Showing papers by "Giovanni F.M. Strippoli published in 2007"

Meta-analysis: Vitamin D Compounds in Chronic Kidney Disease

Abstract: Most patients with advanced kidney disease take vitamin D compounds to prevent secondary hyperparathyroidism. Palmer and colleagues' meta-analysis of 76 randomized trials found no good evidence tha...

Interventions for preventing bone disease in kidney transplant recipients

Abstract: Background People who have chronic kidney disease (CKD) have important changes to bone structure, strength, and metabolism. Children experience bone deformity, pain, and delayed or impaired growth. Adults experience limb and vertebral fractures, avascular necrosis, and pain. The fracture risk after kidney transplantation is four times that of the general population and is related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) occurring with end-stage kidney failure, steroid-induced bone loss, and persistent hyperparathyroidism after transplantation. Fractures may reduce quality of life and lead to being unable to work or contribute to community roles and responsibilities. Earlier versions of this review have found low certainty evidence for effects of treatment. This is an update of a review first published in 2005 and updated in 2007. Objectives This review update evaluates the benefits and harms of interventions for preventing bone disease following kidney transplantation. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 16 May 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria RCTs and quasi-RCTs evaluating treatments for bone disease among kidney transplant recipients of any age were eligible. Data collection and analysis Two authors independently assessed trial risks of bias and extracted data. Statistical analyses were performed using random effects meta-analysis. The risk estimates were expressed as a risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous outcomes together with the corresponding 95% confidence interval (CI). The primary efficacy outcome was bone fracture. The primary safety outcome was acute graft rejection. Secondary outcomes included death (all cause and cardiovascular), myocardial infarction, stroke, musculoskeletal disorders (e.g. skeletal deformity, bone pain), graft loss, nausea, hyper- or hypocalcaemia, kidney function, serum parathyroid hormone (PTH), and bone mineral density (BMD). Main results In this 2019 update, 65 studies (involving 3598 participants) were eligible; 45 studies contributed data to our meta-analyses (2698 participants). Treatments included bisphosphonates, vitamin D compounds, teriparatide, denosumab, cinacalcet, parathyroidectomy, and calcitonin. Median duration of follow-up was 12 months. Forty-three studies evaluated bone density or bone-related biomarkers, with more recent studies evaluating proteinuria and hyperparathyroidism. Bisphosphonate therapy was usually commenced in the perioperative transplantation period (within 3 weeks) and regardless of BMD. Risks of bias were generally high or unclear leading to lower certainty in the results. A single study reported outcomes among 60 children and adolescents. Studies were not designed to measure treatment effects on fracture, death or cardiovascular outcomes, or graft loss.Compared to placebo, bisphosphonate therapy administered over 12 months in transplant recipients may prevent fracture (RR 0.62, 95% CI 0.38 to 1.01; low certainty evidence) although the 95% CI included the possibility that bisphosphonate therapy might make little or no difference. Fracture events were principally vertebral fractures identified during routine radiographic surveillance. It was uncertain whether any other drug class decreased fracture (low or very low certainty evidence). It was uncertain whether interventions for bone disease in kidney transplantation reduce all-cause or cardiovascular death, myocardial infarction or stroke, or graft loss in very low certainty evidence. Bisphosphonate therapy may decrease acute graft rejection (RR 0.70, 95% CI 0.55 to 0.89; low certainty evidence), while it is uncertain whether any other treatment impacts graft rejection (very low certainty evidence). Bisphosphonate therapy may reduce bone pain (RR 0.20, 95% CI 0.04 to 0.93; very low certainty evidence), while it was very uncertain whether bisphosphonates prevent spinal deformity or avascular bone necrosis (very low certainty evidence). Bisphosphonates may increase to risk of hypocalcaemia (RR 5.59, 95% CI 1.00 to 31.06; low certainty evidence). It was uncertain whether vitamin D compounds had any effect on skeletal, cardiovascular, death, or transplant function outcomes (very low certainty or absence of evidence). Evidence for the benefits and harms of all other treatments was of very low certainty. Evidence for children and young adolescents was sparse. Authors' conclusions Bisphosphonate therapy may reduce fracture and bone pain after kidney transplantation, however low certainty in the evidence indicates it is possible that treatment may make little or no difference. It is uncertain whether bisphosphonate therapy or other bone treatments prevent other skeletal complications after kidney transplantation, including spinal deformity or avascular bone necrosis. The effects of bone treatment for children and adolescents after kidney transplantation are very uncertain.

Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients

Abstract: Background Cytomegalovirus (CMV) is the most common virus causing disease and death in solid organ transplant recipients during the first six months post-transplant. Previous systematic reviews have demonstrated the efficacy of antiviral medications used prophylactically or pre-emptively in preventing CMV disease. In this review the efficacy of older agents (immunoglobulins (IgG), anti CMV vaccines and interferon) are examined. Objectives To assess the benefits and harms of IgG, anti CMV vaccines or interferon for preventing symptomatic CMV disease in solid organ transplant recipients. Search strategy We searched the Cochrane Renal Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search: December 2005 Selection criteria Randomised and quasi-randomised controlled trials comparing IgG, anti CMV vaccine or interferon with placebo or no treatment, IgG alone or combined with antiviral medications with antiviral medications or IgG alone in recipients of any solid organ transplant. Data collection and analysis Two of four authors independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Main results Thirty seven trials (2185 participants) were included in this review. There was no significant difference in the risk for CMV disease (16 trials, 770 patients: RR 0.80, 95% CI 0.61 to 1.05), CMV infection (14 trials, 775 patients: RR 0.94, 95% CI 0.80 to 1.10) or all-cause mortality (8 trials, 502 patients: RR 0.57, 95% CI 0.32 to 1.03) with IgG compared with placebo/no treatment. However IgG significantly reduced the risk of death from CMV disease (6 trials, 346 patients: RR 0.33, 95% CI 0.14 to 0.80). There was no difference in the risk for CMV disease (4 trials, 298 patients: RR 1.17, 95% CI 0.74 to 1.86), CMV infection (4 trials, 298 patients: RR 1.16, 95% CI 0.89 to 1.52) or all-cause mortality (2 trials, 217 patients: RR 0.92, 95% CI 0.37 to 2.29) between antiviral medication combined with IgG and antiviral medication alone. There was no significant difference in the risk of CMV disease with anti CMV vaccine or interferon compared with placebo or no treatment. Authors' conclusions Currently there are no indications for IgG in the prophylaxis of CMV disease in recipients of solid organ transplants.

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

Abstract: Microalbuminuria is a strong, consistent and independent risk factor for cardiovascular and renal disease in patients with diabetes and/or hypertension and in the general population. Several randomized trials have shown the efficacy of inhibiting the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) to prevent cardiovascular events and the progression of kidney disease. These 2 classes of drugs are equally effective for renal outcomes in patients with diabetic nephropathy, but only ACEIs have been found to significantly impact the risk of all-cause mortality, predominantly cardiovascular, in patients with diabetic nephropathy. Studies on the cardiorenal efficacy of combined therapy with ACEIs and ARBs in individuals with microalbuminuria or macroalbuminuria and other cardiovascular risk factors have been inconclusive. The Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study aims to address existing questions in this setting. This is a phase III, randomized, comparative, pragmatic trial with prospective randomized open blinded endpoint (PROBE) design. It will evaluate the comparative efficacy of combined therapy with ACEIs and ARBs versus monotherapy with either ACEIs or ARBs in improving cardiovascular and renal outcomes in microalbuminuric or macroalbuminuric individuals at cardiorenal risk. The study will enroll 2,100 patients, selected in a network of internal medicine, diabetology or nephrology outpatient clinics. Patients will be randomly allocated to ACEIs, ARBs or their combination. The study has been approved and funded by the Agenzia Italiana del Farmaco (A.I.F.A.) within the 2005 funding plan for independent research on drugs.

