Non-nephrotoxic Drugs Research Articles

Conversion to belatacept after lung transplantation: Report of 10 cases.

Calcineurin inhibitors (CNIs) remain the cornerstone of maintenance immunosuppression (IS) after lung transplantation (LTx), although CNI-related life-threatening toxic effects may occur. Belatacept, a novel immunosuppressant that blocks a T-cell co-stimulation pathway, is a non-nephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, there are only a few reports of belatacept conversion as a CNI-free or CNI-sparing IS treatment. We reviewed a series of 10 LTx recipients with conversion to a CNI-free belatacept IS regimen within the first year post-LTx (n = 7) or a belatacept/low-dose CNI combination after the first year (n = 3). Use of belatacept was triggered by severe renal failure in 9 patients and under-IS with previous other IS-related toxicities in 1 patient. Mean estimated glomerular filtration rate after starting belatacept significantly improved at 6 months after initiation and at the last-follow-up (p = 0.006, and p = 0.002 respectively). The incidence of recurrent and/or severe acute cellular rejection (ACR) episodes was high in patients with CNI-free belatacept-based IS (n = 4/7). Chronic graft allograft dysfunction developed in 2 of 9 recipients under belatacept IS. Belatacept was stopped in 6 patients because of recurrent/severe ACR (n = 3), recurrent opportunistic infections (n = 1), center modified policy (n = 1), or other cause (n = 1). Early conversion to CNI-free belatacept-based IS improved renal function in this series but was counterbalanced by a high incidence of recurrent ACR, including life-threatening episodes. Other studies are needed to better determine the indications for its use after LTx, possibly with lower immunological risk IS regimens, such as CNI-sparing belatacept.

Drug-induced nephrotoxicity

Many drugs are nephrotoxic, affecting the kidneys by different mechanisms. Renal iatrogenicity mainly affects patients with risk factors. Measures to prevent drugs nephrotoxicity include using of non-nephrotoxic drugs whenever possible, dose adjustment if the drug cannot be replaced, avoiding the simultaneous use of several nephrotoxic drugs, correcting the risk factors related to the patient, assessing renal function at the beginning of the treatment and monitoring it during treatment.

MO1003ONSET OF BRAIN TOXOPLASMA GONDII ABSCESSES IN RENAL TRANSPLANT RECIPIENT IN THERAPY WITH BELATACEPT

Abstract Background Belatacept is a new non-nephrotoxic anti-rejection drug that blocks the CD80 / CD86-CD28 complex, that normally activates T lymphocytes. Although the BENEFIT study proposes its use at the forefront of immunosuppressive therapy to prevent renal transplant rejection, the risk of opportunistic infections should not be underestimated, as demonstrated by the following clinical case. Case report We report the case of a 71-year-old male kidney transplant recipient that at 7-month follow-up showed a relevant rise of serum creatinine up to 3.8 mg/dl related to graft rejection. The patient started a cycle of treatment with Belatacept in accomplishment to international studies, with improvement in renal function (serum creatinine: 2.8 mg/dl). After 8 months of therapy, due to the appearance of left brachio-crural hypoasthenia, a brain CT and a brain MRI (both without contrast media because of the severe graft dysfunction) were consecutively performed. Imaging revealed multiple nodular formations in the right hemisphere, compatible with brain abscesses or neuro-lymphoma. Belatacept was promptly suspended, a rachicentesis for liquor analysis performed, and a broad spectrum empiric antibiotic therapy was started on Infectious Disease Specialist advice. After Toxoplasma Gondii positivity was found by PCR on cerebrospinal fluid, neuro-lymphoma was excluded and the patient was switched to a targeted antibiotic therapy with Trimethoprim / Sulfamethoxazole (dose adjusted to renal function) for 6 weeks and subsequently, a maintenance course with Sulfadiazine and Pyrimethamine. During treatment, brain lesions showed progressive reduction, with marked clinical improvement and stabilization of renal function (eGFR 25 ml / min). Conclusions As far as is known in the literature, this is the first case of Toxoplasma Gondii brain infection that can be correlated with the use of Belactacept. The appearance of a severe opportunistic infection, in a short period of time after the introduction of Belatacept, could indicate the direct role of Belatacept in the development of these brain abscesses and indicates the importance of carefully evaluating the use of the drug in elderly patients with reduced renal function, in which adequate prophylactic therapy would be particularly indicated.

