Renal Dose Research Articles

Implications of using modification of diet in renal disease versus Cockcroft–Gault equations for renal dosing adjustments

The drug-dosing implications of using modification of diet in renal disease (MDRD) versus Cockcroft-Gault equations were analyzed. This retrospective, cohort-controlled study evaluated the implications of using MDRD versus Cockcroft-Gault equations for renal dosing adjustments in patients with stage III-V chronic kidney disease. Dosing simulations were completed for each patient using both MDRD and Cockcroft-Gault methods and then compared to published manufacturer dosing recommendations. Bland-Altman analysis assessed agreement of MDRD and Cockcroft-Gault estimates. Contingency tables were used to evaluate the clinical relevance of dosing adjustments in terms of medication overdoses and underdoses. Data from 4698 patients with stage III-V chronic kidney disease were analyzed. Use of the MDRD equation overestimated the need for dosing adjustments for patients with creatinine clearance (CL(cr)) values of <30 mL/min/1.73 m(2) and underestimated the need for patients with a CL(cr) of >50 mL/min/1.73 m(2). For medication-dosing thresholds, MDRD was associated with an underdose rate of 7.3% and an overdose rate of 9.6% (p < 0.01 for both). For MDRD adjustments within medication-dosing ranges, both overdoses and underdoses occurred in up to 12.4% (p < 0.01). Total dosing errors for MDRD ranged from 9.8% to 18.2%, depending on the medication (p < 0.01). Significant variability exists between the MDRD and Cockcroft-Gault equations for spot dosing adjustments. Use of MDRD estimates with current manufacturer dosing guidelines may result in subtherapeutic medication therapies for patients with stage IV or V disease and supratherapeutic therapies for patients with stage III disease.

In Vitro Inhibition of Platelet Aggregation in Response to Increasing Concentrations of Tirofiban in Patients with Significant Renal Insufficiency

Patients with impaired renal function are a growing subset at higher risk for cardiovascular complications due to vasculopathic state, inducing accelerated atherosclerosis and arteriosclerosis. These patients are at increased risk for complications after coronary interventions, especially major bleeding events. As a result, this at-risk population of patients has not been well studied in most of the major clinical trials evaluating coronary interventions. Of particular interest is the optimal dosing of glycoprotein IIb-IIIa inhibitors in the setting of acute myocardial infarction. In this study, we attempted to find the in vitro concentration of tirofiban required to inhibit platelet aggregation to <10% in patients with moderate to severe renal insufficiency. A total of 21 patients were divided into two groups based on estimated creatinine clearance (group 1 <46ml/min; group 2 >46ml/min). Platelet-rich plasma from each subject was then incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), and light transmission aggregometry assay was used to assess the degree of platelet aggregation in response to adenosine diphosphate (ADP). Patients in group 1 had a baseline platelet aggregation of 45%, which decreased to 10% at a 25.0ng/ml concentration of tirofiban; the effect was enhanced to a platelet aggregation of <5% at higher doses. In contrast, subjects in group 2 with creatinine clearance >or=46ml/min had an average platelet aggregation inhibition of 12% with 50ng/ml of tirofiban.We found a significant decrease in platelet aggregation in group 2 at 25, 37.5, and 50ng/ml of tirofiban (p<0.05) in comparison with group 1. Our data indicate that patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.We suggest further clinical trials to define an objective means to calculate proper renal dosing of glycoprotein IIb-IIIa inhibitors in these patients to prevent potentially fatal complication of major hemorrhagic events.

Prevención de acontecimientos adversos mediante ajuste posológico renal en pacientes ancianos institucionalizados

