The importance of correct estimation of renal function for drug treatment in hospitalized elderly patients, especially women: A prospective observational study
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AIM: To compare renal function by several GFR formulas (particularly cystatin C eGFR-"CAPA") in relation to renal risk drugs (RRDs) in patients admitted to two geriatric wards in a university geriatric department. MATERIALS AND METHODS: This was a prospective quality improvement study including 108 patients, 2/3 women, age ≥ 75 years, admitted with multimorbidity. Renal function tests were performed with Cockcroft & Gault with uncalibrated (C&Guc) and calibrated creatinine (C&Gcc), and 3 - 4 points' iohexol clearance (mGFR) in mL/min, and eGFR with MDRD4, CKD-EPI, CAPA, and BIS2 clearance in mL/min/1.73m2. Agreement was tested by Bland & Altman analysis. The number and type of RRDs were analyzed. RESULTS: Measured GFR, C&Gcc, and C&Guc were mean 37, 39, and 32 mL/min, respectively. Estimated GFR by MDRD4, CKD-EPI, CAPA, and BIS2 were mean 56, 52, 45, and 40 mL/min/1.73m2, respectively. Compared to mGFR, women had significantly higher clearance for all estimates except for C&Gcc and C&Guc. C&Gcc, C&Guc, and BIS2 showed the lowest bias. 38 RRDs were identified. 96 patients used a mean of 2.3 RRDs per patient, and 1.7 RRDs needed dose adjustments. Cardiovascular drugs and analgesics were the most frequent RRDs. DISCUSSION: The C&Gcc, C&Guc, and BIS2 equations gave the best estimate of kidney function in relation to mGFR for drug dosing in the elderly. The eGFR methods showed significantly higher clearance than mGFR, C&Gcc, C&Guc, and BIS2. RRDs that needed dose adjustment were common in this geriatric population. If the eGFR formulas (MDRD4, CKD-EPI, and CAPA) are used instead of C&Gcc, C&Guc, and BIS2, higher and potentially more risky doses of RRDs may be administered to geriatric patients over 75 years, women in particular.

Pharmacokinetics of transdermal buprenorphine patch in the elderly.

PURPOSE: Transdermal buprenorphine patches provide comparable pain relief to that of low-potency opioids in elderly individuals. However, specific data on their use in elderly individuals is limited. This study investigated and compared the PK of buprenorphine transdermal patches in elderly (≥ 75 years) versus younger (50-60 years) individuals. METHODS: This was a multiple-dose, open-label, parallel-group study in healthy volunteers split into two age groups (younger, 50-60 years; elderly, ≥ 75 years) with 37 individuals in each. Study participants received two consecutive 7-day buprenorphine 5 µg/h transdermal patch applications, and blood samples were collected on the week of the second patch application [day 7 (predose), days 8, 9, 10, 12, and 14] to determine PK at steady state. Pharmacokinetic parameters were determined for buprenorphine and norbuprenorphine. Safety was assessed by analyzing adverse events, hematology, clinical chemistry, urine analysis, vital signs, electrocardiogram (ECG), and physical examinations. RESULTS: The area under the plasma concentration-time curve at steady state (AUC(tau)), measured over one dosing interval, was similar for elderly [mean ± standard deviation (SD) 9,940 pg/h/ml (4,827 pg/h/ml] and younger [mean ± SD 11,309 (3,670 pg/h/ml] individuals. Bioequivalence was not demonstrated between groups, which may be attributable to the relatively high level of variability in individual plasma profiles. More adverse events were reported by younger (216) than elderly (164) study participants. CONCLUSIONS: No dosage alterations are necessary for PK reasons when treating elderly people with buprenorphine transdermal patches.

Metabolism of alprazolam (a marker of CYP3A4) in hemodialysis patients with persistent inflammation.

