioprine and methylprednisolone entered the therapeutic protocol of this study. All patients followed up last year had stable graft function (serum creatinine less than 2 mg/dl). Hypertension was treated by nifedipine retard and occasionally by furosemide. Patients with a renal artery graft stenosis, at least as judged by technetium-scan imaging were excluded. In order to evaluate the possible role of ACE inhibitors on hypertension and proteinuria, perindopril 4 mg/daily was added for two months to the above regimen. Two patients, who showed a reversible deterioration of renal function during treatment and three who did not comply to the therapeutic protocol were excluded. Systolic and diastolic blood pressure as well as 24 h urine protein was found to be significantly (p < 0.01) reduced at the end of the two-month combined treatment with perindopril and nifedipine retard in comparison to the result of monotherapy with nifedipine retard. GFR and ERPF showed no significant difference (NS) between the two modes of treatment. It is suggested that the combined treatment with nifedipine retard and perindopril is more effective than the monotherapy with nifedipine retard in the management of moderate to severe post-transplant hypertension and proteinuria of renal transplant patients.
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PMID:Management of moderate to severe hypertension and proteinuria by nifedipine retard and perindopril after renal transplantation. 860 9

There is no generally accepted treatment for primary focal segmental glomerulosclerosis (FSGS). Steroids alone and steroids plus cyclophosphamide can be expected to induce a remission of the proteinuria in only 27% of patients. Probably the majority of FSGS patients will reach ESRD over the extended course of their disease. In addition to the work presented in this study, there have been many reports of the potential effectiveness of cyclosporine (CSA) on reducing the proteinuria of FSGS. This study was undertaken to test the efficacy and safety of a 6-month course of CSA in a double-blinded, prospectively randomized, placebo-controlled trial in children with corticosteroid-resistant FSGS. The potential inhibitory effect of hypercholesterolemia on the proteinuria-reducing actions of CSA was also assessed. Twenty-five patients with FSGS were randomized to receive either placebo or CSA for 6 months. Twelve of the 12 patients that received CSA experienced a diminution of their proteinuria as opposed to only two of the 12 placebo-treated patients. Proteinuria was significantly reduced from 151.7 +/- 162.4 mg/kg per 24 h at Week 0 to 36.9 +/- 42.3 at the end of the study in the group that received CSA (P < 0.05). There was no significant change in the proteinuria of the patients in the placebo group. A significant correlation between the percentage change of proteinuria over the 6 months of the study and the prestudy serum cholesterol levels (r = 0.79, P < 0.05) was seen in the CSA group. A partial correlation analysis controlling for the effects of serum cholesterol uncovered a significant relationship between average CSA level and proteinuria change (r = -0.76, P < 0.05). The fractional decline in GFR over the course of the study was not significantly different between the CSA and placebo-treated groups. In conclusion, CSA reduces proteinuria, increases serum albumin levels, and can be expected, therefore, to reduce the symptoms of nephrotic syndrome. Hypercholesterolemia antagonizes this effect of CSA.
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PMID:A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. 880 10

