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Query: UMLS:C0020473 (hyperlipidemia)
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Chronic glomerulonephritis (GN) is one of the leading causes of end-stage renal disease (ESRD). The possibilities for successful treatment in the earliest stages are still limited. Immunosuppressive treatment leads to complete or partial remission only in some patients. Even then, a non-immunological evolution to chronic renal insufficiency often enters a progressive course. By applying a consistent strategy for their individual evaluation and management, it is possible to improve the outcome of patients with GN. The early referral to a nephrologist and an early histomorphological diagnosis; the precise assessment of the type of injury, i.e. proliferative or non-proliferative; the indices of activity and chronicity; and the prognostic indicators are helpful for the therapeutic approach. The goal of the management of GN has to be to suppress the disease with minimum side effects of the treatment. Many unanswered questions and controversies remain concerning the immunosuppressive therapy. A precise distinction is needed between the problematic assertions and evidence-based protocols. A common task for the treatment of all types of chronic GN should be the protection of renal structure and function: control of blood pressure, action on renal haemodynamics and proteinuria via pharmacological inhibition of the renin-angiotensin system, control of hyperlipidaemia and limitation of fibrosis. Some novel and promising pharmacological approaches to extracellular matrix accumulation and chronic interstitial fibrosis are in progress.
Nephrol Dial Transplant 2003 Jul
PMID:The treatment of glomerular disease--a compromise between the standard and the individual approach. 1281 65

Plasma exchange was used for many years as the method of extracorporeal removal of antibodies and/or immune complexes that may be involved in the pathogenesis of renal diseases. Recently low-density lipoprotein (LDL)-apheresis and immunoadsorption were also introduced into nephrological practice. LDL-apheresis, designed originally as a rescue treatment for refractory hyperlipidaemia, appeared also to be effective in certain glomerulopathies, resistant to other treatment strategies. Similarly, immunoadsorption can be employed successfully in the treatment of different nephropathies, of both immunological and non-immunological pathogenesis. This method may also be effective as rescue treatment in some cases of acute rejection and recurrence of certain nephropathies after renal transplantation. The major advantage of both methods is their increased selectivity compared with standard plasma exchange. In addition, these techniques need no supplement fluid (namely fresh frozen plasma), which allows for markedly increased efficacy of the treatment as well as substantial reduction of infection risks.
Nephrol Dial Transplant 2003 Jul
PMID:LDL-apheresis and immunoadsorption: novel methods in the treatment of renal diseases refractory to conventional therapy. 1281 74

Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well-being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long-term application.
Ther Apher Dial 2003 Aug
PMID:Low-density lipoprotein apheresis: an overview. 1288 19

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
Ther Apher Dial 2004 Jun
PMID:Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy. 1515 77

Hyperlipidaemia is a frequent complication after renal transplantation. As to whether total cholesterol (TC) and triglyceride levels are risk factors for cardiovascular disease and graft survival is controversial. The prevalence of hypercholesterolaemia in the transplanted population in Spain has increased over the years, going from 38.8% in 1990 to 48% in 1998. In contrast, the prevalence of hypertriglyceridaemia being approximately 20%, has not shown any significant variation. Transplant recipients with high cholesterol were characterized by increased age, lower proportion of males, higher mean body mass index, lower proportion of HCV antibodies, reduced time on dialysis and diabetes. Patients with high cholesterol were more frequently treated with cyclosporine + MMF + prednisone and less frequently treated with tacrolimus + MMF + prednisone. Hypertriglyceridaemia was more frequent in patients treated with cyclosporine + MMF + prednisone, and these patients showed significantly higher creatinine plasma levels at 1 year and were more frequently treated with lipid-lowering agents. Hypertriglyceridaemia at 3 months after transplantation is associated with worse graft survival (RR 1.078; CI 1.07-1.143; P = 0.011) and greater cardiovascular mortality (RR 1.265; CI 1.20-1.428; P = 0.0002), while treatment with statins has a protective effect on the graft survival (RR 0.64; CI 0.512-0.888; P = 0.0051). In conclusion, in the renal transplant population in Spain, hypertriglyceridaemia rather than hypercholesterolaemia, may exert a deleterious effect on graft and patient survival.
Nephrol Dial Transplant 2004 Jun
PMID:The effects of hyperlipidaemia on graft and patient outcome in renal transplantation. 1519 40

Recent advances in immunosuppressive drug regimens have changed the outcome after liver transplantation significantly in the last two decades. However, chronic rejection and long-term graft survival remains a major problem. Side effects like drug-induced nephrotoxicity, hypertension, osteoporosis, hyperlipidaemia and neuropathy of some immunosuppressive agents play an essential role in long-term allograft and patient survival. This review outlines the current treatment of short- and long-term immunosuppression in liver transplanted patients, it summarizes the treatment of acute and chronic rejection, describes the complications and side effects of immunosuppressive therapy and points out the current use of immunosuppressive therapy in living-related liver transplantation.
Nephrol Dial Transplant 2004 Jul
PMID:Immunosuppression and modulation in liver transplantation. 1524 Aug 45