Retrospective Study of Acute Kidney Injury Incidence in Patients with Newly Diagnosed Acute Promyelocytic Leukemia.

PurposeAcute promyelocytic leukemia (APL) constitutes 5–10% of all cases of newly diagnosed acute myeloid leukemia. However, data on the epidemiology and risk factors for acute kidney injury (AKI) in patients with newly diagnosed APL are lacking. This study determined the incidence rate of AKI during induction chemotherapy for patients with newly diagnosed APL and the risk factors for AKI.Patients and MethodsWe conducted a retrospective observational study of patients with newly diagnosed APL in the Shonan Kamakura General Hospital between April 2004 and April 2020. Data of 27 patients with newly diagnosed APL were analyzed. The patients were classified as no AKI and AKI stages 1, 2 or 3.ResultsThe incidence rate of AKI during induction chemotherapy was 40% (11/27). Among patients who developed AKI, four patients experienced AKI stage 3, and two patients required renal replacement therapy. No significant differences were found in the white blood cell count and baseline renal function between the groups; however, D-dimer and C-reactive protein levels upon admission were significantly higher in patients with AKI than in patients without AKI. Among patients who developed AKI, in hospital mortality at 90 days was 36% (4/11), which was significantly higher than among patients without AKI (p = 0.02). Patients who developed AKI were administered vancomycin more frequently, while almost all blood culture results were negative.ConclusionIncidence of AKI development in patients with newly diagnosed APL during induction chemotherapy was approximately 40%. Moreover, patients who developed AKI tended to be administered vancomycin more frequently. Unnecessary use of vancomycin should be avoided in patients with newly diagnosed APL, and using alternative non-nephrotoxic drugs should be considered for patients at risk of AKI.

Nephroprotective Effects of Dioscoreaalata and Moriengaolifera on Cisplatin Induced Nephrotoxicity in Rats

Nephrotoxicity, which is caused by mostly due to medication, is one of most important global health problem. Drugs are a common source of acute kidney injury. Drugs shown to cause nephrotoxicity exert their toxic effects by one or more common pathogenic mechanisms. . Most drugs found to cause nephrotoxicity exert toxic effects by one or more common pathogenic mechanisms. These include altered intraglomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Drug-induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Cisplatin, one of the many drugs, is responsible for severe nephrotoxicity. General preventive measures to avoid nephrotoxicity include using alternative non-nephrotoxic drugs; correcting risk factors; assessing baseline renal function before initiation of therapy, followed by adjusting the dosage; monitoring renal function and vital signs during therapy; and avoiding nephrotoxic drug combinations, using of several nephroprotective agents including medicinal plant extracts. Promising results showed that the use of some medicinal plant extracts (Dioscoreaalata and Moriengaolifera) gave rise to moderate restoration of normal physiology of kidney and liver of mice.
 TAJ 2018; 31(1): 46-51

Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis.

Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Comorbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model. In patients suffering from hypertension, both median serum creatinine and blood urea nitrogen (BUN) were higher (81.9 versus 75.8 μmol/L, p < 0.001 and 6.0 versus 5.7 mmol/L, p = 0.005, respectively). Such a difference could not be observed in patients with diabetes. In patients with COPD, only serum creatinine was higher (81.1 versus 77.3 μmol/L, p = 0.004). In the whole cohort, we found that while at the time of lung cancer diagnosis the ratio of patients in the pathological range (PRR) was 8.67% for serum creatinine (median: 75 μmol/L) and 14.16% for BUN (median: 5.4 mmol/L), at the time of bone metastasis the PRR for serum creatinine increased to 16.11% (median: 77.0 μmol/L) and for BUN to 24.07% (median: 6.0 mmol/L), which is a significant increase for both parameters (p < 0.001). For the whole cohort, the last laboratory results showed a 26.37% PRR for serum creatinine and 45.66% PRR for BUN (significant increase for both, p < 0.001). Multivariate analysis revealed that patients with hypertension had a higher chance for switching to the pathological range sooner (p = 0.033, HR: 1.372, CI: 1.025-1.835). Also, the appearance of the bone metastasis correlated with an acceleration of the onset of such a switch (p < 0.001, HR: 2.655, CI: 1.581-4.456). Our results suggest that renal function is impaired in a significant proportion of patients with lung cancer and highlight the importance of non-nephrotoxic drug in the management of bone metastases.

Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis.

Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Co-morbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model. In patients suffering from hypertension, both median serum creatinine and blood urea nitrogen (BUN) were higher (81.9 versus 75.8 μmol/l, p<0.001 and 6.0 versus 5.7 mmol/l, p=0.005, respectively). Such a difference could not be observed in patients with diabetes. In COPD patients, only serum creatinine was higher (81.1 versus 77.3 μmol/l, p=0.004). In the whole cohort, we found that while at the time of lung cancer diagnosis the ratio of patients in the pathological range (PRR) was 8.67% for serum creatinine (median: 75 μmol/l) and 14.16% for BUN (median: 5.4 mmol/l), at the time of bone metastasis the PRR for serum creatinine increased to 16.11% (median: 77.0 μmol/l) and for BUN to 24.07% (median: 6.0 mmol/l), which is a significant increase for both parameters (p<0.001). For the whole cohort, the last laboratory results showed a 26.37% PRR for serum creatinine and 45.66% PRR for BUN (significant increase for both, p<0.001). Multivariate analysis revealed that patients with hypertension had a higher chance for switching to the pathological range sooner (p=0.033, HR: 1.372, CI: 1.025-1.835). Also, the appearance of the bone metastasis correlated with an acceleration of the onset of such a switch (p<0.001, HR: 2.655, CI: 1.581-4.456). Our results suggest that renal function is impaired in a significant proportion of lung cancer patients and highlight the importance of non-nephrotoxic drug in the management of bone metastases. This article is protected by copyright. All rights reserved.

Effect of an Early Switch to Belatacept Among Calcineurin Inhibitor-Intolerant Graft Recipients of Kidneys From Extended-Criteria Donors.

Transplant recipients receiving a kidney from an extended-criteria donor (ECD) are exposed to calcineurin inhibitor (CNI) nephrotoxicity, as demonstrated by severe delayed graft function and/or a low GFR. Belatacept is a nonnephrotoxic drug that is indicated as an alternative to CNIs. We reported 25 cases of conversion from a CNI to belatacept due to CNI intolerance within the first 6 mo after transplantation. The mean age of the recipients was 59 years, and 24 of 25 patients received ECD kidneys. At the date of the medication switch, 12 of 25 patients displayed a calculated GFR (cGFR) <15 mL/min, six patients remained on dialysis, and the biopsies showed evidence of acute tubular damage associated with severe vascular or tubulointerstitial chronic lesions. Three patients did not recover renal function, and three patients died during the follow-up period. Among the remaining patients, renal function improved: The cGFR was 18.28 ± 12.3 mL/min before the medication switch compared with 34.9 ± 14.5 mL/min at 1 year after conversion to belatacept (p = 0.002). Tolerance of and compliance with belatacept were good, and only one patient experienced acute rejection. Belatacept is an effective therapy that preserves renal function in kidney transplant patients who are intolerant of CNIs.

Detection of Drug-Drug Interactions Inducing Acute Kidney Injury by Electronic Health Records Mining.