Uncontrolled or refractory nephrotic syndrome (NS), seen in a variety of glomerular disorders, leads to end-stage renal disease (ESRD). This study describes the use and efficacy of cyclosporine (CSA) for the treatment of refractory NS in 83 children seen over a 10-year period. The histological diagnosis leading to the NS was focal segmental glomerulosclerosis (FSGS) in 51% (n = 42), IgM nephropathy in 20% (n = 17), membranoproliferative glomerulonephritis in 10% (n = 8), lupus nephritis in 6% (n = 5), human immunodeficiency virus (HIV) nephropathy in 5% (n = 4), minimal change disease in 7% (n = 6), and membranous nephropathy in 1% (n = 1) of patients. During CSA therapy the mean proteinuria of the study population decreased from 5.14 g/24 h (4.80 g/m2 per 24 h) to 1.23 g/24 h (0.92 g/m2 per 24 h) (P < 0.001), the mean serum albumin increased from 2.13 g/dl to 3.53 g/dl (P < 0.001), the mean serum cholesterol decreased from 364 mg/dl to 223 mg/dl (P < 0.001), and the mean serum creatinine increased from 0.77 mg/dl to 1.2 mg/dl (P < 0.01). When analyzed by histological diagnosis, similar significant trends of reduction in proteinuria were seen in all but the lupus group. There was a rise in serum creatinine following the use of CSA in patients with FSGS, lupus nephritis, and HIV nephropathy; however the elevated serum creatinine was only significant in patients with FSGS. At the end of the study period, 20 patients had reached ESRD, of which 11 had FSGS, 5 had lupus nephritis, and 4 were patients with HIV nephropathy. Fifty-four patients were in remission at the end of the study period (48 with proteinuria < 100 mg/24 h and 6 with proteinuria < 500 mg/24 h). In conclusion, among children with refractory NS, CSA induced a remission in a large proportion. However toxicity, as noted by the rise in serum creatinine, was observed in several patients. Since this toxicity may be drug induced or a natural progression of the disease, careful monitoring and close follow-up are essential.
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PMID:One-center experience with cyclosporine in refractory nephrotic syndrome in children. 1010 Feb 85

Cyclosporin (CSA) has significantly reduced both incidence and severity of acute rejection, and brought excellent graft survival rates. Chronic CSA nephrotoxicity seems to be the second most important diagnosis responsible for the late graft failure. CSA-associated arteriolopathy (CAA) is well known as a characteristic lesion of chronic CSA nephrotoxicity by graft biopsies. There are few reports on the long-term outcome of renal transplant patients with biopsy-proven chronic CSA nephrotoxicity after diagnosis of CAA. We conducted two studies, the long-term outcome of the patients with CAA, and the FGS lesion related to CAA. Seventy-four CAA patients continued on CSA therapy after diagnosis of CAA were classified into two groups by outcome of the graft after follow-up: the functioning graft group (n = 30) and the graft-loss group (n = 44). There was no significant difference in severity of CAA grade between the functioning and graft-loss groups. Concomitant lesion of chronic rejection but not severity of CAA was the most important risk factor of graft loss for CAA patients in our study. Of a total of 54 recipients with FGS lesion, 32 patients (59%) were diagnosed as CAA-associated glomerulopathy (CAG) accompanied with severe CAA. Eighteen of 32 CAG patients lost their grafts after follow-up. Their serum creatinine level at biopsy was higher than that of the functioning group; however, there was no significant difference in daily proteinuria at biopsy between two groups. We have tried to reduce CSA dosage to maintain lower blood levels than the usual optimal target levels, but did not discontinue CSA after diagnosis of severe CAA and FGS lesion. In 15 isolated pure CAG patients, those with increasing daily proteinuria exceeding 2 g lost their graft function even after reducing CSA administration. The change in daily proteinuria seems to be a useful indicator for late graft loss in the patients of FGS lesion with severe CAA. CAA is not specific for chronic CSA nephrotoxicity, and FGS lesion is also a non-specific lesion often developed in renal allografts. Our study revealed clinicopathological characteristics of chronic CSA nephrotoxicity. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. FGS lesion accompanied by CAA is considered as a new concept of CAG, and increasing proteinuria in patients with CAG is a good indicator for poor outcome. These results will contribute towards an appropriate therapeutic plan for renal transplant patients undergoing long-term CSA treatment.
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PMID:Chronic cyclosporin nephropathy: long-term effects of cyclosporin on renal allografts. 1179 91