OBJECTIVE: To investigate the impact of persistent inflammation in hemodialysis (HD) patients on the pharmacokinetics of alprazolam, a cytochrome P450 (CYP) 3A4 substrate, and its metabolites and the role of HD in the impact of persistent inflammation in this clinical context. METHODS: The study population comprised 26 HD patients (mean age 64 years, range 27-79 years; 19 men, 7 women) who were given 1 mg of alprazolam orally in the evening before the day of HD. Unconjugated and conjugated alprazolam and its 4-hydroxy and α-hydroxy metabolites were measured by liquid chromatography-mass spectrometry at 10, 34 (start of HD) and 38 (end of HD) h after intake. C-reactive protein (CRP) was measured weekly beginning 2 months before study initiation, and alpha 1-acid glycoprotein and 4ß-hydroxycholesterol were measured at baseline. CYP3A4 activity was estimated as the ratio of unconjugated alprazolam to 4-hydroxyalprazolam between 10 and 34 h following alprazolam intake. RESULTS: After a single dose of alprazolam, plasma concentrations of unconjugated alprazolam and its metabolites decreased gradually, and unconjugated 4-hydroxyalprazolam was eliminated more rapidly than unconjugated alprazolam by HD. In contrast, the plasma concentrations of conjugated alprazolam and its conjugated metabolites increased during the 34 h following drug intake and the subsequent HD decreased their levels by almost 80%. The ratio of unconjugated alprazolam to 4-hydroxyalprazolam was correlated with CRP levels (r(s) = 0.49, P = 0.01). There was no significant correlation between CYP3A4 activity measured by alprazolam (4-hydroxylation) and alpha 1-acid glycoprotein or 4ß-hydroxycholesterol. Conjugated alprazolam was also found in the plasma. CONCLUSIONS: The correlation between CYP3A4 activity (assessed by alprazolam 4-hydroxylation) and CRP level suggests that inflammation may downregulate CYP3A4 activity. If confirmed, this could have major implications for drug dosing in persistently inflamed patients.

Influence of the CYP2D6 polymorphism and hemodialysis on codeine disposition in patients with end-stage renal disease.

OBJECTIVE: We studied the influence of three factors on drug disposition: genetic polymorphism, impaired renal excretion of drug metabolites, and the possible elimination by hemodialysis (HD), using codeine as a model drug. METHODS: Based on the genotyping of three CYP2D6 polymorphisms in 228 HD patients, nine extensive metabolizers (EMs) and two poor metabolizers (PMs) were given a single oral dose of 50 mg codeine phosphate. Plasma concentrations of its metabolites codeine-6-glucuronide (C6G), morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were determined after 2, 4, 6, 8 and 24 h (beginning of the HD session) and again after 4 h of HD (28 h). Codeine metabolites in plasma were quantitated by liquid chromatography-mass spectrometry (LC-MS). RESULTS: The concentrations of C6G in plasma were high and similar in EMs and PMs. Two hours after the codeine intake, the mean concentration of M3G was 210 nM in EMs vs. 3.5 nM in PMs. The M6G metabolite concentrations could be quantitated in EMs but were below the limit of quantification in PMs (<1 nM). All three codeine metabolites/glucuronides remained unchanged or even increased until the start of HD, and thereafter, the concentrations decreased dramatically during the HD procedure. CONCLUSIONS: Formation of the codeine metabolites M3G and M6G was dependent on the CYP2D6 genotype, as previously shown in healthy individuals. Elimination of glucuronides in these patients was absent until HD was performed. These factors need to be taken into consideration when drugs metabolized by CYPs are prescribed in HD patients.

Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9.

PURPOSE: The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported. METHODS: We present a patient with Behçet's disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed. RESULTS: The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls. CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.

Daily dialyses decrease plasma levels of brain natriuretic peptide (BNP), a biomarker of left ventricular dysfunction.

Brain natriuretic peptide or B-type natriuretic peptide (BNP) is a sensitive marker of heart disease. Plasma levels of BNP increase in left ventricular failure and determination of plasma BNP has become a useful tool in the diagnosis of heart failure. Hemodialysis (HD) patients may have elevated plasma levels of BNP, particularly predialysis, that correlate with echocardiographic signs of left ventricular dysfunction. High BNP levels are also a strong predictor of mortality in both nonrenal and HD patients. We studied plasma BNP levels in patients who changed from conventional thrice-weekly dialysis to daily dialysis 6 times a week while maintaining a total weekly time on dialysis of 12 hr. Twelve HD patients, mean age 55 years, had 4 hr of conventional thrice-weekly treatment for 4 weeks. Predialysis and postdialysis blood samples were obtained at the last dialysis. Patients were then dialyzed for 2 hr, 6 times weekly, for 4 weeks (daily dialysis). Again, predialysis and postdialysis blood samples were collected at the last HD. Brain natriuretic peptide plasma concentrations were determined by immunoradiometric assay. Predialysis BNP levels decreased from 194+/-51 ng/L (68+/-19 pmol/L; mean+SE) during thrice-weekly HD to 113+/-45 ng/L (41+/-18 pmol/L; p = 0.001) after 4 weeks on daily dialysis. With thrice-weekly HD, predialysis BNP levels were higher than postdialysis levels: 120+/-26 ng/L (39+/-8 pmol/L; p = 0.059). With daily dialysis, predialysis BNP levels did not differ significantly from postdialysis levels. Elevated predialysis plasma levels of BNP, considered sensitive and early markers of left ventricular dysfunction, decreased when patients were changed from conventional thrice-weekly HD to daily dialysis maintaining total hours of dialysis per week constant. Given the accumulated evidence that BNP is a biomarker of left ventricular dysfunction and can be used for risk stratification and guidance in pharmacotherapy of heart failure, daily dialysis appears to lead to less cardiac distress.