Introduction To present a protocol based on renal dosage adjustment developed to reduce the risk of adverse events in elderly people institutionalized in a geriatric centre and to determine the degree of adaptation to this protocol. Material and method First, we designed a renal adjustment protocol to identify residents with creatinine clearance below 60 ml/min, review drug therapy and optimize dosage regimens, if necessary. Then, we evaluated the feasibility of this protocol and adaptation of clinical practice to this protocol through a cross-sectional study of all the residents in the centre. Results Among the 163 residents assessed by Cockroft-Gault, there were 126 residents with creatinine clearance below 60 ml/min (77%; 95% CI, 70–83). Seventeen residents were excluded due to intake of protein supplements or to extreme body mass index. Once the treatments were reviewed, 152/876 (17%; 95% CI, 15–20) prescriptions suitable for renal adjustment were found. In 135/152 prescriptions (89%; 95% CI, 83–93) the dosage was appropriate to creatinine clearance and 17 (11%; 95% CI, 6–17) were considered as potentially optimizable. For these 17 prescriptions, a proposal for dosage adjustment or monitoring was made, which was accepted in 16 cases and rejected in 1 case (metformin in a patient with 44 ml/min creatinine clearance and poor glycemic control). Conclusions A high percentage of the institutionalized elderly have a creatinine clearance below 60 ml/min. Given that a not inconsiderable proportion of their prescribed medication is susceptible to renal adjustment, the implementation of a protocol for renal adjustment and renal function follow-up could help to reduce the risk of adverse events.

Paliperidone ER - A novel antipsychotic

Paliperidone ER is metabolite of risperidone (9-hydroxy-risperidone) formulated as OROS extended release system, which facilitates its once daily use and improves treatment compliance. It is indicated not only in schizophrenia but also in schizoaffective disorder and bipolar mania. Due to lack of interactions of CYP enzymes, minimal or no pharmacological interactions are evident. Due to favorable pharmacodynamic profile i.e. antagonism of 5HT 2A , �± 1 and D2; it has improved positive and negative symptoms (reduction in PANSS score), reduced extra pyramidal side effects and efficacy. Only renal failure patients demand dose reduction. In various therapeutic trials, paliperidone ER has shown better efficacy than placebo and olanzapine, also delays symptoms recurrence of schizophrenia. Paliperidone ER has caused various adverse effects like akathisia, headache, increase serum prolactin level and weight gain but serum lipid, glucose and insulin level remained unaffected. Paliperidone ER has increased the number of annual stable days and more cost effective than other atypical antipsychotics.

Impact of Pharmacy-Generated Recommendations on Antibiotic Therapy in a Community Hospital

Purpose To examine the impact of a pharmacy-initiated antibiotic review service on the appropriateness of antibiotic therapy at a community hospital. Methods A retrospective review was conducted that assessed antibiotic prescribing before implementation of an antibiotic review service, followed by an interventional phase that assessed the impact of pharmacy-generated recommendations. Medical records were evaluated for appropriateness of antibiotic therapy. For records reviewed retrospectively, potential recommendations for improvement of antibiotic appropriateness were documented. Potential recommendations were based on evidence-based practice guidelines and pertained to organism susceptibilities, renal dosage adjustments, intravenous-to-oral conversion, duplication, duration, and indication for therapy. During the interventional phase, recommendations were directed to the prescribing physician via telephone or written communication. Patient charts were revisited regularly to assess for potential new recommendations and to determine acceptance of previous recommendations. Results At initial review, 95 (59%) orders reviewed retrospectively were considered appropriate. A total of 73 potential recommendations for improving appropriateness of retrospective orders were recorded. At completion of follow-up, overall appropriateness of retrospective orders decreased to 57%. Prospectively, 115 (57%) orders were considered appropriate at initial review. Physicians accepted 39 (71%) of the 55 recommendations generated for improving appropriateness of these orders. Pharmacy-generated recommendations were successful in improving the number of appropriate prospective orders by 13% ( P = 0.004) and identified a cost savings of approximately $12,000. Conclusion The pharmacy-initiated antibiotic review service has been well accepted by physicians and appears to have a positive impact on the number of appropriately prescribed antibiotic orders. Complete implementation of this review service may demonstrate greater impact.

Treatment of Patients with Relapsed/Refractory Multiple Myeloma (MM) with Lenalidomide and Dexamethasone with or with Bortezomib Depending on Prior Neurotoxicity: Prospective Evaluation of the Impact of Cytogenetic Abnormalities and Assessment of Bone Met.