Identifying Patients at Risk for Microalbuminuria via Interaction of the Components of the Metabolic Syndrome: A Cross-Sectional Analytic Study

Abstract: Background and objectives: The objective of this study was to investigate correlates of risk for having microalbuminuria in individuals with one or more cardiovascular risk factors. Design, setting, participants, & measurements: The study involved 1919 individuals who attended general practice settings, were aged 55 to 75 yr, and did not have a history of cardiovascular events or diabetes but had one or more cardiovascular risk factors. A tree-based regression technique and multivariate analysis were used to identify distinct, homogeneous subgroups of patients with different likelihood of having microalbuminuria; interaction between correlates of microalbuminuria and risk for microalbuminuria was also investigated. Results: The prevalence of microalbuminuria was 5.9%. Patients who did not have hypertension and had postload glycemia 150 mg/dl and fibrinogen levels in the upper tertile were associated with a significantly higher risk for microalbuminuria. Conclusions: The likelihood of having microalbuminuria in a population-based study of elderly individuals is strongly related to the interaction between the components of the metabolic syndrome, particularly hypertension, insulin resistance, and impaired glucose tolerance.

[Calcimimetics, phosphate binders, vitamin D and its analogues for treating secondary hyperparathyroidism in chronic kidney disease: guideline from the Italian Society of Nephrology].

Abstract: Background The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only In the present guideline, evidence of the use of calcimimetics, phosphate binders, vitamin D and vitamin D analogues for treating secondary hyperparathyroidism in chronic kidney disease (CKD) is presented Methods SR of RCT and RCT on interventions for secondary hyperparathyroidism in CKD were identified referring to a Cochrane Library and Renal Health Library search (2005 update) Results Three SR and 8 RCT were found addressing this intervention issue Methodological quality of available RCT was suboptimal according to current methodological standards Calcimimetics used in patients receiving haemodialysis or peritoneal dialysis are more effective than placebo in controlling secondary hyperparathyroidism (reduced parathyroid hormone levels, calcium levels and phosphorus levels) All phosphate binders are effective in controlling hyperphosphatemia but different doses are to be used with different agents to achieve similar targets Dosing needs to be adjusted according to phosphorus levels Vitamin D and its analogues are recommended in CKD patients, although there is no significant evidence of superiority of individual agents in head-to-head comparisons Dosing should be based on baseline parathyroid hormone levels, but the risk of hypercalcemia should also be considered Conclusion Available evidence suggests that calcimimetics, phosphate binders and vitamin D or its analogues are effective in the treatment of secondary hyperparathyroidism Superiority of individual agents or doses is still deeply debated Further studies are necessary to test these issues

[Treating lupus nephritis: guideline from the Italian Society of Nephrology].

Abstract: Background The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of lupus nephritis (LN) treatment is presented. Methods SR of RCT and RCT on different therapeutic options for LN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Results One SR of 25 RCT and 6 further RCT were available to address this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. In LN patients, combining cyclophosphamide (CyA) and steroids as induction therapy results in a reduced risk of serum creatinine doubling compared to steroids alone, although there is no evidence of significant survival advantage and risk of ovarian failure was demonstrated (evidence from SR). The association of azathioprine (Aza) and steroids significantly reduces the risk of all-cause mortality compared to steroids alone (evidence from SR). No significant survival advantages from the association of plasma exchange and CyA or Aza are proven (evidence from SR). No significant differences on renal and survival endpoints are demonstrated with different dosing of CyA (evidence from RCT). Conclusion In LN patients available evidence supports the hypothesis that immunosuppressive agents reduce the risk of all-cause mortality and the risk of progressive renal disease. Further studies are necessary to test new immunosuppressive agents such as mycophenolate mofetil in severe LN patients.