Vasoactive Peptide Levels after Change of Dialysis Mode.

BACKGROUND/AIMS: Plasma concentrations of the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) are increased in end-stage renal disease. Improvement in hemodynamic stability has been reported when switching from hemodialysis (HD) to on-line hemodiafiltration (ol-HDF). The aim of this study was to investigate plasma concentrations of NT-proBNP, BNP and neuropeptide Y (NPY) during a 1-year follow-up, after a change from high-flux HD to postdilution ol-HDF. Additional variables were also studied, e.g. pulse wave velocity and ordinary clinical parameters. METHOD: We conducted a prospective, single-center study including 35 patients who were switched from HD to HDF. Plasma concentrations of NT-proBNP, BNP and NPY before and after dialysis were measured at baseline (i.e. HD) and at 1, 2, 4, 6 and 12 months on HDF. RESULTS: All three peptide levels decreased significantly during HD and HDF when comparing concentrations before and after dialysis. Mean absolute value (before/after) and relative decrease (%) before versus after dialysis was 13.697/9.497 ng/l (31%) for NT-proBNP, 62/40 ng/ml (35%) for BNP and 664/364 pg/l (45%) for NPY. No significant differences were observed when comparing predialysis values over time. However, postdialysis NT-proBNP concentration showed a significant decrease of 48% over time after the switch to HDF. CONCLUSION: The postdialysis plasma levels of NT-proBNP, BNP and NPY decreased significantly during both dialysis modes when compared to before dialysis. The postdialysis lowering of NT-proBNP increased further over time after the switch to ol-HDF; the predialysis levels were unchanged, suggesting no effect on its production in the ventricles of the heart.

Which Medication Is the Patient Taking at Admission to the Emergency Ward? Still Unclear Despite the Swedish Prescribed Drug Register.

INTRODUCTION: Correct information on patients' medication is crucial for diagnosis and treatment in the Emergency Department. The aim of this study was to investigate the concordance between the admission chart and two other records of the patient's medication. METHODS: This cohort study includes data on 168 patients over 18 years admitted to the Emergency Ward between September 1 and 30, 2008. The record kept by the general practitioner and the patient record of dispensed drugs in the Swedish Prescribed Drug Register were compared to the admission chart record. RESULTS: Drug record discrepancies of potential clinical significance between the admission chart record and the Swedish Prescribed Drug Register or general practitioner record were present in 79 and 82 percent, respectively. For 63 percent of the studied patients the admission chart record did not include all drugs registered in the Swedish Prescribed Drug Register. For 62 percent the admission chart record did not include all drugs registered in the general practitioner record. In addition, for 32 percent of the patients the admission chart record included drugs not registered in the Swedish Prescribed Drug Register and for 52 percent the admission chart record included drugs not found in the general practitioner record. The most discordant drug classes were cardiovascular and CNS-active drugs. Clinically significant drug record discrepancies were more frequent in older patients with multiple medication and caregivers. CONCLUSION: The apparent absence of an accurate record of the patient's drugs at admission to the Emergency Ward constitutes a potential patient safety hazard. The available sources in Sweden, containing information on the drugs a particular patient is taking, do not seem to be up to date. These results highlight the importance of an accurate list of currently used drugs that follows the patient and can be accessed upon acute admission to the hospital.

Development of a computerised decisions support system for renal risk drugs targeting primary healthcare.