While risk of acute kidney injury (AKI) is a well documented adverse effect of some drugs, few studies have assessed the relationship between drug-drug interactions (DDIs) and AKI. Our objective was to develop an algorithm capable of detecting potential signals on this relationship by retrospectively mining data from electronic health records. Data were extracted from the clinical data warehouse (CDW) of the Hôpital Européen Georges Pompidou (HEGP). AKI was defined as the first level of the RIFLE criteria, that is, an increase ≥50% of creatinine basis. Algorithm accuracy was tested on 20 single drugs, 10 nephrotoxic and 10 non-nephrotoxic. We then tested 45 pairs of non-nephrotoxic drugs, among the most prescribed at our hospital and representing distinct pharmacological classes for DDIs. Sensitivity and specificity were 50% [95% confidence interval (CI) 23.66-76.34] and 90% (95% CI 59.58-98.21), respectively, for single drugs. Our algorithm confirmed a previously identified signal concerning clarithromycin and calcium-channel blockers (unadjusted odds ratio (ORu) 2.92; 95% CI 1.11-7.69, p=0.04). Among the 45 drug pairs investigated, we identified a signal concerning 55 patients in association with bromazepam and hydroxyzine (ORu 1.66; 95% CI 1.23-2.23). This signal was not confirmed after a chart review. Even so, AKI and co-prescription were confirmed for 96% (95% CI 88-99) and 88% (95% CI 76-94) of these patients, respectively. Data mining techniques on CDW can foster the detection of adverse drug reactions when drugs are used alone or in combination.

Multiple Myeloma and Renal Failure

Renal failure (RF) occurs in approximately 20-30% of multiple myeloma (MM) patients at diagnosis and in more than 50% of patients with advanced disease. The pathogenesis of RF is related to the production of monoclonal light chains that can damage either the tubule (myeloma kidney) or the glomeruli (light chain deposition disease or amyloid light-chain amyloidosis). In the past, the prognosis of patients with MM and RF was considered poor due to the limited number of effective and non-nephrotoxic drugs that were available. At present, novel drugs acting both on MM clone and on bone marrow microenvironment have been introduced into clinical practice; among them, bortezomib-containing regimens have proved to be the most effective. High-dose myeloablative therapy followed by autologous stem cell rescue can also be proposed in younger patients with no other relevant comorbidities.

Drug-induced nephrotoxicity

Drug-induced nephrotoxicity is an extremely common condition and is responsible for a variety of pathological effects on the kidneys. Drug-induced acute renal failure (ARF) accounted for 20% of all ARF cases. Drugs showed to cause nephrotoxicity exert their toxic effects by one or more common pathogenic mechanisms. Although it is impossible to present all the drugs causing the nephrotoxicity, this article will summarize the mechanism of injury associated with particular common medications, discuss clinical presentations, renal markers, and evaluate strategies that prevent or minimize renal injury. Drug-induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patient-related risk factors, drug-related risk factors, and preemptive measures, coupled with vigilance and early intervention. General preventive measures include using alternative non-nephrotoxic drugs whenever possible; correcting risk factors, if possible; assessing baseline renal function before initiation of therapy, followed by adjusting the dosage; monitoring renal function and vital signs during therapy, and avoiding nephrotoxic drug combinations. Surprisingly, little information is available to guide us with respect to avoiding complications in critical illness; therefore, it is necessary to follow the guidelines.

Conversion to Everolimus in Liver Transplant Patients With Renal Dysfunction

Calcineurin inhibitor (CNI) immunosuppressive therapy post–liver transplantation (OLT) is important to reduce graft rejection episodes. However, these drugs show important side effects, particularly renal dysfunction (RDF). Changing from CNI to a nonnephrotoxic drug, as mammalian target of rapamycin (mTOR) inhibitor may solve the problem. Our objective was to evaluate renal function (RF) among liver transplant patients initially receiving CNI, among whom the patients with RDF were converted completely or partially to an mTOR inhibitor like everolimus (EVE). We performed a prospective study in liver transplant patients from 2000 to 2009. Creatinine levels and creatinine clearances (Cockroft-Gault) expressed as mean values ± standard deviations were measured pre- and postswitch for comparisons using Wilcoxon nonparametric tests. Six patients were converted fully or partially to EVE. Their mean age at the moment of introducing the new therapy was 52.2 ± 13.6 years (range = 28–60). Immunosuppression time prior to switching from CNI to EVE was 23.8 ± 26.6 months (range = 6–70). Postconversion follow-up was 25.8 ± 16.5 months (range = 8–42). All patients showed improvement in RF. The creatinine level improvement was significant (P = .03) namely, from a mean of 2.26 ± 0.49 to 1.21 ± 0.57 mg/dL. Glomerular filtration rate improved from a mean of 40 ± 15.13 to 72.60 ± 17.3 mL/min/m2 (P = .03). Conversion from CNI to EVE improved creatinine concentrations and creatinine clearances with long-term effects free of graft rejection.