Current structure and organization for renal patient assistance in Italy

Abstract: Background. Given the public health challenge and burden of chronic kidney disease, the Italian Society ofNephrology (SIN) has compiled a national census of Renal Units (RU) existing in the twenty Italian regions related to the year 2004. Methods. An on-line questionnaire including 158 items explored structural and human resources, organization aspects, activities and epidemiological data in SIN, 2004. Results. The census identified 363 public RU, 303 satellite Dialysis Centres (DC) and 295 private DC totalling 961 DC [16.4 per million population (pmp)]. The inpatient renal beds were 2742 (47 pmp). Renal and dialysis activity was performed by 3728 physicians (64 pmp), of whom 2964 (80%) were nephrologists. There was no permanent medical assistance in 41% of satellite DC. There were 1802 renal admissions pmp and 99 renal biopsies pmp. The management of acute renal failure (13 456 cases; 230 pmp) represented a relevant proportion of the activities conducted in public RU. In 2004 there were 9858 new cases of end-stage kidney disease requiring renal replacement therapy (RRT) (169 pmp). On 31 December 2004, 60 058 patients were on RRT (1027 pmp), 43 293 of which (740 pmp) were on dialysis and 16 765 (287 pmp) with renal graft. Conclusions. This census of the Italian RU and DC in 2004 provides decision makers and healthcare stakeholders with detailed data for benchmarking and has financial implications for the public health system. Similar analyses may be conducted in other countries permitting standardization of medical and cost-related aspects of renal care.

Urticaria and angioedema in renal cell cancer patients treated with IL-2.

Abstract: Interleukin-2 therapy has produced significant improvement in a proportion of patients with renal cell cancer. Dermatologic side effects, such as erythema, have been very common. However, we could find only 2 reports of urticaria in the medical literature. Here, we report 8 patients with renal cell cancer who developed urticaria in association with interleukin-2 therapy. The hives tended to occur at the end of a treatment cycle. Skin tests with IL-2 were negative in two patients. Urticaria did not worsen or consistently occur with repeated courses of interleukin-2 and anaphylaxis was not observed in any patient. Six of the 8 patients previously had urticaria unrelated to IL-2 therapy.

[Haemoglobin targets for chronic kidney disease: guideline from the Italian Society of Nephrology].

Abstract: BACKGROUND The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of optimal haemoglobin (Hb) target levels in chronic kidney disease (CKD), either for pre-dialysis, dialysis or renal transplanted patients, is presented. METHODS SR of RCT and RCT on different Hb target levels in patients with CKD were identified, referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS Four SR (19 RCT) were found addressing the point. Methodological quality of available trials was suboptimal. In CKD patients (non-dialysis patients) Hb targets of 11.3 g/dL should be preferred to Hb >13.5 g/dL (evidence from RCT). A Hb target of 11.0-11.5 g/dL should be preferred in CKD patients receiving dialysis treatment without significant cardiac disease, since no survival benefits has been showed with Hb >14 g/dL (evidence from RCT). The optimal Hb target in haemodialysis patients with severe cardiac disease should be 10.0-10.5 g/dL (evidence from SR). Increases in Hb target lev-els are associated with improved quality of life, although this was mainly noticed in observational studies and in few RCT often relying on unvalidated quality of life assessment scales. CONCLUSION In CKD patients current available evidence supports the hypothesis that optimal Hb targets should be low to subnormal.

[Antiviral prophylaxis and pre-emptive therapy for the prevention of Cytomegalovirus infection in renal transplant recipients: guideline from the Italian Society of Nephrology].

Abstract: Background The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of antiviral prophylaxis and pre-emptive treatment for preventing cytomegalovirus (CMV) infection in kidney transplant recipients is presented. Methods SR of RCT and RCT on antiviral prophylaxis and pre-emptive treatment for CMV infection in kidney transplant recipients were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Results Evidence from 4 SR of RCT was gathered to address this issue. Methodological quality of available RCT included in these SR was suboptimal. Antiviral prophylaxis is associated with a significant reduction in the risk of CMV infection and all-cause mortality in CMV-negative and CMV-positive renal transplant recipients from CMV-positive donors, regard-less of the immunosuppressive treatments used (evidence from SR). Pre-emptive therapy has been found to be effective in preventing CMV disease but not all-cause mortality in these patients, even if evidence is less satisfactory compared to data on antiviral prophylaxis (evidence from SR). There is insufficient evidence of conclusive recommendations on treatment of CMV-negative recipients of renal transplants from CMV-negative donors. Conclusion In kidney transplant patients current available evidence supports the hypothesis that antiviral prophylaxis and pre-emptive therapy are effective in preventing CMV disease; but antiviral should be the treatment of choice. Further studies are necessary on the treatment of CMV-negative recipients from CMV-negative donors.