Lenalidomide and dexamethasone (RD) is an effective combination for patients with relapsed/refractory MM and the addition of bortezomib (BRD) may be associated with improved activity. In an ongoing prospective study patients with pre-existing peripheral neuropathy grade <2 receive BRD and those with grade ≥ 2 receive RD. Purposes of this study: 1) Inclusion of patients with renal impairment and dosing of lenalidomide according to a proposed normogram; 2) impact of cytogenetic abnormalities on response and progression; 3) evaluation of bone metabolism markers before and after treatment. Up to July 2008, 53 patients have been included regardless of their performance status and renal function; the only exclusion criterion is prior treatment with lenalidomide. Patients with prior neuropathy grade<2 receive B at a dose 1 mg/m2 on days 1, 4, 8 and 11, R at a dose of 15 mg daily for 14 days (or at a lower dose if creatinine clearance (CrCl) <30 ml/min) and D 40 mg PO on days 1 to 4. Courses are repeated every 21 days. Patients with prior neuropathy grade 32 receive R on days 1 to 21 according to creatinine clearance (25 mg/day for CrCl>50 ml/min, 10 mg/day for CrCl 30–50 ml/min, 15 mg every other day for CrCl 15–30 ml/min, and for patients on dialysis 15 mg three times per week on the day after dialysis) and D 40 mg PO on days 1–4 and 15–18 for the first 4 cycles and only on days 1–4 thereafter, every 28 days. At baseline, conventional metaphase cytogenetics and FISH (after cell sorting) for del13q, del17p, add1q21, t (4;14), t (14;16) is performed in all patients. All patients receive DVT prophylaxis with aspirin 100 mg unless they were already on coumadine or LMWH for pre-existing DVT or for other indications, mainly atrial fibrillation. So far 23 patients have received BRD and 30 patients RD. Median time from first treatment to this study is 35 months (range 3–217) and median number of prior treatments are 3 (range 1 to 8). Prior treatment with thalidomide (thal): 85% (53% thal resistant), prior treatment with B: 83% (45% B resistant), prior treatment with D: 100% (D resistant (65%), presence of at least one adverse cytogenetic abnormality by FISH in 45.5%, non-hyperdiploid karyotype in 23%. Thirty percent of patients had baseline CrCl < 50 ml/min, LDH>300 IU/dL (normal <225 IU/dL) in 19%, ISS 3 in 34%. Patient characteristics and cytogenetic findings were similar among BRD and RD treated patients with the exception of more B-pretreated patients in BRD. On intent to treat basis, 48 patients are evaluable for response so far: 52% achieved at least a PR (31% PR, 13% VGPR, 8% CR). Response after BRD and RD was 52% for both. Response in thal-resistant and B-resistant patients: 32% and 50% respectively. At least a PR according to del13q, del17q, t(4;14), add1q21 was documented in 33%, 17%, 33% and 27% of patients respectively, in 80% of patients with hyperdiploid and in 10% with a non-hyperdiploid karyotype (p=0.007). Among 41 patients on low-dose aspirin, only one developed DVT. Hematologic toxicities≥G3 included anemia (19%), thrombocytopenia (17%), neutropenia (32%). In patients receiving RD deterioration of neuropathy was recorded in 27%. After BRD, 35% of patients experienced Grade 32 neuropathy. Other common toxicities included infections (≥G3 in 17%) and fatigue (≥G3 in 21%). Variables associated with shorter time to progression included thalidomide resistance, high LDH, non-hyperdiploid karyotype and FISH abnormality. After treatment with either RD or BRD, RANKL serum levels as well as markers of bone resorption (CTX and TRACP-5b) were significantly reduced. However, the reduction of RANKL and RANKL/osteoprotegerin ratio was higher after BRD than after RD (p=0.02). BRD patients also reduced dickkopf-1 (Dkk-1) serum levels, while RD patients showed a slight increase of serum Dkk-1 [p (BRD vs. RD)=0.01]. In only BRD patients an increase in bone formation markers (bALP and osteocalcin; p=0.01) was shown. We conclude that RD and BRD may be active in several patients with thal and/or B resistance. These regimens are clearly more active in patients with hyperdiploid karyotypes and they may overcome to a certain extend the adverse prognosis of cytogenetic abnormalities detected by FISH but not that of del17p. Low-dose aspirin prophylaxis is effective. The addition of bortezomib to RD is associated with higher anti-osteoclastic effect and with enhanced osteoblastic activity.