Achieving long-term graft survival and optimal patient health are ultimate clinical goals in renal transplantation. Many factors negatively impact long-term transplant outcomes, including graft rejection, renal dysfunction and increased cardiovascular burden. Additionally, glucose metabolism disturbance, also a cardiovascular risk factor, influences morbidity and mortality. As such, careful consideration of the immunosuppressive strategy and its impact on these factors is critical to optimizing outcomes. Large-scale clinical trials and registry studies conducted over the past decade have demonstrated tacrolimus to be a cornerstone immunosuppressant in renal transplantation. Compared with ciclosporin treatment, tacrolimus has been shown to be associated with decreased acute and chronic rejection, improved renal function over the long term post-transplant, as evidenced by lower serum creatinine concentrations and a slower decline in the glomerular filtration rate, and a superior cardiovascular risk profile, as demonstrated by lower incidences of hyperlipidaemia and hypertension. The incidence of new-onset diabetes in patients receiving tacrolimus is low due to continued refinement of tacrolimus-based regimens and a better understanding of the effects of tacrolimus on metabolic parameters. Together, these findings may translate into improved long-term transplant outcomes with tacrolimus-based immunosuppression. In fact, long-term follow-up results from multicentre trials plus data from registry analyses are already documenting improved survival with this cornerstone immunosuppressant.
Nephrol Dial Transplant 2004 Dec
PMID:Improving long-term renal transplant outcomes with tacrolimus: speculation vs evidence. 1557 22

Although renal transplantation offers survival and quality of life advantages as a renal replacement therapy, a substantial proportion of transplant recipients develop worsening of preexisting medical diseases or new complications, including sequelae of rejection, new onset diabetes after transplantation (NODAT), hyperlipidemia, opportunistic infections, cancer, and other systemic diseases secondary to immunosuppression. Management of these problems can be a complex endeavor due to medication interactions that often affect immunosuppression levels. However, successful management of the chronic medical problems associated with renal transplantation can prolong the life span of the graft and the patient.
Semin Dial
PMID:Management of the well renal transplant recipient: outpatient surveillance and treatment recommendations. 1639 16

We aimed to investigate prognostic factors for a composite end-point of end-stage renal disease (ESRD) and the progression of renal disease in Japanese patients with chronic renal disease. Using a composite end-point comprising a doubling of serum creatinine (sCr), an increase in sCr level to 6.0 mg/dL, or initiation of dialysis and renal transplantation caused by ESRD, we examined data obtained in a prospective cohort study. The present study consisted of 641 patients who were 20 years of age or older with chronic renal disease caused by diabetic nephropathy, glomerulonephritis, or nephrosclerosis, and who had baseline sCr levels of 5.0 mg/dL or less. The following criteria were examined as prognostic factors: sex; age; elapsed time from initial diagnosis; disease underlying the nephropathy (diabetic or non-diabetic); complications with hypertension, hyperlipidemia, or anemia; baseline sCr level; therapeutic regimen, including use of ACE inhibitors or Ca2+ -channel blockers; and diet. A log-rank test was used for univariate analysis, and Cox regression analysis was used for multivariate analysis. Underlying disease (diabetic or non-diabetic), baseline sCr level, and Ca2+ -channel blocker therapy were significantly related to event incidence. In the present study, we identified underlying disease and baseline sCr level as important prognostic factors for a composite end-point in a predialysis patient population in both the early and middle stages of renal disease. These factors should be considered as balancing variables for randomization in future clinical studies.
Ther Apher Dial 2006 Feb
PMID:Prognostic factors for a composite end-point of renal outcomes in patients with chronic kidney disease. 1655 40

Over the last decade, there has been a decrease in acute graft rejection rates following renal transplantation; however, this has not corresponded with an improvement in long-term outcomes of transplantation. One of the major causes of long-term morbidity and mortality in renal transplant recipients is cardiovascular disease. Immunosuppressive regimens, especially those including steroids and calcineurin inhibitors, have a negative role in the induction of cardiovascular risk factors. The proliferation signal inhibitors (PSIs)/mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown considerable promise in reducing acute rejection in renal transplant recipients. Although PSIs are associated with an increase in hyperlipidaemia (hypercholesterolaemia and hypertriglyceridaemia), which is a major risk factor for atherosclerosis and associated cardiovascular disease, recent studies with sirolimus have demonstrated protection from atheroma progression in hyperlipidaemic apolipoprotein E-deficient mice. Here, we summarize the results of pre-clinical and clinical studies with sirolimus and everolimus, with particular emphasis on the beneficial and adverse effects that these drugs exert on the cardiovascular system, and the underlying molecular mechanisms.
Nephrol Dial Transplant 2006 Jul
PMID:Potential role of proliferation signal inhibitors on atherosclerosis in renal transplant patients. 1681 51


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