Inmunosupresión en el trasplante hepático: pautas renoprotectoras

Both acute and chronic renal insufficiency are highly prevalent in liver transplant recipients. The etiology is multifactorial, with administration of nephrotoxic drugs playing a major role. Calcineurin inhibitors (CNI) (cyclosporin and tacrolimus) are the mainstay of immunosuppressive therapy in liver transplantation and produce acute and chronic nephrotoxicity. There are three main strategies to prevent renal injury: a) reduction of CNI to minimal levels accompanied by the use of an adjuvant drug such as azathioprine, mycophenolate mofetil or mammalian target of rapamycin (mTOR) inhibitors; b) complete withdrawal of CNI, using non-nephrotoxic drugs in their place; and c) use of protocols without CNI from the outset. The present article reviews these three strategies as well as their influence on renal function and on the results of liver transplantation.

Conversion From Calcineurin Inhibitor to Either Mycophenolate Mofetil or Sirolimus Improves Renal Function in Liver Transplant Recipients With Chronic Kidney Disease: Results of a Prospective Randomized Trial

Background Chronic kidney disease (CKD) has emerged as a significant cause of morbidity and a risk factor for mortality after orthotopic liver transplantation (OLT). The use of calcineurin inhibitor (CNI)-based immunosuppression is an important etiologic factor for developing CKD. CNI discontinuation or minimization protocols with replacement of the CNI with non-nephrotoxic drugs, such as mycophenolate mofetil (MMF) or sirolimus (SRL), may have the potential to preserve or recover renal function. Patients and Methods In this prospective, randomized, single-center study with CNI discontinuation, OLT recipients with CKD (measured glomerular filtration rate [GFRm] 15–45 mL/min/1.73 m 2) were randomized to either SRL or MMF-based immunosuppression. The main objective was to study the effect of CNI discontinuation on renal function. Secondary aims were to assess the frequency of biopsy-proven acute rejection episodes (BPAR) and adverse events (AE). Renal function was followed with GFRm using 51-Chromium EDTA clearance at baseline, 3 months, and 1 year. Patients were stratified according to baseline GFRm > versus <30 mL/min/1.73 m 2. The 25 patients were enrolled for MMF (n = 13) or SRL (n = 12). The median age at inclusion was 59 years (range, 25–66) and the median number of years after OLT was 4.4 (range, 1–13). Twenty-two patients were followed up for a year; MMF (n = 12) and SRL (n = 10). Results Mean GFRm for the whole cohort (n = 25) was 31+/−8 mL/min/1.73 m 2 at baseline. After 3 months the GFRm (n = 23) increased to 40+/−10 mL/min/1.73 m 2 ( P = .0001) and at 1 year 42 +/− 11 mL/min/1.73 m 2 (n = 22). There was not significant difference between the MMF and the SRL study arms. The cohort (n = 8) with baseline GFRm <30 mL showed a 63% ( P = .003) increased filtration after 1 year. There was no significant difference in the frequency or severity of AE between the study arms with the exception of oral ulcerations and persistent hypertriglyceridemia in the SRL group. Two deaths occurred, 1 in each study arm, both probably unrelated to the change in immunosuppression. There were no BPAR episodes. Conclusion CNI discontinuation and replacement with either MMF or SRL resulted in a significant improvement in renal function even in those patients with severe CKD. The protocol was effective with no acute rejection episodes. The SRL arm showed a higher frequency of oral apthous ulcerations and hypertriglyceridemia. Future studies addressing long-term renal function after CNI discontinuation are needed.

Remplacement des inhibiteurs de la calcineurine par des inhibiteurs du signal de prolifération après transplantation rénale : indications, résultats et inconvénients

In the kidney transplant patient, calcineurin inhibitor (CNI) treatment is a major risk factor for chronic allograft nephropathy (CAN). Immunosuppressive strategies based on non-nephrotoxic drugs such as proliferation signal inhibitors (PSIs) have been conceived to reduce or even interrupt CNIs. CNI conversion, with progressive cessation over 3 months with a PSI can significantly improve renal function, notably if the patient presents proteinuria less than 0.8 g/day and if conversion is undertaken early, when the glomerular filtration rate (GFR) is 40 ml/min or greater. In these conditions GRF improvement is associated with a histological CADI score and chronic lesion markers. Nevertheless, replacing CNIs with a PSI can occasionally induce proteinuria that is potentially related to direct toxicity of the PSI on the podocytes, which must be monitored to prevent recurrence of nephrotoxicity lesions.