Response to Letter Regarding Article, “Renal Vasodilatory Action of Dopamine in Patients With Heart Failure: Magnitude of Effect and Site of Action”

HomeCirculationVol. 118, No. 17Response to Letter Regarding Article, “Renal Vasodilatory Action of Dopamine in Patients With Heart Failure: Magnitude of Effect and Site of Action” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter Regarding Article, “Renal Vasodilatory Action of Dopamine in Patients With Heart Failure: Magnitude of Effect and Site of Action” Uri Elkayam, Tien M.H. Ng, Parta Hatamizadeh, Munir Janmohamed and Anilkumar Mehra Uri ElkayamUri Elkayam Division of Cardiology, University of Southern California, Keck School of Medicine, Los Angeles, Calif Search for more papers by this author , Tien M.H. NgTien M.H. Ng Division of Cardiology, University of Southern California, Keck School of Medicine, Los Angeles, Calif Search for more papers by this author , Parta HatamizadehParta Hatamizadeh Division of Cardiology, University of Southern California, Keck School of Medicine, Los Angeles, Calif Search for more papers by this author , Munir JanmohamedMunir Janmohamed Division of Cardiology, University of Southern California, Keck School of Medicine, Los Angeles, Calif Search for more papers by this author and Anilkumar MehraAnilkumar Mehra Division of Cardiology, University of Southern California, Keck School of Medicine, Los Angeles, Calif Search for more papers by this author Originally published21 Oct 2008https://doi.org/10.1161/CIRCULATIONAHA.108.780817Circulation. 2008;118:e676Drs Lema and Canessa point out the important intersubject variability of plasma levels of dopamine, which has been shown in normal volunteers. These differences may also be related to the interpatient variability in dopamine dose producing the largest effect on renal blood flow. In our study,1 5 patients demonstrated a maximal increase in renal blood flow at a dopamine dose ≤3 μg · kg−1 · min−1, whereas 3 patients demonstrated a maximal increase in renal blood flow at a dose of 5 μg · kg−1 · min−1, and 5 patients demonstrated a maximal increase in renal blood flow at dose of 10 μg · kg−1 · min−1. The majority of the patients, therefore, exhibited the greatest response to dopamine at doses greater than the traditional “renal dose.”DisclosuresNone.Reference1 Elkayam U, Ng TM, Hatamizadeh P, Janmohamed M, Mehra A. Renal vasodilatory action of dopamine in patients with heart failure: magnitude of effect and site of action. Circulation. 2008; 117: 200–205.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails October 21, 2008Vol 118, Issue 17 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.108.780817 Originally publishedOctober 21, 2008 PDF download Advertisement SubjectsCardiorenal Syndrome

Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction

The liver plays a central role in the pharmacokinetics of the majority of drugs. Liver dysfunction may not only reduce the blood/plasma clearance of drugs eliminated by hepatic metabolism or biliary excretion, it can also affect plasma protein binding, which in turn could influence the processes of distribution and elimination. Portal-systemic shunting, which is common in advanced liver cirrhosis, may substantially decrease the presystemic elimination (i.e., first-pass effect) of high extraction drugs following their oral administration, thus leading to a significant increase in the extent of absorption. Chronic liver diseases are associated with variable and non-uniform reductions in drug-metabolizing activities. For example, the activity of the various CYP450 enzymes seems to be differentially affected in patients with cirrhosis. Glucuronidation is often considered to be affected to a lesser extent than CYP450-mediated reactions in mild to moderate cirrhosis but can also be substantially impaired in patients with advanced cirrhosis. Patients with advanced cirrhosis often have impaired renal function and dose adjustment may, therefore, also be necessary for drugs eliminated by renal exctretion. In addition, patients with liver cirrhosis are more sensitive to the central adverse effects of opioid analgesics and the renal adverse effects of NSAIDs. In contrast, a decreased therapeutic effect has been noted in cirrhotic patients with beta-adrenoceptor antagonists and certain diuretics. Unfortunately, there is no simple endogenous marker to predict hepatic function with respect to the elimination capacity of specific drugs. Several quantitative liver tests that measure the elimination of marker substrates such as galactose, sorbitol, antipyrine, caffeine, erythromycin, and midazolam, have been developed and evaluated, but no single test has gained widespread clinical use to adjust dosage regimens for drugs in patients with hepatic dysfunction. The semi-quantitative Child-Pugh score is frequently used to assess the severity of liver function impairment, but only offers the clinician rough guidance for dosage adjustment because it lacks the sensitivity to quantitate the specific ability of the liver to metabolize individual drugs. The recommendations of the Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to study the effect of liver disease on the pharmacokinetics of drugs under development is clearly aimed at generating, if possible, specific dosage recommendations for patients with hepatic dysfunction. However, the limitations of the Child-Pugh score are acknowledged, and further research is needed to develop more sensitive liver function tests to guide drug dosage adjustment in patients with hepatic dysfunction.