OBJECTIVES: To assess general practitioners (GPs) experience from the implementation and use of a renal computerised decision support system (CDSS) for drug dosing, developed for primary healthcare, integrated into the patient's electronic health record (EHR), and building on estimation of the patient's creatinine clearance (ClCG). DESIGN: Qualitative research design by a questionnaire and a focus group discussion. SETTING AND PARTICIPANTS: Eight GPs at two primary healthcare centres (PHCs). INTERVENTIONS: The GP at PHC 1, and the project group, developed and tested the technical solution of the CDSS. Proof-of-concept was tested by seven GPs at PHC 2. They also participated in a group discussion and answered a questionnaire. A web window in the EHR gave drug and dosage in relation to ClCG. Each advice was according to three principles: If? Why? Because. OUTCOME MEASURES: (1) The GPs' experience of 'easiness to use' and 'perceived usefulness' at PHC 2, based on loggings of use, answers from a questionnaire using a 5-point Likert scale, and answers from a focus group discussion. (2) The number of patients aged 65 years and older with an estimation of ClCG before and after the implementation of the CDSS. RESULTS: The GPs found the CDSS fast, simple and easy to use. They appreciated the automatic presentation of the CICG status on opening the medication list, and the ability to actively look up specific drug recommendations in two steps. The CDSS scored high on the Likert scale. All GPs wanted to continue the use of the CDSS and to recommend it to others. The number of patients with an estimated ClCG increased 1.6-fold. CONCLUSIONS: Acceptance of the simple graphical interface of this push and pull renal CDSS was high among the primary care physicians evaluating this proof of concept. The graphical model should be useful for further development of renal decision support systems.

Neuropeptide-Y and atrial natriuretic peptide as prognostic markers in patients on hemodialysis.

We conducted a study of the influence of the vasoactive peptides atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) on survival of patients on hemodialysis and their association and relative importance with cardiac and clinical variables. Thirty-three hemodialysis patients were characterized by age, sex, diagnosis, blood pressure, serum (S)-albumin, serum (S)-urea, hemoglobin, dialysis dose, weight gain, duration of dialysis, cardiac hypertrophy, volume, failure, and ischemia and plasma levels of ANP and NPY. The outcomes were analyzed for early deaths (< 1 year) and for all deaths. The association of the variables to early deaths and all deaths, respectively, was studied in Cox proportional hazard analyses. The variables were also studied in three hierarchical steps: clinical variables only, clinical and cardiac variables, and all variables. For all deaths, the independent variables were plasma NPY (pmol/L) (hazard ratio [HR] = 1.035, p = 0.004), heart volume (ml/m2) (HR = 1.009, p = 0.001), and S-albumin (g/L) (HR = 0.750, p = 0.034). For early deaths, the independent variables were predialysis ANP (pmol/L) (HR = 1.008, p = 0.034) and NPY (pmol/L) (HR = 1.031, p = 0.026). In the hierarchical study, excluding the vasoactive peptides, heart volume, heart failure and S-albumin were independently associated with all deaths, and mean arterial blood pressure was associated with early death. When also excluding the cardiac parameters, S-albumin was associated with all deaths and mean arterial blood pressure with early death. In conclusion, plasma levels of the vasoactive peptides ANP and NPY are the most important group in a hierarchy of variables that predict imminent death in hemodialysis patients, and NPY is associated with late death. ANP and NPY apparently sum up the detrimental influence of many factors in hemodialysis patients.

The effects of hemodialysis treatment on the level of DNA strand breaks and oxidative DNA lesions measured by the comet assay.

Hemodialysis patients have a higher risk for oxidative stress-related complications, such as cardiovascular disease and cancer. The increased level of oxidative stress is due to several factors, e.g., the hemodialysis treatment itself and the uremic state. In the present study, the effects of dialysis treatment on the level of DNA breaks and oxidative DNA lesions in mononuclear cells were measured with the comet assay. Factors possibly affecting DNA damage (reported as % DNA in tail) such as the duration of dialysis, time since last dialysis session, years of dialysis treatment, nutritional status (measured as protein catabolic rate), age, and diabetes were also investigated. The levels of DNA breaks (13.6 ± 4.7 before dialysis) and oxidative DNA lesions (7.9 ± 4.8 before dialysis) were significantly higher in dialysis patients (n = 31) compared to the levels of DNA breaks (5.8 ± 1.1) and oxidative DNA lesions (3.4 ± 1.7) in 10 healthy controls (P < 0.001). A decrease of DNA breaks was observed after dialysis (P = 0.038), and the level of oxidative DNA lesions was higher when the time between two treatment sessions were 68 hours compared to 44 hours (P < 0.001). Older subjects had a higher level of DNA breaks (P = 0.003), a good nutritional status predicted a lower level of DNA breaks (P < 0.001), and the duration of the dialysis session was inversely correlated with oxidative DNA lesions (P = 0.014). Diabetes or years of dialysis treatment did not affect DNA damage. The observations in the present study suggest that accumulation of uremic toxins induce DNA damage. The hemodialysis treatment seems to change the DNA damage.