[Use of statins for preventing cardiovascular and renal outcomes in patients with chronic kidney disease excluding dialysis: guideline from the Italian Society of Nephrology].

Abstract: Background The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the efficacy of statins in chronic kidney disease patients (CKD, non-dialysis patients) is presented. Methods SR of RCT and RCT on statins in CKD (non-dialysis) patients were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. Results Three SR and 36 RCT were found addressing this intervention issue. Methodological quality of the relevant RCT was suboptimal. There is no enough evidence to suggest that statins are associated with a significant reduction in the risk of serum creatinine doubling or of end-stage renal disease in CKD patients (evidence from SR and RCT). Statins compared to placebo or no treatment are associated with significant improvements in proteinuria (evidence from SR). Statins are also associated with significant reduction in the risk of cardiovascular events and mortality in CKD patients (evidence from SR and RCT) and in renal transplant recipients (evidence from RCT), and no significant increases in the risk of rhabdomyolysis and hepatotoxicity in CKD patients. Conclusion Available evidence supports the hypothesis that statins should be recommended in CKD patients (non-dialysis patients) on the basis of significant evidence of cardiac and renal protection and no evidence of significant harms. Further studies are necessary to test this hypothesis in selected patient populations.

[Therapeutic strategies for membranous nephropathy: guideline from the Italian Society of Nephrology].

Abstract: Background The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of interventions for idiopathic membranous nephropathy (MN) is presented. Methods SR of RCT and RCT on interventions for MN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Results Three SR and 18 RCT were available to address this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. In patients with MN, nephrotic syndrome and normal renal function, methylprednisolone and chlorambucil or cyclophosphamide for 6 months alternately increase the probability of nephritic syndrome remission (evidence from SR) and long-term renal protection (evidence from RCT). Other drugs (ACTH and cyclosporine) are associated with nephrotic syndrome remission, but there is no evidence of significant effects on renal function (evidence from RCT). In patients with impaired renal function, association of corticosteroids and cytotoxic agents is proven to cause a short-term delay of renal damage progression, even though benefits are counterbalanced by complications (evidence from RCT). Conclusion In patients with MN, nephrotic syndrome and normal renal function, current available evidence supports the hypothesis that primary intervention should be the association of corticosteroids and cytotoxic agents. Secondary therapeutic choices include ACTH and cyclosporine. Further studies are necessary to test new immunosuppressive agents such as mycophenolate mofetil.

[Immunosuppressive and non-immunosuppressive agents for patients with IgA nephropathy: guideline from the Italian Society of Nephrology].

Abstract: Background The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of the use of immunosuppressive and non-immunosuppressive treatments in IgA nephropathy (IgAN) is presented. Methods SR of RCT and RCT on treatment in patients with IgAN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. Results Two SR of RCT (13 and 3 RCT, respectively), and 18 further RCT were available to address this issue. Methodological quality of available trials was suboptimal. In patients with IgAN and normal or mildly impaired renal function, steroids significantly delay the progression to end stage kidney disease (evidence from SR) and improve proteinuria. Associating steroids and cytotoxic agents (cyclophosphamide followed by oral azathioprine) proves effective in patients with rapidly progressive renal disease (evidence from RCT). Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers significantly improve proteinuria (evidence from RCT), but there are no conclusive data on efficacy on hard patient level endpoints. There are no conclusive data available on the use of a therapy combining these agents. Conclusion In IgAN patients current evidence supports the hypothesis that immunosuppressive agents delay the progression to end stage renal disease. Further studies are necessary to test this hypothesis in selected patient populations.