An Easy Irradiation Technique (Partial Half-Beam) to Reduce Renal Dose in Radiotherapy of Cervical Cancer Including Paraaortic Lymph Nodes

: For radiation treatment of patients with cervical cancer and a high risk for paraaortic lymph node involvement, an easy three-dimensional (3-D) conformal irradiation technique (partial half-beam [PHB]) for protection of organs at risk, especially of renal tissue, was developed. : In five consecutive female patients a computed tomography scan was performed. Dose-volume histograms of the renal tissue and other organs at risk were analyzed for PHB, three other 3-D conformal techniques, and an intensitymodulated radiotherapy (IMRT) technique. : The PHB technique reduced the renal volume and volumes of other organs at risk exposed to radiation doses when comparing all patients to the other 3-D conformal techniques. With use of the IMRT technique more renal tissue volume received very low radiation doses (</= 6.8 Gy) whereas the D(10)was lower than with the PHB technique. : In female patients with cervical cancer and high risk for paraaortic lymph node involvement, the use of the PHB technique is recommended to reduce renal radiation exposure, if no IMRT technique should be applied. The PHB technique is very easily and fast applicable.

Estimation of renal function and its potential impact on carboplatin dosing in children with cancer

Renal function-based carboplatin dosing is used routinely in paediatric oncology clinical practice. It is important that accurate assessments of renal function are carried out consistently across clinical centres, a view supported by recently published British Nuclear Medicine Society (BNMS) guidelines for measuring glomerular filtration rate (GFR). These guidelines recommend the use of a radioisotope method for GFR determination, with between two and five blood samples taken starting 2 h after radioisotope injection and application of the Brochner-Mortensen (BM) correction factor. To study the likely impact of these guidelines, we have investigated current practices of measuring GFR in all 21 Children's Cancer and Leukaemia Group (CCLG) paediatric oncology centres in the United Kingdom. This information was used to evaluate the potential impact on renal function-based carboplatin dosing using raw 51Cr-EDTA clearance data from 337 GFR tests carried out in children with cancer. A questionnaire survey revealed that between two and four samples were taken after isotope administration, with BM and Chantler corrections used in 38% (8/21) and 28% (6/21) of centres, respectively. A change from Chantler to BM correction, based on the BNMS guidelines, would result in a >10% decrease in carboplatin dose in at least 15% of patients and a >25% decrease in 2% of patients. A greater proportion of patients would have an alteration in carboplatin dose when centres not using any correction factor implement the BM correction. The increase in estimated 51Cr-EDTA half-life observed by omitting the 1 h sample decreases carboplatin dose by >10% in 23–52% of patients and by >25% in 3% of patients. This study highlights current variations in renal function measurement between clinical centres and the potential impact on carboplatin dosing. A standard methodology for estimating GFR should be followed to achieve uniform dosing in children with cancer.

GIPERPARATIREOZ POSLEALLOTRANSPLANTATsII TRUPNOY POChKII ORTOTOPIChESKOY TRANSPLANTATsII SERDTsA

Analyses of frequency, rate, main rise mechanisms of hyperparatyroidism and its role in bone losses were estimated in crossmatch research of 158 kidney and 25 heart recipients. Hyperparathyroidism frequency was more following kidney then heart transplantation (74% vs 36%, p=0,000), PTH level being higher in kidney recipients and in women higher then in men with kidney transplant. Hyperparathyroidism in women was associated with hemodialysis duration before operation and the estrogen level which was more in pre- then in postmenopause while PTH level was lesser in pre- then postmenopause. In men PTH level as in heart as in kidney groups was associated with renal function and cumulative prednisolone doses. Hyperparathyroidism in men and women after kidney transplantation followed aхial BMD losses so as in men after kidney and heart transplantation -periferal skeleton (femoral neck) BMD losses.