Renal function estimations and dose recommendations for dabigatran, gabapentin and valaciclovir: a data simulation study focused on the elderly.

OBJECTIVES: The thrombin inhibitor dabigatran is mainly excreted by the kidneys. We investigated whether the recommended method for estimation of renal function used in the clinical trials, the Cockcroft-Gault (CGold) equation and the estimated glomerular filtration rate (eGFR) modification of diet in renal disease equation 4 (MDRD4), differ in elderly participants, resulting in erroneously higher dose recommendations of dabigatran, which might explain the serious, even fatal, bleeding reported. The renally excreted drugs gabapentin and valaciclovir were also included for comparison. DESIGN: A retrospective data simulation study. PARTICIPANTS: Participants 65 years and older included in six different studies. MAIN OUTCOME MEASURE: Estimated renal function by CG based on uncompensated ('old Jaffe' method) creatinine (CGold) or by MDRD4 based on standardised compensated P-creatinine traceable to isotope-dilution mass spectrometry, and the resulting doses. RESULTS: 790 participants (432 females), mean age (±SD) 77.6±5.7 years. Mean estimated creatinine clearance (eCrCl) by the CGold equation was 44.2±14.8 ml/min, versus eGFR 59.6±20.7 ml/min/1.73 m(2) with MDRD4 (p<0.001), absolute median difference 13.5, 95% CI 12.9 to 14.2. MDRD4 gave a significantly higher mean dose (valaciclovir +21%, dabigatran +25% and gabapentin +37%) of all drugs (p<0.001). With MDRD4 58% of the women would be recommended a full dose of dabigatran compared with 18% if CGold is used. CONCLUSIONS: MDRD4 would result in higher recommended doses of the three studied drugs to elderly participants compared with CG, particularly in women, and thus increased the risk of dose and concentration-dependent adverse reactions. It is important to know which method of estimation of renal function the Summary of Products Characteristics was based on, and use only that one when prescribing renally excreted drugs with narrow safety window. Doses based on recently developed methods for estimation of renal function may be associated with considerable risk of overtreatment in the elderly.

Phosphorus dynamics during hemodialysis.

We studied phosphorus (P) dynamics and its relation to urea dynamics in a wide range of dialyses by measuring predialysis and postdialysis serum P levels and all removed P and urea in dialysate during 455 hemodialyses. Dialyses were performed at different frequencies (range 3-6 treatments/wk); duration of dialysis (t) (range 80-560 minutes), varied blood and dialysate flow, and with high-flux and low-flux membranes. Kt/V-P, Kt/V-urea, weekly removal of P-and urea and removal volumes (Vr) and their relationships to varying dialyses, and predialysis concentrations, and protein catabolic rates were studied in linear and multiple regression analyses. A weekly dialysis time of > 30 hours was needed to maintain serum P concentration normal without the use of phosphate binders. Vr-P as a percentage of body weight was dependent on predialysis serum P and increased steeply as predialysis serum P decreased and dialysis time was prolonged. There was no relationship between Vr-urea and Vr-P. Phosphorus removal per week was mainly dependent on weekly frequency, and time on dialysis and > 38 h/wk were necessary to remove the recommended P intake. Phosphorus shows highly variable dynamics during dialysis. The body maintains extracellular P concentration by releasing P from large compartments when the dialysis time is prolonged and the serum concentration of P decreases during dialysis. Vr-P shows huge variation between patients and in an individual patient, depending on predialysis serum P. Kt/V is inaccurate in describing P removal. To remove P efficiently, it is most important to perform long and more frequent hemodialysis.

Adverse drug reactions and impaired renal function in elderly patients admitted to the emergency department: a retrospective study.