Idiopathic membranous nephropathy (IMN) remains one of the most common causes of the nephrotic syndrome (NS) in adults. Although the natural history is extremely variable, approximately two thirds of the patients will have persistent high-grade proteinuria and/or develop renal failure over a decade of observation. On the other hand, the remaining third of patients will remit spontaneously and potentially toxic therapy should be avoided in this group. Our capacity to predict which patient will progress at an early stage of the disease has improved substantially in the past 10 years. We present the data from studies of cyclosporine (CSA) and mycophenolate mofetil (MMF) treatment of IMN with their level of evidence in support of efficacy. In addition, based on data related to predicting prognosis, we assign a risk for progression category to the trial patients at entry into these studies. The data are presented in this format so the reader will be able to better discern the risk benefit of treatment within each category and the rationale for our subsequent grade of recommendation for the use of these agents in IMN. CSA has been shown in randomized controlled trials in both the medium and high risk of progression categories of IMN patients to improve proteinuria and preserve renal function at least in the short term in up to two thirds of patients. Other studies suggest prolonged therapy beyond 6 months to 1 year may reduce the high relapse rate after CSA treatment supporting more long-term, continuous, or combination therapy in IMN treatment. The data in favor of MMF treatment of this disease is much weaker and are derived from pilot studies. Only one report applied MMF specifically to IMN patients. In these medium to high risk of progression patients, approximately one-half had a 50% reduction in their baseline proteinuria without a significant alteration in their serum creatinine level. MMF's role as a single agent or as adjunctive therapy in the treatment of IMN needs more rigorous evaluation.
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PMID:Mycophenolate mofetil and cyclosporine therapy in membranous nephropathy. 1283 95

Chronic CSA nephrotoxicity is the second most important diagnosis responsible for the late graft failure. CSA associated arteriolopathy (CAA) is a well-known lesion of chronic CSA nephrotoxicity. The clinicopathological characteristics and the significance of CSA nephrotoxicity have changed following reduction in CSA doses and implementation of monitoring of blood levels. Seventy-four CAA patients on CSA therapy were classified as functioning (n=30) or loss groups (n=44). There was no significant difference in severity of CAA. The concomitant lesion of chronic rejection, but not the severity of CAA, was the most important risk factor for graft loss. Among 54 recipients with focal segmental glomerulosclerosis lesions (FGS), 32 (59%) were diagnosed as CAA associated glomerulopathy (CAG). Eighteen of the 32 CAG patients lost their grafts upon follow-up. Decreasing the CSA dosage to maintain lower blood levels than the usually optimal concentrations, but not discontinuation of CSA, has been useful to retard the progression of graft dysfunction in half of 15 isolated pure CAG patients. Patients with increasing daily proteinuria exceeding 2 grams lost their graft function despite CSA reductions. CAA is not a specific lesion of chronic CSA nephrotoxicity; the FGS lesion is also a nonspecific lesion often seen in renal allografts. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. The FGS lesion accompanying CAA is considered to be CSA-associated glomerulopathy. These data contribute to therapeutic plans for renal transplant patients during long-term CSA treatment.
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PMID:Cyclosporine nephrotoxicity: how does it affect renal allograft function and transplant morphology? 1504 48

Hepcidin is a small, defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. We studied correlations of hepcidin concentrations with markers of iron status, erythropoietin therapy, and markers of inflammation among 130 kidney allograft recipients. In addition, we assessed the prevalence of anemia and its relation to hepcidin. Soluble receptor of transferrin (sTfR), high-sensitivity C-reactive protein (hsCRP), TNF-alpha, interleukin (IL)-6, prohepcidin, and hepcidin were measured using commercially available kits. According to the WHO definition, the prevalence of anemia was 28%. Among anemic recipients we found a significantly higher values of serum creatinine, serum prohepcidin, hepcidin, (hsCRP), TNF-alpha, IL-6, ferritin, and proteinuria in addition to more frequent use of rapamycin and significantly lower use of CSA with lower CSA concentrations, as well as lower cholesterol, hemoglobin, and estimated glomerular filtration rate (eGFR) (by the Modification of Diet in Renal Disease equation). Serum prohepcidin significantly correlated with creatinine, GFR, time after transplantation, albumin, hsCRP, IL-6, and TNF-alpha, whereas hepcidin-25 correlated with serum iron, ferritin, hsCRP, IL-6, hemoglobin, transferrin saturation (TSAT), creatinine, and GFR. Multiple regression analysis showed that prohepcidin was independently related only to GFR and ferritin. Upon multiple regression analysis, predictors of serum hepcidin were eGFR, ferritin, and hsCRP, explaining 79% of the variation of hepcidin values. In conclusion, the prevalence of anemia was relatively high among a population of kidney allograft recipients. The pathogenesis of anemia is mulitfactorial. Elevated hepcidin levels among kidney transplant recipients may be due to low-grade inflammation, which is frequently encountered in this population, and mainly to impaired renal function, but it did not seem to be a major pathogenetic factor for anemia in this population.
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PMID:A possible role of hepcidin in the pathogenesis of anemia among kidney allograft recipients. 1985 75