Improper Renal Dosing in Long-Term Care Facilities

With advancing age, physiologic changes occur that affect drug metabolism. Possibly the most predictable function decline in geriatric population is renal function. The prescribing habits of physicians and the attention given to patient renal function was investigated. Data was collected from two nursing facilities in southeastern Georgia. Based on two models of prescribing habits and using logistic regression estimates, we concluded that physicians do not follow recommendations for dose adjustment of renally excreted medications in these two facilities. We recommend that physicians consider evaluating current medications and establishing a base line for renal function and degree of decline.

Costs Associated with Developing and Implementing a Computerized Clinical Decision Support System for Medication Dosing for Patients with Renal Insufficiency in the Long-term Care Setting

A team of physicians, pharmacists, and informatics professionals developed a CDSS added to a commercial electronic medical record system to provide prescribers with patient-specific maximum dosing recommendations based on renal function. We tracked the time spent by team members and used US national averages of relevant hourly wages to estimate costs. The team required 924.5 hours and $48,668.57 in estimated costs to develop 94 alerts for 62 drugs. The most time intensive phase of the project was preparing the contents of the CDSS (482.25 hours, $27,455.61). Physicians were the team members with the highest time commitment (414.25 hours, $25,902.04). Estimates under alternative scenarios found lower total cost estimates with the existence of a valid renal dosing database ($34,200.71) or an existing decision support add-on for renal dosing ($23,694.51). Development of a CDSS for a commercial computerized prescriber order entry system requires extensive commitment of personnel, particularly among clinical staff.

Low-molecular-weight heparin in patients with chronic renal insufficiency

Low-molecular-weight heparin (LMWH) has largely replaced unfractionated heparin for the treatment of venous thromboembolism. The predictable anticoagulant effect of LMWH is seen across almost all patient populations, with few exceptions. However, because LMWH is primarily eliminated through the kidneys, patients with renal insufficiency are at risk of LMWH accumulation and bleeding complications. The risk of LMWH accumulation and bleeding is dependent on several factors including the degree of renal insufficiency, dose and type of LMWH. These risks are greatest when therapeutic doses of LMWH are used in patients with creatinine clearance less than 30 ml/min. Prophylactic dose LMWH does not appear to be associated with an increased bleeding risk, but has not been evaluated in large trials. LMWHs with a higher molecular weight may be less prone to accumulation and bleeding. LMWH must be used carefully in patients with renal insufficiency, particularly in those with severe renal impairment.

Abciximab: a review and update for clinicians

The glycoprotein (GP) IIb/IIIa receptor serves as the final common pathway of platelet-thrombus formation. Thus, the GP IIb/IIIa receptor has been identified as a target for the prevention of thrombus formation during acute coronary syndromes and/or percutaneous coronary intervention. While there are several intravenous GP IIb/IIIa inhibitors available, abciximab has proven to be a dependable agent with unique properties. Based on American College of Cardiology, American Heart Association and Society for Angiography and Interventions guidelines, compared with the other available intravenous GP IIb/IIIa inhibitors, abciximab receives the highest recommendation for use in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Abciximab is also unique in that there is no need for renal dosing and its effects are mostly reversible with platelet transfusions.

Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors

Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours with (90)Y-DOTATOC and (177)Lu-DOTATATE is promising. The kidney is the critical organ and despite renal protection, function loss may become evident years later. The aim of this study was to analyse renal parameters in patients who had undergone dosimetry before PRRT. Among those in protocols at our institution, 28 patients were considered: 23 received (90)Y-DOTATOC (3.8-29.2 GBq, median 12.2) and five received (177)Lu-DOTATATE (20.7-29.2 GBq, median 23.2). Patients were followed up after therapy for creatinine and creatinine clearance loss (CCL) for 3-97 months (median 30). Renal doses and bio-effective doses (BED) were calculated (MIRD, LQ model). After (90)Y-DOTATOC toxicity on creatinine according to NCI criteria occurred in nine cases (seven grade 1, one grade 2, one grade 3), CCL at 1 year was >5% in 12 cases and >10% in eight. A 28-Gy BED threshold was observed in patients with risk factors (mainly hypertension and diabetes), while it was 40 Gy in patients without risk factors. Probably due to the low number of patients, despite the absence of severe toxicity after hyper-fractionated PRRT, clear correlations between fractionation and toxicity could not be found. After (177)Lu-DOTATATE, no toxicity occurred in 1-2 year follow-up; CCL at 1 year >5% occurred in three patients and >10% in two. Our results indicate the importance of clinical screening for risk factors: In this case, a BED <28 Gy is recommended. Fractionation of therapy is important in order to decrease toxicity, and further studies are needed to evaluate its clinical impact.

Overdose Rate of Drugs Requiring Renal Dose Adjustment: Data Analysis of 4 Years Prescriptions at a Tertiary Teaching Hospital

To determine the overdose rate of drugs that require renal dose adjustment and factors related with overdose. Total of 23,635,210 records of prescriptions and laboratory data of inpatients at a tertiary teaching hospital for the period from January 2002 to December 2005. A clinical data mart was constructed. A knowledge base containing dose adjusting information about 56 drugs was built. One day dose was compared to the reference dose adjusted to the patient's renal function. Considering the patient's renal function, 5.3% of drug doses were excessive. The overdose rate in the patients with moderate to severe renal insufficiency was 28.2%. Only 25% of physicians were responsible for 50.6% of the overdoses. Of 56 drugs studied, 10 drugs, including ranitidine, amoxicillin, and piperacillin/tazobactam, were involved in 85.4% of the overdoses. The physicians with high overdose rate had patients with more impaired renal function (correlation coefficient = 0.192, P < .001). There were negative correlation between clinical experiences of physician and overdose rate (correlation coefficient = -0.221, P < .001) and workload of prescription (correlation coefficient = -0.446, P < .001), when excluding interns from the analyses. There was positive correlation between workload of prescription and overdose rate (correlation coefficient = 0.361, P < .001). A clinical data mart was useful to analyze the vast amount of electronic hospital data. Drug overdose is quite common among inpatients with renal insufficiency. Only a few drugs are responsible for most of drug overdoses. The physicians' clinical experience, workload of prescriptions, and patients' renal function are correlated with drug overdose.

Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age > or =18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.

Rx Report

Rx Report

Renal Vasodilatory Action of Dopamine in Patients With Heart Failure

BACKGROUND: A "renal dose" of dopamine is often used to increase renal blood flow; however, data on the magnitude of effect and site of action in patients with heart failure are scarce. METHODS AND RESULTS: Renal effects of intravenous dopamine (1, 2, 3, 5, and 10 mug . kg(-1) . min(-1)) were evaluated in 13 patients with chronic heart failure. Renal blood flow was calculated from renal artery cross-sectional area measured with intravascular ultrasound and renal blood flow velocity-time integral measured by the intravascular Doppler technique. Cross-sectional area increased and was significantly higher than baseline (0.30+/-0.04 cm(2)) at 5 mug . kg(-1) . min(-1) (0.36+/-0.05 cm(2)) and 10 mug . kg(-1) . min(-1) (0.38+/-0.06 cm(2)). The velocity-time integral was significantly higher than baseline (22+/-3 cm) at doses of 3 and 5 mug . kg(-1) . min(-1) (both 31+/-4 cm). Renal blood flow increased, whereas renal vascular resistance decreased, reaching statistical significance at 2 mug . kg(-1) . min(-1) through 10 mug . kg(-1) . min(-1). Cardiac output gradually increased, reaching statistical significance at doses of 5 and 10 mug . kg(-1) . min(-1) (5.5+/-0.5 and 6.1+/-0.7 versus 4.5+/-5.2 L/min at baseline), but the increase in renal blood flow appeared proportionately larger than corresponding increases in cardiac output. CONCLUSIONS: Dopamine is associated with an increase in renal blood flow in patients with heart failure. This effect is due to dilation of both the large conductance and small resistance renal blood vessels. Further evaluation of the efficacy and safety of dopamine for improvement of renal function in hospitalized patients with heart failure is warranted.