BACKGROUND: Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk. OBJECTIVES: To study ADRs as a cause of acute hospital admissions in a defined cohort of elderly patients (aged >or=65 years) registered to receive home healthcare services, with special reference to impaired renal function as a possible risk factor. METHODS: This was a retrospective study of 154 elderly patients aged >or=65 years admitted to the emergency department of a university hospital in Stockholm, Sweden, in October-November 2002. Estimated creatinine clearance (eCL(CR)) was calculated from the Cockcroft-Gault formula, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation. ADRs were defined according to WHO criteria. All medications administered to patients at admission and at discharge were collated. These and other data were collected from computerized hospital records. RESULTS: ADRs were judged to contribute to or be the primary cause of hospitalization in 22 patients, i.e. 14% of 154 patients registered to receive home healthcare. Eleven of the 22 patients were women. All but one ADR were type A. Excessive doses or drugs unsuitable in renal insufficiency were present in seven patients in the ADR group compared with only four patients in the group without ADRs (p = 0.0001). Patients with ADRs did not differ significantly from those without ADRs in relation to age, plasma creatinine, eCL(CR), weight or number of drugs prescribed at admission. However, women with ADRs were significantly older than women without ADRs (mean +/- SD age 88.8 +/- 5.7 years vs 82.5 +/- 8.0 years, respectively; p = 0.014) and had significantly lower mean +/- SD eCL(CR) values (25.5 +/- 10.8 and 37.1 +/- 17.1 mL/min, respectively; p = 0.035). Median MDRD eGFR was significantly higher than median eCL(CR) (59 [range 6-172] mL/min/1.73 m2 vs 38 [range 5-117] mL/min, respectively; p = 0.0001). CONCLUSIONS: In elderly patients registered to receive home healthcare, 14% of hospital admissions were primarily caused by ADRs. One-third of these ADRs were related to impaired renal function, generally in very old women. These ADRs may be avoided by close monitoring of renal function and adjustments to pharmacotherapy (drug selection and dose), particularly in very elderly women.

Renal function in community-dwelling frail elderly. Comparison between measured and predicted glomerular filtration rate in the elderly and proposal for a new cystatin C-based prediction equation.

BACKGROUND AND AIMS: There is a great need to evaluate renal function regularly in elderly people. This study aimed at analyzing renal function in stable, community-dwelling elderly people of 75 years and over, to compare measured and predicted glomerular filtration rates (GFR) and to develop an accurate prediction equation for this age group. METHODS: Forty-five ambulatory elderly people in stable health in ordinary living were randomly selected into four age-classes, aged 75-95. Demographic data, personal activities of daily living, continuous drug prescriptions, body composition, blood pressure and blood chemistry were analysed. GFR was measured as Iohexol clearance based on three time-points 3, 4 and 7 hours after Iohexol injection. RESULTS: Mean GFR was well preserved in all four age-classes. The GFR range was 18-83 mL/min and declined with age. The Cockcroft-Gault prediction equation systematically underestimated measured GFR. A new 'GFRA' prediction equation is presented, based on the inverse of serum cystatin C and independent of gender, body surface area, body weight, lean body mass or serum creatinine. The proposed equation underestimated measured GFR with a mean of only 0.1 mL/min, had better precision compared with the Cockcroft-Gault equation, and was evaluated by the method of cross-validation. CONCLUSIONS: GFR exhibits extensive heterogeneity in frail, community-dwelling elderly people. The proposed GFRA was clearly more precise than the Cockcroft-Gault prediction equation in the study group. However, it needs to be validated in a larger population of elderly subjects, including more individuals in stable health with substantially reduced renal function in whom GFR is measured by a reference method with adequate sampling time.

Concentrations of vitamin C, vitamin B12 and folic acid in patients treated with hemodialysis and on-line hemodiafiltration or hemofiltration.

OBJECTIVE: Uncertainty has arisen as to whether vitamin supplements are needed by dialysis patients, in particular those treated by means of hemofiltration or hemodiafiltration using highly permeable (high-flux) filters. We therefore measured the concentrations of vitamin C, cobalamin (vitamin B12) and folic acid in conventional (low-flux) dialysis patients and in those receiving on-line treatment (hemofiltration or hemodiafiltration). MATERIAL AND METHODS: Plasma (P-)ascorbate, serum (S-)cobalamin and S-folate concentrations were measured before and after a treatment session in 15 patients treated with low-flux hemodialysis and in 14 treated with on-line hemofiltration or hemodiafiltration. The patients' vitamin supplementations were also recorded. RESULTS: P-ascorbate concentrations were lowered by 51% and 53% in the hemodialysis and on-line groups, respectively after treatment and this reduction was significant (p<0.001). Concentrations below the reference values were found in 12/14 patients not receiving vitamin C supplementation. S-cobalamin did not decrease in the hemodialysis or on-line groups. S-folates did not change significantly in the hemodialysis or filtration groups. Patients without folacin supplementation had low values. CONCLUSIONS: P-ascorbate was reduced by both dialysis and filtration treatments. Neither S-cobalamin nor S-folate were reduced by dialysis or filtration treatments.