Improvement of renal function after the switch from a calcineurin inhibitor to everolimus in liver transplant recipients with chronic renal dysfunction

Chronic renal dysfunction is a frequent and severe complication in solid-organ transplant recipients. Calcineurin inhibitors (CNIs) are the main pathogenic factors of renal dysfunction. Switching from CNIs to nonnephrotoxic drugs, such as mammalian target of rapamycin inhibitors (everolimus and sirolimus), can improve renal function in these patients, but available data about the efficacy and safety of everolimus in liver transplant recipients are scarce. Twenty-one liver transplant recipients (19 males, mean age = 60.6 +/- 7.8 years) with chronic renal dysfunction (creatinine >or= 1.5 mg/dL) were prospectively included. The basal creatinine values were 1.79 +/- 0.39 mg/dL (range = 1.50-2.90 mg/dL). The basal creatinine clearance, evaluated with the Cockroft-Gault formula, was 54.64 +/- 12.47 mL/minute. Everolimus was initiated at a dosage of 0.75 mg twice daily, with target levels of 3 to 8 ng/mL. The withdrawal of CNIs was initiated after the target levels of everolimus were reached. Periodic controls of the weight, arterial pressure, liver function tests, serum creatinine, everolimus levels, proteinuria, creatinine clearance, and glomerular filtration rate at days 30, 90, 180, and 360 were made. After a median follow-up of 19.8 months, the respective creatinine values at 30, 90, 180, and 360 days were 1.68 +/- 0.40 (P = 0.012 with respect to basal values), 1.67 +/- 0.34 (P = 0.107), 1.70 +/- 0.41 (P = 0.521), and 1.57 +/- 0.30 mg/dL (P = 0.047). The respective creatinine clearance values at 30, 90, 180, and 360 days were 58.64 +/- 16.50 (P = 0.013 with respect to basal values), 59.49 +/- 13.27 (P = 0.028), 59.82 +/- 16.83 (P = 0.124), and 64.46 +/- 16.79 mL/minute (P = 0.025). CNIs were withdrawn in 20 recipients (95.2%). Rejection was not detected in any case. In conclusion, the application in liver transplant recipients with chronic renal dysfunction of an immunosuppressive protocol with everolimus and the withdrawal of CNIs was associated with an initial improvement of renal function tests without an increase in the risk of rejection.

Minimiser l’insuffisance rénale avec les inhibiteurs du signal de prolifération chez les malades transplantés

Chronic renal dysfunction is a multifactorial and frequent event after organ transplantation. The measurement or the estimation of glomerular filtration rate is essential to detect early progressive renal dysfunction. Proliferation signal inhibitors are nonnephrotoxic immunosuppressive drugs which may be useful to minimize calcineurin inhibitors-related side effects through a conversion strategy. Most studies in the setting of kidney transplantation showed improvement in glomerular filtration rate as high than conversion was early. Proliferation signal inhibitors may be included quickly in new immunosuppressive regimen for liver transplanted patients with chronic renal dysfunction.

Mammalian Target of Rapamycin Inhibition Prevents Glomerular Hypertrophy in a Model of Renal Mass Reduction