The outcomes of children with severe proliferative lupus nephritis (LN) were examined using a new mycophenolate and cyclosporine-based (MMF-CSA) induction protocol. Sixteen children with LN (WHO class III and IV), 31.3% of whom required dialysis at induction, were retrospectively studied. Median MMF dose was 942 mg/m( 2)/day. Thirteen patients (81%) with persistent proteinuria received CSA. Clinical and laboratory parameters were compared at pre-induction, 6 and 12 months. Treatment outcome was defined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal function, haematuria, proteinuria and serological markers (complements C3, C4 and anti-dsDNA). Comparing these parameters at induction, 6 months and 12 months, respectively, SLEDAI (25.4 +/- 8.7 versus 3.2 +/- 2.9 versus 2.9 +/- 2.8), serum C3 (47 +/- 21 versus 107 +/- 27 versus 111 +/- 38 mg/dl), C4 (12 +/- 14 versus 23 +/- 14 versus 22 +/- 11 mg/dl) and urine protein (6.97 +/- 7.09 versus 0.98 +/- 1.56 versus 0.21 +/- 0.13 g/ day/1. 73 m(2)) improved significantly (p < 0.05). Anti-dsDNA titres decreased in 73% by 6 and 12 months (p < 0.05). Complete renal remission was achieved in 7/16 (43.8%) at 6 months and 12/16 (75%) at 12 months, the rest achieving partial remission with no treatment failures. In conclusion, a combination MMF-CSA protocol is an effective therapeutic alternative for induction of children with severe proliferative LN, resulting in significant clinical and serological improvement with minimal adverse effects.
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PMID:Good outcomes with mycophenolate-cyclosporine-based induction protocol in children with severe proliferative lupus nephritis. 2058 Oct 19

Whether preoperative proteinuria associates with adverse renal outcomes after cardiac surgery is unknown. Here, we performed a secondary analysis of a prospectively enrolled cohort of adult patients undergoing coronary artery bypass grafting (CABG) at a medical center and its two affiliate hospitals between 2003 and 2007. We excluded patients with stage 5 CKD or those who received dialysis previously. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2+ to 4+). Among a total of 1052 patients, cardiac surgery-associated acute kidney injury (CSA-AKI) developed in 183 (17.4%) patients and required renal replacement therapy (RRT) in 50 (4.8%) patients. In a multiple logistic regression model, mild and heavy proteinuria each associated with an increased odds of CSA-AKI, independent of CKD stage and the presence of diabetes mellitus (mild: OR 1.66, 95% CI 1.09 to 2.52; heavy: OR 2.30, 95% CI 1.35 to 3.90). Heavy proteinuria also associated with increased odds of postoperative RRT (OR 7.29, 95% CI 3.00 to 17.73). In summary, these data suggest that preoperative proteinuria is a predictor of CSA-AKI among patients undergoing CABG.
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PMID:Preoperative proteinuria predicts adverse renal outcomes after coronary artery bypass grafting. 2111 18


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