Sirolimus (SRL) is a potent and specific immunosuppressive drug used in organ transplantation, as basic therapy or in combination with calcineurin inhibitors. Although SRL is a nonnephrotoxic drug, many reports have related its use with the development of proteinuria, especially after conversion. Therefore, the aim of this study was to elucidate the interrelation between early and late SRL administration on the development of glomerular hypertrophy and proteinuria in a model of renal mass reduction (RMR). Rats underwent 2/3 cryoablation of the left kidney and subsequent right nephrectomy (n=42) or sham operations (n=29). Two weeks before (early study) or 12 weeks after (late study) surgery, SRL or vehicle was administered three times weekly. Creatinine clearance and proteinuria were determined throughout the study, and a complete histologic analysis was performed at the end of the study. Treatment with SRL had no effect on creatinine clearance, independently of the administration time. Four weeks after RMR, a significant increase in proteinuria was observed. Proteinuria was stabilized after early and late SRL administration, whereas vehicle-treated animals showed a further increase in proteinuria. Glomerular hypertrophy was strongly associated with proteinuria, and early SRL introduction prevented glomerular enlargement. The histologic analysis showed less structural damage in the two groups of animals treated with SRL than in the control group. Although early SRL introduction blocked glomerular hypertrophy, SRL treatment revealed the potential to halt progression of proteinuria and histologic damage at any time of administration in a model of RMR.

Renal function evolution in cancer patients. Results of the IRMA-2 study

e20574 Background: In 2007, the IRMA-1 study reported the high prevalence of renal insufficiency (RI) in cancer patients. Because of this high frequency, the IRMA-2 study started to investigate the evolution of renal function in cancer patients. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005. Data included: sex, age, weight, serum creatinine (SCR), haemoglobinemia, type of tumour, metastasis (bone and/or visceral) anticancer drugs. Dialysis, myeloma and lymphoma patients were not included. Glomerular filtration rate was estimated with the abbreviated RD (aRD) formula at the inclusion. Patients were retrospectively followed during 2 years after the inclusion, every 6 months, from March 2005 (T0) to March 2007 (T24). Results: 4945 cancer patients (breast 1816, colorectal 747, lung 463, ovarian 294, prostate 251) were included in 19 cancer centre in France. Median age 60.0, mean weight 66.2, 62.8% were women. Mean GFR decreased from 90.8 ml/min/1.73m2 to 83.7 over the two years (table). Meanwhile, the prevalence of RI increased, reaching 62.9% and 17.5% for a GFR&lt;90 and &lt;60, respectively at T24 (table). Among the 4945 patients, 193 (7.6% of the 2525 patients who were alive at the end of the study) had a SCR determination at each time point. Among the 641 patients with a SCR at T0 and at T24, 41.6% of those with a GFR&gt;=90 at T0 had a GFR&lt;90 at T24. Furthermore, 17.7% of patients with mild renal insufficiency (60 to 90) at T0 had a GFR&lt;60 at T24. Conclusions: IRMA-2 shows that renal function decreases rapidly in cancer patients with a loss in GFR of more than 3.5 mL/min/1.73m2 per year. This suggests that cancer patients are more exposed to a deterioration of renal function and that it should be closely monitored with at least a regular estimation of renal function, for instance every 6 months. So far, such a follow-up is not performed in clinical practice. Furthermore, drug therapy should be reevaluated, dosages adjusted when necessary, and some potentially nephrotoxic drugs changed for less or non-nephrotoxic drugs if possible. No significant financial relationships to disclose.

Actualización en el tratamiento del herpes zóster

The systemic treatment of herpes zoster shortens the healing process, and prevents or alleviates pain and other acute or chronic complications, especially when it is administered in the first 72 hours after symptoms appear. This treatment is especially indicated in patients over the age of 50 and in those who, regardless of age, have head and neck involvement, especially in herpes zoster ophthalmicus. The drugs approved in Europe for the systemic treatment of herpes zoster are aciclovir, valaciclovir, famciclovir and brivudine. Brivudine shows greater effectiveness against the varicellazoster virus than aciclovir and its derivatives, and can be given just once a day for seven days, compared to multiple doses of the latter. As opposed to the others, brivudine is a nonnephrotoxic drug that should not be administered to immunodepressed patients or to those being treated with 5-fluorouracil. The treatment of herpes zoster to reduce pain should be combined with analgesics and neuroactive agents (amitriptyline, gabapentin, etc.). While corticosteroids are of dubious efficacy in the treatment of post-herpes neuralgia, the intensity and duration of the pain can be reduced with some topical treatments (capsaicin, lidocaine patches, etc.). Finally, this review discusses treatment guidelines for special locations (cranial nerves) and different subpopulations (children, pregnant women, immunodepressed patients, etc.).